Proefschrift van de Put

RHEGMATOGENOUS RETINAL DETACHMENT

Incidence, risk factors, postoperative

recovery & vision related quality of life

M.A.J. van de Put

RH

EG

MA

TO

GE

NO

US R

ET

INA

L D

ET

AC

HM

EN

T In

ciden

ce, risk factors, p

ostoperative recovery &

vision related

qu

ality of life M

.A.J. van

de P

ut

INVITATION

For the public defense of the thesis:


Mathijs van de Put

Wednesday, December 10th, 2014

11 A.M.Academy building

University of GroningenBroerstraat 5Groningen

Noon Reception

Academy building

2 P.M. Informal reception

Café de Oude WachtGed. Zuiderdiep 3 Groningen

Mathijs van de PutBoumaboulevard 3239723 ZS Groningen

T: [email protected]

Paranymphs

Roel van de PutT: 0614278881

[email protected]

Jelle VehofT: 0644949999

[email protected]


Incidence, risk factors, postoperative recovery & vision related quality of life

M.A.J. van de Put

VandePut.indd 1 4-11-2014 14:15:45

The research presented in this study was financially supported by:

De Professor Mulder Stichting, Stichting Blindenhulp. Stichting Nederlands Oogheelkundig

Onderzoek.

Publication of this thesis was financially supported by:

De Professor Mulder Stichting, Rijksuniversiteit Groningen, Alcon Nederland B.V., Theapharma,

Ursapharm, AMO Abbot Medical Systems, Rockmed, Ophthec, Bausch & Lomb, Oculenti,

ZEISS, Allergan, ABN-Amro bank.

Copyright © 2014 M.A.J. van de Put

All rights reserved. No parts of this thesis may be reproduced, stored in a retrieval system, or

transmitted, in any form or by any means, electronical, mechanical, photocopying, recording, or

otherwise, without the written permission of the author and the publisher holding the copyright

of the published articles.

ISBN: 978-90-367-7361-4

e-ISBN: 978-90-367-7360-7

Printed by: Gildeprint

Cover design: Gildeprint

Lay-out: M.A.J. van de Put & Gildeprint

VandePut.indd 2 4-11-2014 14:15:45

Rhegmatogenous Retinal Detachment

Incidence, risk factors, postoperative recovery & vision related quality of life

Proefschrift

ter verkrijging van de graad van doctor aan de

Rijksuniversiteit Groningen

op gezag van de

rector magnificus prof. dr. E. Sterken

en volgens besluit van het College voor Promoties.

De openbare verdediging zal plaatsvinden op

woensdag 10 december 2014 om 11:00 uur

door

Mathijs Arnoldus Johannes van de Put

geboren op 6 november 1981

te Tilburg

VandePut.indd 3 4-11-2014 14:15:45

Promotor

Prof. dr. J.M.M. Hooymans

Copromotor

Dr. L.I. Los

Beoordelingscommissie

Prof. dr. R.J.W. de Keizer

Prof. dr. J.E.E. Keunen

Prof. dr. H.P.H. Kremer

VandePut.indd 4 4-11-2014 14:15:45

Paranimfen

R.J.S. van de Put, MSc

Dr. J. Vehof

VandePut.indd 5 4-11-2014 14:15:45

VandePut.indd 6 4-11-2014 14:15:45

“Stay hungry, stay healthy, be a gentleman, believe strongly in yourself and go beyond limitations.”

– Arnold Schwarzenegger –

Voor Raquel & Aaron

VandePut.indd 7 4-11-2014 14:15:45

VandePut.indd 8 4-11-2014 14:15:45

Contents | 9

CONTENTS

Chapter 1 General introduction 11

Part I EPIDEMIOLOGY

Chapter 2 The incidence of rhegmatogenous retinal detachment surgery in the

North of the Netherlands 27

Chapter 3 The incidence of rhegmatogenous retinal detachment in The Netherlands 43

Ophthalmology 2013 120: 616-622.

PART II CLINICAL STUDIES

Chapter 4 Design and validation of a method to determine the position of the

fovea by using the optic nerve-head to fovea distance of the fellow eye 61

Plos One, May 2013: 8:5:e99787

Chapter 5 Postoperative recovery of visual function after macula-off

rhegmatogenous retinal detachment 77

Plos One, June 2014: 9:6:e99787

Chapter 6 Postoperative vision-related quality of life in macula-off

rhegmatogenous retinal detachment and its relation to visual function 93

Submitted

Chapter 7 Postoperative metamorphopsia in macula-off rhegmatogenous retinal

detachment: associations with visual function, vision related quality of

life, and optical coherence tomography findings 117

Submitted

Chapter 8 Summary & conclusions 131

Chapter 9 Dutch summary & conclusions 135

VandePut.indd 9 4-11-2014 14:15:45

10 | Contents

Appendices

Abbreviations 141

Acknowledgements 143

List of publications 147

Biography 148

VandePut.indd 10 4-11-2014 14:15:45

Chapter 1

General introduction

VandePut.indd 11 4-11-2014 14:15:45

12 | Chapter 1

INTRODUCTION

Rhegmatogeneous retinal detachment (RRD) refers to a detachment between the neuroretina

and the underlying retinal pigment epithelium (RPE) due to one or more breaks / tears in the

neuroretina (rhegma means break in Greek).[1] The outer neuroretina, consisting of rods and cones,

is the light sensitive layer of the eye.[2] The RPE is responsible for outer neuroretinal metabolism.[2] In addition, the RPE is responsible for keeping the neuroretina in its attached position, by the

outward movement of fluid across the RPE and towards the choroid.[2] For an RRD to develop, a

cascade of events has to take place.

PATHOPHYSIOLOGY OF RHEGMATOGENOUS RETINAL DETACHMENT

The first event in this cascade is posterior vitreous detachment (PVD).[1-3] The vitreous body is a

gel-like structure and fills the eye. The greatest part of vitreous consists of water (98-99%).[4] The

remaining part consist of inorganic salts and organic lipids of low molecular weight (1%).[4-5] A small

percentage of vitreous consist of macromolecules (0.1%) (i.e glycosaminoglycans (i.e. hyaluronan),[4-6]

proteoglycans,[4-5] glycoproteins,[7-9] collagens (responsible for maintaining stabilisation of the

vitreous gel)[10-16] and noncollagenous structural proteins).[8,17-18] With advancing age, morphological

changes in the vitreous take place.[3,19-20] There is a progressive increase in the volume of liquefied

spaces (synchisis),[3,19-20] and an increase in optically dense areas (syneresis).[3,21] Synchisis is

characterized by the replacement of vitreous gel by liquefied vitreous (free of collagen fibrils)

which is surrounded by optically dense structures and condensations.[3,19-20] As these alterations

progress with age, they may interfere with the passage of light and cause symptoms referred to

as “mouches volantes” or floaters.[1] During aging, posterior vitreoretinal attachments weaken,

and anterior vitreoretinal adhesions increase.[22-24] Finally, these processes may lead to a PVD, a

separation between the vitreous cortex and the retina.[1,3] Because of traction of the vitreous at the

retina, patients may experience flashes of light, and a tear may occur in the retina.[1]

The formation of a retinal tear is the second step in the cascade.[25-26] Retinal tears occur in about

15% of patients with acute PVD.[26] These tears most likely occur at the peripheral (equatorial

and anterior) retina were the vitreous is most firmly attached to the retina.[27] Finally, as a result

of the tear(s) in the retina, fluid from the vitreous cavity can penetrate through the tear in the

neuroretina, in the potential subretinal space between the neuroretina and the RPE.[1] As long as

the rupture is open, and the RPE pump remains overwhelmed (depending on the distance between

RPE and neuroretina), an RRD tends to extend itself due to gravity, as the subretinal fluid is

heavier than the vitreous. This will eventually result in a total detachment of the retina.[1]

VandePut.indd 12 4-11-2014 14:15:45

General introduction | 13

1Approximately 126 million sensory cells are present in the neuroretina.[2] Histologically, - viewed

from vitreous to RPE – the neuroretina consists of the internal limiting membrane (ILM), nerve

fiber layer ((NFL i.e. the axons of the ganglion cell layer), ganglion cell layer, inner plexiform layer,

inner nuclear layer, outer plexiform layer, outer nuclear layer (i.e. the nuclei of the photoreceptors),

external limiting membrane (ELM), and the rod and cone inner and outer segments.[2] The

photoreceptor cells can be divided into rods (sensitive to dark and light changes) and cones (color

differences).[2] Central visual function (visual acuity, contrast acuity, and color vision) occurs

particularly with the macula, which primarily consists of cones.[2] In darker conditions, vision

depends on the periphery of the retina containing predominantly rods and fewer cones.[2] The

metabolic needs of the inner layers of the neuroretina are met by the central retinal artery and its

branches.[2] The metabolism of the outer layers of the neuroretina is largely dependent on their

attachment to a well-functioning RPE.[2] During an RRD, the outer layers of the neuroretina get

deprived of their immediate source of nourishment through the RPE and choroid.[28] As a result of

an RRD, the neuroretina gets dependent on the subretinal fluid for nourishment.[28] Depending on

the duration of the detachment and the distance between the neuroretina and the RPE, irreversible

retinal damage may occur.[28-39]

RISK FACTORS OF RHEGMATOGENOUS RETINAL DETACHMENT

Patients at risk for developing RRD are those of 55-65 years of age, and of male gender.[40-48]

Particular at risk are eyes of patients who have had previous cataract extraction (CE), ocular

trauma, or who are myopic.[40-53]

Age & posterior vitreous detachment

There is a strong association between increasing age and RRD.[40-53] The high incidence rates of

RRD at 55-65 years of age, may well be explained by the occurrence of a PVD around this age.[3,25]

PVD is generally assumed to be the main cause of RRD,[3,25] PVD is a rarity in individuals younger

than 50 years of age; on average, its onset is at 60 years, with increasing prevalence thereafter.[3,25]

Male gender

Many studies observed a preponderance for RRD in males.[44-47,53-55] A possible explanation for this

may be differences in the prevalence of the other risk factors in males in contrast to females. For

instance, symptomatic PVD even though more common in females than males,[3,56-58] is more often

complicated by a retinal tear in males, possibly resulting in a higher attributable RRD risk in

males.[25] In addition, some suggested that the attributable risk of RRD from ocular trauma may

be higher in males than in females,[54] which will consequently lead to a higher RRD incidence in

males.[54] Finally, a history of cataract surgery or myopia may be more prevalent in males.

VandePut.indd 13 4-11-2014 14:15:45

14 | Chapter 1

Cataract surgery

The cumulative risk of RRD is increased in eyes with a history of CE.[41,50] The RRD risk in

eyes with a history of CE depends on the surgical technique used.[50] Intracapsular cataract

extraction (ICCE) holds the highest and extracapsular cataract extraction (ECCE), yields the

second highest risk of RRD.[50,59-60] Both techniques have been replaced by the safer procedure

of phacoemulsification, which holds the lowest risk of the three surgical techniques.[50] Several

theories concerning the pathophysiological mechanisms on phakic versus post-CE RRD have

been advocated. First, a newly induced PVD[61-63] in non-PVD eyes can occur, because CE causes

mechanical[44] and biochemical changes[63] in the vitreous.[61-63] Also, a second mechanism could be

at play, namely, the altered mechanical forces at the anterior vitreous base area because of the loss

of lens volume.[64]

Ocular trauma

Direct and indirect injuries may give rise to RRD.[65] Direct injuries, such as penetrating and

perforating trauma, may give rise to two types of RRD.[65] The first type is an RRD at the time

of trauma, owing to the trauma.[65] The second is an RRD at a later stage, due to cicatrisation and

traction of scar tissue.[65] Indirect injuries act not as the primary cause of RRD but merely as the

precipitating agent in an eye already prone to retinal tearing.[65] The sudden strain may luxate

the formation of a tear in a predisposed area of the retina (i.e. degenerative changes or region of

weakness).[65]

Myopia

It has consistently been found that high myopia is associated with RRD.[40-41,43] Myopia as a risk

factor of RRD may be due to the more common presence of degenerative changes in the peripheral

retina, as well as the development of early degeneration of the vitreous in myopic eyes.[66] It has

been estimated that about two-thirds of RRD cases occur in myopes, whereas in more than half of

these no other obvious cause was noted.[66] Moreover, they tend to develop RRD at an earlier age

than hypermetropes and emmetropes.[66] The peak incidence of RRD in myopes is at ages 36 to

40 years as compared to a peak incidence of 55 to 65 years in the entire population.[66]

RRD-incidence in relation to the prevalence of risk factors

The annual incidence of primary RRD is reported to be between 8 and 14 per 100,000 persons,

with a peak incidence in the 7th decade of life.[40-48,51-55] Population ageing is a shift in the

distribution of a country’s population towards older ages. This is usually reflected in an increase

in the population’s mean or median ages, a decline in the proportion of the population composed

of children, and a rise in the proportion of the population that is elderly. Population ageing is

widespread across the world. It is most advanced in the most highly developed countries. The

incidence of PVD increases in the elderly population, and is a significant risk factor for acquiring

VandePut.indd 14 4-11-2014 14:15:45


1RRD.[3,56] In addition, the prevalence of cataract and hence cataract extractions, another significant

risk factor of RRD, increases in the elderly population.[50] Population aging may therefore lead to

a higher incidence of RRD in aging populations.

TREATMENT OF RHEGMATOGENOUS RETINAL DETACHMENT

Historical perspective

Because of Gonin, a surgical therapy for RRD patients became available almost 100 years ago.

Before this, acquiring an RRD would eventually in almost all cases implicate blindness.[67-68]

Gonin recognized that - although all patients had a variable presentation - the aim of the treatment

had to be to close or effectively isolate the perforation in the retina, resulting in reattachment

of the detached retina.[67] To do so, a watertight adhesion between the neuroretina and choroid

surrounding the retinal tear had to be made, followed by drainage of subretinal fluid.[67]

Although the basic principle as proposed by Gonin, remained the cornerstone of the

treatment of RRD, the methods to do so evolved.[67] Gonin used thermocautery to close the retinal

hole.[67] Thermocautery was replaced by diathermy.[68] To reduce further chorioretinal reaction,

cryoapplication was introduced.[68] Silicone was introduced as buckling or encircling material to

close the retinal hole.[68] Others realised that drainage of subretinal fluid was not essential for

reattachment of the retina.[67] The surgical success rate kept increasing by the introduction of these

new techniques.

However, in some cases surgical attempts to reattach the retina fail. This is mainly due to

proliferative vitreoretinopathy (PVR).[69] PVR is the development of contractile membranes

around the retina, detaching or preventing attachment of the neuroretina to the RPE, which

occurs in 5-10% of cases.[70-73] Further, some retinal detachments were inoperable due to PVR.

The development and introduction of the trans pars plana vitrectomy (TPPV) by Machemer

became the solution for these challenging cases.[68,74-76] Further developments were the introduction

of intraocular tamponading gases, silicone oils, and smaller vitrectomes. Today, the following

surgical methods are used: pneumatic retinopexy, scleral buckling, and trans pars plana vitrectomy

(TPPV). With these methods, surgical reattachment of the detached retina is successful in > 95%

of cases after one or more surgical procedures.[77-78] Surgical failure is primarily caused by severe

PVR.[70-73] Other causes are new- or missed breaks.

Pneumatic retinopexy

In pneumatic retinopexy, a bubble of expandable gas (e.g. hexafluoride (SF6)) is injected into the

eye.[68,79-81] When the detached neuroretina becomes reattached to the RPE, cryocoagulation or

lasercoagulation is performed at the location of the tear.[68,79-81] This technique can be successfully

VandePut.indd 15 4-11-2014 14:15:45

16 | Chapter 1

used in case of one tear or multiple tears within 1 clock hour if the tear is localized within the

superior 8 clock hours (8 to 4 o’clock), and there are no abnormalities such as PVR.[68]

Scleral buckling surgery

In scleral buckling, an encircling band may be sutured around the circumference of the sclera,

under the ocular muscles.[67-68] A grooved (radial, circumferential, or other) buckle (solid silicone

rubber or silicone sponge) is placed either directly at the sclera at the level of the tear or placed

under an encircling band at the level of the tear.[67-68] Using this method, an indentation in the eye

wall is created causing the underlying choroid and sclera to press against the retinal tear and close

it.[67-68] To reduce the volume of subretinal fluid, transscleral puncture can be performed.[67-68]

Thereafter, applying cryocoagulation around the tear can achieve adhesion of the retina.[67-68] In

addition, a bubble of expandable gas (e.g. hexafluoride (SF6)) may be injected into the eye to

achieve adhesion between the neuroretina and the underlying choroid.[67-68] This technique is most

commonly performed in case of one or more tears (i.e. horseshoe shaped tear, round holes, ora

dialysis), and a retinal detachment extending over one or two quadrants.[82]

Trans Pars Plana Vitrectomy

TPPV is the surgical removal of vitreous through sclerotomies, (small incisions in the pars

plana).[68,74-76] Sclerotomies are made at 3-5 mm from the corneal limbus.[68,74-76] The slerotomies

can be of various sizes, they can be self-sealing or non-self sealing, and the vitreous cavity can be

accessed through the sclerotomies with or without the use of trocars. One of the sclerotomies is

used for fluid infusion to maintain intraocular pressure. The other two sclerotomies enable the

surgeon to work bimanually. A high intensity fibre optic light source (inserted through one of the

sclerotomies) is used to illuminate the inside of the eye during surgery. After removing the vitreous,

drainage of subretinal fluid through a retinal tear is performed. Thereafter, endolasercoagulation

or exocryocoagulation around the tear can achieve adhesion of the retina. To maintain some

degree of postoperative pressure on the retina and to achieve stronger adhesion, a gas bubble

or oil can be injected. This technique is indicated in the more challenging cases of RRD (i.e.

severe proliferative vitreoretinopathy (PVR), giant retinal tears and those presenting with vitreous

haemorrhage).[68,74-76]

Choosing a surgical technique

Primary cases of RRD vary from relatively local detachment with one tear to total detachments,

with numerous tears, and severe PVR. Therefore it is impossible to dogmatize the choice of

technique for particular cases. The common sense is to use the simplest method applicable to a

particular case of RRD (i.e. pneumatic retinopexy or scleral buckling in relatively straightforward

cases, and TPPV in more challenging cases). In between this spectrum of relatively straightforward

cases and more challenging ones, there is a grey zone. The selection of one particular surgical

VandePut.indd 16 4-11-2014 14:15:45


1procedure in these cases is still a matter of ongoing debate, although, a shift towards TPPV in

these cases has been observed in several countries including the Netherlands.[83-88]

POSTOPERATIVE RECOVERY OF VISUAL FUNCTION

Postoperative recovery of visual function in rhegmatogenous retinal detachment

The postoperative recovery of visual function may be disappointing in RRD patients. This is

particularly true in macula-off RRD. For example, only 42% of macula-on detachment eyes

achieve 20/40 visual acuity or better, whereas only 37% of macula-off detachment eyes achieve

20/50 visual acuity or better.[77-78] Postoperative contrast acuity scores after macula-off RRD are

lower when compared to a control group of similar age[89] and to fellow eyes.[32] Postoperative color

vision disturbances are significantly more present in macula-off RRD eyes, when compared to

their healthy fellow eyes.[32,36] In addition, in macula-off RRD postoperative metamorphopsia is a

highly prevalent problem that occurs in around two-thirds of patients. Postoperative vision related

quality of life is worse in macula-off RRD patients compared to macula-on RRD patients.[90-91]

Vision related quality of life is strongly related to postoperative visual function (i.e. best corrected

visual acuity (BCVA), contrast acuity, and color vision disturbances) in macula-off RRD patients.[92-94]

Postoperative recovery of visual function in macula-off detachments

The most important factors that may negatively influence functional recovery after macula-off

RRD are a longer duration of macular detachment,[29-30,36,42,77,95-97] and a larger height of macular

detachment at presentation.[28,36-39,77] In contrast to the above mentioned, a shorter or longer

duration of macular detachment within the first week (24 hours – 1 week) does not affect final

visual outcome.[29-30,33] It is therefore common clinical practice to consider macula-off RRD eyes

with macular detachment of one week a surgical urgency, but not an emergency. Within the first

week of macular detachment, a lower height of macular detachment is associated with better

postoperative visual acuity.[37]

HYPOTHESIS ADRESSED

We had several main goals while conducting this study. Our first goal was to identify disease

incidence and risk factors for acquiring RRD in our population (both in our own adherent

population in the North of the Netherlands, as well as in the entire Dutch population). Our

second goal was to identify various factors that influence postoperative recovery of visual function

in macula-off RRD (prior to this we validated a measuring method to obtain reliable results).

VandePut.indd 17 4-11-2014 14:15:45

18 | Chapter 1

Our third goal was to determine postoperative vision related quality of life in macula-off RRD,

and to determine which factors (postoperative visual function, surgery or patient related factors)

have an effect on the vision related quality of life. Our final goal was to determine postoperative

metamorphopsia prevalence, and its relation to postoperative optical coherence tomography (OCT)

disturbances. In addition, we were interested if these disturbances affect visual function, and hence

vision related quality of life.

To achieve these various goals, we first determined RRD incidence in the North of the Netherlands,

and in the Netherlands. In chapter 2 we describe both the incidence of RRD surgery, and risk

factors in 2008 and 2009 in the North of the Netherlands. Additional analyses are performed

to demonstrate that RRD surgery incidence in this area remains steady over a two-year period.

We state that in case of RRD surgery, the subpopulation in the North of the Netherlands can be

considered as representative for the entire Dutch population. Chapter 3 describes the incidence

of RRD and macula-off RRD in the Netherlands in 2009. In addition, we give descriptive

information on risk factors, such as the percentage of patients with previous cataract extraction,

and the distribution of age and gender in our RRD population in relation to demographic

characteristics of our population. We also comment on a possible increase in RRD incidence in

our population due to population aging. Chapter 4 describes a measuring method to determine

the position of the fovea by ultrasonography (USG), using fundus photographs. This method was

designed to be able to determine macular height in our prospective study on the recovery of visual

function after surgery for macula-off RRD. In that way, we could evaluate the effect of macular

height on the postoperative recovery of visual function in macula-off RRD. In Chapter 5 the

effect of various pre-operative factors (age, preoperative refractive error, duration, and height of

macular detachment) on the postoperative recovery of visual function in macula-off RRD patients

is described. Chapter 6 comments on postoperative vision related quality of life in macula-off

RRD patients. In addition, correlations with postoperative visual function are addressed as well as

various patient related factors. In Chapter 7, the prevalence of postoperative metamorphopsia is

addressed and its relation with OCT disturbances is evaluated as well as the effect of both aspects

on vision related quality of life. In Chapters 8 & 9 an English summary and a Dutch summary

are provided.

VandePut.indd 18 4-11-2014 14:15:46


1REFERENCES

1. D’Amico DJ (2008) Primary retinal detachment. N Engl J Med 359: 2346-2354.

2. Weiss JS (2009) Basic anatomy. In: Retina and vitreous. In: Regillo C, Holekamp N, Johnson MW,

Kaiser PK, Hermann D et al. editors. Basic and Clinical Science Course. pp. 7-17.

3. Foos RY, Wheeler NC. (1982) Vitreoretinal juncture. Synchysis senilis and posterior vitreous

detachment. Am Acad Ophthalmol 89: 1502-1512.

4. Scott JE. (1992) The chemical morphology of the vitreous. Eye 6: 553-555.

5. Scott JE. (1995) Extracellular matrix, supramolecular organization and shape. J Anat 187: 259-269.

6. Meyer K, Palmer JW. (1934) The polysaccharide of the vitreous humor. J Biol Chem. 107: 629-634.

7. Haddad A, de Almeida JC, Laicine EM, Fife RS, Pelletier G. (1990) The origin of the intrinsic

glycoproteins of the rabbit vitreous body: an immunohistochemical and autoradiogahic study. Exp

Eye Res. 50: 555-561.

8. Bishop PN. (2000) Structural macromolecules and supramolecular organization of the vitreous gel.

Prog Rein Eye res. 19: 323-344.

9. Reardon AJ, le Goff M, Briggs MD, McLeod D, Sheehan JK, et al. (2000) Identification in vitreous

and molecular cloning of opticin, a novel member of the family of leucine-rich repeat proteins of the

extracellular matrix. J Biol Chem 275: 2123-2121.

10. Bishop PN, Crossman MV, McLeod D, Ayad S. (1994) Extraction and characterization of the tissue

forms of collagen types II and IX from bovine vitreous. Biochem J. 229: 497-505.

11. Ayad S, Weiss JB. (1984) A new look at vitreous-humour collagen. Biochem J. 218: 835-840.

12. Mayne R, Brewton RG, Wright DW, Ren ZX. (1991) Morpholocial and biochemical studies of the

structure of the vitreous and the zonular fibres. Biochem Soc Trans. 19: 868-871.

13. Seery CM, Davison PF. (1991) Collagens of the bovine vitreous. Invest Ophthalmol Vis Sci. 32: 1540-

1550.

14. Brewton RG, Wright DW, Mayne R. (1991) Structural and functional comparison of type IX collagen-

proteoglycan from chicken cartilage and vitreous humor. J Biol Chem. 266: 4752-4757.

15. Warman M, Kimura T, Muragaki Y, Castagnola P, Tamei H, et al. (1993) Monoclonal antibodies

against two epitopes in the human alpha I (IX) collagen chain. Matrix. 13: 149-156.

16. Wright DW, Mayne R. (1988) Vitreous humor of chicken contains two fibrillar systems: an analysis of

their structure. J Ultrastruc Mol Struct Res. 100: 224-234.

17. Haddad A, Laicine EM, de Almeida JC, Costa MS. (1990) Partial characterization, origin and turnover

of glycoproteins of the rabbit vitreous body. Exp Eye Res. 51: 139-143.

18. Nguyen BQ, Fife RS. (1986) Vitreous contains a cartilage-related protein. Exp Eye Res. 43: 375-382.

19. Balazs EA, Denlinger JL (1982) Aging changes in the vitreus. In: Sekuler R, Kline D, Dismukes K,

editors. Aging and human visual function. New York: Alan R Liss. pp. 45-58.

20. O’Malley P (1976) The patterns of vitreous syneresis – a study of 800 autopsy eyes-. In: Irvine R,

O’ Malley P, editors. Advances in vitreous surgery. Springfield: C. Thomas. pp. 17-33.

VandePut.indd 19 4-11-2014 14:15:46

20 | Chapter 1

21. Sebag J. (1987) Age related changes in human vitreous structure. Graefe’s Arch Clin Exp Ophthalmol.

225: 89-93.

22. Sebag J. (1991) Age-related differences in the human vitreoretinal interface. Arch Ophthalmol. 109:

966-971.

23. Wang J, McLeod D, Henson DB, Bishop PN. (2003) Age-dependent changes in the basal retinovitreous

adhesion. Invest Ophthalmol Vis Sci. 44: 1793-1800.

24. Teng CC, Chi HH. (1957) Vitreous changes and the mechanism of retinal detachment. Am J

Ophthalmol. 44: 335-356.

25. Novak MA, Welch RB. (1984) Complications of acute symptomatic posterior vitreous detachment

Am J Ophthalmol. 97: 308-314.

26. Kanksi JJ. (1975) Complications of acute posterior vitreous detachment. Am J Ophthalmol. 80: 44-

46.

27. Smolin. (1965) Statistical analysis of retinal holes and tears. Am. J. Ophthalmol. 60: 1055-1058.

28. Machemer R. (1968) Experimental retinal detachment in the owl monkey. II. Histology of the retina

and pigment epithelium. Am J Ophthalmol 66: 396-410.

29. Burton TC. (1982) Recovery of visual acuity after retinal detachment involving the macula. Trans Am

Ophthalmol Soc 80: 475-497.

30. Diederen RMH, La Heij AC, Kessels AGH, Goezinne F, Liem AT et al. (2007) Scleral buckling surgery

after macula-off retinal detachment; worse visual outcome after more than 6 days. Ophthalmology

114: 705-709.

31. Hassan TS, Sarrafizadeh R, Ruby AJ, Garretson BR, Kuczynski B, et al. (2002) The effect of duration

of macular detachment on results after the scleral buckle repair of primary, macula-off retinal

detachments. Ophthalmology 109: 146-152.

32. Özgür S, Esgin H. (2007) Macular function of successfully repaired macula-off retinal detachments.

Retina 27: 359-364.

33. Ross WH, Kozy DW. (1998) Visual recovery in macula-off rhegmatogenous retinal detachments.

Ophthalmology 105; 2149-2153.

34. Mervin K, Valter K, Maslim J, Lewis G, Fisher S, et al. (1999) Limiting photoreceptor death and

deconstruction during experimental retinal detachment; the value of oxygen supplementation. Am J

Ophthalmol 128: 155-164.

35. Davies EWG. (1972) Factors affecting recovery of visual acuity following detachment of the retina.

Trans Ophthalmol Soc UK 92: 335-342.

36. Kreissig I. (1977) Prognosis of return of macular function after retinal reattachment. Mod Probl


37. Ross WH, Lavina A, Russel M, Maberley D. (2005) The correlation between height of macular

detachment and visual outcome in macula-off retinal detachments of ≤ 7days’ duration. Ophthalmology

112; 1213-1217.

VandePut.indd 20 4-11-2014 14:15:46


138. Mowatt L, Tarin S, Nair RG, Menon J, Price NJ. (2010) Correlation of visual recovery with macular

height in macula-off retinal detachments. Eye 24: 323-327.

39. Lecleire-Collet A, Muraine M, Menard JF, Brasseur G. (2005) Predictive visual outcome after macula-

off retinal detachment surgery using optical coherence tomography. Retina 259: 44-53.

40. Wilkes SR, Beard CM, Kurland LT, et al. (1982) The incidence of retinal detachment in Rochester,

Minnesota, 1970-1978. Am J Ophthalmol. 94: 670-673.

41. Haimann MH, Burton TC, Brown CK. (1982) Epidemiology of retinal detachment. Arch Ophthalmol.

100: 289-292.

42. Laatikainen L, Tolppanen EM, Harju H. (1985) Epidemiology of rhegmatogenous retinal detachment

in a Finnish population. Acta Ophthalmol (Copenh). 63: 59-64.

43. Tornquist R, Stenkula S, Tornquist P. (1987) Retinal detachment. A study of a population-based

patient material in Sweden 1971-1981. I. Epidemiology. Acta Ophthalmol (Copenh). 65: 213-222.

44. Rowe JA, Erie JC, Baratz KH, et al. (1999) Retinal detachment in Olmsted County, Minnesota, 1976

through 1995. Ophthalmology. 106: 154-9.

45. Algvere PV, Jahnberg P, Textorius O. (1999) The Swedish Retinal Detachment Register. I. A database

for epidemiological and clinical studies. Graefes Arch Clin Exp Ophthalmol. 237: 137-144.

46. Polkinghorne PJ, Craig JP. (2004) Northern New Zealand Rhegmatogenous Retinal Detachment

Study: epidemiology and risk factors. Clin Experiment Ophthalmol. 32: 159-163.

47. Mitry D, Charteris DG, Yorston D, et al, Scottish RD Study Group. (2010) The epidemiology and

socioeconomic associations of retinal detachment in Scotland: a two-year prospective population-

based study. Invest Ophthalmol Vis Sci. 51: 4963-4968.

48. Ivanišević M, Bojić L. (1998-1999) The incidence of nontraumatic phakic rhegmatogenous retinal

detachment in Split-Dalmatia County, Croatia. Int Ophthalmol. 22: 197-199.

49. Olsen G, Olsen RJ. (2000) Update on a long-term, prospective study of capsulotomy and retinal

detachment rates after cataract surgery. J Cataract Refract Surg. 26: 1017-1021.

50. Lois N, Wong D. (2003) Pseudophakic retinal detachment. Surv Ophthalmol. 48: 467-487.

51. Zou H, Zhang X, Xu X, et al. (2002) Epidemiology survey of rhegmatogenous retinal detachment in

Beixinjing District, Shanghai, China. Retina. 22: 294-299.

52. Sasaki K, Ideta H, Yonemoto J, et al. (1995) Epidemiologic characteristics of rhegmatogenous retinal

detachment in Kumamoto, Japan. Graefes Arch Clin Exp Ophthalmol. 233: 772-776.

53. Beijing Rhegmatogenous Retinal Detachment Study Group. (2003) Incidence and epidemiological

characteristics of rhegmatogenous retinal detachment in Beijing, China. Ophthalmology. 110: 2413-

2417.

54. Wong TY, Tielsch JM, Schein OD. (1999) Racial difference in the incidence of retinal detachment in

Singapore. Arch Ophthalmol. 117: 379-383.

55. Limeira-Soares PH, Lira RP, Arieta CE, Kara-José N. (2007) Demand incidence of retinal detachment

in Brazil. Eye (Lond). 21: 348-352.

VandePut.indd 21 4-11-2014 14:15:46

22 | Chapter 1

56. Kanski JJ. (1975) Complications of acute posterior vitreous detachment. Am J Ophthalmol. 80: 44-

46.

57. Chuo JY, Lee TY, Hollands H, et al. (2006) Risk factors for posterior vitreous detachment: a case-

control study. Am J Ophthalmol. 142: 931-937.

58. Hayreh SS, Jonas JB. (2004) Posterior vitreous detachment: clinical correlations. Ophthalmologica.

218: 333-343.

59. Hoogendoorn D. (1988) Extracapsular and intracapsular lens extraction in cataract [in Dutch]. Ned

Tijdschr Geneeskd. 132: 1434-1438.

60. Clark A, Morlet N, Ng JQ, et al. (2011) Whole population trends in complications of cataract surgery

over 22 years in Western Australia. Ophthalmology. 118: 1055-1061.

61. Friedman Z, Neumann E, Hyams S. (1973) Vitreous and peripheral retina in aphakia: a study of 200

non-myopic aphakic eyes. Br J Ophthalmol. 57: 52-57.

62. Friedman Z, Neumann E. (1975) Posterior vitreous detachment after cataract extraction in non-

myopic eyes and the resulting retinal lesions. Br J Ophthalmol. 59: 451-454.

63. Österlin S. (1977) On the molecular biology of the vitreous in the aphakic eye. Acta Ophthalmol(Copenh).

55: 353-361.

64. Hilding AC. (1954) Alterations in the form, movement, and structure of the vitreous body in aphakic

eyes. AMA Arch Ophthalmol. 52: 699-709.

65. Duke-Elder S. (1967) Detachment and folding of the retina. In: Duke-Elder, editor. Chapter 7

Detachment and folding of the retina.In: Diseases of the retina. pp. 784-786.

66. Duke-Elder S. (1967) Detachment and folding of the retna. In: Duke-Elder, editor. Chapter 7


67. Dellaporta AN. (1999) Retinal detachment surgery: Historical notes. Doc. Ophthalmologica Advances

in Opthalmology. 99: 259-272.

68. Duke-Elder S. (1967) Detachment and folding of the retina. In: Duke-Elder, editor. Chapter 7


69. Peyman GA, Schulman J. (1985) Proliferative vitreoretinopathy and chemotherapeutic agents. Surv


70. Pastor JC. (1998) Proliferative vitreoretinopathy: an overview. Surv Ophthalmol. 43: 3-18.

71. Pastor JC, Rodrigueze de la Rua, Martin F. (2002) Proliferative vitreoretinopathy: risk factors and

pathobiology. Prog Retin Eye Res. 21: 127-144.

72. Charteris DG. (1995) Proliferative vitreoretinopathy: pathobiology, surgical management, and

adjunctive treatment. Br J Ophthamol. 79: 953-960.

73. Asaria RH, Charteris DG. (2006) Proliferative vitreoretinopathy: developments in pathogenesis and

treatment. Compr Ophthalmol Update. 7: 179-185.

74. Machemer R, Buettner H, Norton EW, Parel JM. (1971) Vitrectomy: a pars plana approach. Trans Am

Acad Ophthalmol Otolaryngol. 75: 813-820.

VandePut.indd 22 4-11-2014 14:15:46


175. Machemer R, Buettner H, Parel JM. (1972). A new consept of vitreous surgery. I. Instrumetation. Am

J Ophthalmol. 73: 1-7

76. Machemer R, Buettner H, Parel JM. (1972). Vitrectomy: a pars plana approach. Technical improvements

and further results. Trans Am Acad Ophthalmol Otolaryngol. 76: 462-466.

77. Tani PT, Robertson DM, Langworthy A (1981) Prognosis for central vision and anatomic reattachment

in rhegmatogenous retinal detachment with macula detached. Am J Ophthalmol 92: 611-620

78. Pastor JC, Fernández I, Rodríguez de la Rúa E, et al. (2008) Surgical outcomes for primary

rhegmatogenous retinal detachments in phakic and pseudophakic patients: the Retina 1 Project –

report 2. Br J Ophthalmol. 92: 378-382.

79. Friberg TR, Eller AW. (2001) Laser pneumatic retinopexy for repair of recurrent retinal detachment

after failed scleral buckle—ten years experience. Ophthalmic Surgery and Lasers. 32: 13-18.

80. Sharma T, Badrinath SS, Mukesh BN, et al. (1997) A multivariate analysis of anatomic success of

recurrent retinal detachment treated with pneumatic retinopexy. Ophthalmology. 104: 2014-2017.

81. Ando F, Hirose H, Nagasaka T, Takahashi K, Sekiryu T. (1993) Treatment of retinal detachment with

giant tear by pneumatic retinopexy. Eur J Ophthalmol. 3:201-206

82. Weiss JS (2009) Basic anatomy. In: Retina and vitreous. In: Regillo C, Holekamp N, Johnson MW,

Kaiser PK, Hermann D et al. editors. Basic and Clinical Science Course. pp. 361-364.

83. Heimann H, Bartz-Schmidt KU, Bornfeld N, Weiss C, Hilgers RD, Foerster MH. (2007) Scleral

buckling versus primary vitrectomy in rhegmatogenous retinal detachment: a prospective randomized

multicenter clinical study. Ophthalmology. 114: 2142-2154.

84. Amadieh H, Moradian S, Faghihi H, et al. (2005) Anatomic and visual outcomes of scleral buckling

versus primary vitrectomy in pseudophakic and aphakic retinal detachment: six-month follow-up

results of a single operation: report no. 1. Ophthalmology. 112: 1421-1429.

85. Brazitikos PD, Androudi S, Christen WG, Strangos NT. (2005) Primary pars plana vitrectomy versus

scleral buckle surgery for the treatment of pseudophakic retinal detachment: a randomized clinical

trial. Retina. 25: 957-964.

86. Mendrinos E, Dang-Burgener NP, Stangos AN, Sommerhalder J, Pournaras CJ. (2008) Primary

vitrectomy wthout scleral buckling for pseudophakic rhegmatogenous retinal detachment. Am J

Ophthalmol. 145: 1063-1070.

87. Arya AV, Emerson JW, Englebert M, Hagedoorn CL, Adelman RA. (2006) Surgical management of

pseudophakic retinal detachments: a meta-analysis. Ophthalmology. 113: 1724-1733.

88. Weichel ED, Martidis A, Fineman MS, et al. (2006) Pars plana vitrectomy versus combined pars plana

vitrectomy-scleral buckle for primary repair of pseudophakic retinal detachments. Ophthalmology.

113: 2033-2040.

89. Anderson C, Sjöstrand J. (1981) Contrast sensitivity and central vision in reattached macula. Acta


90. Okamoto F, Okomota Y, Hiraoka T, Oshika T. (2008) Vision-related quality of life and visual function

after retinal detachment surgery. Am J Ophthalmol. 146: 85-90.

VandePut.indd 23 4-11-2014 14:15:46

24 | Chapter 1

91. Okamoto F, Okamoto Y, Fukuda S, et al. (2010) Vision-related quality of life and visual function after

vitrectomy for various vitreoretinal disorders. Invest Ophthalmol Vis Sci. 51: 744-751.

92. Tranos PG, Ghazi-Nouri SM, Rubin GS, et al. (2004) Visual function and subjective perception of

visual ability after macular hole surgery. Am J Ophthalmol 138: 995-1002.

93. Ghazi-Nouri SM, Tranos OG, Rubin GS, et al. (2006) Visual function and quality of life following

vitrectomy and epiretinal membrance peel surgery. Br J Ophthalmol 90: 559-562.

94. Klein R, Moss SE, Klein BE, et al. (2001) The NEI-VFQ-25 in people with long-term type 1 diabetes

mellitus: the Wisconsin Epidemiologic Study of Diabetic Retinopathy. Arch Ophthalmol 119: 733-

740.

95. Gundry MF, Davies EWG (1974) Recovery of visual acuity after retinal detachment surgery. Am J


96. Reese AB (1937) Defective central vision following successful operations for detachment of the retina.

Am J Ophthalmol 20: 591-598.

97. Jay B (1965) The functional cure of retinal detachments. Trans Ophthalmol Soc UK 85: 101-110.

VandePut.indd 24 4-11-2014 14:15:46

PART I

EPIDEMIOLOGY

VandePut.indd 25 4-11-2014 14:15:46

VandePut.indd 26 4-11-2014 14:15:46

Chapter 2

The incidence of rhegmatogenous retinal detachment

surgery in the North of the Netherlands

Mathijs A.J. van de Put,1,2 Ilja M. Nolte,3 Johanna M.M. Hooymans,1,2 Leonoor I. Los.1,2

1 Department of Ophthalmology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

2 W.J. Kolff Institute, Graduate School of Medical Sciences, University of Groningen, the Netherlands.3 Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University

Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

VandePut.indd 27 4-11-2014 14:15:46

28 | Chapter 2

ABSTRACT

Purpose: To estimate the incidence of rhegmatogenous retinal detachment surgery (RRD) in the

North of the Netherlands in 2008.

Methods: Retrospectively, using the surgical logs, all patients, if permanent residents of the

North of the Netherlands, who had had surgery for primary RRD between January first, 2008

and January first, 2009, at the University Medical Center Groningen and the Antonius Hospital

Sneek, were included. Excluded were patients operated on for RRD before 2008 and exudative,

tractional, or traumatic retinal detachments. Information on date of birth, gender, affected eye,

date of surgery, and prior cataract extraction (CE) in the affected eye was obtained. Using our data

(n=297 eyes), we determined RRD surgery incidence in our population (1,704,783 people, census

2008), age distribution, male-to-female ratio, and prevalence of prior cataract extraction in RRD

patients. Note: We conducted a comparable study in the entire Netherlands in which data on

RRD surgery from January first, 2009 until January first, 2010 were collected. For comparison,

data regarding the North of the Netherlands from that study will be briefly summarized in the

present manuscript.

Results: RRD surgery incidence was 17.4/100,000 people per year (95% confidence interval [CI]

= 15.4 - 19.4). RRD surgery incidence was highest, with 53.86/100,000 people per year, among

individuals between 65 and 69 years of age, and increased significantly from age 50 years onwards

(p < 0.01). It occurred 1.9 times as often in males as compared to females, and of all RRD patients,

39.7% had had prior CE. We observed no statistically significant differences in overall annual

RRD surgery incidence rates between 2008 and 2009 population in the North of the Netherlands.

Conclusions: RRD surgery incidence in a given population is dependent on its demography. The

population older than 50 years, and males are more susceptible to RRD. The annual incidence

rates of RRD surgery in the North of the Netherlands are stable over a period of time.

VandePut.indd 28 4-11-2014 14:15:46

RRD incidence in the North of the Netherlands | 29

2

INTRODUCTION

Rhegmatogenous retinal detachment (RRD), which refers to a separation of the neurosensory

retina from the underlying retinal pigment epithelium due to a defect in the retina, is a potentially

blinding ophthalmic pathology.[1] Despite treatment advances, functional results remain poor,

with only 42% of all RRD eyes achieving ≥ 20/40 vision, and only 37% achieving ≥ 20/50 in

macula-off detachments.[2-3]

In Western populations, the annual RRD surgery incidence over the past forty years has been

reported as between 6.9 and 18.2 cases per 100,000 persons per year.[4-13] During the 1970s, yearly

RRD surgery incidence rates were 6.1-9.8 cases per 100,000 persons,[4-7] increasing to 11.8-17.9

cases per 100,000 persons during the 1990s.[8-10] A recent study conducted in a relatively young

population reported an incidence of 12.05 cases per 100,000 people,[11] whereas another recent

study in a relatively older population reported an incidence of 18,2 cases per 100,000 people.[13]

Differences between these studies may be explained either by methodological differences (e.g.

different inclusion criteria, and differences in the provision of health care),[4-13] or differences in the

prevalence of risk factors for RRD (e.g. demographic characteristics (age and gender),[4-13] prevalence

of myopia, and volume of cataract surgery).[4-7,14]

We were interested in the overall and age-specific annual incidence rates of RRD surgery in

the North of the Netherlands. Since the incidence of RRD in our population cannot be reliably

measured, RRD surgery was taken as a proxy hereof.

METHODS

Study population

The North of the Netherlands is composed of the provinces of Drenthe, Friesland, and Groningen.

Based on the 2008 census, the total population of the North of the Netherlands consisted of

1,704,783 people.[15] To be included in this study as an RRD case, the patient must have been

permanent resident of one of the above provinces in 2008. Patients residing outside the above

provinces were excluded.

All RRD patients from the area studied have been operated on either at the University Medical

Center Groningen (UMCG) or the Antonius Hospital Sneek. The North of the Netherlands is

a relatively isolated region in the Netherlands and the above mentioned hospitals are the only

locations within this region where RRD-surgery is being performed. Therefore, we may assume

that all RRD patients from Drenthe, Friesland, and Groningen will be referred to the UMCG or

the Antonius hospital Sneek by regional ophthalmologists. In addition, patients from outside the

three northern provinces may also be referred to either one of these hospitals. The latter patients

can easily be identified by checking their address and they were excluded from the present study.

VandePut.indd 29 4-11-2014 14:15:46

30 | Chapter 2

In a national study on RRD surgery, confirmation of this referral pattern was obtained for the year

2009.[13]

Both centers agreed to participate in this study. There are no patients lost to private practice,

because vitreoretinal surgery in the Netherlands is not performed in private practices.

Ethics statement

The internal review board (IRB) of the University Medical Center Groningen waived the need

for IRB approval. The study has adhered to the tenets of the Declaration of Helsinki. The

internal review board committee of the UMCG waived the need for IRB approval and therefore

also implicitly approved that obtaining written consent from the patients was not necessary and

therefore written consent was not obtained.

Data collection

Data were collected retrospectively. All cases of primary RRD operated on from January 1, 2008,

until January 1, 2009, were identified using the surgical logs and included. In the Netherlands,

it is mandatory to keep a log of all performed surgeries. The logs contain patient specific data

(name, data of birth, gender, and address), and surgery specific data (surgeon, surgical procedure,

indication for surgery). The surgical logs were partly digital and partly hand-written. After

identifying patients by using the logs, the patients’ charts were obtained and checked for additional

information by one of the authors (MP).

Rhegmatogenous retinal detachment was defined as a retinal elevation with any retinal break

(found before or during surgery). All eyes with prior detachments or tractional (i.e. due to

fibrovascular proliferation in proliferative diabetic retinopathy or retinopathy of prematurity),

exudative (i.e. due to uveitis or scleritis), and traumatic (defined as a clear history of ocular trauma

followed by retinal dialysis, occurring simultaneously with or following intraocular foreign body

removal, or occurring simultaneously with or following ocular penetrating or perforating injury)

retinal detachments were excluded. Patients with hereditary vitreoretinopathy (i.e. Sticklers

vitreoretinopathy) were included. Reoperations within the study period were excluded (i.e. only

the first surgical intervention was counted). Data for 297 eyes were included in the analyses.

Information collected included patient’s age, gender, affected eye, macula-off or macula-on

detachment, residence, date of RRD surgery, and history of CE. Macula-off RRD was defined as a

macular elevation prior to or during surgery, or a visual acuity (VA) of less than 10/20 that could

not be explained by other stated pathology.

Because all the surgical logs and the patients’ charts were checked by one of the authors (MP),

we have a high diagnostic accuracy, and can therefore be rather sure that tractional, exudative,

and traumatic cases are excluded and that the included cases are true rhegmatogenous retinal

detachments. There was no missing data, because the surgical logs always contained patients’

specific data, as date of birth, gender, address and surgery specific data, as date of surgery. In

VandePut.indd 30 4-11-2014 14:15:46


2

addition, the patients’ charts always stated preoperative data as lens status, macular status, VA, and

pre- and intra-operative funduscopic aspect, and presence of retinal breaks.

Statistical analyses

The overall and age-specific annual incidence rates were calculated by dividing the number of new

cases by target population size. Bilateral cases were counted separately, as these are a rarity. A 95%

confidence interval of all the incidence rates was calculated. For comparing proportions we used

the Chi-square test. A P-value £ 0.05 was considered statistically significant. All statistical analyses

were performed using SPSS software package 12.0 (SPSS Inc., Chicago IL, USA) or Microsoft

Office Excel 11 (Microsoft Corp., Redmond WA, USA).

Note: We conducted a comparable study in the entire Netherlands in which data on RRD surgery

from January first, 2009 until January first, 2010 were collected. For comparison, data regarding the

North of the Netherlands from that study will be briefly summarized in the present manuscript.[13]

RESULTS

Annual incidence rate of RRD surgery in 2008

Among the 1,704,783 residents of the three northern Dutch provinces in 2008, 297 new cases

of RRD were treated either at the ophthalmology department of the UMCG (n=255) or at the

ophthalmology department of the Antonius Hospital (n=42) (Table 1). Therefore, the overall

annual incidence rate of RRD surgery was 17.4/100,000 people (95% CI = 15.4 - 19.4).

Right and left eyes, macular status

Of all patients, 291 (98.0%) suffered from a unilateral RRD, and three had a bilateral RRD. In

unilateral RRD cases, 166 right and 125 left eyes were involved. Three patients suffered from

bilateral RRD during the study period, resulting in a bilateral RRD rate of 1.0%. A detached

macula was found in 172 eyes (57.9%).

Age and gender distribution

The median age of the patients was 60 years (range = 5-90). The median age did not differ

between males (median 60, range 5-89 years) and females (median 61, range 19-90 years). There

was a significant increase in age-specific annual incidence rates of RRD surgery from 50 years

of age onwards (p < 0.01), and a significant decrease from 70 years of age onwards (p < 0.05)

(Table 1, Figure 1). We noticed a peak age-specific annual incidence rate at 65-69 years of age, of

53.9/100,000 people (95% CI = 37.8 - 70.0) (Figure 1).

VandePut.indd 31 4-11-2014 14:15:46

32 | Chapter 2

0

10

20

30

40

50

60

70

80

< 5

5-9

10-14

15-19

20-24

25-29

30-34

35-39

40-44

45-49

50-54

55-59

60-64

65-69

70-74

75-79

80-84

85-89

90-94

95-100In

cide

nce

per

100,

000

peop

le

Age (Years)

Total Males Females

Figure 1: The incidence of rhegmatogenous retinal detachment in the North of the Netherlands per 100,000

people in 2008.

Table 1: Actual numbers of individuals and incidences of rhegmatogenous retinal detachment per age

category in the population of the North of the Netherlands for males, females, and all individuals in 2008.

Age range(years)

Number of individualsa

Total with RRD Males with RRD Females with RRD M-F ratiob

Total Male Female Number Incidence Number Incidence Number Incidence< 5 93.9 48.0 45.9 0 0 0 0 0 0 NA5-9 104.6 53.5 51.1 1 0.96 1 1.87 0 0 NA10-14 101.5 51.8 49.7 0 0 0 0 0 0 NA15-19 104.8 53.4 51.4 3 2.86 2 3.74 1 1.95 2:120-24 105.5 54.4 51.1 4 3.79 1 1.84 3 5.87 0.3:125-29 95.1 49.2 45.9 5 5.26 5 10.16 0 0 NA30-34 97.6 49.5 48.0 2 2.05 0 0 2 4.16 NA35-39 126.5 64.4 62.2 5 3.95 3 4.66 2 3.22 1.5:140-44 130.1 65.9 64.2 13 9.99 9 13.66 4 6.23 2.3:145-49 126.7 63.5 63.1 15 11.84 10 15.74 5 7.92 2.0:150-54 121.1 61.1 60.0 35 28.89 22 35.99 13 21.66 1.7:155-59 116.1 58.8 57.3 54 46.53 37 62.93 17 29.69 2.2:160-64 110.8 55.9 54.9 54 48.76 35 62.64 19 34.62 1.8:165-69 79.8 39.6 40.3 43 53.86 30 75.81 13 32.29 2.3:170-74 66.3 31.2 35.1 21 31.66 11 35.23 10 28.48 1.1:175-79 53.4 23.0 30.3 23 43.11 15 65.19 8 26.37 1.9:180-84 38.5 14.3 24.2 11 28.58 7 48.93 4 16.54 1.8:185-89 22.7 7.1 15.6 7 30.85 5 70.16 2 12.85 2.5:1≥ 90 9.8 2.2 7.6 1 10.20 0 0 1 13.27 NATotal 1704.8 847.0 857.8 297 17.42 193 22.79 104 12.12 1.9:1RRD: rhegmatogenous retinal detachment; NA: not applicable. aActual number is given number*1000. bMale-to-female ratio.

VandePut.indd 32 4-11-2014 14:15:46


2

Phakic RRD eyes and RRD eyes with prior CE

Of the 297 RRD cases, 179 involved phakic eyes (60.3%), and 118 involved eyes with prior CE

(39.7%). The median age of phakic RRD patients was 59 years (range 4-89). This did not differ

between males (median age 59, range 5-89 years) and females (median age 58, range 19-85 years).

We noticed an increase in absolute numbers of RRD in phakic eyes from age 45 onwards, peaking

at 55-59 years of age (n = 42) and decreasing thereafter (Figure 2). Among the 179 phakic-RRD

cases, 118 involved males (65.7%), and 61 involved females (34.3%), resulting in a male-to-female

ratio of 1.9:1. At age 75-79 years, there is a turning point in the proportion of phakic RRD eyes

compared to RRD eyes with a history of CE (Figure 3).

0

5

10

15

20

25

30

35

40

45

< 5

5-9

10-14

15-19

20-24

25-29

30-34

35-39

40-44

45-49

50-54

55-59

60-64

65-69

70-74

75-79

80-84

85-89

90-94

95-100A

bsol

ute

num

ber

of p

atie

nts

Age (Years)

Absolute number of RRD patients with history of cataract extractionAbsolute number phakic patients

Figure 2: Absolute numbers of phakic RRD eyes and RRD eyes with a history of cataract extraction.

VandePut.indd 33 4-11-2014 14:15:47

34 | Chapter 2

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

< 5

5-9

10-14

15-19

20-24

25-29

30-34

35-39

40-44

45-49

50-54

55-59

60-64

65-69

70-74

75-79

80-84

85-89

90-94

95-100

Prop

orti

on

Age (years)

Proportion of phakic-RRD eyes Proportion RRD-eyes with history of cataract extraction

Figure 3: Proportion of phakic RRD eyes and RRD eyes with a history of cataract extraction.

The median age of patients with RRD in eyes with prior CE was 64 years (range 22-90). Among

the 118 cases, 75 involved males (63.6%), and 43 involved females (36.4%), resulting in a male-

to-female ratio of 1.7:1. The median age was 64 years for males (age range 39-88) and females (age

range 22-90). We noticed an increase in absolute numbers of RRD in eyes with prior CE from age

40 onwards, peaking at 60-64 (n = 19), and 65-69 years of age (n = 19) and decreasing thereafter

(Figure 2).

Annual incidence rate of RRD surgery in 2009

For comparison, data regarding the North of the Netherlands from a comparable study in the

entire Netherlands in which data on RRD surgery from January first, 2009 until January first,

2010 were collected will be analysed.[13] Of the 1,708,821 residents of the three northern Dutch

provinces in 2009,[15] 308 new cases of RRD were treated. Therefore, the overall annual RRD

surgery incidence was 18.0/100,000 people (95% CI = 16.0 – 20.0). A detached macula was found

in 189 eyes (61,4%). The median age of patients was 60 years (range = 10-91). A peak incidence was

observed at 65-69 years of age, with an incidence of 47.0/100,000 people (95% CI = 32.2 – 61.7).

Among the 308 incident cases, 193 involved males (63%) resulting in a male-to-female ratio of

1.7:1. The annual overall incidence rate of RRD surgery was 22.7/100,000 (95% CI = 19.5 – 25.9)

in males and 13.4/100,000 (95% CI = 10.9 – 15.8) in females, and this difference was statistically

significant.

A history of CE was present in 106 cases (32.6%). Patients with a history of CE had a higher

median age (66 years of age) compared to the median age of phakic patients (58 years of age). The

absolute number of phakic patients peaked at 55-59 years of age (n = 47) and decreased thereafter.

VandePut.indd 34 4-11-2014 14:15:47


2

An increase in absolute numbers of RRD in eyes with prior CE was observed from age 45 onwards.

Peak values were seen at 65-69 years of age (n = 15) and decreased thereafter. At 75-79 years of

age there was a turning point in the proportion of phakic RRD eyes compared to RRD eyes with

a history of CE.

We observed no statistically significant differences in overall annual RRD surgery incidence

rates between the 2008 and 2009 population in the North of the Netherlands. Neither did these

incidence rates differ significantly from the overall annual RRD surgery incidence rate in the entire

Netherlands in 2009. The same observations were made for annual RRD incidence rates in males

and females.

We observed no significant differences between the proportions of pseudophakic and phakic RRD

patients in the North of the Netherlands between 2008 and 2009, and the North of the Netherlands

and the Netherlands in 2009. We observed statistically significant differences between proportions

of macula-on and macula-off RRD patients in the North of the Netherlands between 2008 (42%

macula-off) and 2009 (61% macula-off, P <0.00001), and between The North of the Netherlands

between 2009 (61% macula-off) and The Netherlands (54% macula-off) in 2009 (p = 0.0221).

DISCUSSION

The overall annual incidence rate of RRD surgery in 2008 in our population is high when

compared to earlier reports in Western populations.[4-13] In line with previous reports, a peak age-

specific annual incidence rate of RRD surgery was observed in the population 65-69 years of

age, and a second smaller one at 75-79 years of age, while males were overrepresented in all age

categories.[7,9] This suggests that the overall annual RRD surgery incidence is strongly dependent

on demographic characteristics (i.e., age and gender distribution) in a given population. We

noticed the highest numbers of phakic RRD patients at ages 55-59 years, and the highest numbers

of post-CE RRD patients at ages 60-69 years. Also, the proportion of post-CE RRD increased

with advancing age. Both observations may suggest that phakic and post-CE RRD are different

entities. The fact that RRD is still a sight-threatening condition is underscored by the presence of

a macular detachment in more than half of the patients.

Annual incidence rate of RRD

The provided high overall annual incidence rate of RRD surgery in the North of the Netherlands

in 2008 of 17.4/100,000 does not seem to be an incidental overestimation, since an overall annual

incidence rate of 18.0/100,000 (95% CI = 16.0 – 20.0) in 2009 was observed in this area. Also, the

North of the Netherlands seems to be a good proxy for the entire Netherlands where an overall

annual incidence rate of 18.9/100,000 (95% CI = 11.4 – 18.8)) in 2009 was found.[13]

VandePut.indd 35 4-11-2014 14:15:47

36 | Chapter 2

RRD and age/population aging

The strong association between annual incidence rates of RRD surgery and age has been reported

extensively.[4-10,13,17-19] This association has been found to be strongest in phakic RRD patients.[4-

10,13,17-19] Posterior vitreous detachment (PVD) is generally assumed to be the main cause of RRD

in phakic eyes, since RRD is frequently associated with acute symptomatic PVD.[1] PVD is a rarity

in individuals younger than 50 years of age; on average, its onset is at 60 years, with increasing

prevalence thereafter.[20] This may well explain the median age and age peak in phakic RRD

observed in our and other studies.[4-10,13,17-19] The relationship between PVD and age is in line with

described lower annual incidence rates of RRD surgery in relatively younger populations[6-7,17]

versus higher annual incidence rates of RRD surgery in relatively older population,[8,13] including

our own.

RRD and gender

The gender difference in annual incidence rates of RRD surgery observed in our study is supported

by others,[8-11,13,17] but it is not found consistently.[5-7,18-19] One possible explanation for these

inconsistencies may be a slightly unequal distribution of males and females across the age groups,

although in most studies, as in our own, an equal distribution is found.[6-9,13]

Both population aging and specific demographic characteristics in our population (i.e. age

distribution and gender) could have contributed to the high annual incidence rate of RRD surgery

observed in our population. Remarkably, there seems to be a broad variety in annual incidence

rates of RRD surgery in demographically comparable populations, when comparing the older,[4-5]

the more recent,[8,13] and our own studies.[13] The discrepancy between the expected effect of

demography and true annual incidence rates of RRD in different studies may indicate that factors

other than age and gender must be responsible for this.

RRD and cataract extraction

One possible explanation may be the success of modern cataract surgery, since it has been

postulated that the cumulative risk of RRD is increased by a factor of 5 in eyes with a history

of CE,[5] and the number of cataract extractions in the Netherlands has grown significantly over

the last two decades. The increase in performed CE can be attributed to population aging, and

hence a higher prevalence of cataracts. In addition, because of the success of phacoemulsification

for CE, there has been a tendency to perform CE at an earlier stage. Both factors have resulted

in a higher volume of CE performed in the recent past. (Estimated numbers for the Netherlands

are 38,000 CE performed in 1991; 80,000 in 1998; and 120,000 in 2003).[20] In line with this

and in contrast to others, we found a high percentage of RRD patients with prior CE.[4,10-11,13] In

parallel to the increase in the volume of cataract surgery in the Netherlands, there has been a shift

in surgical technique. Extracapsular cataract extraction (ECCE) has been replaced by the safer

procedure of phacoemulsification.[22-23] Furthermore, intracapsular cataract extraction (ICCE), the

VandePut.indd 36 4-11-2014 14:15:47


2

procedure holding the highest risk of postoperative RRD, has just about been abandoned.[22-23]

Even though the relatively safer phacoemulsification technique probably mitigates the RRD risk

in pseudophakic eyes to some extent, the overall contribution of CE to annual incidence rates of

RRD surgery seems to be significant.

Unfortunately, reliable incidence rates for phakic versus post-CE RRD cannot be provided, since

the prevalence of phakic versus post-CE eyes in most populations, including our own, is unknown

due to incomplete registration systems.[4,10-11,13] The differences in the shapes of the age-related

distribution curves between phakic and post-CE RRD, and the shift in the proportion of phakic

versus post-CE RRD eyes with advancing age, may be suggestive that phakic and post CE-RRD

are different entities.[8,14,21,22-25]

Several theories concerning the pathophysiological mechanisms on phakic versus post-CE RRD

have been advocated. First, a newly induced PVD[24-25] in non-PVD eyes can occur because CE

causes mechanical[8] and biochemical changes[26] in the vitreous.[24-26] Also, a second mechanism

could be at play, namely, the altered mechanical forces at the anterior vitreous base area because of

the loss of lens volume.[27] This second mechanism would also explain the more anteriorly located

small horseshoe-shaped tears that are frequently found in RRD eyes with prior CE.[27]

RRD and refractive errors

It has consistently been found that high myopia is associated with RRD, especially bilateral RRD.[4,5,7] Therefore, an increase in the prevalence of myopia in our population may have contributed

partly to the increase in annual incidence rates of RRD surgery in our population. Unfortunately,

we could not make any assumption on the relationship between RRD and myopia, as the

distribution of refractive errors in our population is not known. Furthermore, in that they are

only for two consecutive years, our data are too limited to draw any conclusions as to the risk

of developing bilateral RRD. The risk of bilateral RRD varies among populations: for instance,

in Sweden, 11.2% of subjects had bilateral RRD over a time period of ten years[4-7] compared to

6.7% in Minnesota (USA)[8] over a time period of twenty years.[8] In all series, fellow eyes have an

increased risk of developing RRD in due course.[8,11,13]

RRD and macula

Macular status at presentation is an important prognostic indicator of visual outcome.[2,3]

We identified high numbers of macula-off detachment in our population.[8-9,13] One possible

explanation for this high number was our chosen definition of macula-off detachment. Not only

was the clinical observation of subretinal fluid before or during surgery regarded as macula-off

detachment, but we also included all eyes with VA ≤ 10/20 in the macula-off-group. Other possible

explanations for this high rate of macula-off detachments include patient’s and doctor’s delay and

rapidly progressive detachments. Patient’s delay could be partly due to the inattention of the

patient, and unfamiliarity with RRD and its symptoms in the general population. Given the peak

VandePut.indd 37 4-11-2014 14:15:47

38 | Chapter 2

annual incidence rates of RRD surgery at a given age and the possible relationship with previous

CE, it could be helpful to better inform the population at highest risk. For instance, opticians and

optometrists could inform patients in need of optical correction for (high) myopia or presbyopia

on clinical symptoms of RRD. Furthermore, ophthalmologists may stress the increased RRD risk

after CE and the accompanying symptoms thereof, in line with, for example, the CE guidelines of

the Dutch Ophthalmic Society.[20]

Study characteristics

The annual incidence rates of RRD surgery provided in our manuscript are highly reliable, as our

study adhered to crucial factors in obtaining its data. We evaluated a relatively large-sized and

stable population and study data were collected over the same period as the demographical data to

which they were compared.[5-8,11] In contrast, other studies accumulated data over several years, and

thus their populations may have fluctuated because of immigration and emigration.[4,6-10,17] Also,

demographic characteristics (e.g., age and gender distribution) are less reliable if the study period

differs from the period over which the demographic data have been accumulated.

The provided annual incidence rates of RRD surgery may be regarded as a proxy for total annual

RRD incidence rates in the North of the Netherlands. One may assume that virtually all patients

suffering from an RRD in the Netherlands will visit an ophthalmologist and will be referred for

treatment, because the health-care system in the Netherlands is affordable, easily accessible, and

of high quality. However, we do not have data on the number of RRD patients that do not seek

ophthalmological care due to various reasons. Such data could only be acquired by a cross sectional

population study. Further, we do not have data on the number of patients that refuse surgery or will

be ineligible for surgery, but we assume these numbers to be small. Also, we excluded traumatic

RRD (retinal dialysis) and reoperations, whereas some other studies included such patients.[4-10,17-19]

In all retrospective and prospective studies designed to acquire data on RRD surgery incidence,

researchers have to define eligible cases. It is inevitable that the chosen definition of RRD is of

some influence on the observed incidence of RRD surgery. In addition, we cannot fully exclude

the possibility that incidental patients had surgery elsewhere. All these aspects may have resulted

in a slight underestimation of the true annual incidence rate of RRD. Another limitation is the

retrospective character of the study.

CONCLUSION

Annual incidence rates of RRD surgery in the North of the Netherlands are high-, stable, and they

seem to be representative for annual incidence rates of RRD surgery in the entire Netherlands.

Differences in annual incidence rates of RRD surgery between populations can predominantly be

explained by the prevalence of risk factors (i.e., age-distribution, gender, prevalence of refractive

VandePut.indd 38 4-11-2014 14:15:47


2

errors, phakic eyes versus eyes with previous CE) in the population studied.[4-11,13] Therefore, annual

incidence rates of RRD surgery in the next decennia will probably be determined by population

aging and trends in CE.

ACKNOWLEDGEMENTS

We would like to acknowledge V.W. Renardel de Lavalette, E.A. Huiskamp, F.P. Gunning, and

D. Humalda, for their help and efforts in acquiring accurate data.

VandePut.indd 39 4-11-2014 14:15:47

40 | Chapter 2

REFERENCES

1. D’Amico DJ. (2008) Primary retinal detachment. N Engl J Med. 359: 2346-2354.

2. Tani PT, Robertson DM, Langworthy A. (1981) Prognosis for central vision and anatomic reattachment

in rhegmatogenous retinal detachment with macula detached. Am J Ophthalmol. 92: 611-620.

3. Pastor JC, Fernández I, Rodríguez de la Rúa E, Coco R, Sanabria-Ruiz Colmenares MR, et al. (2008)

Surgical outcomes for primary rhegmatogenous retinal detachments in phakic and pseudophakic

patients: the Retina 1 Project – report 2. Br J Ophthalmol. 92: 378-382.

4. Wilkes SR, Beard CM, Kurland LT, Robertson DM, O’Fallon WM. (1982) The incidence of retinal

detachment in Rochester, Minnesota, 1970-1978. Am J Ophthalmol. 94: 670-673.

5. Haimann MH, Burton TC, Brown CK. (1982) Epidemiology of retinal detachment. Arch Ophthalmol.

100: 289-292.


in a Finnish population. Acta Ophthalmol. 63: 59-64.

7. Törnquist R, Stenkula S, Tornquist P. (1987) Retinal detachment. A study of a population-based

patient material in Sweden 1971-1981. I. Epidemiology. Acta Ophthalmol. 65: 213-222.

8. Rowe JA, Erie JC, Baratz KH, Hodge DO, Gray DT et al. (1999) Retinal detachment in Olmsted

County, Minnesota, 1976 through 1995. Ophthalmology. 106: 154-159.

9. Algvere PV, Jahnberg P, Textorius O. (1999)The Swedish Retinal Detachment Register. I. A database

for epidemiological and clinical studies. Graefes Arch Clin Exp Ophthalmol. 237: 137-144.


Study: epidemiology and risk factors. Clin Exp Ophthalmol. 32: 159-163.

11. Mitry D, Charteris DG, Yorston D, Siddiqui MA, Campbell H et al. (2010) The epidemiology and


based study. Invest Ophthalmol Vis Sci. 51: 4963-4968.


detachment in Split-Dalmatia county, Croatia. Int Ophthalmol. 22: 197-199.

13. Van de Put MAJ, Hooymans JMM, Los LI (2013) The incidence of rhegmatogenous retinal detachment

in The Netherlands. Ophthalmology. 120: 616-622.


detachment rates after cataract surgery. J Cataract Refract Surg. 26: 1017-1021.

15. Statline. Centraal Bureau voor de Statistiek. Population, sex, age, marital status and region,

January 1. Updated June 2012 [in Dutch]. Available at: http://statline.cbs.nl/StatWeb/

publication/default.aspx?DM=SLNL&PA=03759NED&D1=0-2&D2=97-117&D3=5-7&D4=20-

21&HDR=T&STB=G2%2cG1%2cG3&VW=T. Accessed September 2, 2013.

16. Novak MA, Welch RB. (1984) Complications of acute symptomatic posterior vitreous detachment.


VandePut.indd 40 4-11-2014 14:15:47


2

17. Li X. (2003) Incidence and epidemiological characteristics of rhegmatogenous retinal detachment in

Beijing, China. Ophthalmology. 110: 2413-2417.

18. Zou H, Zhang X, Xu X, Wang X, Liu K et al. (2002) Epidemiology survey of rhegmatogenous retinal

detachment in Beixinjing District, Shanghai, China. Retina. 22: 294-299.

19. Sasaki K, Ideta H, Yonemoto J, Tanaka S, Hirose A et al. (1995) Epidemiologic characteristics of

rhegmatogenous retinal detachment in Kumamoto, Japan. Graefes Arch Clin Exp Ophthalmol. 233:

772-776.

20. Dutch Ophthamologic Society. Evidence based Guidelines [in Dutch]. Cataract Directive [in Dutch].

Available at: http://www.oogheelkunde.org/uploads/O-/YK/O-YKAeJ3BV0MX4w-6QLD0Q/

Cataract-Richtlijn-110306-excl.-hoofdstuk-6.pdf. Accessed April 16, 2013.


detachment. Am Acad Ophthalmol. 89: 1502-1512.

22. Hoogendoorn D. (1988) Extracapsulaire en intracapsulaire lensextracties bij cataract. [Extracapsular

and intracapsular lens extraction in cataract] Ned Tijdschr Geneeskd. 132: 1434-1438.

23. Clark A, Morlet N, Ng JQ, Preen DB, Semmens JB. (2011) Whole population trends in complications

of cataract surgery over 22 years in Western Australia. Ophthalmology. 118: 1055-1061.

24. Friedman Z, Neumann E, Hyams S. (1973) Vitreous and peripheral retina in aphakia. A study of 200

non-myopic aphakic eye. Br J Ophthalmol. 57: 52-57.


myopic eyes and the resulting retinal lesions. Br J Ophthalmol. 59: 451-454.

26. Österlin S. (1977) On the molecular biology of the vitreous in the aphakic eye. Acta Ophthalmol

(Copenh). 55: 535-561.


eyes. AMA Arch Ophthalmol. 52: 699-709.

VandePut.indd 41 4-11-2014 14:15:47

VandePut.indd 42 4-11-2014 14:15:47

Chapter 3

The incidence of rhegmatogenous retinal

detachment in The Netherlands

Ophthalmology 2013 120: 616-622.

The Dutch Rhegmatogenous Retinal Detachment Study Group

Writing Committee:

Mathijs A.J. Van de Put1,2, Johanna M.M. Hooymans 1,2, Leonoor I. Los1,2


2 W.J. Kolff Institute, Graduate School of Medical Sciences, University of Groningen, the Netherlands.

VandePut.indd 43 4-11-2014 14:15:47

44 | Chapter 3

ABSTRACT

Purpose: To estimate the incidence and characteristics of rhegmatogenous retinal detachment

(RRD) in the Netherlands in 2009.

Methods: By reviewing surgical logs cases of primary RRD repair in 2009 were identified. Exclusion

criteria included RRD prior to 2009, exudative, tractional, or traumatic retinal detachments.

Patient demographics, date of surgery and lens status were documented. RRD incidence and 95%

confidence intervals (CI) were calculated. Age distribution, male-to-female ratio, and proportion of

RRD patients with prior cataract extraction (CE) were determined. A Student’s t-test was used to

examine differences in the incidence of RRD between groups.

Results: The annual RRD incidence was 18.2/100,000 people (95% confidence interval [CI] =

11.4 - 18.8) with a peak incidence of 52.5/100,000 people (95% confidence interval [CI] = 29.4 -

56.8) between 55-59 years of age. Bilateral RRD rate was 1.67%. Macula-off presentation occurred

in 54.5% of all RRD patients. Prior CE was noted in 33.5% of RRD eyes. The male-to-female ratio

was 1.3:1, and RRD incidence was statistically significantly more frequent in males (P < 0.0001).

Conclusions: Rhegmatogenous retinal detachment is predominantly a disease of the population

over 50 years of age, and males are more susceptible to RRD. The annual RRD incidence is highly

dependent on demographic characteristics.

VandePut.indd 44 4-11-2014 14:15:47

RRD incidence in the Netherlands | 45

3

INTRODUCTION

Rhegmatogenous retinal detachment (RRD), which refers to a separation of the neurosensory

retina from the underlying retinal pigment epithelium due to a defect in the retina, is a potentially

blinding ophthalmic pathology.[1] Despite advances in treatment, functional results remain poor,

with only 42% of all RRD eyes achieving ≥ 20/40 vision, and only 37% achieving ≥ 20/50 in

macula-off detachments.[2,3]

In Western populations (e.g., Europe, United States, Australia), the annual incidence of

rhegmatogenous retinal detachment (RRD) was 6.1-9.8 cases per 100,000 people during the

1970s, increasing to 11.8-17.9 cases per 100,000 people in the 1990s.[4-12] A recent study reported

an incidence of 12.05 cases per 100,000 people at the beginning of the twenty-first century in a

relatively young population,[11] whereas another study in the Netherlands found an incidence of

17.42/100,000 people per year in a relatively older population.[13]

The broad variety in RRD incidence rates over the past forty years may be explained by the

pathophysiology of RRD. Because of a complicated posterior vitreous detachment (PVD),[14]

and to a lesser extent as a late consequence of a previous cataract extraction (CE),[15] RRD occurs

predominantly at an advancing age.[4-12] Consequently, the RRD incidence is higher in relatively

older populations,[13], and lower in relatively younger populations.[11]

The purpose of this study was to estimate the incidence and describe the characteristics of RRD

in the Netherlands in 2009.

METHODS

Study population

The population of the Netherlands, based on the 2009 census, was approximately 16,485,787.[16]

To be included in this study as an RRD case, the patient must have been a permanent resident of

the Netherlands in 2009. All Dutch RRD patients are operated on in one of sixteen centers with a

capacity for vitreoretinal surgery, and all sixteen centers participated in this collaborative study as

the “Dutch RRD Study Group.” The internal review board (IRB) of the University Medical Center

Groningen waived the need for IRB approval in all centers. The study has adhered to the tenets of

the Declaration of Helsinki.

Data collection

Data were collected retrospectively. All cases of primary RRD operated on from January 1, 2009,

until January 1, 2010, were identified using the surgical logs. Surgery for RRD was defined as

conventional surgery, trans pars plana vitrectomy, and pneumatic retinopexy. Cases of solely laser

barricade were not counted as surgery. Rhegmatogenous retinal detachment was defined as a retinal

VandePut.indd 45 4-11-2014 14:15:47

46 | Chapter 3

elevation with any retinal break (found before or during surgery). All eyes with prior detachments

– or tractional, exudative, and traumatic (retinal dialysis) retinal detachments – were excluded.

Reoperations within the study period were excluded (i.e., only the first surgical intervention was

counted).

The information collected included patient’s age, gender, and affected eye, macula-off or macula-

on detachment, date of RRD surgery, and history of CE. Macula-off RRD was defined as a

macular elevation prior to or during surgery, or a visual acuity of less than 10/20 that could not be

explained by other stated pathology, such as media opacities, amblyopia, macular or optic nerve

pathology. All data were entered into a computer database.

In order to compare RRD incidence rates in our population to other populations we conducted

a PubMed database search using the search terms “incidence”, “population”, “epidemiology”,

“rhegmatogenous”, and “retinal detachment” in different combinations.


The annual incidence rate was calculated by dividing the number of new cases by the target

population size. Bilateral cases were counted separately, as these are a rarity. A 95% confidence

interval (CI) of the incidence rate was calculated. A Student’s t-test was used to examine differences

in the incidence of RRD between two groups (total RRD incidence in males versus females,

RRD incidence in males versus females in the different age categories, RRD incidence between

consecutive age categories for the total RRD population, and for males and females, respectively).

A P-value < 0.05 was considered significant. Statistical analyses were performed using Microsoft

Office Excel 11.0 (Microsoft Corp., Washington, USA).

RESULTS

Among the 16,485,787 residents of the Netherlands in 2009, 2998 new cases of RRD were treated.

The incidence of RRD in the Netherlands in 2009 was 18.2/100,000 people (95% confidence

interval [CI] = 11.4 - 18.8). Of all patients, 50 suffered from bilateral RRD, resulting in a bilateral

RRD rate of 1.67%. A detached macula was found in 1633 eyes (54.5%), and the macula was

attached at presentation in 1365 eyes (45.5%).

Age and gender distribution

The median age of the patients was 60 years (range = 9-99). This did not differ between males

(median age 60 years [range 9-91]), and females (median age 60 years [range 10-99 years]). There

was a significant increase in RRD incidence from 34 years of age onwards (P = 0.0036), and a

significant decrease in incidence from 74 years of age onwards (P = 0.0033) (Table 1, Figure 1).

VandePut.indd 46 4-11-2014 14:15:47


3

We noticed a peak incidence at 55-59 years of age with an incidence of 52.5/100,000 people (95%

confidence interval [CI] = 29.4 - 56.8) (Figure 1).

Table 1: Actual numbers of individuals and incidences of rhegmatogenous retinal detachment per age

category in the population of the Netherlands for males, females, and all individuals in 2009.

Age range(years)

Number of individualsa

Total with RRD Males with RRD Females with RRD M-F ratiob

Total Male Female Number Incidence Number Incidence Number Incidence< 5 931.6 476.7 454.9 0 0 0 0 0 0 NA5-9 1010.6 517.0 493.6 1 0.10 1 0.2 0 0 NA10-14 980.9 502.0 478.9 9 0.92 4 0.8 5 1.0 0.8:115-19 1010.5 516.3 494.3 14 1.39 1 0.2 13 2.6 0.1:120-24 996.9 504.3 492.5 34 3.41 20 4.0 14 2.8 1.4:125-29 992.0 498.4 493.6 37 3.73 16 3.2 21 4.3 0.8:130-34 1008.4 504.6 503.9 30 2.97 17 3.4 13 2.6 1.3:135-39 1236.6 620.7 615.9 65 5.26 33 5.3 32 5.2 1.0:140-44 1295.6 655.7 639.9 114 8.80 68 10.4 46 7.2 1.4:145-49 1271.5 641.0 630.5 210 16.52 121 18.9 89 14.1 1.3:150-54 1157.7 581.5 576.2 380 32.82 214 36.8 166 28.8 1.3:155-59 1081.1 544.2 536.9 567 52.45 328 60.3 239 44.5 1.4:160-64 1040.6 522.2 518.4 536 51.51 327 62.6 208 40.1 1.6:165-69 747.8 368.2 379.6 366 48.95 211 57.3 155 40.8 1.4:170-74 603.5 283.3 320.2 289 47.89 160 56.5 129 40.3 1.4:175-79 489.3 210.7 278.7 182 37.19 93 44.2 89 31.9 1.4:180-84 345.8 129.2 216.6 108 31.23 64 49.5 44 20.3 2.4:185-89 200.6 61.9 138.8 43 21.43 19 30.7 24 17.3 1.8:190-94 67.9 15.9 52.1 11 16.20 4 25.2 7 13.5 1.9:1≥ 95 16.8 2.9 14.0 2 11.88 0 0 2 14.3 NATotal 16485.8 8156.3 839.4 2998 18.19 1701 20.9 1296 15.6 1.3:1RRD: rhegmatogenous retinal detachment; NA: not applicable. a Actual number is given number*1000. b Male-to-female ratio.

VandePut.indd 47 4-11-2014 14:15:48

48 | Chapter 3

0

10

20

30

40

50

60

70

< 5

5-9

10-14

15-19

20-24

25-29

30-34

35-39

40-44

45-49

50-54

55-59

60-64

65-69

70-74

75-79

80-84

85-89

90-94

95-100

Age (years)

Inci

denc

e pe

r 10

0,00

0 pe

ople

Total Males Females

Figure 1: The incidence of rhegmatogenous retinal detachment in the Netherlands per 100,000 people in

2009.

Among the 2998 incident cases of RRD, 1701 involved males (56.7%), and 1296 involved females

(43.3%), resulting in a male-to-female ratio of 1.3:1. The incidence of RRD was 20.9/100,000

people (95% confidence interval [CI] = 19.9 - 21.9) in males, and 15.6/100,000 people (95%

confidence interval [CI] = 14.7 - 16.4) in females, respectively. The incidence differed significantly

between males and females in the total group (P < 0.0001), and in the subpopulations aged 15-19

(P = 0.0006), 40-44 (P = 0.027), 45-49 (P = 0.018), 50-54 (P = 0.0088), 55-59 (P = 0.0002), 60-64

(P < 0.0001), 65-69 (P = 0.0007), 70-74 (P = 0.0023), 75-79 (P = 0.016), 80-84 (P < 0.0001), and

85-89 years (P = 0.044), respectively.

RRD in phakic eyes and eyes with prior CE

Of the 2998 RRD cases, 66.5% involved phakic eyes, and 33.5% involved eyes with prior CE.

The median age of phakic RRD patients was 58 years (range 10-99). This did not differ between

males (median age 59 years [range 14-91]) and females (median age 58 years [range 10-99]). We

noticed an increase in absolute numbers of RRD in phakic eyes from age 35 onwards, peaking at

55-59 years of age (n = 406), and decreasing thereafter (Figure 2). Among the 1994 phakic RRD

cases, 1105 involved males (55.4%), and 888 involved females (44.5%), resulting in a male-to-

female ratio of 1.2:1. At age 75-79 years, there is a turning point in the percentage of phakic RRD

eyes compared to RRD eyes with a history of CE (Figure 3).

The median age of patients with RRD in eyes with prior CE was 64 years (range 9-91). The median

age was 63 years (range 9-91) for males, and 65 years (range 17-91) for females. We noticed an increase

in absolute numbers of RRD in eyes with prior CE from age 40 onwards, peaking at 60-64 years

VandePut.indd 48 4-11-2014 14:15:48


3

of age (n = 166), and decreasing thereafter (Figure 2). Among the 1004 cases, 596 (59.4%) involved

males, and 408 (40.6%) involved females resulting in a male-to-female ratio of 1.5:1.

0

50

100

150

200

250

300

350

400

450

< 5

5-9

10-14

15-19

20-24

25-29

30-34

35-39

40-44

45-49

50-54

55-59

60-64

65-69

70-74

75-79

80-84

85-89

90-94

95-100

Age (years)

RR

D-e

yes

Absolute number of RRD-eyes with history of cataract extraction

Absolute number of phakic RRD-eyes

Figure 2: Absolute numbers of phakic rhegmatogenous retinal detachment (RRD) eyes and RRD eyes with

a history of cataract extraction.

0%

20%

40%

60%

80%

100%

< 5

5-9

10-14

15-19

20-24

25-29

30-34

35-39

40-44

45-49

50-54

55-59

60-64

65-69

70-74

75-79

80-84

85-89

90-94

95-100

Age (years)

Prop

ortio

n

Proportion of RRD-eyes with a history of cataract extraction

Proportion of phakic RRD-eyes

Figure 3: Proportion of phakic rhegmatogenous retinal detachment (RRD) eyes and RRD eyes with a

history of cataract extraction.

VandePut.indd 49 4-11-2014 14:15:48

50 | Chapter 3

DISCUSSION

As far as we are aware, we are reporting in this paper the highest RRD incidence rate thus far,

which is in line with the increasing RRD incidence rates that have been reported over the past

forty years.[4-12] Most importantly, the RRD incidence rates provided in our manuscript are highly

reliable due to the population studied (i.e., the population studied was one of the largest, most

stable, and well-defined populations), and the opportunity for uniform data collection (i.e., uniform

diagnosis because of cooperation with “the Dutch RRD Study Group”). In line with previous

reports, a peak incidence was observed in the middle-aged (55-59 years of age), while males were

overrepresented in almost all age categories.[4-12,17-19] This suggests that RRD incidence is strongly

dependent on demographic characteristics such as age and gender distribution. We noticed the

highest numbers of phakic RRD patients at ages 55-59 years, and the highest numbers of post-CE

RRD patients at ages 60-64 years. Also, the proportion of post-CE RRD increased with advancing

age. Both observations suggest that phakic and post-CE RRD are different entities. The fact that

RRD is still a sight-threatening condition is underscored by the presence of a macular detachment

in more than half of the patients.


Differing incidence rates between populations and within a population over a different time

period can well be explained by the studied population (i.e., size, stability, defined borders, and the

accessibility of the health-care system), and by the study design, including definition of diagnosis,

and further by the prevalence of risk factors (i.e., age distribution, prevalence of refractive errors,

phakic eyes, and eyes with previous CE) in the population studied.[4-12, 17-21] The provided RRD

incidence rates in our manuscript are highly reliable, as our study adhered to the crucial factors in

obtaining incidence rates. First, the studied population was one of the largest populations studied

thus far.[4-12] Second, other studies accumulated data over several years, and thus their populations

may have fluctuated because of immigration and emigration.[4,6-10,20] Demographic characteristics

(e.g., age and gender distribution) are less reliable if the study period differs from the period, over

which the demographic data have been accumulated. Further, the studied population was well

defined, because there was minimal cross-border consumption of health care (i.e., surrounding

countries have different languages, health-care accessibility, and health-care systems). In addition,

we can assume that virtually all patients suffering from an RRD in the Netherlands visit an

ophthalmologist, and are referred for treatment, because the health-care system in the Netherlands is

affordable, easily accessible, and of high quality. Virtually no patients will refuse surgery. Exceptions

may exist, however, for patients with very advanced stages of proliferative vitreoretinopathy (PVR)

or who are in very poor health. Finally, definitions of RRD differed between studies. For instance,

we excluded traumatic RRD (retinal dialysis) and reoperations, whereas other studies included

such patients, resulting in slightly higher RRD incidences.[4-10,17,18,20,21]

VandePut.indd 50 4-11-2014 14:15:48


3

The reported RRD incidence rate in our population may be underestimated. For instance, we used

surgical care as a proxy for RRD incidence. In addition, it could be possible that a small proportion

of Dutch RRD patients might have been operated on outside the Netherlands. Another limitation

could be the retrospective character of the study.

RRD and age/population aging

The strong association between RRD incidence rates and age has been reported extensively. This

association has been found to be strongest in phakic RRD patients.[4-10,17,18,20] Posterior vitreous

detachment (PVD) is generally assumed to be the main cause of RRD in phakic eyes, since RRD

is frequently associated with acute symptomatic PVD.[14,22] PVD is a rarity in individuals younger

than 50 years of age; on average, its onset is at 60 years, with increasing prevalence thereafter.[22] This

may well explain the observed median age and age peak in phakic RRD in our and other studies.[4-10,17,18,20] Pathophysiologically, this relationship is confirmed by the general presence of horseshoe-

shaped tears at the central border of the vitreous base.[14,23] The relationship between PVD and age

is in line with described lower RRD incidences in relatively younger populations[11,12,19,21] versus

higher RRD incidences in relatively older populations, including our own.[6-8,16]

RRD and gender

The observed gender difference in RRD incidence in our study is supported by others,[8-11,19-21] but

it is not found consistently.[5-7,17,18] Previous authors suggested that the attributable risk of RRD

from ocular trauma may be higher in males than in females,[19] and consequently lead to a higher

RRD incidence in males. We excluded traumatic RRD, and in addition the attributable risk of

RRD from ocular trauma is reportedly low.[5,18,21] Although, high myopia has been considered an

important risk factor for RRD,[4,5,7] the prevalence of myopia in the Dutch population is equal for

males and females.[24] However, symptomatic posterior vitreous detachment (PVD) even though

more common in females than males[22, 25-27] is more often complicated by a retinal tear in males,

possibly resulting in a higher attributable RRD risk in males.[14] In addition, previous CE increases

the risk of developing a PVD in due course[28,29]. In concordance to previous reports,[30] in the

Netherlands the male-to-female ratio regarding CE was 2:3 as registered by cataract surgeons

from 2000-2012 in the online cataract database of the Dutch Ophthalmologic Society (Dutch

Ophthalmologic Society. Cataract Quality Registration [in Dutch][database online]). This in

contrast to the overrepresentation of males in absolute pseudophakic RRD numbers in our and

other studies.[30,31] One possible explanation for these inconsistencies may be a slightly unequal

distribution of males and females across the different age groups.[4,6-9]

VandePut.indd 51 4-11-2014 14:15:48

52 | Chapter 3

RRD and cataract extraction

It has been postulated that the cumulative risk of RRD is increased by a factor of 5 in eyes with

a history of CE.[5] Possibly, the volume of performed CE in our population in recent years may be

partly responsible for the high RRD incidence rates observed in this population.[32]

The increase in performed CE can be attributed to population aging, and hence a higher prevalence

of cataracts. In addition, because of the success of phacoemulsification for CE, there has been a

tendency to perform CE at an earlier stage.[33,34] Both factors have resulted in a higher volume of CE

performed in the recent past. (Estimated numbers for the Netherlands are 38,000 CE performed

in 1991; 80,000 in 1998; and 120,000 in 2003).[32]

In line with this, and in contrast to others, we found a high percentage of RRD patients with

prior CE.[4,10,11] In parallel with the increase in the volume of cataract surgery in the Netherlands,

there has been a shift in surgical technique. Extracapsular cataract extraction (ECCE) has been

replaced by the safer procedure of phacoemulsification.[35,36] Furthermore, intracapsular cataract

extraction (ICCE), the procedure holding the highest risk of postoperative RRD, has just about

been abandoned.[35,36] Even though the relatively safer phacoemulsification technique probably

mitigates the RRD risk in pseudophakic eyes to some extent, the overall contribution of CE to

RRD incidence still seems to be significant.

Unfortunately, reliable incidence rates for phakic versus post-CE RRD cannot be provided, since

the prevalence of phakic versus post-CE eyes in most populations, including our own, is unknown

due to incomplete registration systems.[4,10,11] The differences in the shapes of the age-related

distribution curves between phakic and post-CE RRD, and the shift in the proportion of phakic

versus post-CE RRD eyes with advancing age suggest that phakic and post CE-RRD are different

entities.[8,14,22,35-38] Several theories concerning the pathophysiological mechanisms on phakic versus

post-CE RRD have been advocated. First, a newly induced PVD[37,38] in non-PVD eyes can occur,

because CE causes mechanical[8] and biochemical changes[39] in the vitreous.[37-39] Also, a second

mechanism could be at play, namely, the altered mechanical forces at the anterior vitreous base

area because of the loss of lens volume.[40] This second mechanism would also explain the more

anteriorly located small horseshoe-shaped tears that are frequently found in RRD eyes with prior

CE.[40]

RRD, refractive error, and bilaterality

It has consistently been found that high myopia is associated with RRD, especially bilateral RRD.[4,5,7] Unfortunately, we could not make any assumption on the relationship between RRD and

myopia, as the distribution of refractive errors in our population is not known. Furthermore, in

that they are only for one single year, our data are too limited to draw any conclusions as to the risk

of developing bilateral RRD. The risk of bilateral RRD varies among populations: for instance,

in Sweden, 11.2% of subjects had bilateral RRD over a time period of ten years[4-7] compared to

VandePut.indd 52 4-11-2014 14:15:48


3

6.7% in Minnesota (USA)[8] over a time period of twenty years.[8] In all series, fellow eyes have an

increased risk of developing RRD in due course.[8,11]

RRD and macular status

Macular status at presentation is an important prognostic indicator of visual outcome.[2,3] We

identified high numbers of macula-off detachment in our population.[8,9] One possible explanation

for this high number was our chosen definition of macula-off detachment. Not only was the clinical

observation of subretinal fluid, before or during surgery, regarded as macula-off detachment but

eyes with VA ≤ 10/20 not explained by other ophthalmic pathology were also considered as such.

This results in higher numbers of macula-off detachments compared to studies using lower VA

values as a cut-off point. Both methods have their limitations, and the gold standard to determine

pre-operative macular status would be performing a macular optical coherence tomography (OCT)

and / or ultrasonography, but such tests are not routinely performed in RRD patients. Other

explanations for this high rate of macula-off detachments include patient’s and doctor’s delay, or

rapidly progressive detachments. Patient’s delay could be partly due to inattention on the part of

the patient, and unfamiliarity with RRD and its symptoms in the general population. Given the

peak incidence at a given age and the possible relationship with previous CE, it could be helpful to

better inform the population at highest risk. For instance, optometrists could inform patients with

(high) myopia or presbyopia about the clinical symptoms of RRD. Furthermore, in ophthalmology

departments it could be useful to emphasize the increased RRD risk after CE. This would be in

line with the current CE guidelines from the Dutch Ophthalmic Society, which clearly state this

risk.[32]

CONCLUSION

In summary, RRD incidence is highly dependent on demographic characteristics such as age and

gender. Males have a higher risk than females, and a peak incidence is found at 50-55 years of

age. A possible explanation for the high RRD incidence rate in our population may be due to the

volume of performed CE in our population. We expect the RRD incidence in Western populations

to increase due to an increase in the proportion of persons of advanced age (i.e., population aging),

who therefore are at an increased risk for the development of RRD and cataract over the next

decades.

Our data could be used to identify and inform those subpopulations at highest risk for RRD

about the signs and symptoms of this disease. This possibly could result in a decrease in patient’s

delay and, concomitantly, in a decrease in macular detachment rates. In addition, our data can be

a helpful tool for anticipating future health-care demand in the Netherlands.

VandePut.indd 53 4-11-2014 14:15:48

54 | Chapter 3

REFERENCES

1. D’Amico DJ. (2008) Primary retinal detachment. N Engl J Med 359: 2346-2354.

2. Tani PT, Robertson DM, Langworthy A. (1981) Prognosis for central vision and anatomic reattachment

in rhegmatogenous retinal detachment with macula detached. Am J Ophthalmol 92: 611-620.


rhegmatogenous retinal detachments in phakic and pseudophakic patients: the Retina 1 Project–-

report 2. Br J Ophthalmol 92: 378-382.

4. Wilkes SR, Beard CM, Kurland LT, et al. (1982) The incidence of retinal detachment in Rochester,

Minnesota, 1970-1978. Am J Ophthalmol 94: 670-673.

5. Haimann MH, Burton TC, Brown CK. (1982) Epidemiology of retinal detachment. Arch Ophthalmol

100: 289-292.


in a Finnish population. Acta Ophthalmol (Copenh) 63: 59-64.

7. Tornquist R, Stenkula S, Tornquist P. (1987) Retinal detachment. A study of a population-based

patient material in Sweden 1971-1981. I. Epidemiology. Acta Ophthalmol (Copenh) 65: 213-222.

8. Rowe JA, Erie JC, Baratz KH, et al. (1999) Retinal detachment in Olmsted County, Minnesota, 1976

through 1995. Ophthalmology 106: 154-159.

9. Algvere PV, Jahnberg P, Textorius O. (1999) The Swedish Retinal Detachment Register. I. A database

for epidemiological and clinical studies. Graefes Arch Clin Exp Ophthalmol 237: 137-144.


Study: epidemiology and risk factors. Clin Experiment Ophthalmol 32: 159-163.

11. Mitry D, Charteris DG, Yorston D, et al, Scottish RD Study Group. (2010) The epidemiology and


based study. Invest Ophthalmol Vis Sci 51: 4963-4968.


detachment in Split-Dalmatia County, Croatia. Int Ophthalmol 22: 197-199.

13. Van de Put MAJ, Hooymans JMM, Los LI. (2010) De incidentie van rhegmatogene ablatio retinae in

het Noorden van Nederland [Incidence of rhegmatogenous retinal detachment in the North of the

Netherlands]. Paper presented at: The Dutch Ophthalmic Society annual meeting, March 26, 2010;

Maastricht).

14. Novak MA, Welch RB. (1984) Complications of acute symptomatic posterior vitreous detachment.

Am J Ophthalmol 97: 308-314.


detachment rates after cataract surgery. J Cataract Refract Surg 26: 1017-1021.

VandePut.indd 54 4-11-2014 14:15:48


3

16. Statline. Centraal Bureau voor de Statistiek. Population, sex, age, marital status and region, January 1.

Updated June 2012 [in Dutch]. Available at: http://statline.cbs.nl/StatWeb/publication/default.

aspx?DM=SLNL&PA=03759NED&D1=1-2&D2=97-117&D3=5-7&D4=20&VW=T. Accessed July 17,

2012.

17. Zou H, Zhang X, Xu X, et al. (2002) Epidemiology survey of rhegmatogenous retinal detachment in

Beixinjing District, Shanghai, China. Retina 22: 294-299.

18. Sasaki K, Ideta H, Yonemoto J, et al. (1995) Epidemiologic characteristics of rhegmatogenous retinal

detachment in Kumamoto, Japan. Graefes Arch Clin Exp Ophthalmol 233: 772-776.

19. Wong TY, Tielsch JM, Schein OD. (1999) Racial difference in the incidence of retinal detachment in

Singapore. Arch Ophthalmol 117: 379-383.

20. Beijing Rhegmatogenous Retinal Detachment Study Group. (2003) Incidence and epidemiological

characteristics of rhegmatogenous retinal detachment in Beijing, China. Ophthalmology 110: 2413-

2417.

21. Limeira-Soares PH, Lira RP, Arieta CE, Kara-José N. (2007) Demand incidence of retinal detachment

in Brazil. Eye (Lond) 21: 348-352.


detachment. Ophthalmology 89; 1502-1512.

23. Mahroo OA, Dybowski R, Wong R, Williamson TH. (2013) Characteristics of rhegmatogenous

retinal detachment in pseudophakic and phakic eyes. Eye (Lond) 27: 1063-1069.

24. Hendricks TJ, de Brabander J, Vankan-Hendricks MH, et al. (2009) Prevalence of habitual refractive

errors and anisometropia among Dutch schoolchildren and hospital employees. Acta Ophthalmol 87:

538-543.

25. Kanski JJ. (1975) Complications of acute posterior vitreous detachment. Am J Ophthalmol 80: 44-46.

26. Chuo JY, Lee TY, Hollands H, et al. (2006) Risk factors for posterior vitreous detachment: a case-

control study. Am J Ophthalmol 142: 931-937.

27. Hayreh SS, Jonas JB. (2004) Posterior vitreous detachment: clinical correlations. Ophthalmologica

218: 333-343.

28. Ripandelli G, Coppé AM, Parisi V, et al. (2007) Posterior vitreous detachment and retinal detachment

after cataract surgery. Ophthalmology 114: 692-697.

29. Hikichi T. (2012) Time course of development of posterior vitreous detachments after

phacoemulsification surgery. Ophthalmology 119: 2102-2107.

30. Tuft SJ, Gore DM, Bunce C, et al. (2012) Outcomes of pseudophakic retinal detachment. Acta


31. Sheu SJ, Ger LP, Chen JF. (2007) Male sex as a risk factor for pseudophakic retinal detachment after

cataract extraction in Taiwanese adults. Ophthalmology 114: 1898-1903.

32. Dutch Ophthamologic Society. Evidence based Guidelines [in Dutch]. Cataract Directive [in Dutch].

Available at: http://www.oogheelkunde.org/uploads/O-/YK/O-YKAeJ3BV0MX4w-6QLD0Q/Cataract-

Richtlijn-110306-excl.-hoofdstuk-6.pdf Accessed August 24, 2012.

VandePut.indd 55 4-11-2014 14:15:48

56 | Chapter 3

33. Tobacman JK, Zimmerman B, Lee P, et al. (2003) Visual acuity following cataract surgeries in relation

to preoperative appropriateness ratings. Med Decis Making 23: 122-130.

34. de Larrea NF, Blasco JA, Aguirre U, et al. (2010) Appropriateness of phacoemulsification in Spain. Int

J Qual Health Care 22: 31-38.

35. Hoogendoorn D. (1988) Extracapsular and intracapsular lens extraction in cataract [in Dutch]. Ned

Tijdschr Geneeskd 132: 1434-1438.

36. Clark A, Morlet N, Ng JQ, et al. (2011) Whole population trends in complications of cataract surgery

over 22 years in Western Australia. Ophthalmology 118: 1055-1061.

37. Friedman Z, Neumann E, Hyams S. (1973) Vitreous and peripheral retina in aphakia: a study of 200

non-myopic aphakic eyes. Br J Ophthalmol 57: 52-57.


myopic eyes and the resulting retinal lesions. Br J Ophthalmol 59: 451-454.

39. Österlin S. (1977) On the molecular biology of the vitreous in the aphakic eye. Acta Ophthalmol(Copenh)

55: 353-361.


eyes. AMA Arch Ophthalmol 52: 699-709.

VandePut.indd 56 4-11-2014 14:15:48


3

The Dutch Rhegmatogenous Retinal Detachment Study Group

WRITING COMMITTEE

University Medical Center Groningen, Groningen

J.M.M. Hooymans, L.I. Los, M.A.J. Van de Put.

STUDY GROUP MEMBERS

The following investigators belong to the Dutch rhegmatogenous retinal detachment study group;

Rotterdam Eye Hospital, Rotterdam

P.R. Van den Biesen, E.W. Lindstedt, J.C. Van Meurs, K.A. Van Overdam, M.A.H. Veckeneer.

University Medical Center St Radboud, Nijmegen

N. Crama, C.B. Hoyng, B.J. Klevering, T. Theelen, M.A.D. Tilanus.

University Medical Center Groningen, Groningen

J.M.M. Hooymans, E.A. Huiskamp, L. I. Los, I.M. Nolte, G. Postma, M.A.J. Van de Put,

V.W. Renardel de Lavalette.

Amsterdam Medical Center, Amsterdam

H.M. Bijl, S.Y. Lesnik Oberstein, M. Mura, H.S. Tan.

University Medical Center Utrecht, Utrecht

R. Van Leeuwen, P.A.W.J.F. Schellekens, J.S. Stilma.

VU University Medical Center, Amsterdam

M.I. Bosscha, J.W.M. Reichert-Thoen, P.J. Ringens, W.A.E.J. De Vries-Knoppert.

Academic Medical Center Maastricht, Maastricht

F. Goezinne, E.C. La Heij, T.A. Liem, I.J. Lundqvist.

Maxima Medical Center, Eindhoven

F.T. Kerkhoff.

Catharina Hospital, Eindhoven

E.J.G.M. Van Oosterhout, R.P.C. Rademaker.

Medical Center Alkmaar, Alkmaar

E.M. Busch, D.J. Treskes.

Isala Clinics, Zwolle

R.P.G. Feenstra.

Erasmus University Medical Center, Rotterdam

G.H.S. Buitendijk, E. Kiliç, R.W.A.M. Kuijpers, J.R. Vingerling.

Leiden University Medical Center, Leiden

W. Swart.

Antonius Hospital, Sneek

F.P. Gunning,. D. Humalda.

Deventer Hospitals, Deventer

V.P.T. Hoppenreijs.

VandePut.indd 57 4-11-2014 14:15:48

58 | Chapter 3

Rivierenlanden Hospitals, Tiel

M.N. Copper.

Canisius-Wilhelmina Hospital, Nijmegen

A.J.J.M. Rademakers.

VandePut.indd 58 4-11-2014 14:15:48

PART II

CLINICAL STUDIES

VandePut.indd 59 4-11-2014 14:15:48

VandePut.indd 60 4-11-2014 14:15:48

Chapter 4

Design and validation of a method to determine

the position of the fovea by using the optic nerve-

head to fovea distance of the fellow eye

Plos One, May 2013: 8:5:e99787

Mathijs A.J. van de Put¹,2, Fara Nayebi¹, Danna Croonen¹, Ilja M. Nolte3,

Wouter J. Japing¹, Johanna M.M. Hooymans¹,2, Leonoor I. Los¹,2

1. Department of Ophthalmology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

2 W.J. Kolff Institute, Graduate School of Medical Sciences, University of Groningen, the Netherlands.3. Department of Epidemiology, University Medical Center Groningen,

University of Groningen, Groningen, The Netherlands.

VandePut.indd 61 4-11-2014 14:15:49

62 | Chapter 4

ABSTRACT

Purpose: To measure the optic nerve-head to fovea distance (NFD) on fundus photographs in

fellow eyes, and to compare the NFD between fellow eyes.

Methods: Diabetic patients without retinopathy, ophthalmologic congenital malformations,

retinal or choroidal scars, or a more than 45° rotated optic nerve-head (n=183) who were screened by

fundus photography at the University Medical Center Groningen, the Netherlands from January

1st 2005 until January 1st 2006 were included. The NFD was measured in left and right eyes both

from the center and from the rim of the optic nerve-head. To determine inter- and intra-observer

agreement, repeated measurements by one observer (n=3) were performed on all photographs and

by two observers on 60 photographs (30 paired eyes). The effect of age, gender, and refractive error

on NFD was analysed.

Results: The correlation of NFDs between the left and the right eye was 0.958 when measured

from the center of the optic nerve-head (mean difference 0.0078 mm. ±SD 0.079 (95% limits

of agreement -0.147 – 0.163)) and 0.963 when measured from the rim (mean difference 0.0056

±SD 0.073 (95% limits of agreement -0.137 – 0.149)). Using the NFD between fellow eyes

interchangeably, resulted in a standard error of 0.153 mm. Intra- and inter-observer variability was

small. We found a significant effect of age (center of the optic nerve-head (P = 0.006) and rim of

the optic nerve head (P = 0.003)) and refractive error (center of optic nerve-head (P < 0.001) and

rim of optic nerve head (P < 0.001)) on NFD.

Conclusions: The NFD in one eye provides a confident, reproducible, and valid method to address

the position of the fovea in the fellow eye. We recommend using the NFD measured from the

center of the optic nerve-head since the standard error by this method was smallest. Age and

refractive error have an effect on NFD.

VandePut.indd 62 4-11-2014 14:15:49

Optic nerve-head to fovea distance | 63

4

INTRODUCTION

In macula-off rhegmatogenous retinal detachment (RRD), visual recovery is highly variable,

even after successful reattachment of the macula.[1-3] The height of macular detachment has been

coined as a potential factor influencing visual recovery.[4-5] Height of macular detachment is defined

by the distance between the fovea and the retinal pigment epithelium and can be measured by

ultrasonography.[4-5]

Because of its resolution, it is impossible to recognize the foveal dip by ultrasonography.[6-8] The

optic nerve-head can be recognized by ultrasonography, and may thus serve as a landmark for foveal

position, provided the optic nerve-head to fovea distance (NFD) is known.[6-12] Physiologically, the

NFD varies between individuals.[9-12] Factors known to influence the NFD include developmental

disturbances,[13] foci of chorioretinitis,[13] fibrous traction bands,[13] an unequal distribution of

retinal vessels,[14-15] an uneven distribution of collagen tissue in the lamina cribrosa,[16] and a tilted

or rotated optic nerve-head.[17-23] Also, age, gender and refraction possibly influence the NFD.[11]

Since it is impossible to make direct measurements of the fundus of a living eye, information on

an individual NFD must be obtained by measurements of an image of the fundus.[24] This can

be difficult when changes in the position of the fovea as in macula-off RRD interfere with an

imaging technique.[3-5] While there is considerable variation in NFD between individuals, both

NFDs within one individual are correlated.[10-12] We evaluated whether the NFDs measured on a

fundus photograph of one individual could be used interchangeably between both eyes to obtain a

valid method to determine the position of the fovea in macula-off RRD by ultrasonography.

Such a method enables our research group to precisely determine the distance between the fovea

and the retinal pigment epithelium in macula-off RRD in our research project on the possible

relationship between recovery of visual function and height of macular detachment. This method

could also be adapted for use in optical coherence tomography based studies on foveal thickness in

situations of unilateral pathology where the fovea cannot be recognised morphologically because

of diffuse thickening of the macula and central fixation may be affected by the macular pathology.

Examples hereof include subretinal neovascularisation, diffuse diabetic macular edema, and diffuse

macular thickening associated with an epiretinal membrane. A prerequisite in these situations

would be the relative normality of the fellow fovea. In addition, it would be interesting to evaluate

whether anatomical symmetry with regard to NFDs exists between fellow eyes.

METHODS

Study population

Retrospectively, we selected 400 diabetic patients who were enrolled in our diabetic screening

program and underwent routine examination involving a fundus photograph of both eyes once

VandePut.indd 63 4-11-2014 14:15:49

64 | Chapter 4

yearly at the University Medical Center Groningen from January 1st, 2005 until January 1st,

2006 from our IMAGEnet 2000™ 2.53© database (Topcon™ Europe BV, Leicestershire, UK)

for Windows 2000™ digital imaging system (Microsoft™ Corp, SF, Cal, US). The patients were

chosen in such a way that the number of patients were approximately equal in seven age groups

(20-29, 30-39, 40-49, 50-59, 60-69, 70-79, and 80-89 years of age). The research adhered to

the tenets of the Declaration of Helsinki and the Ethics Committee of the University Medical

Center Groningen decided that approval was not required for this study. All 400 patients were

asked to sign an informed consent form. Patients were excluded when written consent was not

obtained (n=174) or when the quality or field of view of one of the fundus photographs prevented

accurate measurements (n=11). In addition, all patients with diabetic retinopathy, ophthalmologic

congenital malformations, retinal or choroidal scars, or a more than 45° rotated optic nerve-head

on photographic imaging were excluded (n=16).[13-23] Therefore, our study population consisted

of 199 patients. Information on age, gender, visual acuity (VA), refraction, and prior cataract

extraction (CE) was obtained from the patients’ charts. Patients with an uncorrected Snellen VA of

≥ 0.8 were assumed to be emmetropic.

Measurements of nerve-head to fovea distance

Digital fundus photographs were made by two experienced medical photographers, 30 minutes

after the administration of one drop of tropicamide 0.5% and one drop of phenylefrine 2.5% in

both eyes, using a xenon lamp for illumination of 300 WS at the maximum, under a 50° angle,

using the TRC-50 IX fundus camera, (Topcon™ Europe B.V., Leicestershire, UK).

On each fundus photograph, the circumference of the optic nerve-head was manually marked

using the software program IMAGEnet™ 2000 2.53©. The observers were instructed to take the

edge of the optic nerve head and not the peripapillary atrophy region (if present). Major and minor

axes were drawn manually on the marked circumference of the optic nerve head. The axes were

defined as the longest vertical and horizontal diameters. The position of the fovea was visually

identified as the darkest appearing spot at the center of the macular area. Then, two lines were

drawn manually; one from the intersection of the major and minor axis and one from the border

of the optic nerve head (Fig. 1).

Observer 1 (FN) made three repeated measurements of both NFD lengths in both eyes of all

subjects in succession to mirror the clinical approach to multiple measurements taken serially. This

method decreases the chance of outliers, as divergent measurements are more easily identified. For

analysis of agreement of NFD between fellow eyes the average of the three repeated measurements

was taken. A standard error, defined as the difference between the 95% limits of agreement and the

mean difference, ≤ 0.2 mm was considered clinically sufficient to implement this method as this is

the lateral resolution of our ultrasonography instrument (ultrasonography B 5.0 Quantel medical,

France). To determine interobserver variability regarding manually drawing lines at and making

measurements on fundus photographs, observer 2 (LIL) also made three repeated measurements on

VandePut.indd 64 4-11-2014 14:15:49


4

both NFD lengths in both eyes of thirty subjects enrolled in our study independent of observer 1.

In all repeated measurements, the circumference of the optic nerve head, major and minor axes,

and the two lines between optic nerve head and fovea were drawn again, and the measurements

were fully repeated.

Magnification

Uncorrected length measurements on disc photos are unreliable because of variations in the degree

of magnification.[24-28] Magnification strongly depends on the vergence of the internal axis of the

eye.[28] The true image size T can be calculated by multiplying, the image size I at the photograph

with, the camera constant k, and the refractive power of the human eye D:[27, 29]

T I k D= ⋅ ⋅

Our camera system uses this formula to calculate the true image size. However, the system assumes

that the eye is emmetropic, i.e. it assumes an eye refractive power of D = 60 diopter (dpt). For an

ametropic eye one has to correct the magnification factor of the eye/camera system. In these cases

the true image size T ’ can be calculated by multiplying the true image size T determined by the

camera software with a corrective factor given by:[27,29] 1−

G

D

, where G is the glass refraction of

the ametropic eye:

T TG

D= ⋅ −

1

Because the true refraction of patients who had undergone CE was unknown, these patients (n=16)

were excluded from further analysis, resulting in a final study population of 183 subjects.

Statistical analysis

Outlier analysis was performed to identify divergent measurements. Mean, standard deviations

(SD) and ranges of the NFD were calculated for both eyes. A paired t-test was used to compare

refraction differences between eyes. To test for agreement between the NFDs in fellow eyes and

between repeated measurements made by different observers on fundus photographs, we made

diagnostic plots as proposed by Bland and Altman[30] and calculated the Pearson’s correlation

coefficients, mean, SD and the 95% limits of agreement and the 95% confidence interval (CI) for

the 95% limits of agreement. Intra- and inter-observer agreement was determined to check the

validity of the NFD measurements using Bland and Altman diagnostic plots and the 95% limits

of agreement.[30] Differences between intra- and inter-observer measurements were tested using

repeated measurements analysis of variance.

A Student’s t-test was performed to compare gender differences in NFD. Linear regression analysis

was performed to determine the influence of age and refractive error on NFD. For these analyses

the dependent variable was the NFD averaged over the six repeated measurements of both eyes.

VandePut.indd 65 4-11-2014 14:15:50

66 | Chapter 4

P-values < 0.05 were considered to be statistically significant. Statistical analyses were performed

using SPSS software version 16.0© (SPSS inc, Chicago, Ill, US).

Figure 1a: Optic nerve-head to fovea distance measured from the center (A) of the optic nerve head. 1b.

Optic nerve-head to fovea distance measured from the rim (B) of the optic nerve-head.

RESULTS

Within our study population (age range 20-87yrs), age groups (20-29, 30-39, 40-49, 50-59, 60-69,

and 70-79 years of age) had similar numbers of patients, whereas age group 80-89 had slightly

lower numbers than the other groups (Fig. 2). Mean age was 52 years. A similar number of males

and females were included (49.2% male: 50.8% female). Table 1 shows the characteristics of the

refraction for the 183 pairs of eyes and the characteristics of NFDs measured from the center

and the rim of the nerve-head in 183 right and left eyes. There was no significant difference

between refractive errors in both eyes. The median difference in refractive error was 1.28 dpt.

(range 0.06 – 7.06 dpt.). Outlier analysis on three repeated measurements for both distances in

each eye identified one outlier. We could not find any probable cause for this outlier. Therefore we

excluded this measurement from further analysis.

VandePut.indd 66 4-11-2014 14:15:50


4

Table 1: Characteristics of study population (n = 183); Gender, mean, standard deviations (SD) and range

for refractive errors in diopters and optic nerve-head to fovea distance (NFD) measured from the rim and the

center of the optic nerve-head in 183 right eyes (OD) and left eyes (OS) in mm.

Measurement N Gender m:f Mean SD Range ≤-5* >-5 <0* 0* > 0 < 5* ≥ 5*Refraction OD 183 90:93 -0.12 1.6 -7.50 – 6.50 3 45 90 44 1Refraction OS 183 90:93 -0.11 1.6 -7.50 – 6.25 4 43 91 44 1NFDa N Gender m:f Mean SD RangeOD 183 90:93 4.73 0.28 4.04 – 5.39OS 183 90:93 4.72 0.27 4.00 – 5.33NFDb N Gender m:f Mean SD RangeOD 183 90:93 3.87 0.27 3.17 – 4.48OS 183 90:93 3.86 0.27 3.08 – 4.48a: Center of the optic nerve-head. b: Rim of the optic nerve-head. *diopters

Figure 2: Distribution of age and gender in 183 individuals.

VandePut.indd 67 4-11-2014 14:15:50

68 | Chapter 4

Optic nerve-head to fovea distance

Figure 3 shows the diagnostic plots of agreement of NFDs measured in fellow eyes from the center

of the optic nerve-head. Nine measurements (4.9%) made from the center of the optic nerve-head,

and 12 measurements (6.6%) made from the rim of the optic nerve-head, were outside the 95%

limits of agreement and no relationships between the mean and the difference were observed

indicating that the measurement errors are normally distributed as required. The correlation of

NFDs between fellow eyes was 0.958 when measured from the center of the optic nerve head and

0.963 when measured from the rim (Table 2). The average differences in NFD and the corresponding

95% limits of agreement in case of three repeated measurements are given in Table 2. These limits

fall within the lateral resolution of our ultrasonography-instrument which is 0.2 mm, and hence

the measurements of NFD are interchangeable between left and right eyes. When NFD would

have been measured only once, the upper limit of the confidence interval for the upper limit of

agreement for NFD measured from the center of the optic nerve head (=0.195 mm) is smaller than

0.2, which implies that the error in this measurement is still acceptable.

Figure 3a: NFD measured from the center of the optic nerve-head of the right eye (OD) plotted against

this measurement of the left eye (OS) together with the line of equation (N = 183). 3b. The distribution of

differences between the NFDs measured in fellow eyes from the center of the optic nerve-head (N = 183).

3c. The difference between NFDs against NFD averaged over both eyes measured from the center of the

optic nerve-head between fellow eyes. The solid line indicates the mean and the dotted lines the 95% limits

of agreement (N= 183).

VandePut.indd 68 4-11-2014 14:15:50


4

Table 2: Pearson’s correlation coefficient R and agreement measurements for optic nerve-head fovea distances

in left and right eyes.

Measurement R Mean SDa 95% Limits of agreement and 95 % CICenter of the optic nerve-head Lower limit & 95% CI Upper limit & 95% CIRepeated measurements 0.958 0.0078 0.079 -0.147 (-0.167, -0.127) 0.163 (0.143, 0.182)Single measurement 0.085 -0.159 (-0.180,-0.137) 0.174 (0.153,0.195)Rim of the optic nerve-head Lower limit & 95% CI Upper limit & 95% CIRepeated measurements 0.963 0.0056 0.073 -0.137 (-0.156, -0.119) 0.149 (0.130, 0.167)Single measurement 0.079 -0.150 (-0.170,-0.130) 0.161 (0.141,0.181)a SD for single measurements = √ [(SD difference for average of three measurements)2 + (SD within three measurements of observer 1)2 + (SD within three measurements of observer 2)2].

There was no significant difference in NFD between males and females. There was a significant

effect of age and refraction on NFD. When measured from the center of the optic nerve-head, we

found that NFD decreased by 0.062 mm (P < 0.001) per unit increase in spherical equivalent of

refraction (Figure 4), and NFD decreased with aging by 0.0029 mm (P = 0.006) per year of age

(R² = 0.206) (Figure 5). When measuring NFD from the rim of the optic nerve-head we observed

a decrease in NFD by 0.050 mm (P < 0.001) per unit increase in spherical equivalent of refraction

and by 0.0031 mm (P = 0.003) per year of age (R² = 0.165).

Figure 4: The spherical equivalent of the refractive error of 183 patients plotted against the mean NFD

measured form the center of the optic nerve-head of both eyes (ODS) together with the line of equation

(N = 183).

VandePut.indd 69 4-11-2014 14:15:50

70 | Chapter 4

Figure 5: The age of 183 patients plotted against the mean NFD measured form the center of the optic

nerve-head of both eyes (ODS) together with the line of equation (N = 183).

Validity of measurements

No intra-observer difference between the three measurements was observed for both observers

(Table 3). Inter-observer differences were significant for NFD measured from the rim of the optic

nerve-head for both the left eye (P = 0.0072) and the right eye (P = 9.3 10-7), but not for NFD

measured from the center of the optic nerve-head. Observer 2 measured the distance from the rim

of the optic nerve-head to the fovea 0.164 mm. shorter in the right eye (95% limits of agreement:

-0.141 – 0.468 for a single measurement; -0.120 – 0.447 for triple measurements) and 0.076 mm.

in the left eye (-0.222 – 0.374 single; -0.206 – 0.358; triple) (Table 4; Figure 6). The upper limits

of agreement were large for all four measurements ranging from 0.141-0.222, with three of them

being larger than the lateral resolution of 0.2 mm implying that these measurement errors are

unacceptable.

VandePut.indd 70 4-11-2014 14:15:51


4

Figure 6a: NFD made by observer 1 plotted against this measurement made by observer 2 together with the

line of equation. b. the distribution of differences of the NFDs between the two observers. c. The difference

between NFDs against NFD averaged over both observers. The solid line indicates the mean and the dotted

lines the 95% limits of agreement.

Table 3: Intra- and inter-observer differences between optic nerve-head to fovea distance (NFD) measurements

made from the center and the rim of the optic nerve-head in 30 right eyes (OD) and 30 left eyes (OS).

Measure Test Mean Square F P-valueCenter of the optic nerve-head OD Within observer 1 0.00247 1.47 0.24

Within observer 2 0.00210 0.94 0.40Between observer 1 & observer 2 0.03784 2.60 0.12

OS Within observer 1 0.00092 0.59 0.56Within observer 2 0.00076 0.45 0.64Between observer 1 & observer 2 0.01096 0.99 0.33

Rim of the optic nerve-head OD Within observer 1 0.00163 0.99 0.38

Within observer 2 0.00007 0.022 0.98Between observer 1 & observer 2 1.20324 38.40 9.3 10-7

OS Within observer 1 0.00400 2.88 0.064Within observer 2 0.00001 0.004 1.00Between observer 1 & observer 2 0.26019 8.35 0.0072

VandePut.indd 71 4-11-2014 14:15:51

72 | Chapter 4

Table 4: Pearson’s correlation coefficient R and agreement measurements for the averages of three

measurements made by two observers on the optic nerve-head to fovea distance (NFD) mm. from the center

of the optic nerve-head and the rim of the optic nerve-head in 30 right eyes (OD) and 30 left eyes (OS).

Measurement R Mean SDa 95% Limits of agreement and 95 % CICenter of the optic nerve-head OD Lower limit & 95% CI Upper limit & 95% CIThree repeated measurements 0.961 -0.029 0.098 -0.222 (-0.283, -0.161) 0.164 (0.103, 0.225)Single measurement 0.111 -0.247 (-0.316,-0.178) 0.189 (0.120,0.258)Center of the optic nerve-head OS Lower limit & 95% CI Upper limit & 95% CIThree repeated measurements 0.970 0.016 0.086 -0.153 (-0.206, -0.099) 0.184 (0.131, 0.237)Single measurement 0.098 -0.176 (-0.236,-0.115) 0.207 (0.146,0.267)Rim of the optic nerve-head OD Lower limit & 95% CI Upper limit & 95% CIThree repeated measurements 0.923 -0.164 0.145 -0.447 (-0.536, -0.357) 0.120 (0.030, 0.209)Single measurement 0.156 -0.468 (-0.565,-0.372) 0.141 (0.045,0.238)Rim of the optic nerve-head OS Lower limit & 95% CI Upper limit & 95% CIThree repeated measurements 0.914 -0.076 0.144 -0.358 (-0.448, -0.269) 0.206 (0.117, 0.296)Single measurement 0.152 -0.374 (-0.468,-0.280) 0.222 (0.128,0.316)a SD for single measurements = √ [(SD difference for average of three measurements)2 + (SD within three measurements of observer 1)2 + (SD within three measurements of observer 2)2]

DISCUSSION

We have shown that NFDs measured on fundus photographs are highly correlated between eyes

and moreover that the limits of agreement fall within the acceptable boundary set by the lateral

resolution of the B-mode ultrasonography-instrument. This implies that using NFDs from fellow

eyes interchangeably provides an applicable, confident, and reproducible method to determine

the position of the fovea by ultrasonography. This method can help overcome the experienced

difficulties in cases in which an assessment of macular morphology is needed. In addition, we

found a high correlation, an equal distribution of differences and good agreement between

repeated measurements on fundus photographs when NFD was measured from the center of the

optic nerve-head by the same and by different observers. When NFD was measured from the rim

of the optic nerve-head, we observed an inter-observer difference. Therefore, the latter method was

found to be less reliable.

In contrast, we found a broad range of NFDs in our study population illustrating large inter-

individual differences in normal eyes. The described differences could be partly explained by the

significant correlation between NFD and age and between NFD and refraction. These results show

that the use of the described method is a more accurate method to determine the position of the

fovea for ultrasonography measurements compared to the use of any fixed NFD.

The good agreement between the NFDs in fellow eyes found in our study is partly supported by

previous studies.[10-12] Moreover, in our study individual differences in NFD seem to be smaller

than those reported by previous studies.[10-12] This may be due to differences in study design

VandePut.indd 72 4-11-2014 14:15:51


4

relating to the study populations and the study method. Our study population was relatively

large and consisted of essentially normal eyes (diabetic patients without signs of retinopathy).

Possibly confounding factors included refraction, gender, and age in the subgroup over 70 years

of age. Refraction and gender were no selection criteria. Mean refraction turned out to be slightly

myopic. We found a high agreement between the refractive errors in fellow eyes, and differences

in refractive errors between fellow eyes turned out to be small. This implies that our conclusions

cannot be extrapolated to persons with significant anisometropia. In the entire group, similar

numbers of males and females were included, but there was a somewhat unequal inclusion of males

and females in the different age groups. Study populations in previous studies were smaller or not

equally distributed with regard to age.[10-12] Furthermore, in previous studies, the prevalence of

moderate (-0.5 to -5 D) and high myopia (≥ -5) was higher and the agreement between refractive

error between fellow eyes was unknown.[10-11]

In addition, differences between our results and those of others could be explained by the method

of correcting for magnification.[10-12] We corrected for magnification by using the spherical

equivalent of the refraction using a formula previously described by Bengtsson,[25,27-28] whereas

others corrected for magnification by using keratometric data and the spherical equivalent of the

refraction using a formula previously described by Littmann.[31] Bengtsson et al. showed in their

comparative study that although correcting for magnification using the axial length is the gold

standard, other methods to correct for magnification are almost equally accurate.[27-28] Correcting

for magnification by means of the spherical equivalent of the refraction is the most comprehensive

and easy to practice method to correct for magnification.[27-28] If correction for the influence of the

glass refraction is considered to be unsatisfactory, correction based on measurements of the axial

length seems to be the only alternative.[27-28] However if ultrasonography has to make sense, other

errors must be rectified as well. Therefore we recommend to correct for magnification by the

method described by Bengtsson et al.[27-28]

Our study found a significant positive correlation between increasing myopia and NFD. Previous

studies showed either no correlation with myopia or a significant increase in NFD in highly myopic

eyes.[11-12] With regard to age, we found significantly shorter NFDs with increasing age. In contrast,

previous studies found significantly longer NFDs with increasing age, or an absence of such a

correlation.[11-12] Possible explanations of a shorter NFD with increasing age include a cohort effect

or a real effect due to shrinkage of the eye. Assuming a positive correlation between body height

and NFD, NFD would gradually increase in younger persons in parallel with an increasing mean

body height as measured over the past decennia in the Netherlands.[32] Alternatively, a slight

shrinkage of the eye during a lifetime could occur due to a general shrinkage of connective tissues

in aging persons. These explanations remain speculative since our study and previous ones are

cross-sectional and therefore do not give direct information on longitudinal changes. Further, our

study shows no significant relationship between gender and NFD in concordance with others.[11-12]

VandePut.indd 73 4-11-2014 14:15:51

74 | Chapter 4

Our study provides limits of agreement, when using NFDs in fellow eyes interchangeably and

standard errors can therefore be easily calculated. In contrast, other studies solely provided Pearson’s

correlation coefficients.[10-11] High correlations found when two methods measure similar quantities

inform about the validity of the methods, but they fail to inform about the agreement between

methods or whether they can be used interchangeably.[30]

CONCLUSION

In conclusion, we found that the assessment of the position of the fovea by using the NFDs

measured on fundus photographs interchangeably between fellow eyes is highly reliable. Differences

between observers were the main source of variability, in particular when the NFD was measured

from the rim of the optic nerve-head. This finding, in conjunction with the known accuracy of

ultrasonography, should provide those who need to make an assessment of macular height in

macula-off RRD with a helpful, confident, reproducible, and valid method.

ACKNOWLEDGEMENTS

We thank P.H.M. van Loosdrecht for his advisory role on the magnification of the eye-camera

system.

VandePut.indd 74 4-11-2014 14:15:51


4

REFERENCES



2. Chisholm IA, McClure E, Foulds WS. (1975) Functional recovery of the retina after retinal detachment.

Trans Ophthalmol Soc U K 95: 167-172.


Ophthalmology 105: 2149-2153.

4. Mowatt L, Tarin S, Nair RG, Menon J, Price NJ. (2010) Correlation of visual recovery with macular

height in macula-off retinal detachments. Eye 24: 323-327.

5. Ross W, Lavina A, Russell M, Maberley D. (2005) The correlation between height of macular

detachment and visual outcome in macula-off retinal detachments of < or = 7 days’ duration.


6. Coleman DJ. (1972) Reliabillity of ocular and orbital diagnosis with B-scan ultrasound. Am J


7. Bronson NR, Fisher YL, Pickering NC, Trayner EM. (1976) Ophthalmic contact B-scan ultrasonography

for the clinician. Westport: Intercontinental Publications Inc. 1-25 p.

8. Pavlin CJ, Harasiewicz K, Sherar MD, Foster FS. (1991) Clinical use of ultrasound biomicroscopy.


9. Straatsma BR, Foos RY, Spencer LM. (1969) Transactions of the New Orleans Academy of

Ophthalmology. St Louis: the C.V. Mosby Co.1-27 p.

10. Williams TD, Wilkinson JM. (1992) Position of the Fovea Centralis with Respect to the Optic Nerve

Head. Optometry and Vision science 69: 369-377.

11. Chihara E, Chihara K. (1994) Covariation of optic disc measurements and ocular parameters in the

healthy eye. Graefes Arch Clin Exp Ophthalmol 232: 265-271.

12. Rohrschneider K. (2004) Determination of the location of the fovea on the fundus. Invest Ophthalmol

Vis Sci 45: 3257-3258.

13. Duke-Elder WS. (1964) Normal and Abnormal development, part 2. London: H Kimpton. 654 p.

14. Levene RZ. (1992) Unusual optic discs in primary open-angle glaucoma. Ann Ophthalmol 14: 617-

620.

15. Chihara E, Honda Y. (1992) Preservation of nerve fiber layer by retinal vessels in glaucoma.


16. Quigley HA, Addicks EM. (1981) Regional differences in the structure of the lamina cribrosa and

their relation to glaucomatous optic nerve damage. Arch Ophthalmol-Chic 99: 137-143.

17. Friedman B. (1942) Unusual disciform retinal lesion with heterotopia maculae. Arch Ophthalmol-

Chic 28: 444-448.

18. Cohen IJ, Weisberg HK.. (1950) Vertical heterotopia of the macula. Arch Ophthalmol-Chic 44: 419-

423.

VandePut.indd 75 4-11-2014 14:15:51

76 | Chapter 4

19. Jonas JB, Gusek GC, Naumann GOH. (1988) Optic disc, cup and neuroretinal rim size, configuration

and correlations in normal eyes. Invest Ophthalmol Vis Sci 29: 1151-1158.

20. Keilhauer C, Zollmann J, Schrader W, Delori FC. (2003) Verlagert sich mit zunehmenden Alter die

Fovea relativ zur Papille? Ophthalmologe 100: 164.

21. Fletcher DC, Schuchard RA. (1997) Preferred retinal loci: relationship to macular scotomas in a low

vision population. Ophthalmology 104: 632-638.

22. Mikuni M, Ishii K, Makabe R. (1960) Diameter of the disc in Japanese subjects. Klin Monatsbl

Augenheilkd 136: 544-557.

23. Jonas JB, Gusek GC, Guggenmoos-Holzmann I, Naumann GOH. (1988) Size of the optic nerve

scleral canal and comparison with intravital determination of optic disc dimensions. Graefes Arch

Clin Exp Ophthalmol 226: 213-215.

24. Balazsi AG, Drance SM, Schulzer M, Douglas GR. (1984) Neuroretinal rim area in suspected glaucoma

and early chronic open-angle glaucoma. Arch Ophthalmol-Chic 102: 1011-1014.

25. Bengtsson B. (1976) The variation and covariation of cup and disc diameters. Acta Ophthalmol-Scan

54: 804-818.

26. Jonas JB, Gusek GC, Guggenmoos-Holzmann I, Naumann GOH. (1988) Variabillity of the real

dimensions of normal human optic discs. Graefes Arch Clin Exp Ophthalmol 226: 332-336.

27. Bengtsson B, Krakau CET. (1977) Some essential optical features of the Zeiss fundus camera. Acta

Ophthalmol-Scan 55: 123-131.

28. Bengtsson B, Krakau CET. (1992) Correction of optic disc measurements on fundus photographs.

Graefes Arch Clin Exp Ophthalmol 230: 24-28.

29. Gullstrand A. (1909) von Helmholtz H. Physiologischen Optik. Hamburg: Verlag von Leopold Voss.

299-306 p.

30. Bland JM, Altman DG. (2003) Applying the right statistics: analyses of measurement studies.

Ultrasound Obstet Gynecol 22: 85-93.

31. Littman H. (1982) Zur Bestimmung der wahren Größe eines Objektes auf dem Hintergrund des

lebenden Auges. Klin. Monatsbl Augenh 180: 286-289.

32. Mean body height as measured over the past decennia in the Netherlands [in Dutch]. Available at:

http://statline.cbs.nl/statWeb/publication/?DM=SLNL&PA=37446&D1=0-21&D2=a&VW=T Accessed

August 9, 2014.

VandePut.indd 76 4-11-2014 14:15:51

Chapter 5

Postoperative recovery of visual function after

macula-off rhegmatogenous retinal detachment

Plos One, June 2014: 9:6:e99787

Mathijs A.J. van de Put¹,2, Danna Croonen¹, Ilja M. Nolte3,

Wouter J. Japing1, Johanna M.M. Hooymans1,2, Leonoor I. Los1,2

1 Department of Ophthalmology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

2 W.J. Kolff Institute, Graduate School of Medical Sciences, University of Groningen, Groningen, the Netherlands.3 Department of Epidemiology, University of Groningen, University Medical

Center Groningen, Groningen, the Netherlands.

VandePut.indd 77 4-11-2014 14:15:51

78 | Chapter 5

ABSTRACT

Purpose: To determine which factors affect the recovery of visual function in macula off

rhegmatogenous retinal detachment (RRD).

Methods: In a prospective study of forty-five patients with a primary macula-off RRD of 24 hours

to 6 weeks duration, the height of the macular detachment was determined by ultrasonography.

At 12 months postoperatively, best corrected visual acuity (BCVA), contrast acuity, and color

confusion indexes (CCI) were obtained.

Results: Macular detachment was present for 2 – 32 (median 7) days before repair. A shorter

duration of macular detachment was correlated with a better saturated CCI (p = 0.0026) and

lower LogMAR BCVA (better Snellen visual acuity)(p = 0.012). Also, a smaller height of macular

detachment was correlated with a lower LogMAR BCVA (p = 0.0034). A younger age and lower

pre-operative LogMAR BCVA at presentation were both correlated with better postoperative

contrast acuity in the total group (age: p = 1.7x10-4 and pre-operative LogMAR BCVA: p = 0.0034).

Conclusions: Functional recovery after macula-off RRD is affected by the duration and the height

of the macular detachment. Recovery of contrast acuity is also affected by age and BCVA at

presentation.

VandePut.indd 78 4-11-2014 14:15:51

5

Postoperative recovery 79

INTRODUCTION

Rhegmatogenous retinal detachment (RRD) with an incidence of 18.2/100,000 people per year in

the Netherlands[1] is a potentially blinding ophthalmic pathology.[2-3] The treatment modality of

RRD is surgical reattachment of the retina.[4] Contrary to the high anatomical success rate[2-3, 5-8]

the prognosis for the recovery of visual acuity (VA) may be disappointing. Permanent functional

damage is particularly observed if the macula is detached,[9-17] which occurs in about 50% of

cases. [1]

Factors that may influence functional recovery after macula-off RRD include preoperative VA,[2]

duration of macular detachment,[2,9,11,18-22] height of macular detachment,[2,15, 22-25] age,[2,22] and

refractive error.[22] Most studies consider only the recovery of visual acuity and lack data on other

aspects of macular function such as contrast acuity and color vision.[26,27,29]

The timing of optimal surgical intervention remains inconclusive. Burton observed that

postoperative VA was dependent on the preoperative duration of macular detachment in RRD

patients.[9] However, he and others suggested that a delay in surgical repair between 24 hours and

7 to 9 days does not preclude good functional recovery after macula-off RRD[9,11,14] and should not

be expected to have a significant effect on final visual outcome.[11,14]

The absence of a relation between the duration of the macular detachment within the first week and

functional recovery may be a misguided assumption, since the effect of the height of the macular

detachment has not been considered in most studies.[2,15,22-25,29] Also, such an assumption is not in

line with animal experiments, in which a progressive loss of photoreceptor cells is seen already

within the first week of retinal detachment,[15] and it has been demonstrated that photoreceptor cell

degeneration increases as the height of the macular detachment is increased.[15,16]

The few studies on the influence of the height and the duration of the macular detachment on the

postoperative recovery of VA[23,24] found that – within the first week of macular detachment – a lower

height of macular detachment was associated with better postoperative visual acuity. Furthermore,

previous studies relate to the outcomes for patients who have undergone “conventional” (buckling)

surgery.[2,9,11,14,18-22] However, in recent years trans pars plana vitrectomy (TPPV) is often used as

a primary procedure, which might affect postoperative recovery.[30] Finally, follow-up periods in

these studies ranged from 3 to 24 months,[2,9,11,14,18-21,23,24] whereas it is known that postoperative VA

can improve gradually, reaching a maximum value between 6 – 12 months postoperatively.[10,31]

In order to gain a better insight in factors influencing the long term postoperative recovery of

visual function after macula-off RRD, our study aimed to establish the relative contributions of

a number of factors including both the duration and the height of the macular detachment to

various aspects of visual recovery (i.e. best corrected visual acuity (BCVA), contrast acuity, and

color vision).

VandePut.indd 79 4-11-2014 14:15:51

80 | Chapter 5

METHODS

In this prospective observational study we studied patients with a first presentation of macula-

off RRD who underwent successful reattachment surgery, after 24 hours to 6 weeks of macular

detachment. The research protocol was approved by the University Medical Center Groningen

(UMCG) review board ethics committee, and was carried out in accordance with the tenets of the

declaration of Helsinki. The study was registered with the Dutch Trial Register (NTR839). All

patients were operated on at the ophthalmology department of the UMCG. The study was carried

out over a four year period (February 1, 2007 - February 1, 2011).

Adult patients visiting the ophthalmology department of the UMCG with a first presentation of

RRD with a macular detachment of 24 hours to 6 weeks duration were invited to participate in

this study. We defined the moment of macular detachment as the subjective loss of VA, since an

objective method to determine this moment does not exist. Patients with a macular detachment

of < 24 hours were excluded, because in our current treatment strategy these are scheduled as

emergency surgeries and inclusion in the study would interfere with this.

Included in the study were patients of 18 years and older who had given their written informed

consent. In addition, patients had to be able to pinpoint their drop in VA to a specific 24-hour

period in case of a 24-hour to 1 week macular detachment, and to a period of less than one week

in case of a macular detachment of one to six weeks. Surgery was performed within 24-72 hours

after presentation at the department. The cut-off point of ≤ 1 week or > 1 week was chosen,

based on results of previous studies.[11,14] Patients with macular detachment of more than 6 weeks

duration were excluded, because they are considered rare and yield a worse prognosis.[9] Excluded

were patients with a bilateral RRD, a history of congenital or acquired pathology with an effect

on visual function in one or both eyes, or pathology observed at presentation after their macula-off

RRD (i.e. pathology of the cornea, lens, vitreous body, retina (including macula and optic nerve),

and scleritis). Patients with a congenital defect in color vision were included. In addition, patients

who had a re-detachment during the follow-up period were excluded.

Macula-off RRDs of less than one week duration were scored per day, and of more than one week

duration they were scored as 11 days (1-2 weeks duration), 18 days (2-3 weeks duration), 25 days

(3-4 weeks duration), 32 days (4-5 weeks duration), and 39 days (5-6 weeks duration), respectively.

We acquired the following patients’ characteristics: age, gender, affected eye, ophthalmic history,

general history. Using standardised protocols, the refractive error and BCVA using the Early

Treatment of Diabetic Retinopathy Study (ETDRS) chart were determined for the affected and

fellow (control) eye.[27] All BCVA measurements were converted to logMAR equivalents of ETDRS

visual acuity for analysis. Light perception or hand movements were coded as logMAR VA of 3.0.

The height of the macular detachment was determined by optical coherence tomography (OCT)

and by ultrasonography using the B-mode scanner at a frequency of 20 MHz.

VandePut.indd 80 4-11-2014 14:15:51

5


For OCT measurements, the STRATUS 3000 OCT (Carl Zeiss Ophthalmic System, Dublin, CA)

was used. The height of macular detachment was defined as the distance between the outer surface

of the photoreceptor layer and the inner surface of the retinal pigment epithelial layer (RPE, second

high reflective line). This distance was measured using the analysis program by placing calipers at

both surfaces at the foveal dip.

To measure the height of the detachment at the position of the central macula by ultrasonography,

the relative positions of the central macula and the optic nerve head were determined before

performing a ultrasonography. For this purpose, digital fundus photographs of both eyes were

made using the TRC-50 IX fundus camera (Topcon 9B ltd. UK). On both fundus photographs,

the distance between the optic nerve head and fovea was measured using the software package

IMAGEnet2000 2.53. The measured distance in the affected eye was used to determine the central

position of the macula and at this position the height of the macular detachment was measured

by ultrasonography (20 MHz HF long focus B-scan transducer, Quantel Medical Cinescan S,

V:5.06) (Figure 1). In those cases (i.e. bullous retinal detachment), in which the measurement of

the distance between the macula and optic nerve head could not be performed on the photograph

of the affected eye, the measurement of this distance in the fellow eye was used.[32] In each patient,

two measurements were made with the patient in an upright position (as this represents the

position most patients would have taken for most of the time before presentation during the day)

and the average of both measurements was used for further analysis. In addition, in each patient,

two measurements were made in a lying position and averaged for analysis.

Most patients (n = 26) had a maximum height of macular detachment in a sitting position. However

some had a maximum height when measured in a lying position (n = 19). We hypothesized that the

maximum height (independent of position) might be valuable in predicting functional outcome.

Therefore, calculations were done again with the mean of the two measurements obtained at the

position of maximum height of the macular detachment.

At twelve months postoperatively, we measured BCVA using the ETDRS chart,[27] contrast acuity

using the Pelli Robson chart,[26] Farnsworth D-15 saturated, and Lanthoni desaturated color

confusion indexes (CCI).[28] All measurements were done in the affected and non-operated fellow

(control) eye.

Because of an increased risk of cataract development after trans pars plana vitrectomy, which may

influence postoperative measurements, we scored the level of cataract using the lens opacities

classification system III (LOCS III) in both eyes at fixed post-operative intervals.[33] In addition,

BCVA was assessed at these time points, and in case of a visually significant cataract a cataract

extraction was performed before the 12 month measurement.

Depending on the distribution of the variable, either a one-tailed paired Student’s t-test (normal

distribution) or a Mann-Whitney U test (non-normal distribution) was used to explore statistical

differences in visual function. Pearson’s (normal distribution) or Spearman’s coefficient (non-

VandePut.indd 81 4-11-2014 14:15:51

82 | Chapter 5

normal distribution) was used to determine the correlation between measurements of the operated

and the fellow eyes. For these analyses, p-values below 0.05 were considered statistically significant.

Multivariate forward stepwise regression analyses were performed on the postoperative visual

function variables with duration of the macular detachment, height of the macular detachment,

age, gender, pre-operative BCVA, and preoperative refractive error as independent variables. For

LogMAR BCVA and ln(desaturated CCI), linear regression analysis was used. For log contrast

acuity and saturated CCI, ordinal regression analysis was used, since these were not normally

distributed.

We also analyzed subgroups of patients with a macular detachment of between ≥ 24 hours and ≤ 7

days duration, and of patients with a macular detachment of between > 7 days and ≤ 6 weeks. In

these analyses, only the covariates that were significant for the entire group were included. To test

whether the effects of the covariates were significantly different between short and long duration

of macular detachment, the models were also applied to the entire group with the interaction

terms of the significant covariates with an index variable for short or long duration included. A

statistically significant p-value for the interaction thus indicates that the regression coefficients

differ significantly between the two groups and hence the effect size of the covariate in one group

is larger compared to the effect size in the other group.

Because four outcome variables of visual function recovery were tested, we applied a Bonferroni

correction for multiple testing and therefore p-values below 0.0125 were considered statistically

significant. Data were analysed using SPSS software package, version 16.0 (Chicago, Illinois, USA).

VandePut.indd 82 4-11-2014 14:15:51

5


Figure 1: Method to measure the height of the foveal detachment by ultrasonography. 1a. Schematic drawing

of the measurement of the distance between the center of the optic nerve head and fovea, and assessment of

the angle between their connecting line with the horizon. 1b. Drawing of the measurement of the distance

between the center of the optic nerve head (determined by drawing a circle along the outer edge of the

optic disc, excluding the area of peripapillary atrophy) and fovea, and assessment of the angle between their

connecting line with the horizon made on a fundus photograph. 1c. Schematic position of the ultrasound

probe at the correct angle between the horizon and the connecting line between the center of the optic nerve

head and the fovea based on the measurement made on the fundus photograph 1d. Measurement of the

height of the retinal detachment by ultrasonography at the measured distance between the center of the optic

nerve head and the fovea, as obtained by measuring this distance on the fundus photograph.

VandePut.indd 83 4-11-2014 14:15:52

84 | Chapter 5

RESULTS

A total of 56 patients gave their written informed consent. Ten patients were excluded because

of re-detachment. One patient deceased during the study period and was therefore excluded from

the analysis. In two patients, data on color vision were set to missing because of congenital color

blindness.

Table 1 shows the characteristics of our population. The right eye was involved in 22 cases (48.9%)

and the left eye in 23 cases (51.1%). A TPPV (n=39) sometimes combined with an encircling band

(n= 22) was most frequently chosen as the primary surgical procedure (86.7%), and in 6 cases

a scleral buckling procedure was chosen (13.3%). During the twelve month follow-up period,

cataract surgery was performed in 21 out of 29 phakic eyes.

Table 1: Characteristics of the RRD patients.

Number (percentage) Mean age (SD) Scleral buckling / TPPVTotal 45 (100) 61.0(10.6) 6/39M 34 (75.6) 61.6 (10.5) 2/32F 11 (24.4) 59.0 (11.0) 4/7Phakic 29 (64.4) 58.7 (8.9) 6/23M 21(72.4) 59.2 (8.6) 2/19F 8 (27.6) 57.5 (9.5) 4/4Pseudophakic 16 (35.6) 65 (12.3) 0/16M 13 (81.3) 65.5 (11.9) 0/13F 3 (18.8) 63 (13.5) 0/3SD: standard deviation; TPPV: trans pars plana vitrectomy; M: Male F: Female.

Due to the fact that macular height often exceeded the maximum value measurable by OCT, OCT

measurements could be carried out in only 17/45 patients, whereas ultrasonography measurements

could be carried out in all. Therefore, we chose to use the latter technique in our analyses of

macular height.

The median duration of the macular detachment was 7 days (range 2 – 32). The mean height

of the macular detachment in sitting position was 1.37 mm. ± 1.22 (in two patients only one

measurement was taken). We observed no statistically significant difference between mean height

in patients treated by buckle surgery (1.38 mm. ± 0.74) versus TPPV (1.37 mm. ± 1.3) (p=0.988).

Table 2 provides descriptive data and statistics on pre- and post-operative logMAR BCVA, log

contrast acuity, and saturated and desaturated CCI for operated compared to fellow eyes. It

shows that at twelve months postoperatively, all visual function tests are still significantly worse

in operated compared to fellow eyes. There was no statistically significant difference between

postoperative logMAR BCVA, log contrast acuity and saturated and desaturated CCI, between

eyes operated on by buckle or TPPV, nor between phakic and pseudophakic eyes (data not shown).

VandePut.indd 84 4-11-2014 14:15:52

5


Also, in phakic eyes, no relationship was found between LOCS score and outcomes of any of the

above visual function tests (data not shown).

Table 2: Tests of visual functioning in operated and non-operated fellow eyes (n=45).

Visual function Operated Eyes Non-operated Eyes P-value Correlation Mean SD Mean SD P* R†

Visual acuity postoperatively (logMAR) 0.31 0.32 0.054 0.12 <0.0005 0.082Median Range Median Range P** R‡‡

Pre-operative visual acuity (logMAR) 3.00 0.06 - 3.00 0.06 -0.20 – 0.86

<0.0005 0.24

Contrast acuity postoperatively (log) 1.50 0.15 – 1.70 1.55 1.25 – 1.90 0.002 0.19Saturated CCI postoperatively*** 1.13 1.00 –

2.661.00 1.00-2.06 0.03 0.48

Desaturated CCI postoperatively*** 1.76 1.00 – 3.20

1.63 1.00-2.59 0.02 0.70

At twelve months postoperatively, all visual function test outcomes are still significantly worse in operated compared to fellow eyes. * Paired Student’s t-test; † Pearson’s correlation coefficient; ** Wilcoxon rank test; ‡‡ Spearman’s correlation coefficient,***=n=43, because two colorblind patients were excluded.

Table 3 provides the nominally statistically significant results of the regression analyses on post-

operative visual functioning. In the total group, both the duration and the height of the macular

detachment were significantly associated with the recovery of visual function. A longer duration

of the macular detachment was significantly associated with a worse post-operative saturated CCI

(p = 0.0026), and higher LogMAR BCVA (lower Snellen visual acuity) (p = 0.012). A larger height

of the macular detachment was significantly associated with a higher post-operative LogMAR

BCVA (p = 0.0034). Further, both an older age (Log contrast acuity (p = 1.7x10-4)), and a higher

pre-operative LogMAR BCVA (log contrast acuity (p = 0.0034) were significantly associated with

a worse post-operative contrast acuity.

Subgroup analyses in patients with macula-off RRD of ≤ 7 days duration (n=25) and those with

macula-off RRD of > 7 days (n=20) show that most findings remain (nominally) statistically

significant in one or both subgroups. Only height of the macular detachment had a nominally

statistically significantly smaller effect (i.e. smaller regression coefficient b) on LogMAR BCVA in

patients with a macular detachment of 7 days or less compared to those with a macular detachment

of longer than 7 days (p interaction = 0.018).

Also, duration of macular detachment seemed to have a different effect in the two subgroups, but

this difference did not reach statistical significance. Nevertheless, the larger effect size (regression

coefficient b) and the lower p-value in the shorter duration group might argue for a more pronounced

effect of the duration of macular detachment on recovery of BCVA within the first week of macular

detachment compared to after this time point.

VandePut.indd 85 4-11-2014 14:15:52

86 | Chapter 5

Table 3: Factors influencing recovery of visual function 12 months after surgery.

Visual function all patients ≤7 days >7 days Interaction*

B p-value b p-value B p-value B p-value

LogMAR BCVA†

Duration of macular detachment

0.016 0.012 0.046 0.082 0.005 0.65 -0.030 0.11

Height of macular detachment 0.10 0.0034 0.081 0.0076 0.29 0.016 0.22 0.018Log contrast acuity**

Age -0.067 1.7x10-4 -0.071 0.0076 -0.083 0.0027 0.0093 0.44Pre-operative logMAR BCVA -0.49 0.0034 -0.47 0.036 -0.62 0.021 -0.29 0.35Saturated CCI††

Duration of macular detachment

0.081 0.0026 0.22 0.29 0.11 0.0070 -0.098 0.065

Desaturated CCI***

No significant covariatesPresented are the effect sizes (a larger b-value represents a greater effect size) and significances (p-values) of the covariates that are statistically significantly associated with visual function measurements for the total group of 45 patients. Subgroup analyses in patients with macula-off RRD of ≤ 7 days duration (n=25) and those with macula-off RRD of > 7 days duration (n=20) show that most of the findings observed in the entire patient group remain statistically significant. Significant results after multiple testing correction are shown in bold, nominally significant results (p-value < 0.05) are shown in italic.*Effect size of interaction of covariate with short or long duration of macula-off RRD. A statistically significant p-value for the interaction indicates that the regression coefficients differ significantly between the two groups and hence the effect size of the covariate in one group is larger compared to the effect size in the other group.†LogMar analyzed with linear regression.** Log contrast acuity analyzed with ordinal regression with a complementary log-log link function.‡ Saturated CCI analyzed with ordinal regression with a negative log-log link function.*** ln(desaturated CCI) analyzed with linear regression.b: regression coefficient.

For contrast acuity, the effect sizes in the two subgroups did not meet the multiple testing

corrected significance threshold, but both were nominally statistically significant. As additionally

the interaction was not statistically significant, this suggests that the influence of pre-operative

logMAR BCVA on contrast acuity is not affected by the duration of macular detachment.

Finally, calculations with the maximum of the height in sitting or lying position instead of height

in sitting position did not yield significant correlations with any of the functional recovery tests

(data not shown).

VandePut.indd 86 4-11-2014 14:15:52

5


DISCUSSION

We found that visual recovery after macula-off RRD is affected by both the duration and the

height of the macular detachment when measured in sitting position. These factors influence

various aspects of visual recovery in different ways. Recovery of visual acuity is decreased in case of

a larger height or a longer duration of macular detachment. Recovery of contrast acuity is affected

by the age of the patient and the pre-operative LogMAR BCVA. Post-operative saturated color

vision is only related to the duration of the macular detachment.

We found that a longer duration of the macular detachment is associated with a worse recovery of

visual acuity. This is in line with previous studies, which showed a worse postoperative recovery of

visual acuity after longer-standing macula-off RRDs.[2,9,11,14,18-22] In our study, mean post-operative

recovery of VA was higher[2,9-13,14,22,34] and the relationship between the duration of the macular

detachment and the recovery of VA was a little weaker compared to the results of some others,[9,13]

and somewhat stronger when compared to the study of Ross et al.[34]

Differences between the outcomes of these studies can be explained by differences in study design

and studied populations. Some studies were carried out retrospectively,[11-12,34] whilst others, like

our own, were carried out prospectively.[10,13-14,23] Studies may have used different definitions and

examination methods.[10-14,23,34] In- and exclusion criteria were comparable among all studies.[10-14,23,34] Some studies were larger[10-14,34] than our study and some others.[13,23] A smaller study

population may have led to low power to detect some statistical differences.[13,23] The follow-up

period varied between studies and it is known that postoperative VA can improve in the first

postoperative year and sometimes even after one year follow-up.[10-14,23,31,34] A follow-up period of

one year allowed us to perform a cataract extraction prior to the 12 month measurements, whereas

in studies with shorter follow-up periods a visually significant cataract may have caused a lower

VA.[10-14,23,31,34] In contrast to others, we measured VA as accurately as possible by using ETDRS

charts.[10-14,23,27,35] In some studies a scleral buckling procedure was performed in all cases,[2,9,11,14,18-22]

whereas in our and another recent study, both TPPV and conventional surgery were performed.[10] Finally, older age has been pointed out as associated with a worse recovery.[2,22] This could have

influenced outcomes, since mean[10,12,14] or median[34] age differed between studies.

Over the past eighty years, perceptions on the critical period of macular detachment after which

visual prognosis may be compromised, have changed from about 1 month in the earliest studies[2,19]

to about 1 week in the more recent ones.[9,11,14,20-21] Ross et al. observed no statistically significant

difference in post-operative recovery of VA in macula-off RRD patients operated on between 1 to

2 days, 3 to 4 days, and 5 to 7 days after macular detachment.[14] Other recent studies are in line

with this and seem to indicate that a surgical delay within this time period may not adversely affect

postoperative visual function.[13-14,23] Although we observed a statistically significant relationship

between duration of macular detachment and postoperative BCVA in the total study group,

significance was lost in our subgroup analyses, in which we looked separately at patients with a

VandePut.indd 87 4-11-2014 14:15:52

88 | Chapter 5

macular detachment of ≤7 days and those with a detachment >7 days. However, we did observe

that the effect size (regression coefficient b) for the duration of macular detachment was higher and

the p-value was lower within the first week of macular detachment compared to after this time

point. This probably indicates that our study was underpowered to determine the true effect of

delaying surgery within the first week of macular detachment.

In line with others, we identified that a higher macular detachment – when measured in an upright

position - is associated with a worse recovery of BCVA.[2,15,22,24,25] The earliest studies defined macular

height in a dichotomous manner as either bullous or shallow by a clinical estimation of submacular

fluid.[2,22] Even by this crude method, a relationship between bullous macular detachment and a

worse recovery of VA was observed.[2,22] Studies using OCT can only measure shallow macular

detachments accurately[25] and height might be considered dichotomous in case the height of the

detachment surpasses the maximum value measurable by the OCT.[25]

When comparing our results to results of other studies using ultrasonography as a measuring

method of macular height, our study identified a stronger relation between macular height and

postoperative recovery of BCVA compared to Mowatt et al.[24] This difference may be explained by

differences in other variables between both studies, i.e. our study had a larger number of patients,

a shorter median duration of the macular detachment, a worse pre-operative VA, a lower mean

height of the macular detachment, an older age, a longer follow-up period, and a more frequent

use of TPPV as the surgical technique.[24] In addition, we identified the strongest relation (lower

p-value) between macular height and postoperative recovery of BCVA in patients with a macula-

off RRD of shorter duration and the largest effect size (regression coefficient b) between these

factors in the longer duration group. Also in contrast to Mowatt et al.[24] – we observed that a

higher macular detachment at presentation is related to worse postoperative recovery of VA in

macula-off RRD of shorter duration, which is in line with observations made by Ross et al. in a

larger study.[14]

We found no relationship between both the duration and the height of the macular detachment

and postoperative recovery of contrast acuity, a relationship previously observed by others.[13]

Previous studies found that contrast acuity scores after macula-off RRD are lower when compared

to a control group of similar age[35] and to fellow eyes,[13] which is in line with our findings. In our

study, an older age at presentation was highly correlated with a worse postoperative contrast acuity,

a relationship that was previously described for VA.[2,22]

Although previously pointed out as an important factor for postoperative recovery in macula-off

RRD,[2,18] we did not identify pre-operative VA as a significant predictor of postoperative recovery

of LogMAR BCVA. We did identify a relationship between pre-operative VA and postoperative

contrast acuity, which – as far as we are aware – was not previously reported.

We found that a longer duration of the macular detachment is associated with a worse recovery

of color vision. This is in line with previous studies on postoperative color vision after macula-off

VandePut.indd 88 4-11-2014 14:15:52

5


RRD.[13,36] In addition, the longer the duration of the macular detachment, the deeper the color

defect was,[13] particularly if the duration of the macular detachment exceeded 7 days. Kreissig et

al. found postoperative color vision disturbances in half of their patients, in particular, in older

patients.[36] Özgür and Esgin found significantly more color vision defects in macula-off RRD eyes

compared to their healthy fellow-eyes, in a comparable study group.[13] We observed the strongest

relation with a worse recovery of color vision in macula-off RRD of longer duration.

Our study highlights important factors related to the postoperative recovery of visual function,

however there are several limitations. First, there could have been a selection bias, because highly

motivated patients may have participated in this study. Second, the determination of the onset of

the macular detachment remains subjective, and may not always be correct, especially in shallow

detachments where a decrease in VA may be small and pass unnoticed for a prolonged period

of time. Further, we measured macular height in an upright position assuming that this would

best represent the position of the macula in daytime conditions. However, the height of a retinal

detachment may vary depending on posture and this variation has not been taken into account.

The absence of a significant correlation between the maximum height of detachment in sitting or

lying position and functional recovery makes the value of this factor at least questionable. Finally,

the studied population is relatively small and thus our study may have been underpowered to

detect some possible relations.

CONCLUSION

In conclusion, we found that visual recovery after macula-off RRD is affected by both the duration

and the height of the macular detachment. The seemingly strong relationship between the height

of macular detachment and recovery of BCVA might indicate that posturing of macula-off RRD

patients could be valuable. However, at present, we have to be critical with regard to this factor,

which may have been highly variable over time. Therefore, we would recommend to evaluate the

effect of posturing on the height of macular detachment and on visual recovery in a future study.

VandePut.indd 89 4-11-2014 14:15:52

90 | Chapter 5

REFERENCES

1. Van de Put MAJ, Hooymans JM, Los LI; The Dutch Rhegmatogenous Retinal Detachment

Study Group (2013) The incidence of rhegmatogenous retinal detachment in the Netherlands.

Ophthalmology. 120: 616–622.

2. Tani PT, Robertson DM, Langworthy A (1981) Prognosis for central vision and anatomic reattachment

in rhegmatogenous retinal detachment with macula detached. Am J Ophthalmol. 92: 611-620.

3. Pastor JC, Fernández I, Rodríguez de la Rúa E, Coco R, Sanabria-Ruiz Colmenares, et al (2008)

Surgical outcomes for primary rhegmatogenous retinal detachments in phakic and pseudophakic

patients: the Retina 1 Project – report 2. Br J Ophthalmol. 92: 378-382.

4. D’Amico DJ (2008) Primary retinal detachment. N Engl J Med. 359: 2346-2354.

5. Chignell AH, Fison LG, Davies EW, Hartley RE, Gundry MF (1973) Failure in retinal detachment

surgery. Br J Ophthalmol. 57: 525-530.

6. Rachal WF, Burton TC (1979) Changing concepts of failure after retinal detachment surgery. Arch


7. Sharma T, Challa JK, Ravishankar KV, Murugesan R (1994) Scleral buckling for retinal detachment:

predictors for anatomic failure. Retina. 14: 338-343.

8. Grizzard WS, Hilton GF, Hammer ME, Taren D (1994) A multivariate analysis of anatomic success

of retinal detachments treated with scleral buckling. Graefes Arch Clin Exp Ophthalmol. 232: 1-7.

9. Burton TC (1982) Recovery of visual acuity after retinal detachment involving the macula. Trans Am

Ophthalmol Soc. 80: 475-497.

10. Mitry D, Awan MA, Borooah S, Syrogiannis A, Lim-Fat C et al (2012) Long term visual acuity

and the duration of macular detachment: findings from a prospective population based study. Br J

Ophthalmol. 1-4.

11. Diederen RMH, La Heij AC, Kessels AGH, Goezinne F, Liem AT et al (2007) Scleral buckling surgery

after macula-off retinal detachment; worse visual outcome after more than 6 days. Ophthalmology.

114: 705-709.

12. Hassan TS, Sarrafizadeh R, Ruby AJ, Garretson BR, Kuczynski B, et al (2002) The effect of duration

of macular detachment on results after the scleral buckle repair of primary, macula-off retinal

detachments. Ophthalmology. 109: 146-152.

13. Özgür S, Esgin H (2007) Macular function of successfully repaired macula-off retinal detachments.

Retina 27: 359-364.

14. Ross WH, Kozy DW (1998) Visual recovery in macula-off rhegmatogenous retinal detachments.

Ophthalmology. 105; 2149-2153.

15. Machemer R (1968) Experimental retinal detachment in the owl monkey. II. Histology of the retina

and pigment epithelium. Am J Ophthalmol. 66: 396-410.

VandePut.indd 90 4-11-2014 14:15:52

5


16. Mervin K, Valter K, Maslim J, Lewis G, Fisher S, et al (1999) Limiting photoreceptor death and

deconstruction during experimental retinal detachment; the value of oxygen supplementation. Am J


17. Lewis GP, Talaga KC, Linberg KA, Avery RL, Fisher SK (2004) The efficacy of delayed oxygen

therapy in the treatment of experimental retinal detachment. Am J Ophthalmol. 137: 1085-1095.

18. Gundry MF, Davies EWG (1974) Recovery of visual acuity after retinal detachment surgery. Am J


19. Reese AB (1937) Defective central vision following successful operations for detachment of the retina.


20. Jay B (1965) The functional cure of retinal detachments. Trans Ophthalmol Soc UK. 85: 101-110.

21. Davies EWG (1972) Factors affecting recovery of visual acuity following detachment of the retina.

Trans Ophthalmol Soc UK. 92: 335-342.

22. Kreissig I (1977) Prognosis of return of macular function after retinal reattachment. Mod Probl


23. Ross WH, Lavina A, Russel M, Maberley D (2005) The correlation between height of macular

detachment and visual outcome in macula-off retinal detachments of ≤ 7days’ duration. Ophthalmology.

112; 1213-1217.

24. Mowatt L, Tarin S, Nair RG, Menon J, Price NJ (2010) Correlation of visual recovery with macular

height in macula-off retinal detachments. Eye. 24: 323-327.

25. Lecleire-Collet A, Muraine M, Menard JF, Brasseur G (2005) Predictive visual outcome after macula-

off retinal detachment surgery using optical coherence tomography. Retina. 259: 44-53.

26. Mantyjarvi M, Laitinen T (2001) Normal values for the Pelli-Robson contrast sensitivity test. J

Cataract Refract Surg. 27: 261-266.

27. Rosser DA, Cousens SN, Murdoch IE, Fitzke FW, Laidlaw DA (2003) How sensitive to clinical change

are ETDRS logMAR visual acuity measurements? Invest Ophthalmol Vis Sci. 44: 3278-3281.

28. Bowman KJ (1982) A method for quantitative scoring of the Farnsworth panel D-15. Acta Ophthalmol.

60: 907.

29. Wilkinson CP (2009) Mysteries regarding the surgically reattached retina. Trans Am Ophthalmol.

107: 55-59.

30. Minihan M, Tanner V, Williamson TH (2001) Primary rhegmatogenous retinal detachment: 20 years

of change. Br J Ophthalmol. 85: 546-548.

31. Liem AT, Keunen JE, van Meel GJ, van Norren D (1994) Serial foveal densitometry and visual function

after retinal detachment surgery with macular involvement. Ophthalmology. 101: 1945-1952.

32. Van de Put MAJ, Nayebi F, Croonen D, Nolte IM, Japing WJ, et al (2013) Design and validation of a

method to determine the position of the fovea by using the nerve-head to fovea distance of the fellow

eye. PlosOne,8: E62518.

VandePut.indd 91 4-11-2014 14:15:52

92 | Chapter 5

33. Chylack LT Jr., Wolfe JK, Singer DM, Leske MC, Bullimore MA, et al (1993) The Lens Opacities

Classification System III. The Longitudinal Study of Cataract Study Group. Arch Ophthalmol. 111:

831-836.

34. Doyle E, Herbert EN, Bunce C, Williamson TH, Laidlaw DAH (2007) How effective is macula-off

retinal detachment surgery. Might good outcome be predicted. Eye. 21: 534-540.

35. Anderson C, Sjöstrand J (1981) Contrast sensitivity and central vision in reattached macula. Acta


36. Kreissig I, Lincoff B, Witassek B, et al (1981) Color vision and other parameters of macular function

after reattachment. Dev Ophthalmol. 2: 77-85.

VandePut.indd 92 4-11-2014 14:15:52

Chapter 6

Postoperative vision-related quality of life in

macula-off rhegmatogenous retinal detachment

and its relation to visual function

Submitted

Mathijs A.J. van de Put¹,2, Lisette Hoeksema¹,2, Wouter Wanders¹,

Ilja M. Nolte3, Johanna M.M. Hooymans1,2, Leonoor I. Los1,2

1 Department of Ophthalmology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

2 W.J. Kolff Institute, Graduate School of Medical Sciences, University of Groningen, Groningen, the Netherlands.3 Department of Epidemiology, University of Groningen, University Medical

Center Groningen, Groningen, the Netherlands.

VandePut.indd 93 4-11-2014 14:15:52

94 | Chapter 6

ABSTRACT

Objective: To determine the vision-related quality of life (VR-QOL) after surgery for macula-off

rhegmatogenous retinal detachment (RRD) in relation to visual acuity, contrast acuity, and color

vision.

Methods: In a prospective observational study, we included 55 patients with a macula-off RRD.

Best corrected visual acuity (BCVA), color vision (color confusion indices (CCI) saturé and desaturé)

and contrast acuity were measured at 12 months postoperatively in both the RRD eye and the

fellow control eye, and the 25-item National Eye Institute Visual Function Questionnaire (NEI

VFQ-25) was filled out.

Results: Operated and fellow control eyes differed significantly in mean LogMAR BCVA

(P < 0.0001), median Log contrast acuity (P < 0.0001), saturated CCI (P = 0.009), and desaturated

CCI (P = 0.016). Significant correlations were observed between the NEI VFQ-25 overall composite

score and postoperative LogMAR BCVA (R = -0.551, P < 0.0001), contrast acuity (R = 0.472,

P < 0.0001), saturated CCI (R = -0.315, P = 0.023), and desaturated CCI (R = -0.283, P = 0.044).

Conclusions: A lower VR-QOL was highly correlated to a worse postoperative BCVA and contrast

acuity and to a lesser extent to color vision disturbances.

VandePut.indd 94 4-11-2014 14:15:52

6

Postoperative vision related quality of life 95

INTRODUCTION

Rhegmatogenous retinal detachment (RRD), which refers to a detachment of the neurosensory

retina from the underlying retinal pigment epithelium due to a defect in the retina,[1] occurs with

an incidence of 18.2/100,000 people/year in the Netherlands.[2] With surgical intervention, the

detached neuroretina can be reattached to the retinal pigment epithelium in more than 95% of

cases.[3-5] In spite of this high anatomic success rate, functional recovery is often compromised,[6-12]

especially when the macula was detached during the RRD, which happens in about 50% of cases. [2]

Not only best corrected visual acuity (BCVA) is compromised in these cases, other aspects of

central visual function are also compromised after macula-off RRD.[11,13-14] Two modifiable factors

are crucial in the recovery of visual function in these cases.[4,8,15-17] One is the pre-operative duration

of the macular detachment (i.e. a longer duration will result in a lower visual acuity (VA), and

a worse recovery of color vision),[4,8,17] and the preoperative height of the macular detachment

(i.e. an increase in height will result in a lower postoperative BCVA).[15-17] Non-modifiable

factors influencing the postoperative recovery of visual function include age, refractive error, and

preoperative VA.[4,14]

Previous studies identified a strong relation between postoperative visual function and post-

operative vision-related quality of life (VR-QOL) as measured by the National Eye Institute Visual

Functioning Questionnaire-25 (NEI VFQ-25) in patients operated on for various vitreoretinal

disorders, including RRD.[18-25] The NEI VFQ-25 ocular composite score and subscores are further

explained in the Methods. Zou et al. showed that postoperative quality of life is worse in macula-

off compared to macula-on RRD.[18] In Okamoto’s study, postoperative BCVA differed significantly

between macula-on and macula-off RRD, while scores on the NEI VFQ-25 were similar in both

groups of patients.[20] Surprisingly, that study indicated that a worse post-operative contrast acuity

was related to a lower score on the NEI VFQ-25 questionnaire, whereas a low post-operative VA

was not.[20]

We could not find previous studies addressing post-operative quality of life specifically in macula-

off RRD patients in relation to BCVA, contrast acuity and color vision. Therefore, the purpose of

the present study is to determine the postoperative VR-QOL after macula-off RRD one year after

successful reattachment of the retina, and to assess which aspects of postoperative visual function

(VA, contrast acuity, or color vision) are most closely related herewith. In addition, we evaluated

whether pre-operative, intra-operative, and postoperative factors are associated with a difference in

postoperative VR-QOL.

VandePut.indd 95 4-11-2014 14:15:52

96 | Chapter 6

METHODS

Study design

We conducted a prospective observational study in patients with a first presentation of macula-off

RRD who had an attached retina at 12 months after the first surgical procedure. Reattachment

was obtained by one or more surgical procedures. The research protocol was approved by the

University Medical Center Groningen (UMCG) review board ethics committee, and was carried

out in accordance with the tenets of the declaration of Helsinki. The study was registered with the

Dutch Trial Register (NTR839). All patients were operated on at the ophthalmology department

of the UMCG. The study was carried out over a three-year period (February 1, 2007 - February 1,

2010).

Study population

Adult patients visiting the ophthalmology department of the UMCG with a first presentation of

unilateral macula-off RRD of 24 hours to 6 weeks duration were invited to participate in this

study. Included in the study were patients of 18 years and older who had given their written

informed consent. Patients had to be able to pinpoint their drop in VA to a specific 24-hour period

in case of a 24-hour to 1 week macular detachment, and to a period of less than one week in case

of a macular detachment of one to six weeks. The cut-off point of ≤ 1 week or > 1 week is conform

the available literature.[11,13] Patients with macular detachment of more than 6 weeks duration were

excluded, because they are considered rare, and yield a worse prognosis.[9] Surgery was performed

within 24-72 hours after presentation at the ophthalmology department. Excluded were patients

with a history of congenital or acquired pathology with an effect on visual function in one or both

eyes (with the exception of congenital defects in color vision), or pathology observed at presentation

after their macula-off RRD that could influence post-operative VA.

Preoperative measurements

We acquired the following patients’ characteristics: age, gender, affected eye, ophthalmic history

and family history for RRD. In addition, we scored the number of retinal quadrants detached at

presentation, and the presence, and grade of PVR.[26] Using standardised protocols, the refractive

error and BCVA using the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart were

determined in the affected and fellow control eye.[27] All VA measurements were converted to

logMAR equivalents of ETDRS acuity for analysis. Light perception or hand movements were

coded as logMAR VA of 3.0.

Duration and height of macular detachment were determined using the following scoring system.

Macula-off RRDs of less than one week duration were scored per day, and of more than one week

duration they were scored as 11 days (1-2 weeks duration), 18 days (2-3 weeks duration), 25 days

(3-4 weeks duration), 32 days (4-5 weeks duration), and 39 days (5-6 weeks duration), respectively.

VandePut.indd 96 4-11-2014 14:15:52

6


To measure the height of the detachment at the position of the central macula by ultrasonography,

the relative positions of the central macula and the optic nerve head were determined before

performing ultrasonography. For this purpose, digital fundus photographs of both eyes were

made using the TRC-50 IX fundus camera (Topcon 9B ltd. UK). On both fundus photographs,

the distance between the optic nerve head and fovea was measured using the software package

IMAGEnet2000 2.53. The measured distance in the affected eye was used to determine the central

position of the macula and at this position the height of the macular detachment was measured by

ultrasonography. In those cases (i.e. bullous retinal detachment), in which the measurement of the

distance between the macula and optic nerve head could not be performed on the photograph of

the affected eye, the measurement of this distance in the fellow eye was used.[28] In each patient, two

measurements were made with the patient in an upright position (as this represents the position

most patients would have taken for most of the time before presentation during the day) and the

average of both measurements was used for further analysis.

Surgical procedure (intraoperative data)

Based on clinical presentation, patients were either operated on by an external procedure (i.e.

encircling band and / or buckle) or by 20 Gauge TPPV (with or without an encircling band). In

TPPV cases, either a short acting tamponade (i.e. sulphur hexafluoride gas (SF6)) or a long acting

tamponade (i.e. octafluorpropane (C3F8) or silicone oil) was used. Collected data refer to the first

surgical procedure in all cases.

Postoperative measurements

Visual function

At 12 months postoperatively, we measured BCVA using the ETDRS chart,[27] contrast acuity

using the Pelli Robson chart,[29] Farnsworth D-15 saturated, and Lanthoni desaturated color

confusion indexes (CCI).[30] All measurements were done in the affected and fellow control eye.

Information on postoperative success (i.e. primary or secondary) was acquired. Also, the number of

surgical procedures needed to obtain an attached retina, were recorded.

Quality of life

At 12 months postoperatively, patients were requested to self-administer the validated Dutch

version[25] of the NEI VFQ-25 to assess their VR-QOL.[21-25] This questionnaire has been developed

by the research and development corporation (RAND), and funded by the NEI. The NEI VFQ-25

comprises 25 items that require the patient to assess the influence of visual disability and visual

symptoms on generic health domains such as emotional well-being and social functioning, in

addition to task-oriented domains related to daily visual functioning. Each item is assigned to

one of the following twelve subscales: general health, general vision, ocular pain, near activities,

VandePut.indd 97 4-11-2014 14:15:52

98 | Chapter 6

distance activities, vision specific social functioning, vision specific mental health, vision specific

role difficulties, vision specific dependency, driving, color vision, and peripheral vision.[21-25] Each

subscale consists of a minimum of one and a maximum of four items. We used the standard

algorithm to calculate the scale scores. The subscales are 0 to 100 points, where 100 indicates the

highest possible function or minimal subjective impairment. The NEI VFQ-25 overall composite

score (OCS) is calculated as the unweighted average response to all items, excluding the question

on general health.

Cataract

Because of an increased risk of cataract development after TPPV, which may influence postoperative

measurements, we scored the level of cataract using the lens opacities classification system III

(LOCS III) in both eyes at pre-determined post-operative intervals.[31] In addition, BCVA was

assessed at those time points, and in case of a visually significant cataract (n = 26 eyes) a cataract

extraction was performed before the 12 months measurement.


Data were analysed using SPSS software package, version 16.0 (Chicago, Illinois, USA). A one-

tailed paired Student’s t-test (we expect worse visual function in the operated eye) or Wilcoxon

signed rank test was used to explore statistical differences in visual function parameters between

operated and fellow control eyes depending on the distribution of the variable. Spearman’s

correlation coefficients were calculated to explore significant correlations between the different

postoperative visual function parameters. The relationships between age, preoperative factors,

postoperative visual function tests (LogMAR VA, Log contrast acuity, saturated and desaturated

CCI) and the NEI VFQ-25 scores were examined using Spearman’s correlation coefficients. To

determine differences in NEI VFQ-25 OCS and subscores in subgroups we used a Mann-Whitney

U test in case of two groups or a Kruskal-Wallis test in case of more than two groups. In the latter

case post-hoc analyses were performed for pairwise comparisons between subgroups.

All tests were considered statistically significant at a p-value of less than 0.05, except for the

Kruskal-Wallis post-hoc analysis, for which a significance threshold of 0.05 divided by the number

of groups was used.

VandePut.indd 98 4-11-2014 14:15:52

6


RESULTS


RRD-study

A total of 56 patients gave their written informed consent and were included. In 46 patients

retinal re-attachment was obtained after one surgical procedure, whereas ten patients had one or

more re-detachments. One patient died during the study period and was therefore excluded from

analysis. In all remaining 55 patients, the retina was still surgically attached twelve months after

the initial surgical procedure. Missing data further consisted of: visual function tests at 12 months

(n=1), saturated (n=2) and desaturated (n=3) CCI, because of color blindness (n=2) and unknown

reasons (n=1).

Table 1 summarizes the preoperative data on general patient characteristics and type of surgery.

Briefly, the mean age was 60.4 years, more male than female patients were included (2.7:1),

right and left eyes were equally involved, and most eyes were phakic (67.3%). A TPPV was most

frequently chosen as the primary surgical procedure (n=45 (81.8%)). This was combined with an

encircling band in about half the cases (n=27). Data on refractive error could reliably be obtained

in phakic eyes (n=37). In pseudophakic patients, data on refractive error prior to cataract extraction

were not available in 18 eyes. These were coded as missing data. In case of known refractive error,

no significant associations with visual function or NEI VFQ-25 scores were observed.

Table 1: Preoperative patient characteristics, lens status, and type of surgery

Characteristics Number (%) Mean age ± SD Scleral buckling / TPPV (%)Total 55 (100.0) 60.4 ± 11.2 10 (18.2) / 45 (81.8)Male 40 (72.7) 61.4 ± 9.8 5 (12.5) / 35 (87.5)Female 15 (27.3) 57.8 ± 14.4 5 (33.3) / 10 (66.7)Phakic 37 (67.3) 59.5 ± 8.3 10 (27.0) / 27 (73.0)Pseudophakic 18 (32.7) 62.2 ± 15.8 0 (0.0) / 18 (100.0)SD: Standard deviation, TPPV: Trans pars plana vitrectomy.

Postoperative BCVA, Log contrast acuity, saturated and desaturated CCI in operated eyes were

significantly worse than in fellow control eyes (Table 2). We observed high correlations between

postoperative LogMAR BCVA, log contrast acuity, saturated, and desaturated CCI’s (Table 3).

VandePut.indd 99 4-11-2014 14:15:53

100 | Chapter 6

Table 2: Visual function tests in operated versus in fellow control eyes

BCVA N Operated eye, Mean ± SD

Fellow eye, Mean ± SD

P

Preoperative BCVA (LogMAR) 55 2.15 ± 1.10 0.09 ± 0.20 <0.0001Preoperative BCVA (Snellen)a HM 16/20Postoperative BCVA (LogMAR) 54 0.35 ± 0.37 0.05 ± 0.11 <0.0001Postoperative BCVA (Snellen)a 4/10 - 5/10 20/20Postoperative visual function N Operated eye, Median

(ranges)Fellow eye, Median (ranges)

P

Contrast acuity (Log) 54 1.45 (0.00 - 1.70) 1.55 (1.20 - 1.90) <0.0001Color vision saturé CCI 52 1.16 (1.00 - 3.09) 1.00 (1.00 - 2.59) 0.009Color vision desaturé CCI 51/51 1.77 (1.00 - 3.20) 1.52 (1.00 - 2.59) 0.016BCVA: best corrected visual acuity, CCI: Color Confusion Indices, SD: standard deviation, HM: hand movements. Postoperative measurements were performed 12 months after retinal detachment surgery.a Mean LogMAR visual acuity converted to Snellen visual acuity. N: Number of patients. P: P-value

Quality of life

Table 4 presents the outcomes of the NEI VFQ-25 scores in relation to demographic, patient,

and surgical parameters. Overall, scores are relatively high when compared to previous studies on

macula-on and macula-off RRD, epiretinal membrane (ERM) and macular hole (MH) (Table 5).

Only limited differences between subgroups of patients were observed.

Table 3: Spearman’s rank correlation coefficients between LogMAR BCVA, log contrast acuity, and CCI

(saturated and desaturated)

R P-valueLogMAR BCVA / contrast acuity -0.633 <0.0001LogMAR BCVA / saturated CCI 0.556 <0.0001LogMAR BCVA / desaturated CCI 0.446 0.001Contrast acuity / saturated CCI -0.415 0.002Contrast acuity / desaturated CCI -0.393 0.004Saturated CCI/ desaturated CCI 0.734 <0.0001BCVA: best corrected visual acuity, CCI: Color vision Confusion Index. Measurements were performed 12 months after retinal detachment surgery.

In summary, even though only small differences existed between vision related quality of life OCS

and subscale scores, lower scores on vision related quality of life may be related to more extensive

surgery, long-term intraocular tamponades and re-detachment. Patients with a more extensive

retinal detachment had lower scores on the subscales ocular pain (i.e. experienced more ocular pain)

and vision specific role difficulties. Primary surgical success was associated with higher scores on

the subscale near activities and OCS. A higher number of re-detachment surgeries was associated

with lower scores on ocular pain (i.e. more pain) and vision specific mental health. Patients operated

on by TPPV had lower scores on vision specific role difficulties, and patients in whom a TPPV

VandePut.indd 100 4-11-2014 14:15:53

6


was combined with an encircling band scored higher on vision specific mental health. Patients

receiving a shorter acting gas tamponade (SF6) instead of longer acting gas tamponade (C3F8) or

silicone oil were observed to have higher scores on general vision, ocular pain, near activities, vision

specific mental health, driving and on the OCS. Preoperatively pseudophakic patients (RRD eye

or fellow eye) had higher scores on the vision specific mental health subscale than phakic patients.

Table 6 provides information on the Spearman’s correlation coefficients of age, preoperative factors,

and postoperative visual function tests and NEI VFQ-25 outcomes. In general, worse outcomes of

visual function tests are correlated with lower NEI VFQ-25 scores. Correlations between BCVA

or contrast acuity and NEI VFQ-25 scores were more numerous and stronger than those between

color vision and NEI VFQ-25 scores.

VandePut.indd 101 4-11-2014 14:15:53

102 | Chapter 6

Table 4a: NEI VFQ-25 overall composite score and subscale scores (mean ± SD). Nominal significant values

are indicated in bold.

GH GV OP NA DA VSSF VSMH VSRD VSD D CV PV OCSa

(n=55) (n=55) (n=55) (n=55) (n=54) (n=55) (n=55) (n=55) (n=55) (n=45) (n=50) (n=53) (n=55)Total (n=55) 60.5±21.3 71.3±12.0 88.4±15.2 85.6±13.8 86.1±12.6 98.4±4.8 87.6±14.7 88.2±16.2 98.3±5.4 84.2±17.1 97.0±13.0 91.0±16.3 88.9±7.9Gender - Male (n=40) 61.9±20.4 71.0±20.4 87.2±16.6 85.6±13.3 86.8±11.6 97.8±5.6 87.7±15.1 87.2±15.9 97.9±6.2 87.1±15.4 96.4±15.0 91.5±16.7 88.4±84

- Female (n=15) 56.7±24.3 72.0±12.6 91.7±10.2 85.6±15.6 83.9±15.5 100.0±0.0 87.5±14.0 90.8±17.3 99.4±2.2 75.0±19.7 98.3±6.5 90.0±15.8 89.8±6.8P-value 0.256 0.907 0.546 0.861 0.679 0.116 0.899 0.314 0.396 0.052 0.939 0.574 0.777

Familyb - Positive (n=6) 58.3±25.8 63.3±15.1 93.8±10.5 77.8±16.4 81.9±6.3 97.9±5.1 83.3±10.9 87.5±15.8 100.0±0.0 83.3±18.0 100.0±0.0 83.4±25.8 85.24±9.0- Negative (n=49) 60.7±21.0 72.2±11.4 87.8±15.6 86.6±13.4 86.6±13.2 98.5±4.9 88.1±15.1 88.3±16.4 98.1±5.7 84.3±17.3 96.6±13.8 92.0±14.8 89.18±7.8P-value 0.755 0.148 0.380 0.166 0.182 0.653 0.148 0.788 0.327 0.854 0.514 0.467 0.19

Lens (pre-op)

- Phakic (n=37) 62.2±21.7 70.3±10.1 87.8±16.5 84.2±12.8 85.7±12.2 98.7±4.9 84.8±16.0 88.2±16.4 97.8±6.4 82.8±18.2 97.7±9.6 90.0±16.3 88.2±7.8- j-phakic (n=18) 56.9±20.7 73.3±15.3 89.6±12.3 88.4±15.7 86.9±13.9 97.9±4.8 93.4±9.5 88.2±16.3 99.5±2.0 86.9±15.0 95.6±18.2 93.1±16.7 89.9±8.3P-value 0.376 0.390 0.907 0.138 0.530 0.370 0.012 0.960 0.258 0.451 0.980 0.331 0.212

Quadrantsc - 1-2 (n=35) 58.6±19.1 72.0±11.1 91.4±13.5 87.6±12.7 86.9±11.8 99.3±2.9 90.6±9.6 92.1±13.6 98.8±3.6 85.4±18.1 96.9±13.8 90.4±17.4 90.0±6.7- 3-4 (n=19) 61.8±24.1 69.5±13.9 82.2±16.8 81.6±15.6 84.6±14.5 96.7±7.0 82.9±20.6 80.3±18.3 97.4±7.8 81.6±15.7 97.1±12.1 91.7±14.9 86.4±9.8P-value 0.733 0.481 0.017 0.163 0.616 0.084 0.181 0.011 0.630 0.288 0.960 0.970 0.319

PVR - Grade A (n=30) 59.2±22.2 72.7±11.1 90.8±12.3 87.2±13.8 88.8±10.6 99.2±3.2 91.0±8.6 88.3±14.6 98.6±3.8 86.3±13.3 96.3±15.0 90.0±18.1 89.6±6.5- Grade B (n=16) 60.9±15.7 71.3±14.5 85.2±16.6 85.4±15.4 86.1±9.8 96.9±7.2 87.9±11.7 88.3±18.5 99.5±2.1 80.8±22.2 96.4±13.4 90.0±15.8 88.1±9.0- Grade C (n=8) 59.4±26.5 65.0±9.3 84.4±21.9 79.2±10.9 76.0±20.1 98.4±4.4 75.8±28.8 85.9±19.4 94.8±11.7 81.3±26.7 100.0±0.0 96.4±9.4 86.4±11.2P-value 0.866 0.235 0.486 0.227 0.159 0.440 0.347 0.848 0.400 0.955 0.737 0.650 0.899

Durationd - ≤ 1 week (n=29) 60.3±19.5 70.3±11.5 89.66±15.3 86.2±13.4 86.2±12.2 99.1±4.6 90.1±10.8 88.4±14.1 98.3±4.01 84.1±17.6 95.4±17.0 92.9±13.4 89.2±7.1- > 1 week (n=26) 60.6±23.6 72.3±12.7 87.02±15.2 84.9±14.5 86.0±13.3 97.6±5.0 84.9±18.0 88.0±15.5 98.4±6.7 84.3±16.9 98.9±5.2 89.0±19.2 88.2±8.9P-value 0.875 0.746 0.338 0.815 0.874 0.075 0.244 0.708 0.322 0.934 0.620 0.628 0.781

Success rate - Primary (n=45) 58.9±21.4 72.0±12.4 89.7±13.1 87.2±13.8 87.0±12.2 98.6±4.8 89.9±10.9 88.1±15.1 98.7±3.5 87.2±12.9 97.0±13.8 92.1±15.0 89.9±6.7- Secondary (n=10) 67.5±20.6 68.0±10.3 82.5±22.2 78.3±11.9 81.5±14.3 97.5±5.3 77.5±24.0 88.8±21.6 96.7±10.5 67.9±27.4 96.9±8.8 86.1±22.0 83.3±10.9P-value 0.229 0.313 0.104 0.039 0.255 0.333 0.072 0.506 0.865 0.085 0.440 0.480 0.053

Re-detachede - 1 (n=7) 64.3±19.7 68.6±10.7 94.6±6.7 79.8±14.3 81.9±14.4 98.2±4.7 88.4±10.5 91.1±23.6 100.0±0.0 75.0±27.6 95.0±11.2 92.9±18.9 88.1±8.0- 2 (n=3) 75.0±25 66.7±11.5 54.2±19.1 75.0±0 80.6±17.3 95.8±7.2 52.1±29.5 83.3±19.1 88.9±19.2 50.0±23.6 100.0±0.0 62.5±17.7 72.0±8.8P-value 0.458 0.789 0.012 0.479 0.794 0.513 0.027 0.207 0.127 0.241 0.439 0.054 0.053

NEI VFQ-25: National Eye Institute Visual Functioning Questionnaire-25, SD: standard deviation, GH: General Health, GV: General vision, OP: Ocular pain, NA: Near activities, DA: Distance activities, VSSF: Vision Specific Social Functioning, VSMH: Vision Specific Mental Health, VSRD: Vision Specific Role Difficulties, VSD: Vision Specific Dependency, D: Driving, CV: Color Vision, PV: Peripheral Vision, OCS: Overall Composite Score, PVR: Proliferative vitreoretinopathy, TPPV: Trans Pars Plana Vitrectomy. a Average of vision-targeted subscale scores, without GH. b Family history of RRD. c Numbers of detached retinal quadrants at presentation. d Duration of macular detachment. e Number of re-detachments. f TPPV with or without an encircling band. gPostoperative tamponade after TPPV; SF6 gas (short acting) versus C3F8 gas & Silicon oil (long acting). j-phakic: Pseudophakic. External: Conventional surgery (scleral and / or buckling procedure)

VandePut.indd 102 4-11-2014 14:15:53

6


Table 4a: NEI VFQ-25 overall composite score and subscale scores (mean ± SD). Nominal significant values


GH GV OP NA DA VSSF VSMH VSRD VSD D CV PV OCSa

(n=55) (n=55) (n=55) (n=55) (n=54) (n=55) (n=55) (n=55) (n=55) (n=45) (n=50) (n=53) (n=55)Total (n=55) 60.5±21.3 71.3±12.0 88.4±15.2 85.6±13.8 86.1±12.6 98.4±4.8 87.6±14.7 88.2±16.2 98.3±5.4 84.2±17.1 97.0±13.0 91.0±16.3 88.9±7.9Gender - Male (n=40) 61.9±20.4 71.0±20.4 87.2±16.6 85.6±13.3 86.8±11.6 97.8±5.6 87.7±15.1 87.2±15.9 97.9±6.2 87.1±15.4 96.4±15.0 91.5±16.7 88.4±84

- Female (n=15) 56.7±24.3 72.0±12.6 91.7±10.2 85.6±15.6 83.9±15.5 100.0±0.0 87.5±14.0 90.8±17.3 99.4±2.2 75.0±19.7 98.3±6.5 90.0±15.8 89.8±6.8P-value 0.256 0.907 0.546 0.861 0.679 0.116 0.899 0.314 0.396 0.052 0.939 0.574 0.777

Familyb - Positive (n=6) 58.3±25.8 63.3±15.1 93.8±10.5 77.8±16.4 81.9±6.3 97.9±5.1 83.3±10.9 87.5±15.8 100.0±0.0 83.3±18.0 100.0±0.0 83.4±25.8 85.24±9.0- Negative (n=49) 60.7±21.0 72.2±11.4 87.8±15.6 86.6±13.4 86.6±13.2 98.5±4.9 88.1±15.1 88.3±16.4 98.1±5.7 84.3±17.3 96.6±13.8 92.0±14.8 89.18±7.8P-value 0.755 0.148 0.380 0.166 0.182 0.653 0.148 0.788 0.327 0.854 0.514 0.467 0.19

Lens (pre-op)

- Phakic (n=37) 62.2±21.7 70.3±10.1 87.8±16.5 84.2±12.8 85.7±12.2 98.7±4.9 84.8±16.0 88.2±16.4 97.8±6.4 82.8±18.2 97.7±9.6 90.0±16.3 88.2±7.8- j-phakic (n=18) 56.9±20.7 73.3±15.3 89.6±12.3 88.4±15.7 86.9±13.9 97.9±4.8 93.4±9.5 88.2±16.3 99.5±2.0 86.9±15.0 95.6±18.2 93.1±16.7 89.9±8.3P-value 0.376 0.390 0.907 0.138 0.530 0.370 0.012 0.960 0.258 0.451 0.980 0.331 0.212

Quadrantsc - 1-2 (n=35) 58.6±19.1 72.0±11.1 91.4±13.5 87.6±12.7 86.9±11.8 99.3±2.9 90.6±9.6 92.1±13.6 98.8±3.6 85.4±18.1 96.9±13.8 90.4±17.4 90.0±6.7- 3-4 (n=19) 61.8±24.1 69.5±13.9 82.2±16.8 81.6±15.6 84.6±14.5 96.7±7.0 82.9±20.6 80.3±18.3 97.4±7.8 81.6±15.7 97.1±12.1 91.7±14.9 86.4±9.8P-value 0.733 0.481 0.017 0.163 0.616 0.084 0.181 0.011 0.630 0.288 0.960 0.970 0.319

PVR - Grade A (n=30) 59.2±22.2 72.7±11.1 90.8±12.3 87.2±13.8 88.8±10.6 99.2±3.2 91.0±8.6 88.3±14.6 98.6±3.8 86.3±13.3 96.3±15.0 90.0±18.1 89.6±6.5- Grade B (n=16) 60.9±15.7 71.3±14.5 85.2±16.6 85.4±15.4 86.1±9.8 96.9±7.2 87.9±11.7 88.3±18.5 99.5±2.1 80.8±22.2 96.4±13.4 90.0±15.8 88.1±9.0- Grade C (n=8) 59.4±26.5 65.0±9.3 84.4±21.9 79.2±10.9 76.0±20.1 98.4±4.4 75.8±28.8 85.9±19.4 94.8±11.7 81.3±26.7 100.0±0.0 96.4±9.4 86.4±11.2P-value 0.866 0.235 0.486 0.227 0.159 0.440 0.347 0.848 0.400 0.955 0.737 0.650 0.899

Durationd - ≤ 1 week (n=29) 60.3±19.5 70.3±11.5 89.66±15.3 86.2±13.4 86.2±12.2 99.1±4.6 90.1±10.8 88.4±14.1 98.3±4.01 84.1±17.6 95.4±17.0 92.9±13.4 89.2±7.1- > 1 week (n=26) 60.6±23.6 72.3±12.7 87.02±15.2 84.9±14.5 86.0±13.3 97.6±5.0 84.9±18.0 88.0±15.5 98.4±6.7 84.3±16.9 98.9±5.2 89.0±19.2 88.2±8.9P-value 0.875 0.746 0.338 0.815 0.874 0.075 0.244 0.708 0.322 0.934 0.620 0.628 0.781

Success rate - Primary (n=45) 58.9±21.4 72.0±12.4 89.7±13.1 87.2±13.8 87.0±12.2 98.6±4.8 89.9±10.9 88.1±15.1 98.7±3.5 87.2±12.9 97.0±13.8 92.1±15.0 89.9±6.7- Secondary (n=10) 67.5±20.6 68.0±10.3 82.5±22.2 78.3±11.9 81.5±14.3 97.5±5.3 77.5±24.0 88.8±21.6 96.7±10.5 67.9±27.4 96.9±8.8 86.1±22.0 83.3±10.9P-value 0.229 0.313 0.104 0.039 0.255 0.333 0.072 0.506 0.865 0.085 0.440 0.480 0.053

Re-detachede - 1 (n=7) 64.3±19.7 68.6±10.7 94.6±6.7 79.8±14.3 81.9±14.4 98.2±4.7 88.4±10.5 91.1±23.6 100.0±0.0 75.0±27.6 95.0±11.2 92.9±18.9 88.1±8.0- 2 (n=3) 75.0±25 66.7±11.5 54.2±19.1 75.0±0 80.6±17.3 95.8±7.2 52.1±29.5 83.3±19.1 88.9±19.2 50.0±23.6 100.0±0.0 62.5±17.7 72.0±8.8P-value 0.458 0.789 0.012 0.479 0.794 0.513 0.027 0.207 0.127 0.241 0.439 0.054 0.053


VandePut.indd 103 4-11-2014 14:15:53

104 | Chapter 6

Table 4b: NEI VFQ-25 overall composite score and subscale scores (mean ± SD). Nominal significant values


- TPPV (n=45) GH GV OP NA DA VSSF VSMH VSRD VSD D CV PV OCSa

P-value (n=55) (n=55) (n=55) (n=55) (n=54) (n=55) (n=55) (n=55) (n=55) (n=45) (n=50) (n=53) (n=55)Technique - External (n=10) 62.5±21.2 76.0±8.4 90.0±16.5 90.8±10 87.5±11.9 100.0±0.0 90.0±12.2 98.8±4.0 98.3±3.5 85.4±24.3 100.0±0.0 92.5±12.1 91.8±6.0

- TPPV (n=45) 60.0±21.6 70.2±12.5 88.1±15.1 84.4±14.4 85.7±12.9 98.1±5.3 87.1±15.3 85.8±17 98.3±5.8 83.9±15.6 96.3±14.3 90.7±17.3 88.1±8.2P-value 0.847 0.121 0.554 0.235 0.856 0.226 0.472 0.014 0.497 0.322 0.408 0.953 0.209

TPPV &f - Band (n=18) 61.1±21.4 74.4±15.0 89.6±12.3 87.0±16.5 89.8±10.5 98.6±4.0 92.0±10.2 88.2±15.1 99.5±2.0 86.5±14.6 100.0±0.0 91.7±17.1 90.3±7.9Band - No band (n=27) 59.3±22.1 67.4±9.8 87.0±16.8 82.7±12.9 83.2±13.8 97.7±6.0 83.8±17.3 84.3±18.2 97.5±7.2 81.9±16.4 93.8±18.4 90.0±17.7 86.6±8.3

P-value 0.890 0.056 0.755 0.169 0.099 0.694 0.038 0.518 0.318 0.372 0.135 0.699 0.073Tamponadeg - Short acting (n=35) 59.3±21.1 72.6±12.0 91.8±10.9 87.1±13.5 85.6±18.6 98.6±4.0 91.6±8.2 86.4±16.4 99.1±3.4 84.8±20.1 96.9±13.8 91.2±17.3 89.8±6.7

- Long acting (n=10) 62.5±24.3 62.0±11.4 75.0±20.4 75.0±14.2 77.5±15.2 96.3±8.4 71.3±23.0 83.8±19.6 95.8±10.6 65.3±15.3 94.4±16.7 88.9±18.2 81.9±10.2P-value 0.788 0.041 0.012 0.021 0.064 0.657 < 0.001 0.778 0.581 0.004 0.841 0.714 0.018

Lens - Phakic (n=11) 59.1±16.9 74.6±9.3 85.2±21.5 92.4±8.7 87.1±12.0 97.7±7.5 90.3±11.0 90.9±15.9 98.5±3.4 81.3±23.0 95.5±12.6 90.9±12.6 89.8±8.6(Post-op) - j-phakic (n=42) 61.3±22.2 71.0±12.7 89.6±13.5 84.9±13.9 86.9±11.8 98.8±3.7 88.2±14.2 87.2±16.7 98.2±6.0 84.8±15.9 97.4±16.2 92.5±16.2 88.6±7.8

P-value 0.779 0.315 0.981 0.117 0.927 0.965 0.626 0.487 0.641 0.873 0.645 0.387 0.483


VandePut.indd 104 4-11-2014 14:15:53

6


Table 4b: NEI VFQ-25 overall composite score and subscale scores (mean ± SD). Nominal significant values


- TPPV (n=45) GH GV OP NA DA VSSF VSMH VSRD VSD D CV PV OCSa

P-value (n=55) (n=55) (n=55) (n=55) (n=54) (n=55) (n=55) (n=55) (n=55) (n=45) (n=50) (n=53) (n=55)Technique - External (n=10) 62.5±21.2 76.0±8.4 90.0±16.5 90.8±10 87.5±11.9 100.0±0.0 90.0±12.2 98.8±4.0 98.3±3.5 85.4±24.3 100.0±0.0 92.5±12.1 91.8±6.0

- TPPV (n=45) 60.0±21.6 70.2±12.5 88.1±15.1 84.4±14.4 85.7±12.9 98.1±5.3 87.1±15.3 85.8±17 98.3±5.8 83.9±15.6 96.3±14.3 90.7±17.3 88.1±8.2P-value 0.847 0.121 0.554 0.235 0.856 0.226 0.472 0.014 0.497 0.322 0.408 0.953 0.209

TPPV &f - Band (n=18) 61.1±21.4 74.4±15.0 89.6±12.3 87.0±16.5 89.8±10.5 98.6±4.0 92.0±10.2 88.2±15.1 99.5±2.0 86.5±14.6 100.0±0.0 91.7±17.1 90.3±7.9Band - No band (n=27) 59.3±22.1 67.4±9.8 87.0±16.8 82.7±12.9 83.2±13.8 97.7±6.0 83.8±17.3 84.3±18.2 97.5±7.2 81.9±16.4 93.8±18.4 90.0±17.7 86.6±8.3

P-value 0.890 0.056 0.755 0.169 0.099 0.694 0.038 0.518 0.318 0.372 0.135 0.699 0.073Tamponadeg - Short acting (n=35) 59.3±21.1 72.6±12.0 91.8±10.9 87.1±13.5 85.6±18.6 98.6±4.0 91.6±8.2 86.4±16.4 99.1±3.4 84.8±20.1 96.9±13.8 91.2±17.3 89.8±6.7

- Long acting (n=10) 62.5±24.3 62.0±11.4 75.0±20.4 75.0±14.2 77.5±15.2 96.3±8.4 71.3±23.0 83.8±19.6 95.8±10.6 65.3±15.3 94.4±16.7 88.9±18.2 81.9±10.2P-value 0.788 0.041 0.012 0.021 0.064 0.657 < 0.001 0.778 0.581 0.004 0.841 0.714 0.018

Lens - Phakic (n=11) 59.1±16.9 74.6±9.3 85.2±21.5 92.4±8.7 87.1±12.0 97.7±7.5 90.3±11.0 90.9±15.9 98.5±3.4 81.3±23.0 95.5±12.6 90.9±12.6 89.8±8.6(Post-op) - j-phakic (n=42) 61.3±22.2 71.0±12.7 89.6±13.5 84.9±13.9 86.9±11.8 98.8±3.7 88.2±14.2 87.2±16.7 98.2±6.0 84.8±15.9 97.4±16.2 92.5±16.2 88.6±7.8

P-value 0.779 0.315 0.981 0.117 0.927 0.965 0.626 0.487 0.641 0.873 0.645 0.387 0.483


VandePut.indd 105 4-11-2014 14:15:53

106 | Chapter 6

Table 5: NEI VFQ-25 overall composite score and subscale scores for the present study and previously

published studies, mean (SD)

Study Group composition Age GH GV OP NA DA VSSF VSMH VSRD VSD D CV PV OCSVan de Put RRD mac-off 60.4 (11.2) 60.5 71.3 88.4 85.6 86.1 98.4 87.6 88.2 98.3 84.2 97.0 91.0 88.9n=55 12 months (21.3) (12.0) (15.2) (13.8) (12.6) (4.8) (14.7) (16.2) (5.4) (17.1) (13.0) (16.3) (7.9)Okamoto19 RRD mac-on & off 52.3 (13.2) 54.2 70.7 82.4 75.3 75.6 88.2 77.5 78.5 87.2 75.5 94.0 72.2 79.6n=55 3 months (16.6) (14.9) (14.7) (17.3) (16.9) (14.9) (18.4) (24.3) (17.3) (24.0) (10.8) (21.0) (14.2)Okamoto20 RRD mac-on & off 51.9 (13.8) 54.4 71.3 83.3 76.6 76.3 89.2 78.2 79.2 88.1 77.0 94.1 72.5 80.3n=51 6 months (17.1) (13.4) (13.2) (16.1) (15.8) (13.5) (17.2) (22.0) (15.3) (22.0) (10.7) (20.2) (12.5)Schweitzer31 Acute PVD Females: 62.1 (7.6) 80.6 85.8 89.6 89.6 94.4 99.1 91.8 95.7 99.4 87.9 99.1 95.5 93.5n=84 6 weeks Males: 64.5 (6.6) (16.0) (10.9) (12.9) (10.9) (8.3) (3.4) (9.8) (8.6) (3.0) (14.6) (6.1) (11.1) (6.2)Okamoto20 MH 64.3 (9.6) 53.6 69.0 84.8 70.2 72.2 82.7 76.6 78.6 85.7 78.6 85.7 75.8 79.2n=42 3 months (17.1) (14.1) (16.0) (18.8) (19.4) (15.6) (14.1) (21.8) (19.2) (12.6) (19.2) (19.3) (13.0)Hirneiss32 MH 67 (-) 61.1 62.6 88.0 71.3 80.0 84.7 88.5 71.1 88.7 66.8 92.1 85.8 79.1n=59 3 months (18.4) (21.6) (18.0) (20.4) (20.1) (18.6) (19.8) (28.2) (18.7) (30.5) (10.4) (20.5) (15.4)Tranos33 MH 70 (9) 64.2 70.5 84.1 77.2 81.1 92.1 74.7 74.5 88.8 82.6 95.8 88.3 82.4n=26 4 months (18.2) (14.5) (20.4) (22.8) (20.8) (17.5) (27.4) (26.6) (19.5) (29.3) (13.2) (20.1) (14.1)Okamoto20 ERM 67 (8.4) 55.3 69.1 87.9 71.0 73.4 83.0 78.4 76.5 88.9 76.0 89.4 72.7 78.5n=33 3 months (15.0) (11.3) (11.9) (18.2) (16.0) (9.3) (13.1) (20.0) (11.0) (16.9) (12.5) (17.0) (8.4)Ghazi34 ERM 66 (13) 65.8 70.5 86.8 74.6 79.4 94.7 79.5 80.6 91.2 88.0 92.1 86.1 83.3n=20 4 months (27.9) (12.2) (18.4) (24.4) (18.3) (12.7) (22.7) (26.5) (17.0) (8.4) (11.9) (23.0) (15.5)Matsuoka35 ERM 70 (9) 61 68 84 78 77 85 78 85 90 71 89 71 81n=26 12 months (2) (3) (3) (2) (3) (2) (4) (3) (3) (4) (3) (4) (2)

NEI VFQ-25: National Eye Institute Visual Functioning Questionnaire-25, GH: General Health, GV: General vision, OP: Ocular pain, NA: Near activities, DA: Distance activities, VSSF: Vision Specific Social Functioning, VSMH: Vision Specific Mental Health, VSRD: Vision Specific Role Difficulties, VSD: Vision Specific Dependency, D: Driving, CV: Color Vision, PV: Peripheral Vision, OCS: Overall Composite Score, SD: standard deviation, RRD: rhegmatogenous retinal detachment, PVD: posterior vitreous detachment, MH: macular hole, ERM: epiretinal membrane.

VandePut.indd 106 4-11-2014 14:15:54

6


Table 5: NEI VFQ-25 overall composite score and subscale scores for the present study and previously

published studies, mean (SD)

Study Group composition Age GH GV OP NA DA VSSF VSMH VSRD VSD D CV PV OCSVan de Put RRD mac-off 60.4 (11.2) 60.5 71.3 88.4 85.6 86.1 98.4 87.6 88.2 98.3 84.2 97.0 91.0 88.9n=55 12 months (21.3) (12.0) (15.2) (13.8) (12.6) (4.8) (14.7) (16.2) (5.4) (17.1) (13.0) (16.3) (7.9)Okamoto19 RRD mac-on & off 52.3 (13.2) 54.2 70.7 82.4 75.3 75.6 88.2 77.5 78.5 87.2 75.5 94.0 72.2 79.6n=55 3 months (16.6) (14.9) (14.7) (17.3) (16.9) (14.9) (18.4) (24.3) (17.3) (24.0) (10.8) (21.0) (14.2)Okamoto20 RRD mac-on & off 51.9 (13.8) 54.4 71.3 83.3 76.6 76.3 89.2 78.2 79.2 88.1 77.0 94.1 72.5 80.3n=51 6 months (17.1) (13.4) (13.2) (16.1) (15.8) (13.5) (17.2) (22.0) (15.3) (22.0) (10.7) (20.2) (12.5)Schweitzer31 Acute PVD Females: 62.1 (7.6) 80.6 85.8 89.6 89.6 94.4 99.1 91.8 95.7 99.4 87.9 99.1 95.5 93.5n=84 6 weeks Males: 64.5 (6.6) (16.0) (10.9) (12.9) (10.9) (8.3) (3.4) (9.8) (8.6) (3.0) (14.6) (6.1) (11.1) (6.2)Okamoto20 MH 64.3 (9.6) 53.6 69.0 84.8 70.2 72.2 82.7 76.6 78.6 85.7 78.6 85.7 75.8 79.2n=42 3 months (17.1) (14.1) (16.0) (18.8) (19.4) (15.6) (14.1) (21.8) (19.2) (12.6) (19.2) (19.3) (13.0)Hirneiss32 MH 67 (-) 61.1 62.6 88.0 71.3 80.0 84.7 88.5 71.1 88.7 66.8 92.1 85.8 79.1n=59 3 months (18.4) (21.6) (18.0) (20.4) (20.1) (18.6) (19.8) (28.2) (18.7) (30.5) (10.4) (20.5) (15.4)Tranos33 MH 70 (9) 64.2 70.5 84.1 77.2 81.1 92.1 74.7 74.5 88.8 82.6 95.8 88.3 82.4n=26 4 months (18.2) (14.5) (20.4) (22.8) (20.8) (17.5) (27.4) (26.6) (19.5) (29.3) (13.2) (20.1) (14.1)Okamoto20 ERM 67 (8.4) 55.3 69.1 87.9 71.0 73.4 83.0 78.4 76.5 88.9 76.0 89.4 72.7 78.5n=33 3 months (15.0) (11.3) (11.9) (18.2) (16.0) (9.3) (13.1) (20.0) (11.0) (16.9) (12.5) (17.0) (8.4)Ghazi34 ERM 66 (13) 65.8 70.5 86.8 74.6 79.4 94.7 79.5 80.6 91.2 88.0 92.1 86.1 83.3n=20 4 months (27.9) (12.2) (18.4) (24.4) (18.3) (12.7) (22.7) (26.5) (17.0) (8.4) (11.9) (23.0) (15.5)Matsuoka35 ERM 70 (9) 61 68 84 78 77 85 78 85 90 71 89 71 81n=26 12 months (2) (3) (3) (2) (3) (2) (4) (3) (3) (4) (3) (4) (2)

NEI VFQ-25: National Eye Institute Visual Functioning Questionnaire-25, GH: General Health, GV: General vision, OP: Ocular pain, NA: Near activities, DA: Distance activities, VSSF: Vision Specific Social Functioning, VSMH: Vision Specific Mental Health, VSRD: Vision Specific Role Difficulties, VSD: Vision Specific Dependency, D: Driving, CV: Color Vision, PV: Peripheral Vision, OCS: Overall Composite Score, SD: standard deviation, RRD: rhegmatogenous retinal detachment, PVD: posterior vitreous detachment, MH: macular hole, ERM: epiretinal membrane.

VandePut.indd 107 4-11-2014 14:15:54

108 | Chapter 6

Table 6: Spearman’s rank correlation coefficients between age, preoperative factors (height and duration of

retinal detachment), LogMAR BCVA, contrast acuity, CCI (saturated and desaturated), and NEI VFQ-25

subscale scores and OCS. Nominal significant values are indicated in bold.

GH GV OP NA DA VSSF VSMH VSRD VSD D CV PV OCSR (P-value)

Age (years) (n=55) -0.099 -0.098 0.136 -0.005 -0.186 -0.225 0.109 -0.151 -0.156 0.028 -0.246 -0.117 -0.184(0.473) (0.479) (0.323) (0.969) (0.179) (0.098) (0.427) (0.272) (0.256) (0.857) (0.086) (0.403) (0.178)

Heighta (upright) (n=55) -0.151 -0.043 -0.08 -0.238 -0.148 -0.189 0.03 0.20 -0.025 -0.177 -0.121 -0.22 -0.103(0.271) (0.753) (0.562) (0.08) (0.287) (0.167) (0.827) (0.136) (0.854) (0.244) (0.402) (0.113) (0.456)

Durationb (n=29) 0.320 0.253 -0.016 -0.127 -0.088 0.082 -0.064 0.070 -0.033 0.003 0.279 -0.124 0.081≤ 7 days (0.090) (0.186) (0.935) (0.513) (0.657) (0.672) (0.741) (0.719) (0.865) (0.987) (0.159) (0.531) (0.676)Durationb (n=25) 0.142 -0.108 -0.035 -0.106 -0.234 -0.165 -0.165 0.195 -0.158 -0.043 0.132 -0.291 0.048> 7 days ≤ 6 weeks (0.499) (0.609) (0.870) (0.613) (0.260) (0.431) (0.431) (0.349) (0.450) (0.869) (0.559) (0.168) (0.821)LogMAR BCVA (n=54) -0.196 -0.391 -0.304 -0.517 -0.317 -0.196 -0.405 -0.307 -0.121 -0.588 -0.238 -0.163 -0.551

(0.155) (0.003) (0.026) (<0.0001) (0.021) (0.157) (0.002) (0.024) (0.384) (<0.0001) (0.099) (0.243) (<0.0001)Contrast acuity (n=54) 0.058 0.394 0.142 0.470 0.349 0.287 0.264 0.277 0.014 0.466 0.281 0.234 0.472

(0.677) (0.003) (0.305) (<0.0001) (0.010) (0.036) (0.053) (0.042) (0.918) (0.001) (0.051) (0.092) (<0.0001)Saturated CCI (n=52) -0.129 -0.278 -0.268 -0.233 -0.174 -0.248 -0.259 -0.053 0.044 -0.357 -0.192 -0.142 -0.315

(0.363) (0.046) (0.055) (0.096) (0.221) (0.076) (0.064) (0.708) (0.756) (0.019) (0.197) (0.320) (0.023)Desaturated CCI (n=52) -0.099 -0.207 -0.136 -0.138 -0.162 -0.029 -0.152 -0.140 -0.108 -0.200 -0.265 -0.199 -0.283

(0.488) (0.145) (0.342) (0.332) (0.261) (0.842) (0.287) (0.327) (0.449) (0.198) (0.072) (0.166) (0.044)

NEI VFQ-25: National Eye Institute Visual Functioning Questionnaire-25, GH: General Health, GV: General vision, OP: Ocular pain, NA: Near activities, DA: Distance activities, VSSF: Vision Specific Social Functioning, VSMH: Vision Specific Mental Health, VSRD: Vision Specific Role Difficulties, VSD: Vision Specific Dependency, D: Driving, CV: Color Vision, PV: Peripheral Vision, OCS: Overall Composite Score. BCVA: best corrected visual acuity, CCI: Color vision Confusion Index.a Height of the retinal detachment in prone position. b Duration of macular detachment.

VandePut.indd 108 4-11-2014 14:15:54

6


Table 6: Spearman’s rank correlation coefficients between age, preoperative factors (height and duration of

retinal detachment), LogMAR BCVA, contrast acuity, CCI (saturated and desaturated), and NEI VFQ-25

subscale scores and OCS. Nominal significant values are indicated in bold.

GH GV OP NA DA VSSF VSMH VSRD VSD D CV PV OCSR (P-value)

Age (years) (n=55) -0.099 -0.098 0.136 -0.005 -0.186 -0.225 0.109 -0.151 -0.156 0.028 -0.246 -0.117 -0.184(0.473) (0.479) (0.323) (0.969) (0.179) (0.098) (0.427) (0.272) (0.256) (0.857) (0.086) (0.403) (0.178)

Heighta (upright) (n=55) -0.151 -0.043 -0.08 -0.238 -0.148 -0.189 0.03 0.20 -0.025 -0.177 -0.121 -0.22 -0.103(0.271) (0.753) (0.562) (0.08) (0.287) (0.167) (0.827) (0.136) (0.854) (0.244) (0.402) (0.113) (0.456)

Durationb (n=29) 0.320 0.253 -0.016 -0.127 -0.088 0.082 -0.064 0.070 -0.033 0.003 0.279 -0.124 0.081≤ 7 days (0.090) (0.186) (0.935) (0.513) (0.657) (0.672) (0.741) (0.719) (0.865) (0.987) (0.159) (0.531) (0.676)Durationb (n=25) 0.142 -0.108 -0.035 -0.106 -0.234 -0.165 -0.165 0.195 -0.158 -0.043 0.132 -0.291 0.048> 7 days ≤ 6 weeks (0.499) (0.609) (0.870) (0.613) (0.260) (0.431) (0.431) (0.349) (0.450) (0.869) (0.559) (0.168) (0.821)LogMAR BCVA (n=54) -0.196 -0.391 -0.304 -0.517 -0.317 -0.196 -0.405 -0.307 -0.121 -0.588 -0.238 -0.163 -0.551

(0.155) (0.003) (0.026) (<0.0001) (0.021) (0.157) (0.002) (0.024) (0.384) (<0.0001) (0.099) (0.243) (<0.0001)Contrast acuity (n=54) 0.058 0.394 0.142 0.470 0.349 0.287 0.264 0.277 0.014 0.466 0.281 0.234 0.472

(0.677) (0.003) (0.305) (<0.0001) (0.010) (0.036) (0.053) (0.042) (0.918) (0.001) (0.051) (0.092) (<0.0001)Saturated CCI (n=52) -0.129 -0.278 -0.268 -0.233 -0.174 -0.248 -0.259 -0.053 0.044 -0.357 -0.192 -0.142 -0.315

(0.363) (0.046) (0.055) (0.096) (0.221) (0.076) (0.064) (0.708) (0.756) (0.019) (0.197) (0.320) (0.023)Desaturated CCI (n=52) -0.099 -0.207 -0.136 -0.138 -0.162 -0.029 -0.152 -0.140 -0.108 -0.200 -0.265 -0.199 -0.283

(0.488) (0.145) (0.342) (0.332) (0.261) (0.842) (0.287) (0.327) (0.449) (0.198) (0.072) (0.166) (0.044)

NEI VFQ-25: National Eye Institute Visual Functioning Questionnaire-25, GH: General Health, GV: General vision, OP: Ocular pain, NA: Near activities, DA: Distance activities, VSSF: Vision Specific Social Functioning, VSMH: Vision Specific Mental Health, VSRD: Vision Specific Role Difficulties, VSD: Vision Specific Dependency, D: Driving, CV: Color Vision, PV: Peripheral Vision, OCS: Overall Composite Score. BCVA: best corrected visual acuity, CCI: Color vision Confusion Index.a Height of the retinal detachment in prone position. b Duration of macular detachment.

VandePut.indd 109 4-11-2014 14:15:54

110 | Chapter 6

DISCUSSION

In our study on patients with macula-off RRD, NEI VFQ-25 OCS and subscale scores were

relatively high with a mean OCS of 88.5. The best possible score on each question was 100 and

the second best 75 or 80. This means that most patients scored between the best and second best

score. Although the scores were somewhat lower than those in a normal working population and

in a population with posterior vitreous detachment (PVD),[32,37] they were higher when compared

to other studies addressing NEI VFQ-25 scores in RRD patients (Table 5).[19-20] However, it is

difficult to directly compare the results of our study to the results of others, because of differences

in study design.

For example, Okamoto et al.[19-20] who included macula-on and off patients observed lower NEI

VFQ-25 scores than we did.[19-20] Possible explanations for this are that they had a shorter follow-

up time of 6 months, that cataract may have developed in patients operated on by TPPV, and that

different methods were used to perform visual function tests. Remarkably, in Okamoto’s study,

patients were younger and the subgroup of macula-off RRD patients was smaller, whereas that

study excluded patients with PVR and re-detachment.[19-20] Since these factors are associated with a

better postoperative VA, and VA in their study was higher than in ours, one would have expected

the NEI VFQ-25 OCS and subscores to be higher in their study.[19-20]

We observed correlations between NEI VFQ-25 OCS, and subscale scores and postoperative

BCVA, contrast acuity and post-operative CCI. All tested postoperative visual function parameters

were highly correlated with each other. This suggests that BCVA, contrast acuity, and color vision

represent interdependent aspects of macular function. However, our observations suggest that – of

all tested variables – postoperative BCVA and contrast acuity in the RRD-eye are the most

important determinants of postoperative VR-QOL.

In contrast to postoperative visual functioning, other patient and surgery related aspects showed

very few correlations with NEI VFQ-25 outcomes. Correlations observed related to more extensive

surgery, long-term intraocular tamponades and re-detachment. We identified that preoperatively

pseudophakic patients (RRD eye or fellow eye) had higher scores on the vision specific mental

health subscale than phakic patients. The mental health subscale consists of questions about

troubling thoughts about the future and the eyesight. Perhaps, patients with a history of cataract

extraction do not have to worry about undergoing a cataract extraction anymore.

Visual acuity

We observed a significant correlation between post-operative BCVA and NEI VFQ-25 OCS and

the subscale scores general vision, ocular pain, near activities, distance activities, mental health,

role difficulties and driving. In contrast, Okamoto et al. did not find such a relationship.[20] This

might have been due to differences in study design, since they included relatively younger patients

VandePut.indd 110 4-11-2014 14:15:54

6


with macula-on and macula-off RRD. This difference is underlined by the higher postoperative

VA in the study by Okamoto et al.[20]

Generally, VA is considered as a major determinant of VR-QOL. This has been suggested in

studies on macular hole, epiretinal membrane and diabetic retinopathy.[34-35,38] Ophthalmologists

consider post-operative expectations of VA when developing treatment strategies. However, VA

may not always predict other aspects of visual function and NEI VFQ-25 scores are not always

primarily correlated with VA, as was shown in previous studies on RRD.[20]

Contrast acuity

In line with the study by Okamoto et al., we observed a significant correlation between contrast

acuity and NEI VFQ-25 OCS.[20] In that study, the correlation between contrast acuity and the OCS

differed between measurements with different types of charts, thus underlining the importance

of the test method.[20] In a general population, reduced contrast sensitivity was associated with

self-reported vision related disabilities, and it was associated with difficulties in performing tasks

requiring distance judgments, such as night driving, and mobility.[39] This supports the correlation

found in our study between diminished contrast acuity and a lower score on the NEI VFQ-25

subscores general vision, near activities, distance activities, vision related social functioning, vision

related role difficulties, and driving.

Color vision

Although we observed significant correlations between reduced CCI and VR-QOL parameters,

we did not find any papers on a possible relation between both aspects. The observed correlations

were small, and we therefore assume that unilateral, mild color vision defects have less impact on

patients’ well-being and visual functioning than unilateral defects in VA and contrast acuity. Also,

it could be that the fellow eye compensates better for the defect in color vision in the affected eye

than it does for the other two aspects of visual functioning.

Previously, we observed that both the duration and the height of macular detachment have a

profound effect on the postoperative recovery of visual function, particularly BCVA and CCI[17]

In the present study, we observed that BCVA is highly correlated to VR-QOL. Even though we

failed to demonstrate a direct correlation between the height of the macular detachment and

NEI VFQ-25 scores, it might be clinically relevant to evaluate whether posturing of macula-

off RRD patients would have a positive effect on postoperative BCVA and VR-QOL. The goal

thereof would be to prevent a progression of a shallow detachment to a bullous one or to diminish

submacular fluid in an already bullous one.

Limitations

Our study highlights important aspects of the postoperative VR-QOL in macula-off RRD

patients. Some limitations include a possible selection bias towards highly motivated patients,

VandePut.indd 111 4-11-2014 14:15:54

112 | Chapter 6

because they would have been more likely to have participated in this study. In addition, the

studied population is modest. Our sample size is considered adequate for overall analyses,[40] but it

may be too limited for all subgroup analyses, resulting in an underreporting of possibly relevant

associations. In addition, our analyses were performed on the postoperative visual function (BCVA,

contrast acuity, saturated and desaturated CCI) in the RRD eye. The overall good visual function

in the contralateral eye may have compensated for the defects in the RRD eye to a variable extent

with regard to the different aspects of visual function. This may have mitigated the observed

relations with VFQ outcomes to a variable extent.

CONCLUSION

At 12 months postoperatively, BCVA, contrast acuity, and CCI’s in macula-off RRD eyes were still

significantly worse for the operated eyes compared to their fellow control eyes. A lower VR-QOL

(OCS and subscores) had the highest correlation with a worse postoperative BCVA and contrast

acuity (in the RRD-eye). Although less pronounced, postoperative color vision disturbances

(saturated and desaturated CCI) were significantly correlated with the NEI VFQ-25 OCS.

VandePut.indd 112 4-11-2014 14:15:54

6


REFERENCES

1. D’Amico DJ. (2008) Primary retinal detachment. N Engl J Med. 359: 2346-2354.

2. Van de Put MAJ, Hooymans JMM, Los LI; The Dutch Rhegmatogenous Retinal Detachment

Study Group. (2013) The incidence of rhegmatogenous retinal detachment in the Netherlands.

Ophthalmology. 120: 616–622.

3. Sharma T, Challa JK, Ravishankar KV, Murugesan R. (1994) Scleral buckling for retinal detachment:

predictors for anatomic failure. Retina. 14: 338-343.

4. Tani PT, Robertson DM, Langworthy A. Prognosis for central vision and anatomic reattachment in

rhegmatogenous retinal detachment with macula detached. (1981) Am J Ophthalmol. 92: 611-620.


rhegmatogenous retinal detachments in phakic and pseudophakic patients: the Retina 1 Project –

report 2. Br J Ophthalmol. 92: 378-382.

6. Grizzard WS, Hilton GF, Hammer ME, Taren D. (1994) A multivariate analysis of anatomic success

of retinal detachments treated with scleral buckling. Graefes Arch Clin Exp Ophthalmol. 232: 1-7.


Ophthalmol Soc. 80: 475-497.

8. Mitry D, Awan MA, Borooah S, et al. (2012) Long term visual acuity and the duration of macular

detachment: findings from a prospective population based study. Br J Ophthalmol. 00: 1-4.

9. Diederen RMH, La Heij AC, Kessels AGH, et al. (2007) Scleral buckling surgery after macula-off

retinal detachment; worse visual outcome after more than 6 days. Ophthalmology. 114: 705-709.

10. Hassan TS, Sarrafizadeh R, Ruby AJ, et al. (2002) The effect of duration of macular detachment on

results after the scleral buckle repair of primary, macula-off retinal detachments Ophthalmology. 109:

146-152.

11. Özgür S, Esgin H. (2007) Macular function of successfully repaired macula-off retinal detachments

Retina. 27: 359-364.


Ophthalmology. 105; 2149-2153.

13. Anderson C, Sjöstrand J. (1981) Contrast sensitivity and central vision in reattached macula. Acta


14. Kreissig I, Lincoff B, Witassek B, et al. (1981) Color vision and other parameters of macular function

after reattachment. Dev Ophthalmol. 12: 77-85.

15. Ross WH, Lavina A, Russel M, Maberley D. (2005) The correlation between height of macular

detachment and visual outcome in macula-off retinal detachments of ≤ 7days’ duration. Ophthalmology.

112: 1213-1217.

16. Mowatt L, Tarin S, Nair RG, et al. (2010) Correlation of visual recovery with macular height in

macula-off retinal detachments. Eye. 24: 323-327.

VandePut.indd 113 4-11-2014 14:15:54

114 | Chapter 6

17. Van de Put MAJ, Croonen D, Nolte IM, et al. (2014) Postoperative recovery of visual function after

macula-off rhegmatogeneous retinal detachment. PlosOne. 9:6:e99787.

18. Zou H, Zhang X, Xu X, et al. (2011) Vision-related quality of life and self-related satisfaction outcomes

of rhegmatogenous retinal detachment surgery: three-year prospective study. Plos One 6: e28597.


vitrectomy for various vitreoretinal disorders. Invest Ophthalmol Vis Sci. 51: 744-751.

20. Okamoto F, Okomota Y, Hiraoka T, Oshika T. (2008) Vision-related quality of life and visual function

after retinal detachment surgery. Am J Ophthalmol. 146: 85-90.

21. Van der Sterre GW, van de Graaf ES, Verezen CA, et al. (2013) National Eye Institute visual

functioning questionnaire – 25; Dutch Consensus Translation (VFQ-25/NL) http://www.erasmusmc.

nl/mage/publicaties/aanvullingen/3503529?lang. Accessed December 24, 2013.

22. Maguire M. (2004) Complications of age-related macular degeneration prevention trial research

group. Baseline characteristics, the 25-item National eye institute visual functioning questionnaire,

and their associations in the complications of age-related macular degeneration prevention trial

(CAPT). Ophthalmology. 111: 1307-1316.

23. Mangione CM, Berry S, Spritzer K, et al. (1998) Identifying the content area for the 51-item National

Eye Institute visual function questionnaire. Arch Ophthalmol. 116: 227-233.

24. Mangione CM, Lee PP, Pitts J, et al. (1998) Psychometric properties of the National Eye Institute

visual function questionnaire (NEI-VFQ). NEI-VFQ field test investigators. Arch Ophthalmol. 116:

1496-1504.

25. Mangione CM, Lee PP, Guiterrez PR, et al. (2001) Development of the 25-item National Eye Institute

visual function questionnaire. Arch Ophthalmol. 119: 1050-1058.

26. Hilton G, Machemer R, Michels R, et al. The retina society terminology committee. (1983) The

classification of retinal detachment with proliferative vitreoretinopathy. Ophthalmology 90: 121-125.

27. Rosser DA, Cousens SN, Murdoch IE, et al. (2003) How sensitive to clinical change are ETDRS

logMAR visual acuity measurements? Invest Ophthalmol Vis Sci. 44: 3278-3281.

28. Van de Put MAJ, Nayebi F, Croonen D, et al. (2013) Design and validation of a method to determine

the position of the fovea by using the nerve-head to fovea distance of the fellow eye. PlosOne 8: e62518.

29. Mantyjarvi M, Laitinen T. (2001) Normal values for the Pelli-Robson contrast sensitivity test.

J Cataract Refract Surg. 27: 261-266.

30. Bowman KJ. (1982) A method for quantitative scoring of the Farnsworth panel D-15. Acta Ophthalmol.

60: 907.

31. Chylack LT Jr., Wolfe JK, Singer DM, et al. (1993) The Lens Opacities Classification System III. The

Longitudinal Study of Cataract Study Group. Arch Ophthalmol. 111: 831-836.

32. Schweitzer KD, Eneh AA, Hurst J, Bona MD, Rahim KJ, Sharma S. (2011) Visual function analysis

in acute posterior vitreous detachment. Can J Ophthalmol. 46: 232-236.

33. Hirneiß C, Neubauer AS, Gass CA, et al. (2007) Visual quality of life after macular hole surgery:

outcome and predictive factors. Br J Ophthalmol. 91: 481-484.

VandePut.indd 114 4-11-2014 14:15:54

6


34. Tranos PG, Ghazi-Nouri SM, Rubin GS, et al. (2004) Visual function and subjective perception of

visual ability after macular hole surgery. Am J Ophthalmol. 138: 995-1002.

35. Ghazi-Nouri SM, Tranos OG, Rubin GS, et al. (2006) Visual function and quality of life following

vitrectomy and epiretinal membrance peel surgery. Br J Ophthalmol. 90: 559-562.

36. Matsuoka Y, Tanito M, Takai Y, et al. (2012) Visual function and vision-related quality of life after

vitrectomy for epiretinal membranes: a 12 month follow-up study. Invest Opthalmol Vis Sci. 53:

3054-3058.

37. Hirneiss C, Schmid-Tannwald C, Kernt M, et al. (2010) The NEI VFQ-25 vision-related quality of

life and prevalence of eye disease in a working population. Graefes Arch Clin Exp Ophthalmol. 248:

85-92.

38. Klein R, Moss SE, Klein BE, et al. (2001) The NEI=VFQ-25 in people with long-term type 1 diabetes

mellitus: the Wisconsin Epidemiologic Study of Diabetic Retinopathy. Arch Ophthalmol. 119: 733-

740.

39. Rubin GS, Roche KB, Prasada-Rao P, Fried LP. (1994) Visual impairment and disability in older

adults. Optom Vis Sci. 71: 750-760.

40. Mangione CM. (2013) NEI-VFQ Scoring Algorithm – August 2000. Version 2000. http://www.nei.

nih.gov/resources/visionfunction/manual_cm2000.pdf. Accessed December 24, 2013.

VandePut.indd 115 4-11-2014 14:15:54

VandePut.indd 116 4-11-2014 14:15:54

Chapter 7

Postoperative metamorphopsia in macula-off

rhegmatogenous retinal detachment: associations

with visual function, vision related quality of life,

and optical coherence tomography findings

Submitted

Mathijs A.J. van de Put¹,2, Jelle Vehof1,3, Johanna. M.M. Hooymans¹,2, Leonoor. I. Los¹,2


2 W.J. Kolff Institute, Graduate School of Medical Sciences, University of Groningen, Groningen, the Netherlands.3 Department of Twin Research & Genetic Epidemiology, King’s College

London, St. Thomas’ Hospital, London, United Kingdom.

VandePut.indd 117 4-11-2014 14:15:54

118 | Chapter 7

ABSTRACT

Purpose: To evaluate postoperative metamorphopsia in macula-off rhegmatogenous retinal

detachment (RRD) and its association with visual function, vision related quality of life, and

optical coherence tomography (OCT) findings.

Methods: 45 patients with primary macula-off RRD were included. At 12 months postoperatively,

data on metamorphopsia using sine amsler charts (SAC), best corrected visual acuity (BCVA),

letter contrast sensitivity, color vision (saturated and desaturated color confusion indexes), critical

print size, reading acuity, the 25-item National Eye Institute Visual Functioning Questionnaire

(NEI-VFQ-25), and OCT, were obtained.

Results: Metamorphopsia was present in 39 patients (88.6%), with most of them (n=35, 77.8%)

showing only mild metamorphopsia (SAC score =1). Patients with metamorphopsia had significantly

worse postoperative BCVA (p=0.02), critical print size (p<0.0005), and reading acuity (p=0.001)

compared to patients without metamorphopsia. Other visual function outcomes and NEI-VFQ-25

overall composite score were all also somewhat lower in patients with metamorphopsia, but this

did not reach statistical significance. No association with OCT findings was present.

Conclusion: The prevalence of postoperative metamorphopsia in macula-off RRD patients is high,

however, the degree of metamorphopsia is relatively low. When metamorphopsia is present, visual

functions seem to be compromised, while vision related quality of life is only mildly affected.

VandePut.indd 118 4-11-2014 14:15:54

7

Postoperative metamorphopsia 119

INTRODUCTION

The incidence of rhegmatogenous retinal detachment (RRD) is 18.2 cases per 100,000 person-

years. Approximately half of the cases present themselves with macula-off RRD.[1] In addition,

postoperative recovery of visual acuity, contrast sensitivity, and color vision may be unsatisfactory,

even after successful surgery.[2] In macula-off RRD, postoperative metamorphopsia is a highly

prevalent problem that occurs in around two thirds of patients.[3-4]

The pathogenesis of postoperative metamorphopsia remains controversial. Most likely, it is caused

by disturbances in normal retinal anatomy due to poor orientation of photoreceptors after surgery.

Studies on both postoperative metamorphopsia and optical coherence tomography (OCT) have

revealed associations between metamorphopsia and the presence of an epiretinal membrane

(ERM)[3] and/or subretinal fluid.[3-4] However, OCT findings in patients with postoperative

metamorphopsia are often normal.[3-4] In these cases, it has been suggested that metamorphopsia

may occur due to microstructural photoreceptor disruption that may be undetected by spectral

domain OCT examination.[5]

Although many patients present themselves with postoperative metamorphopsia after macula-off

RRD, it remains unknown whether this is associated with the outcomes of other postoperative

visual function tests, and vision related quality of life. For instance, previous studies showed that

lower visual function (best corrected visual acuity (BCVA), letter contrast sensitivity, and color

vision disturbances) after surgery for macula-off RRD is associated with lower vision related

quality of life scores.[6-8] The main goals of this study are to determine whether postoperative

metamorphopsia in macula-off RRD patients is associated with postoperative visual function (best

corrected visual acuity (BCVA), letter contrast sensitivity, color vision disturbances, critical print

size, and reading acuity) and with vision related quality of life. In addition, we evaluated whether

metamorphopsia is associated with OCT findings.

METHODS

Study design

We conducted a prospective observational study. The research protocol was approved by the

University Medical Center Groningen (UMCG) review board ethics committee, and was carried

out in accordance with the tenets of the declaration of Helsinki. All patients had given their

written informed consent. The study was registered with the Dutch Trial Register (NTR839). All

patients were operated on at the ophthalmology department of the UMCG. The study was carried

out over a three-year period (February 1, 2007 - February 1, 2010).

VandePut.indd 119 4-11-2014 14:15:54

120 | Chapter 7

Study population

Patients of 18 years or older, with a first presentation of a unilateral macula-off RRD of 24 hours

to 6 weeks duration, who underwent successful reattachment surgery within 24-72 hours after

presentation at our hospital, were invited to participate in this study. Patients with a macular

detachment of < 24 hours were excluded, because in our current treatment strategy these are

scheduled as emergency surgeries and inclusion in the study would lead to treatment delay.

Patients with macular detachment of more than 6 weeks duration were excluded, because they

are considered rare and yield a worse prognosis.[9] Excluded were patients with bilateral RRD, a

history of congenital or acquired pathology with an effect on visual function in one or both eyes, or

pathology observed at presentation after their macula-off RRD (i.e. pathology of the cornea, lens,

vitreous body, retina (including macula and optic nerve, and scleritis). However, patients with a

congenital defect in color vision were not excluded. In addition, patients who had a re-detachment

during the follow-up period were excluded from the analysis.

Preoperative measurements

We acquired the following patients’ characteristics: age, gender, affected eye, and ophthalmic

history. The surgical technique, i.e. scleral buckling or trans pars plana vitrectomy surgery (TPPV),

was documented. Using standardised protocols, the refractive error and BCVA using the Early

Treatment of Diabetic Retinopathy Study (ETDRS) chart were determined for both the affected

eye and the fellow control eye. All BCVA measurements were converted to logMAR equivalents of

ETDRS acuity for analysis. Light perception or hand movements were coded as logMAR VA of 3.0.

Postoperative measurements

Metamorphopsia

At 12 months postoperatively, all patients were tested for perceived metamorphopsia by showing

them a standard Amsler chart, first at the non-operated eye and then at the operated eye. In case

of perceived metamorphopsia, the modified sine Amsler charts (Amsler SAC) were used, to assess

the degree of metamorphopsia semiquantitatively.[10] The modified sine Amsler charts we used

consist of six different modified Amsler charts. In the center of each chart, the straight lines of the

regular Amsler chart have been replaced by sinusoid lines with a constant frequency but increasing

amplitudes, resulting in representations of different grades of metamorphopsia. The lines of the

different SAC are described by:

f x b x( ) sin= ⋅

, where the amplitude b increases with 0.25 for every consecutive chart. Scores on the sine Amsler

charts ranged from 0 (no metamorphopsia) to 6 (severe metamorphopsia).[10]

VandePut.indd 120 4-11-2014 14:15:55

7


Visual function

At twelve months postoperatively, we measured BCVA using the ETDRS chart, letter contrast

sensitivity using the Pelli Robson chart[11], Farnsworth D-15 saturated, and Lanthoni desaturated

color confusion indexes (CCI)[12], critical print size and reading acuity using the Laboratory of

Experimental Ophthalmology (LEO) reading chart. Critical print size is defined as the smallest

text a patient can read. Reading acuity is the smallest text size a patient can read correctly at his

maximum reading speed. All measurements were performed in the affected and fellow control eye.

Cataract

At 1, 3, 6, and 12 months postoperatively, a full ophthalmic examination was done, including an

assessment of BCVA, and an examination of the fundus. Because of an increased risk of cataract

development after trans pars plana vitrectomy, which may influence postoperative measurements,

we scored the level of cataract using the lens opacities classification system III (LOCS III) in both

eyes at all visits.[13] In case of a visually significant cataract, a cataract extraction was performed

before the 12 month measurement. In addition, LOCS gradings were performed in all phakic

patients at the final visit.

Vision related quality of life

At twelve months postoperatively, patients were requested to self-administer the validated Dutch

version of the National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) to assess

their Vision Related Quality of Life (VR-QOL).[14] This questionnaire has been developed by

the research and development corporation (RAND), and by the National Eye Institute (NEI).

The NEI-VFQ-25 comprises 25 items that require the patient to assess the influence of visual

disability and visual symptoms on generic health domains such as emotional well-being and social

functioning, in addition to task-oriented domains related to daily visual functioning.[15-16] Each

item is assigned to one of the following twelve subscales: general health, general vision, ocular pain,

near activities, distance activities, vision specific social functioning, vision specific mental health,

vision specific role difficulties, vision specific dependency, driving, color vision, and peripheral

vision. Each subscale consists of a minimum of one and a maximum of four items. We used the

standard algorithm to calculate the scale scores. The subscales range from 0 to 100 points, where

100 indicates the highest possible function. The NEI-VFQ-25 overall composite score (OCS) is

calculated as the unweighted average response to all items, excluding the question on general

health.

Optical coherence tomography

At 12 months postoperatively, OCT measurements were performed using the STRATUS 3000

OCT™ (Carl Zeiss Ophthalmic Systems, Dublin, CA) by a single trained observer (ophthalmic

technician) who was only active in collecting, and grading the data independent of the outcomes

VandePut.indd 121 4-11-2014 14:15:55

122 | Chapter 7

of the other measurements. The cross hair scan acquisition protocol was used for qualitative

examination of the macular region. The presence (yes or no) of intraretinal cystic spaces, subretinal

fluid, vitreomacular traction (VMT), and epiretinal membrane (ERM) were assessed. The fast

macular scan acquisition protocol was used for quantitative examination of central retinal thickness

at the foveal dip, defined as the distance between the internal limiting membrane and the outer

surface of the photoreceptor layer. Using the analysis program, a caliper measurement was carried

out by placing one caliper on top of the retina, at the location of the foveal dip, and the other

caliper on the second high reflective line (retinal pigment epithelium). The acquired value was used

to quantify central retinal thickness in three classes based on normative data; atrophic (thickness

< 135 µm.), within normal limits (thickness ≥ 135 µm. and ≤ 205 µm.), or hypertrophic (thickness

> 205 µm.).[17]

Statistical Analysis

Data were analyzed using SPSS software package, version 22.0 (Chicago, Illinois, USA). All

outcome variables were first tested for normality and transformation to a normal distribution

and/or exclusion of outliers was considered. In case of a normal distribution a t-test was used to

compare the difference of the vision-related outcome measures and postoperative vision related

quality of life in patients with and patients without metamorphopsia. In case of a non-normal data

distribution, a Mann-Whitney U-test was used to compare this difference. We performed the same

analyses in the subgroup of patients without OCT disturbances only. We used a Fisher’s exact test

to determine if postoperative OCT disturbances were significantly more frequent in patients with

versus patients without postoperative metamorphopsia. The significance level of this study was set

at a 0.05, two-sided.

RESULTS

A total of 56 patients gave their written informed consent and were included in the study. Ten

patients had one or more re-detachments and one patient deceased during the study period, and

these were subsequently excluded. In total, data of 45 patients were analyzed in this study. Table 1

summarizes patient and ocular characteristics and type of surgery.

VandePut.indd 122 4-11-2014 14:15:55

7


Table 1: Data on patients, operated eyes and surgical procedure

Characteristics Mean ± SD / Median (ranges) / n (%)Number of patients (eyes) 45 (45)Age (y) 61 ± 10.6Sex (male/female) 34 (76%) / 11 (24%)Right eye/left eyePreoperative lens status (Phakic / pseudophakic)

22 (48.9%) / 23 (51.1%)29 (64%) / 16 (36%)

Postoperative lens status (Phakic / pseudophakic) 8 (18%) / 37 (82%)Surgical procedures (scleral buckling/TPPV) 6 (13%) / 39 (87%)Preoperative BCVA (LogMAR) 3.00 (0.06 - 3)Postoperative foveal thickness at 12 months 177 (68 - 562)Postoperative metamorphopsia score (SAC) at 12 months 1 (1 - 6)SD: Standard deviation, TPPV: Trans pars plana vitrectomy. BCVA: Best corrected visual acuity. SAC: Sine Amsler chart.

A TPPV (n=39, 86.7%), with (n=22) or without (n=17) an encircling band was most frequently

chosen as the primary surgical procedure, and in the remaining 6 cases (13.3%) a scleral buckling

procedure was used. During the 12 months follow-up period, cataract surgery was performed

in 21 of 29 pre-operatively phakic eyes, and the LOCS scores in the remaining 8 phakic eyes

did not significantly influence visual function variables (data not shown). During this period,

no other visual co-morbidities were diagnosed. Twelve months postoperatively, metamorphopsia

was present in 39 operated eyes (88.6%), with most of those (n=35, 77.8%) showing only mild

metamorphopsia (Amsler SAC score =1). None of the fellow eyes had metamorphopsia.

Critical print size and desaturated CCI turned out to have a normal distribution and were tested

using a t-test. All other outcome variables (logMAR visual acuity, log letter contrast sensitivity,

color vision (saturated and desaturated CCI), critical print size, reading acuity, and NEI-VFQ-25

OCS and subscales) could not be transformed to a normal distribution and were tested using a

Mann-Whitney U-test. The mean scores of patients with and without metamorphopsia on visual

outcomes and quality of life overall composite score 12 months postoperatively are provided in

Table 2.

All visual outcome variables were worse in patients with metamorphopsia compared to patients

without metamorphopsia (see Figure 1). BCVA, critical print size, and reading acuity reached

statistical significance. As an example, the presence of metamorphopsia was significantly associated

with best corrected visual acuity (p=0.02), leading to a decrease of 0.26 point logMAR in patients

with metamorphopsia. There was a trend that vision related quality of life was also lower in

patients with metamorphopsia (p=0.07). Of the NEI-VFQ-25, all 12 subscales except general health

showed lower quality of life in the metamorphopsia group (data not shown), but only the subscale

near activities reached statistical significance (p=0.04). In the analysis in the subpopulation of

patients without OCT disturbances only (right part of Table 2), we observed a similar effect of

VandePut.indd 123 4-11-2014 14:15:55

124 | Chapter 7

postoperative metamorphopsia on postoperative visual function and vision related quality of life.

Again, BCVA, critical print size, and reading acuity reached statistical significance.

Postoperative OCT disturbances and postoperative metamorphopsia were both present in

21 patients. In two patients postoperative OCT disturbances were present and metamorphopsia

was absent. Postoperative OCT disturbances and postoperative metamorphopsia were both absent

in 4 patients. In 18 patients OCT disturbances were absent and metamorphopsia was present.

We observed no association between postoperative metamorphopsia and the presence of any

postoperative OCT disturbances (p = 0.414). Observed OCT disturbances included: atrophic

retina (n=6, 13.3%), hypertrophic retina (n=14, 31.1%), intraretinal cysts (n=4, 8.9%), subretinal

fluid (n=3, 6.7%), and epiretinal membrane (n=10, 22.2%).

Table 2: Postoperative (12 months) visual function and vision related quality of life in macula-off RRD

patients with and without metamorphopsia

Visual function

Total group (n=45) Patients without OCT abnormalities only (n=22)

Metamorphopsia (n=40)Mean (s.e.)

No metamorphopsia(n=5)Mean (s.e.)

P-value for adifference in groups*

Metamorphopsia(n=19)Mean (s.e.)

No metamorphopsia(n=3)Mean (s.e.)

P-value for adifference in groups*

BCVA (logMAR) 0.33 (0.05) 0.07 (0.04) 0.02 0.29 (0.05) 0.02 (0.03) 0.009Letter contrast sensitivity (Log)

1.36 (0.05) 1.54 (0.04) 0.28 1.47 (0.06) 1.53 (0.07) 0.93

Saturated CCI 1.43 (0.08) 1.03 (0.03) 0.07 1.40 (0.12) 1.04 (0.04) 0.41Desaturated CCI 1.86 (0.10) 1.61 (0.20) 0.37 1.93 (0.14) 1.76 (0.28) 0.64Critical print size

0.53 (0.04) 1.02 (0.15) <0.0005 0.58 (0.06) 1.09 (0.26) 0.009

Reading acuity 0.33 (0.03) 0.67 (0.09) 0.001 0.34 (0.04) 0.77 (0.11) 0.003Vision related quality of lifeOverall composite score NEI-VFQ-25

89.5 (1.1) 94.1 (2.3) 0.07 89.8 (1.6) 95.4 (1.6) 0.11

* Desaturated CCI and Critical print size were tested using a t-test, all other variable were tested using a Mann-Whitney U-test. Significant associations are in bold. s.e.: standard error of the mean, BCVA: Best corrected visual acuity CCI: Color confusion index, NEI-VFQ-25: National Eye Institute Visual Functioning Questionnaire-25.

VandePut.indd 124 4-11-2014 14:15:55

7


Figure 1: Mean values (± 2 standard errors) of patients with and those without metamorphopsia of a. best

corrected visual acuity (logMAR), b. letter contrast sensitivity (Log), c. saturated color confusion index

(CCI), d. desaturated color confusion index (CCI)

VandePut.indd 125 4-11-2014 14:15:55

126 | Chapter 7

e. critical print size, f. reading acuity, and g. overall composite score National Eye Institute Visual Functioning

Questionnaire-25. Differences between groups were tested using an independent t-test (desaturated CCI and

critical print size) or using a Mann-Whitney U-test (best corrected visual acuity (logMAR), letter contrast

sensitivity (Log), saturated CCI, reading acuity, and overall composite score National Eye Institute Visual

Functioning Questionnaire-25) and corresponding p-values are given below the figure.

DISCUSSION

Although the prevalence of postoperative metamorphopsia in this study was high compared

to other studies[3-4], the encountered degree of metamorphopsia was small. All visual outcome

variables were worse in eyes with metamorphopsia. BCVA, letter contrast sensitivity, critical

print size, and reading acuity were significantly worse in operated eyes with metamorphopsia

compared to eyes without metamorphopsia. We did not observe a significant difference in vision

related quality of life in patients with and patients without metamorphopsia, nor did we observe a

significant relation between metamorphopsia and OCT disturbances.

VandePut.indd 126 4-11-2014 14:15:55

7


Differences in study design, (in- and exclusion criteria, follow-up, and method to determine

metamorphopsia) and patient selection (age, and surgical technique) may be responsible for

differences in reported prevalences of postoperative metamorphopsia between our and other

studies.[3-4] Important factors such as duration and height of the macular detachment, refractive

error, and age probably differed between studies.[3-4] For example, the recovery of metamorphopsia

follows a slower time course than the recovery of VA.[18] Therefore, one would expect the prevalence

of postoperative metamorphopsia to be higher in studies with shorter follow-up periods. However,

in our study with a longer follow-up, we observed a higher prevalence of metamorphopsia than

others.[3-4] This may be explained by the fact that other studies included younger patients.[3-4]

A younger age at the time of macula-off RRD is a beneficial prognostic factor for the recovery

of visual function.[2] Similarly, it may also be a beneficial prognostic factor for the recovery of

metamorphopsia. Further, in other studies, TPPV was less often chosen as a surgical technique. [3-4]

Perhaps, performing TPPV leads to more disorganization at the level of the photoreceptors, (i.e.

unintentional vertical displacement of the retina as was demonstrated by Shiragami et al.) and

hence to an increased prevalence of metamorphopsia.[19] Finally, others used a different method to

assess metamorphopsia.[3-4] Okamoto used M-CHARTS, and Wang used the regular Amsler grid

to assess metamorphopsia.[3-4]

The presence of postoperative metamorphopsia was associated with lower scores on all visual

outcome variables and NEI-VFQ-25 OCS. A previous study,[20] observed an improvement in

reading ability in patients after TPPV for macular hole and macular pucker (macular pathologies

often presenting with metamorphopsia), which seems to be in line with our study. Reading acuity

testing will probably be more severely affected by small amounts of metamorphopsia than visual

acuity testing. The former task – recognizing words at maximum reading speed – carries a higher

rate of difficulty than the latter, in which optotypes can be read separately and reading speed is

not an issue. Fortunately for patients, the presence of mild unilateral metamorphopsia after surgery

for macula-off RRD does not seem to affect vision related quality of life. In a previous study

we observed that other factors (postoperative BCVA, letter contrast sensitivity, and color vision

disturbances) are more important in vision related quality of life after macula-off RRD.[6]

One could argue that both visual function loss and metamorphopsia are caused by changes in

the organization of the macular area. However, in the analyses in the subpopulation of patients

without OCT disturbances, we observed a similar association between the presence of postoperative

metamorphopsia and lower scores on all visual outcome variabes and NEI-VFQ-25 OCS. This

suggests that in the absence of OCT disturbances the presence of metamorphopsia also directly

affects postoperative visual function and NEI-VFQ-25 OCS. However, we cannot exclude the

possibility that microstructural changes that are not visible on the OCT we used led to the

associations we found.

We, and others observed that OCT disturbances may be absent in patients with postoperative

metamorphopsia.[3-4] This may partially be caused by differences in used OCT. It is likely that

VandePut.indd 127 4-11-2014 14:15:55

128 | Chapter 7

studies using earlier OCT models report less OCT disturbances than studies using later models,

since the latter give a higher resolution. For example, Okamoto used the Cirrus high definition

spectral-domain OCT, and observed a higher number of OCT disturbances when compared to our

study.[3] A shorter follow-up period is more likely to result in more OCT disturbances as subretinal

fluid and retinal cysts tend to disappear in a time span of 6 to 12 months.[4,21] The shorter follow-

up period in the study of Wang (who used the lower resolution OCT 2 scanner) may explain

their higher number of observed OCT disturbances, when compared to our study.[4] In addition, a

longer follow-up period may be related to the inability to observe microstructural changes in the

organization of the macular area.

The strengths of our study are the long follow-up period, the standardized measuring methods of

metamorphopsia, visual function, vision related quality of life, and the qualitative assessment of

OCT. A limitation of our study is the relatively small sample size and the lack of variation in the

amount of metamorphopsia that together may lack sufficient power to observe the full relations

between variables and outcome measures. The lack of variation in the amount of metamorphopsia

may be related to the limited sensitivity of our testing method for metamorphopsia. This may

be the reason that the postoperative metamorphopsia score was only around 1. A more sensitive

testing method may have resulted in more variation in perceived metamorphopsia.

CONCLUSION

In conclusion, the prevalence of postoperative metamorphopsia in macula-off RRD patients is

high, however, the degree of metamorphopsia is relatively low. When metamorphopsia is present,

visual functions seem to be compromised, while quality of life is only mildly affected.

VandePut.indd 128 4-11-2014 14:15:55

7


REFERENCES

1. Van de Put MAJ, Hooymans JMM, Los LI (2013) The incidence of rhegmatogenous retinal detachment

in the Netherlands. Ophthalmology 120: 616-622.

2. van de Put MAJ, Croonen D, Nolte IM, Hooymans JMM, Los LI (2014) Recovery of visual function

in macula-off rhegmatogenous retinal detachment. PlosOne,9: E99787

3. Okamoto F, Sugiura Y, Okamoto Y, Hiraoka T, Oshika T (2013) Metamorphopsia and optical

coherence findings after rhegmatogenous retinal detachment surgery. Am J Ophtalmol 157: 214-220.

4. Wang Y, Li SY, Zhu M, et al. (2005) Metamorphopsia after successful retinal detachment surgery: an

optical coherence tomography study. Acta Ophthalmol Scand 83: 168-171.

5. Rossetti A, Doro D, Manfré A, Midena E (2010) Long-term follow-up with optical coherence

tomography and microperimetry in eyes with metamorphopsia after macula-off retinal detachment

repair. Eye 44: 4012-4016.

6. Van de Put MAJ, Wanders W, Nolte I, Hooymans JMM, Los LI (2013) Postoperative quality of

life in macula-off rhegmatogenous retinal detachment and its relation to visual function. European

Association for Vision and Eye Research Conference 2013, Nice, France. Acta Ophthalmologica 91:0.

doi:10.1111/j.1755-3768.2013.2411.x.

7. Okamoto F, Okomota Y, Hiraoka T, Oshika T (2008) Vision-related quality of life and visual function

after retinal detachment surgery. Am J Ophthalmol 146: 85-90.


vitrectomy for various vitreoretinal disorders. Invest Ophthalmol Vis Sci 51: 744-751.

9. Burton TC (1982) Recovery of visual acuity after retinal detachment involving the macula. Trans Am


10. Bouwens MD, Meurs JC (2003) Sine Amsler Charts: a new method for the follow-up of metamorphopsia

in patients undergoing macular pucker surgery. Graefes Arch Clin Exp Ophthalmol 241: 89-93.

11. Pelli DG, Robson JG, Wilkins AJ (1988) The design of a new letter chart for measuring contrast

sensitivity. Clin Vision Sci 2: 187-199.

12. Bowman KJ (1982) A method for quantitative scoring of the Farnsworth panel D-15. Acta Ophthalmol

60: 907-916.

13. Chylack LT jr., Wolfe JK. Singer DM, Leske MC, Bullimore MA, et al. (1993) The Lens Opacities

Classification System III. The longitudinal Study of Cataract Study Group. Arch Ophthalmol 111:

831-836.

14. Van der Sterre GW, van de Graaf ES, Verezen CA, et al. (2001) National Eye Institute visual functioning

questionnaire – 25 Nederlandse consensus vertaling (VFQ-25/NL) versie 2001, interviewer versie.

Available:http://www.erasmusmc.nl/mage/publicaties/aanvullingen/3503529 Accessed 20 July 2014.

15. Mangione CM, Lee PP, Pitts J, Gutierrez MA, Berry S, Hays RD, for the NEI-VFQ Field Test

Investigators (1998) Psychomotric properties of the National Eye Institute Visual Function

Questionnaire (NEI-VFQ). Arch Ophthalmol 116: 1496-1504.

VandePut.indd 129 4-11-2014 14:15:56

130 | Chapter 7

16. Mangione CM, Lee PP, Guiterrez PR, Spritzer K, Berry S, Hays RD (2001) Development of the 25-

item National Eye Institute visual function questionnaire. Arch Ophthalmol 119: 1050-1058.

17. Chan A, Duker JS, Ko TH, Fujimoto JG, Schuman JS (2006) Normal macular thickness measurements

in healthy eyes using stratus optical coherence tomography. Arch Ophthalmol 124: 193-198.

18. Liem AT, Keunen, JE, van Meel GJ, van Norren D (1994) Serial foveal densitometry and visual

function after retinal detachment surgery with macular involvement. Ophthalmology 101: 1945-1952.

19. Shiragami C, Shiraga F, Yamaij H, Fukuda K, Takagischi M, Morita M, Kishikami T (2010)

Unintentional displacement of the retina after standard vitrectomy for rhegmatogenous retinal

detachment. Ophthalmology 117: 86-92.

20. Cappello E, Virgili G, Tollot L, Del Borrello M, Menchini U, Zemella M (2009) Reading ability and

retinal sensitivity after surgery for macular hole and macular pucker. Retina 29: 1111-1117.

21. Ricker LJ, Noordzij LJ, Goezinne F, Cals DW, Berendschot TT, Liem AT, Hendrikse F, La Heij EC

(2011) Persistent subfoveal fluid and increased preoperative foveal thickness impair visual outcome

after macula-off retinal detachment repair. Retina 31: 1505-1512.

VandePut.indd 130 4-11-2014 14:15:56

Chapter 8

Summary & conclusions

VandePut.indd 131 4-11-2014 14:15:56

132 | Chapter 8

SUMMARY

The first part of this thesis describes the epidemiology (incidence and predisposing factors)

of rhegmatogenous retinal detachment (RRD) in the North of the Netherlands and in the

Netherlands. The second part consists of clinical studies evaluating the recovery of visual function

after RRD surgery in case of a detached macula. It encompasses a study on the position of the fovea

in relation to the optic nerve-head. The outcome hereof was subsequently used in a prospective

clinical study conducted to evaluate postoperative recovery of visual function in macula-off RRD.

This prospective study also evaluated postoperative vision related quality of life and the prevalence

of postoperative metamorphopsia in this group of patients.

PART I. EPIDEMIOLOGY

In chapter 2, we take RRD surgery incidence rates in the North of the Netherlands as a proxy of

RRD incidence, since the latter are not known in our population. We observed a yearly incidence

of RRD surgery of 17.4 per 100,000 people in 2008, and of 18.0 per 100,000 in 2009. In line

with previous observations, a peak RRD incidence was observed in patients of 65 to 69 years of

age. Males were overrepresented in almost all age categories. The highest numbers of phakic RRD

patients were noted at ages 55 to 59 years. The highest numbers of post- cataract extraction (CE)

RRD patients were noted at ages 60-69 years. At more advanced age, the proportion of post-CE

as compared to phakic RRD increased. This suggests that phakic and post-CE RRD are different

entities. Macular detachment at presentation was seen in 57,9% of the patients. This study was

performed as a pilot study, for the study described in chapter 3. Data collected while conducting

the latter study was added to chapter 2.

In chapter 3, we describe RRD surgery incidence rates in the Netherlands. Because of the high

RRD surgery incidence rates in the North of the Netherlands, we were interested whether this

would also apply to the Netherlands. We observed a yearly incidence of RRD surgery of 18.2 per

100,000 people in 2009, which is comparable to that in the North of the Netherlands and which

is the highest RRD surgery incidence rate reported thus far. Macular detachment at presentation

was seen in 54,5% of the patients.

In this study, observations made on RRD surgery incidence in the North of the Netherlands

(i.e. age and gender distribution, as well as differences between phakic and post CE RRD) were

confirmed.

VandePut.indd 132 4-11-2014 14:15:56

8

Summary & conclusions 133

PART II. CLINICAL STUDIES

In chapter 4, we found that the nerve head to fovea distance (NFD) measured on a fundus

photograph of one eye could be used to predict that distance in the fellow eye. This finding enabled

us to determine the position of the fovea in macula-off RRD by ultrasonography (USG), which was

part of the prospective clinical study described in chapter 5.

In chapter 5, we describe that recovery of visual function after macula-off RRD is affected by both

the duration and the height of the macular detachment. Recovery of best corrected visual acuity

(BCVA) is decreased in case of a larger height or a longer duration of macular detachment. Recovery

of contrast acuity is not affected by either the duration or the height of macular detachment. Post-

operative saturated color vision (CCI) is only related to the duration of the macular detachment.

Although a statistically significant relationship between duration of macular detachment and

postoperative BCVA in the total study group was observed, significance was lost in our subgroup

analyses, in which we looked separately at patients with a macular detachment of ≤7 days and those

with a detachment >7 days.

In chapter 6, we observed that postoperative vision related quality of life was high in our population

of macula-off RRD patients. We observed correlations between the National Eye Institute vision

related quality of life (NEI VFQ-25) composite score and subscale scores and postoperative BCVA,

contrast acuity and post-operative CCI. In contrast to postoperative visual functioning, other

patient and surgery related aspects showed very few correlations with NEI VFQ-25 outcomes. The

correlations observed related to more extensive surgery, long-term intraocular tamponades and

re-detachment.

In chapter 7, we observed a high prevalence of postoperative metamorphopsia in macula-off RRD

patients, whereas the encountered degree of metamorphopsia was small. BCVA, contrast acuity,

critical print size, and reading acuity were significantly worse in patients with metamorphopsia

compared to those without. We did not observe a significant difference in vision related quality

of life in patients with and without metamorphopsia, nor did we observe a significant relation

between metamorphopsia and optical coherence tomography disturbances.

CONCLUSION

The incidence of RRD surgery in our population is highly dependent on demographic characteristics

such as age and male gender. In addition, previous cataract extraction may be a risk factor for

acquiring RRD. We expect the RRD incidence in Western populations (like our own) to increase

because of an increase in the proportion of persons of advanced age (i.e. population aging), who

therefore are at an increased risk for the development of RRD. Macular detachment at presentation

is frequently observed, and this may negatively affect postoperative visual recovery.

VandePut.indd 133 4-11-2014 14:15:56

134 | Chapter 8

We found that both a longer duration and a larger height of the macular detachment negatively

affect postoperative recovery of visual function in macula-off RRD patients. Further, the

prevalence of postoperative metamorphopsia was high in macula-off RRD patients. However, in

patients with postoperative metamorphopsia, the degree of metamorphopsia was relatively low.

Postoperative metamorphopsia in macula-off RRD patients was associated with postoperative

visual function but was not associated with postoperative vision related quality of life. In contrast,

a worse postoperative visual function (i.e postoperative BCVA, contrast acuity and post-operative

CCI) after macula-off RRD was associated with a lower vision related quality of life.

VandePut.indd 134 4-11-2014 14:15:56

Chapter 9

Dutch summary & conclusions

VandePut.indd 135 4-11-2014 14:15:56

136 | Chapter 9

NEDERLANDSE SAMENVATTING

In het eerste deel van dit proefschrift wordt de epidemiologie van rhegmatogene ablatio retinae in

het Noorden van Nederland en Nederland beschreven. Het tweede deel van dit proefschrift betreft

klinische studies ten aanzien van het postoperatieve herstel na rhegmatogene ablatio retinae met

losliggende macula. Ook bevat het de resultaten van een studie waarin wij de relatieve positie van

de fovea ten opzichte van de oogzenuw beschrijven. De resultaten van deze studie werden gebruikt

in een prospectieve klinische studie naar het effect van de duur van de macula loslating en de

hoeveelheid subretinaal vocht ter plaatse van de macula op het postoperatief herstel van de visuele

functie bij patiënten met een rhegmatogene ablatio retinae met losliggende macula. In twee andere

klinische studies werden de visuele functie gerelateerde kwaliteit van leven, en de prevalentie van

postoperatieve metamorfopsie in deze groep patiënten onderzocht.

DEEL I. EPIDEMIOLOGIE

Hoofdstuk 2 beschrijft de incidentie van operaties voor rhegmatogene ablatio retinae in het

Noorden van Nederland. Deze indirecte maat werd gebruikt omdat de incidentie van rhegmatogene

ablatio retinae in een populatie lastig is te bepalen. De incidentie van operaties voor rhegmatogene

ablatio retinae in Nederland in 2008 bedroeg 17.4 per 100.000 inwoners per jaar en in 2009 18.0

per 100.000 inwoners per jaar. Overeenkomstig met eerdere epidemiologische studies naar de

incidentie van rhegmatogene ablatio retinae zagen wij een piek incidentie bij mensen tussen de 65

en 69 jaar. Mannen waren oververtegenwoordigd in bijna alle leeftijdscategorieën. Onder phake

patiënten was de incidentie het hoogst bij patiënten tussen de 55 en 59 jaar. Onder pseudophake

patiënten was de incidentie het hoogst bij patiënten tussen de 60 en 69 jaar. Patiënten met een

rhegmatogene ablatio retinae op latere leeftijd hadden vaker een staaroperatie in de voorgeschiedenis

ten opzichte van jongere patiënten met een rhegmatogene ablatio retinae. Deze observaties lijken

te suggereren dat een staaroperatie een risicofactor voor het ontwikkelen van een rhegmatogene

ablatio retinae is. 57,9% van de patienten had een losliggende macula bij presentatie. Deze studie

werd uitgevoerd als een pilot studie voor de studie beschreven in hoofdstuk 3. Data die werden

verzameld in het kader van laatsgenoemde studie werden toegevoegd aan de resultaten van de

studie beschreven in hoofdstuk 2.

In hoofdstuk 3 wordt de incidentie van operaties voor rhegmatogene ablatio retinae in Nederland

beschreven. Aangezien de incidentie van operaties voor rhegmatogene ablatio retinae in het

Noorden van Nederland zo hoog was, waren wij benieuwd of dit vergelijkbaar is met de incidentie

van operaties voor rhegmatogene ablatio retinae in Nederland. De incidentie van operaties voor

rhegmatogene ablatio retinae in 2009 in Nederland bedroeg 18,2 per 100.000 inwoners per jaar.

Dit is vergelijkbaar met die gevonden in Noord Nederland, en dit is de hoogste incidentie tot nu

VandePut.indd 136 4-11-2014 14:15:56

9

Dutch summary & conclusions 137

toe beschreven in de literatuur. 54,5% van de patiënten had een losliggende macula bij presentatie.

In deze studie werden bovendien de observaties uit de studie in Noord Nederland bevestigd.

DEEL II. KLINISCHE STUDIES

Hoofdstuk 4 beschrijft een studie waarin wij aantonen dat de afstand tussen de fovea en de

oogzenuw gemeten op een fundusfoto in het ene oog gebruikt kan worden om de positie van de

fovea in het andere oog te voorspellen. Deze bevinding stelde ons in staat om in één van de klinische

studies de hoeveelheid subretinaal vocht ter plaatse van de fovea met echografie te bepalen.

In Hoofdstuk 5 wordt het postoperatieve herstel van de visuele functie na rhegmatogene ablatio

retinae met losliggende macula en het effect van preoperatieve karakteristieken op dit herstel

beschreven. Het postoperatieve herstel van de best gecorrigeerde visus bij deze groep patiënten is

afhankelijk van de duur van de macula loslating en de hoeveelheid subretinaal vocht ter plaatse

van de macula. Het postoperatieve herstel van het contrast zien wordt niet beïnvloed door de

duur van de macula loslating of de hoeveelheid subretinaal vocht ter plaatse van de macula.

Postoperatieve stoornissen in het kleurenzien waren ernstiger in het geval van een langere duur van

de macula loslating. De relatie tussen een langere duur van de macula loslating en een lagere best

gecorrigeerde visus was statistisch significant in de gehele onderzoekspopulatie. In de subgroep

analyse (patiënten met een duur van de macula loslating ≤ 7 dagen en patiënten met een duur

van de maculaloslating > 7 dagen & ≤ 6 weken) werden geen significante relaties gezien tussen

best gecorigeerde visus en de duur van de macula loslating en de hoeveelheid subretinaal vocht ter

plaatse van de macula.

Hoofdstuk 6 beschrijft de visuele functie gerelateerde kwaliteit van leven, gemeten met de

National Eye Institute Vision Related Quality of Life 25 vragenlijst (NEI VFQ-25), van patiënten,

12 maanden na operatie in verband met rhegmatogene ablatio retinae met afliggende macula. In

onze populatie was deze visuele functie gerelateerde kwaliteit van leven relatief hoog. We vonden

een correlatie tussen de totale score en score op subschalen van de NEI VFQ-25 vragenlijst en de

postoperatieve best gecorrigeerde visus, het contrast zien, en kleurenzienstoornissen. Daarentegen

observeerden wij weinig andere correlaties tussen de totale score en subschalen van de NEI VFQ-

25 vragenlijst en verscheidene patiënt en chirurgische aspecten. Uitgebreide chirurgie, langdurige

postoperatieve intraoculaire tamponade, en een recidief loslating waren factoren gecorreleerd met

een lagere totale score en scores op subschalen van de NEI VFQ-25 vragenlijst.

In hoofdstuk 7 wordt de prevalentie van postoperatieve metamorfopsie beschreven onder patiënten

die 12 maanden eerder geopereerd zijn in verband met een rhegmatogene ablatio retinae met

losliggende macula. De prevalentie van postoperatieve metamorfopsie in deze patiëntengroep was

hoog, maar de mate van metamorfopsie – indien aanwezig – was gering. Best gecorrigeerde visus,

contrast zien, leessnelheid en leesvisus waren significant lager onder patiënten met postoperatieve

VandePut.indd 137 4-11-2014 14:15:56

138 | Chapter 9

metamorfopsie in vergelijking tot patiënten zonder postoperatieve metamorfopsie. In onze studie

werd geen significant verschil in de visuele functie gerelateerde kwaliteit van leven, gemeten met de

National Eye Institute Vision Related Quality of Life 25 vragenlijst (NEI VFQ-25), geobserveerd

tussen patiënten met en patiënten zonder postoperatieve metamorfopsie. Daarnaast vonden wij

geen significante relatie tussen de aan- of afwezigheid van postoperatieve metamorfopsie en

afwijkingen gevonden met optical coherence tomography (OCT).

CONCLUSIE

De incidentie van chirurgie voor rhegmatogene ablatio retinae lijkt sterk afhankelijk van de

demografische kenmerken van een populatie. Van deze demografische kenmerken lijken de

verdeling van geslacht en leeftijd (met name het aandeel ouderen) in de populatie de belangrijkste

determinanten van de incidentie. Dit kan de hoge incidentie die wij observeerden in onze populatie

verklaren. Cataract extractie lijkt een mogelijke risicofactor voor het ontwikkelen van een

rhegmatogene ablatio retinae. De toenemende vergrijzing van onze populatie zou kunnen leiden

tot een toename van het aantal patiënten met een rhegmatogene ablatio retinae. De vergrijzing

leidt namelijk tot een groter aandeel ouderen at risk voor een rhegmatogene ablatio retinae (groter

aandeel personen met een leeftijd tussen de 55 en 59 jaar en een groter aantal personen dat een

cataract extractie ondergaat). Macula loslating bij presentatie werd vaak gezien en dit kan een

negatief effect hebben op het postoperatieve herstel van de visuele functie.

Het postoperatieve herstel van de visuele functie na rhegmatogene ablatio retinae met losliggende

macula is afhankelijk van de duur van de macula loslating en de hoeveelheid subretinaal vocht

ter plaatse van de macula. De prevalentie van postoperatieve metamorfopsie onder patiënten die

12 maanden eerder geopereerd zijn in verband met rhegmatogene ablatio retinae was hoog, maar

de mate van metamorfopsie was gering. De aanwezigheid van postoperatieve metamorfopsie

heeft geen relatie met een lagere visuele functie gerelateerde kwaliteit van leven, gemeten met de

National Eye Institute Vision Related Quality of Life 25 vragenlijst (NEI VFQ-25). Ook is er geen

relatie tussen de aanwezigheid of afwezigheid van postoperatieve metamorfopsie en afwijkingen

gevonden met optical coherence tomography (OCT). Een lagere postoperatieve visuele functie is

daarentegen wel gecorreleerd met een lagere totale score en score op subschalen van de NEI VFQ-

25 vragenlijst.

VandePut.indd 138 4-11-2014 14:15:56

APPENDICES

VandePut.indd 139 4-11-2014 14:15:56

VandePut.indd 140 4-11-2014 14:15:56

Abbreviations 141

ABBREVIATIONS

B Regression Coefficient

BCVA Best Corrected Visual Acuity

C3F8 Octafluorpropane

CCI Color Confusion Index

CE Cataract Extraction

CI Confidence Interval

CV Color Vision

D Diopter

D Driving

DA Distance Activities,

Dist Distance

Dpt Diopter

ECCE Extracapsular Cataract Extraction

ELM External Limiting Membrane

ERM Epiretinal Membrane

ETDRS Early Treatment of Diabetic Retinopathy Study

F Female

GH General Health

GV General Vision

HM Hand Movements

ICCE Intracapsular Cataract Extraction

ILM Internal Limiting Membrane

IRB Internal Review Board

LEO Laboratorium Experimentele Oogheelkunde

Ln Natural logaritm

LOCS III Lens Opacification Classification System III

Log Logaritm

LogMAR Logaritm of the minimum angle of resolution

M Male

MH Macular Hole

MHz Megahertz

N Number

NA Near Activities

NEI VFQ-25 National Eye Institute Vision Related Quality of Life Questionnaire 25

VandePut.indd 141 4-11-2014 14:15:56

142 | Abbreviations

NFD Optic Nerve-head to Fovea Distance

NTR Nederlands Trial Register (Dutch trial register)

OCS Overall Composite Score

OCT Optical Coherence Tomography

OD Oculus Dextra

OP Ocular Pain

OS Oculus Sinistra

PV Peripheral Vision

PVD Posterior Vitreous Detachment

PVR Proliferative Vitreoretinopathy

R Pearson’s Correlation coefficient

RPE Retinal Pigment Epithelium

RRD Rhegmatogenous Retinal Detachment

SAC Sine Amsler Chart

SD Standard Deviation

SE Spherical Equivalent

SF6 Sulphur Hexafluoride

SRF Subretinal Fluid

TPPV Trans Pars Plana Vitrectomy

UMCG University Medical Center Groningen

USG Ultrasonography

VA Visual Acuity

VR-QOL Vision Related Quality Of Life

VSD Vision Specific Dependency

VSMH Vision Related Mental Health

VSRD Vision Related Role Difficulties

VSSF Vision Specific Social Functioning

VandePut.indd 142 4-11-2014 14:15:56


ACKNOWLEDGEMENTS

Aan het einde van de zomer van 2008 ben ik begonnen met het onderzoek waarvan dit proefschrift

het resultaat is. Een half jaar later zou ik starten met de opleiding tot oogarts op de afdeling

oogheelkunde van het UMCG. In mijn opleidingsplan stond beschreven dat de combinatie

van opleiding en promotie ruim acht jaar zou bestrijken. Op dat moment had ik niet kunnen

voorspellen dat ik de promotie en opleiding, twee jaar eerder dan gepland, zou afronden. Dat de

combinatie opleiding-promotie zo efficiënt en goed is verlopen, is te danken aan het enthousiasme,

de effectieve ondersteuning en de medewerking van velen. Op deze plaats wil ik een aantal mensen

speciaal bedanken voor hun steun die noodzakelijk is geweest voor het slagen van dit proefschrift.

Prof. dr. J.M.M. Hooymans, Anneke, mijn promotor ben ik zeer dankbaar voor het vertrouwen

in mij, zodat ik de opleiding, promotie en nevenactiviteiten voor de LVAO en LVAG heb kunnen

combineren. Ik hoop dat we nog eens samen een rondje lopen op de Noord Nederlandse.

Dr. L.I. Los, Leonie, mijn copromotor, ben ik zeer dankbaar voor de directe begeleiding tijdens

dit project en voor het vertrouwen dat ik kreeg om een landelijke studie uit te voeren. Door haar

talent voor wetenschappelijk schrijven en haar gedegen kennis van de Engelse taal, kon ik de

manuscripten zo goed mogelijk naar tijdschriften sturen. Ik heb de overlegmomenten en haar

scherpe redeneervermogen altijd als uiterst effectief en prettig ervaren.

Prof. dr. J.E.E. Keunen, Prof. dr. H.P.H. Kremer, dank ik voor hun bereidwilligheid zitting te

nemen in de beoordelingscommissie van dit proefschrift. Prof. dr. R.J.W. de Keizer, Rob ik vind

het een eer dat je in de beoordelingscommissie zitting hebt willen nemen. Mijn “oogheelkundige”

onderzoekscarrière is bij jou begonnen. Ik zal dan ook altijd interesse behouden in de caruncula

lacrimalis.

Dr. I.M. Nolte, Ilja, jou ben ik dankbaar voor de hulp en aanwijzingen bij het maken van de

statistische analyses. Drs. W.J. Japing, Wouter ben ik dankbaar voor zijn uitzonderlijk hoge

kennisniveau en beheersing van de ultrasonografie in de oogheelkunde. Jouw expertise was

onmisbaar voor een deel van dit onderzoek. Daarnaast wil ik Lisette Hoeksema, Wouter Wanders,

Fara Nayebi, en Danna Croonen bedanken voor hun inzet voor de manuscripten waaruit het

proefschrift bestaat.

VandePut.indd 143 4-11-2014 14:15:56

144 | Acknowledgements

De volgende netvlieschirurgen in het noorden van Nederland, F.P. Gunning, D. Humalda,

V.W. Renardel de Lavalette, J.M.M. Hooymans, E.A. Huiskamp, en G.P. Postma wil ik bedanken

voor het beschikbaar stellen van data voor twee studies naar de incidentie van rhegmatogene

ablatio retinae. Victor, Angela, en Gina dank ik voor hun inspirerende uitleg en het onderwijs over

het achtersegment.

De overige leden van de werkgroep vitreoretinale chirurgie, P.R. Van den Biesen, E.W. Lindstedt,

J.C. Van Meurs, K.A. Van Overdam, M.A.H. Veckeneer, N. Crama, C.B. Hoyng, B.J. Klevering,

T. Theelen, M.A.D. Tilanus, H.M. Bijl, S.Y. Lesnik Oberstein, M. Mura, H.S. Tan, R. Van

Leeuwen, P.A.W.J.F. Schellekens, J.S. Stilma, M.I. Bosscha, J.W.M. Reichert-Thoen, P.J. Ringens,

W.A.E.J. De Vries-Knoppert, F. Goezinne, E.C. La Heij, T.A. Liem, I.J. Lundqvist, F.T. Kerkhoff,

E.J.G.M. Van Oosterhout, R.P.C. Rademaker, E.M. Busch, D.J. Treskes, R.P.G. Feenstra,

G.H.S. Buitendijk, E. Kiliç, R.W.A.M. Kuijpers, J.R. Vingerling, W. Swart, F.P. Gunning,

D. Humalda, V.P.T. Hoppenreijs, M.N. Copper, en A.J.J.M. Rademakers, wil ik hier bedanken

voor de bereidwilligheid om data beschikbaar te stellen voor de landelijke studie naar de incidentie

van rhegmatogene ablatio retinae in Nederland. Deze landelijke samenwerking resulteerde in een

mooie gezamenlijke publicatie in Ophthalmology.

Kim Westra, Lisette Olie, Liberata Uwantege, Esther Molenaar en Wietse Wieringa wil ik bedanken

voor het verrichten van de vele metingen die aan de basis staan van dit proefschrift. Kim Westra

wil ik bovendien bedanken voor het coördineren van een deel van de studies beschreven in dit

proefschrift.

Zonder secretariële, financiële en ICT-ondersteuning ben je machteloos als onderzoeker. Ik ben

de dames van het stafscretariaat oogheelkunde, Ella Oosterveld, Stella de Rooy en Fenna Fonck,

dankbaar voor de immer goede ondersteuning. In het bijzonder wil ik Fenna bedanken vanwege

haar kunde om de in de vergetelheid geraakte literatuur boven water te krijgen. De twee Wimmen,

Berghuis en Nieuwold wil ik bedanken voor hun financiële deskundigheid. Albert Damhof en

Luuk Mooibroek wil ik bedanken voor de adequate ICT-ondersteuning. Jullie hebben me altijd uit

de brand weten te helpen als ik weer eens vastliep met een ICT-probleem.

De oogartsen in Groningen en omstreken wil ik bedanken voor het verwijzen van patiënten met

een rhegmatogene ablatio retinae. Het grootste deel van de patiënten beschreven in deze studie zijn

namelijk afkomstig uit jullie praktijken.

De subsidieverleners: de Professor Mulder Stichting, Stichting Blindenhulp en de Stichting

Nederlands Oogheelkundig Onderzoek wil ik bedanken voor de financiële ondersteuning. Zonder

subsidieverleners had dit onderzoek niet uitgevoerd kunnen worden.

VandePut.indd 144 4-11-2014 14:15:56


Alle patiënten die hebben meegedaan aan deze studie wil ik hier bedanken. Het is bijzonder dat

u de vele en langdurige metingen hebben weten vol te houden. Zeker wanneer je bedenkt dat de

meesten van u niet direct in de buurt wonen (Het noorden van Nederland beslaat bijna ¼ van het

oppervlak van Nederland).

De ambitie om dit proefschrift te schrijven en het doorzettingsvermogen om het project succesvol

af te ronden, is ontstaan door de begeleiding tijdens mijn eerste schreden op het onderzoekspad.

Op deze plaats wil ik dan ook professor Dörr, dr. Denise Perquin, professor Frank Willem Jansen

en dr. Wendela Kolkman bedanken voor hun begeleiding in deze periode. Professor Dörr, beste

Joep jou wil ik in het bijzonder bedanken. Door jouw begeleiding weet ik dat volharding de basis

is van een succesvol onderzoek. Helaas kan ik je niet meer persoonlijk bedanken voor dat advies.

Jelle, jou wil ik bedanken, omdat je een betrouwbare en goede vriend bent geworden. Ik ben blij

dat wij (Raquel & ik) met jullie (jij & Arjen) zo’n geweldig leuke tijd hebben gehad in Groningen.

Ik hoop dat we in de toekomst veel mooie restaurants gaan bezoeken. Ik ben blij dat je mijn

paranimf wilt zijn.

Mijn clubgenoten, hun vrouwen of vriendinnen (Daan & Lieke, Alistair & Marije, Pablo &

Frederiek, Reinier & Sanne, Martijn & Marcella, Jeroen & Brigitte, Tony, Caspar, Joost & Stephanie,

Jan Bauke, en Pedro) wil ik bedanken voor de aanhoudende belangstelling en vriendschap die zelfs

door de afstand met het jaar groter lijkt te worden.

Mijn schoonfamilie wil ik bedanken voor de leuke en gezellige momenten. Ellen ik vind het

geweldig om te zien hoe gelukkig je bent in Zandvoort en hoe je kunt genieten van Aaron.

Binnenkort kunnen we gelukkig vaker langskomen. En komende zomer hoop ik wel langer op een

surfplank te kunnen blijven staan!

Mijn lieve familie wil ik bedanken voor alle gezelligheid door de jaren heen. Paul, Karen, Maria,

Freddie & Sanderijn, het was prettig om altijd welkom te zijn bij jullie in Bedum. Paul, de

gesprekken over wetenschap en je hulp bij een uitdagende casus over optica waren inspirerend en

hebben ook zeker bijgedragen aan het voltooien van dit proefschrift.

Ook wil ik mijn ouders bedanken voor alle steun door de jaren heen. Jullie hebben mij altijd

met veel geduld gesteund. Toen ik naar Leiden vertrok om te studeren, in Den Haag ging wonen

tijdens mijn coschappen of in Groningen ging wonen voor de opleiding, jullie waren ondanks de

afstand altijd dichtbij. Jullie vreugde toen Aaron werd geboren was overweldigend. Ik hoop dan

ook binnenkort dichter bij jullie in de buurt te wonen.

VandePut.indd 145 4-11-2014 14:15:56

146 | Acknowledgements

Mijn broer(tje) Roel dank ik voor alle avonturen die we sinds onze kinderjaren tot nu toe hebben

beleefd. Wat hebben we een lol gehad en gaan we ook zeker in de toekomst hebben. Ook ben ik

dankbaar dat je zo’n leuke vriendin in Ilona hebt gevonden. Ik ben er trots op dat je mijn paranimf

wilt zijn.

Lieve Raquel, jou wil ik in het bijzonder bedanken. Hoe goed is het, dat we dit samen voor elkaar

hebben gekregen. Zonder jou was het niet gelukt. Het was een druk, maar mooi jaar, zeker met

onze Aaron. Wat een vooruitzicht om binnenkort met zijn vieren te zijn!

Mathijs van de Put

Groningen, oktober 2014

VandePut.indd 146 4-11-2014 14:15:56

List of publications 147

LIST OF PUBLICATIONS

Related to this thesis

1. Van de Put MAJ, Croonen D, Nolte IM, Japing WJ, Hooymans JMM, Los LI; Postoperative

recovery of visual function after macula-off rhegmatogenous retinal detachment. Plos One. 2014 June

2014: 9:6:e99787

2. Van de Put MAJ, Nayebi F, Nolte IM, Croonen D, Japing WJ, Hooymans JMM, Los LI;

Design and validation of a method to determine the position of the fovea by using the nerve-head to fovea

distance of the fellow eye. Plos One May 2013: 8:5:e99787

3. Van de Put MAJ, Los LI, Hooymans JMM for the Dutch rhegmatogenous retinal detachment

study group. The incidence of rhegmatogenous retinal detachment in the Netherlands. Ophthalmology.

2013;120:16-22.

Other publications

4. Van de Put MAJ, Haeseker BAE, de Wolff-Rouendaal D, de Keizer RJW; Squamous cell

carcinoma of the lacrimal caruncle. Eur J Ophthalmol. 2014;24:441-445.

5. Hiemstra E, Kolkman W, Van de Put MAJ, Jansen FW; Retention of skills one year after a

structered laparoscopic simulator training program. Gynecol Surg. 2009;6:229-235.

6. Kolkman W, van de Put MAJ, Trimbos JBMZ, Jansen FW Laparoscopic skills simulator: construct

validity and establishing performance standards for residency training. Gynecol Surg. 2008;5:109-

114.

7. Kolkman W, van de Put MAJ, van den Hout WB, Trimbos JBMZ, Jansen FW; The

implementation of the laparoscopic simulator in gynecological residency curriculum. Surg Endosc.

2007;21:1363-1368.

8. Van de Put MAJ, Perquin DAM, Dörr PJ De voorspellende waarde van Chlamydia trachomatis-

serologie bij fertiliteitonderzoek. Ned Tijdschr Geneeskd S. 2007;10:64-67.

VandePut.indd 147 4-11-2014 14:15:56

148 | Biography

BIOGRAPHY

Mathijs van de Put was born in Tilburg on November 6th 1981. After completing his secondary

school education at the Cobbenhagen College in Tilburg in 2000, he started his medical education

in 2000 at Leiden University. In 2006, he obtained his masters degree in Medicine. During his

study, he assisted at the anatomy laboratory, and he wrote a research paper with Joep Dörr on the

role of C. Trachomatis antibody titers in the assessment of subfertility. He wrote his Master’s thesis

at the gynaecology department under supervision of Frank Willem Jansen. During his internship,

he did additional research at the ophthalmology department of the LUMC, under supervision of

Rob de Keizer. In April 2008, he graduated as a Medical Doctor.

In 2008 he started with the research resulting in this thesis under supervision of Anneke

Hooymans and Leonie Los, and from 2009 onwards he combined this research with his residency

in ophthalmology at the department of Ophthalmology of the University Medical Center

Groningen (UMCG) under supervision of Anneke Hooymans. Most of this residency took place at

the UMCG. As part of this residency, he also worked at the Isala Clinics, Zwolle under supervision

of Khiun Tjia. During his residency, he was board member of the national association of Dutch

ophthalmology residents (LVAO), and a board member of the National association for Dutch

residents (LVAG). In addition, he is a member of the commission for appeal for the Registration

Committee Medical Specialists (RGS). On January 15th 2014, his son Aaron was born. He will

finish his residency in December 2014.

VandePut.indd 148 4-11-2014 14:15:56


Incidence, risk factors, postoperative

recovery & vision related quality of life

M.A.J. van de Put

RH

EG

MA

TO

GE

NO

US R

ET

INA

L D

ET

AC

HM

EN

T In

ciden

ce, risk factors, p

ostoperative recovery &

vision related

qu

ality of life M

.A.J. van

de P

ut

INVITATION

For the public defense of the thesis:


Mathijs van de Put

Wednesday, December 10th, 2014

11 A.M.Academy building

University of GroningenBroerstraat 5Groningen

Noon Reception

Academy building

2 P.M. Informal reception

Café de Oude WachtGed. Zuiderdiep 3 Groningen

Mathijs van de PutBoumaboulevard 3239723 ZS Groningen

T: [email protected]

Paranymphs

Roel van de PutT: 0614278881

[email protected]

Jelle VehofT: 0644949999

[email protected]

Documents

Proefschrift van de Put