DR. BHARTI AHUJA

INTRODUCTIONProliferative retinopathy affecting premature infants of

low birth weight and young gestational age(Terry,1942).

Term was coined by HEATH(1951).

CRUCIAL RISK FACTORS

BIRTH WEIGHTGESTATIONAL AGE OXYGEN SUPPLEMENTATION

Risk factors(associated) Prematurity Hyper/hypoxia Hypotension Acidosis Blood transfusions Sepsis Antioxidant deficiency Apnoea PDA Vitamin E deficiency

IntroductionThe incidence and severity of retinopathy of prematurity (ROP) in extremely premature infants have not been reported since publication of the Early Treatment of ROP study results. The survival rate of these infants continues to increase. We sought to determine the characteristics of ROP in a group of surviving infants <25 weeks estimated gestational age (EGA) at birth compared to a group 25 to 27 weeks EGA at birth.

Methods

Retrospective review of infants born prior to 27 weeks EGA between January 2003 and July 2007 at a level-3 nursery at a regional academic medical center.

Retinopathy of prematurity in extremely premature infants

JOURNAL OF AAPOS,AUG 2009,VOL 13 ISSUE 4, pg 370-73RONALD G.W.TEED,RICHARD A. SAUNDERS

ResultsA total of 231 medical records were reviewed and found to

have analyzable data. Of 79 infants <25 weeks EGA, 69 (87%) developed ROP, compared to 95 of 152 (62%) infants 25 to 27 weeks EGA. Type 1 ROP developed in 23% of infants in the <25 weeks EGA group, compared to 9% of infants in the 25 to 27 weeks EGA group. There was no difference in mean postmenstrual age when type 1 ROP was diagnosed. Lower birth weight predicted increased risk of type 1 ROP in the 25 to 27 weeks EGA group, but not in the <25 weeks EGA group.

ConclusionsExtremely premature infants are more likely to develop

ROP and type 1 ROP, but the incidence may be lower than previously reported. Birth weight may not influence the incidence of type 1 ROP in this group of infants. Type 1 ROP does not develop at an earlier postmenstrual age in the extremely premature infant

Pathogenesis of ROPPHASE I PHASE II

True vasculogenesisOccurs at 8-21 wks of

gestation.Not Under the control of VEGF.Mesenchymal cells

differentiate into capillaries,subsequently develop into arterioles and venules.

Angiogenesis

(Physiologic and pathologic)22-40 wks of gestation.VEGF controls this phase.Proliferating endothelial

cells migrate from existing bld vessels to form new capillaries.

Term newbornPreterm newborn

Relatively less hyperoxic environment

Spindle cells(normal antioxidative property)

Relatively higher hyperoxic envtThin,avascular retina

Spindle cells(defective )

Normal migration and canalization

Gap junctionsAngiogenic factor(VEGF)

Migration and canalization haltNeovascularization at shunt site

REGRESSION

Myofibroblasts from stem cells

Contractile sheet

Mature vessels formation

Spindle cell theory(kretzer etal,1984)

ROP

CURRENT CLASSIFICATION,ICROP,1987

PLUS DISEASE

AREA OF RETINA

INVOLVED

SEVERITY

STAGE 1-5EXTENT IN

CLOCK HOURS

LOCATIONZONES I-III

ICROP STAGING ROP: STAGES

STAGE 1

STAGE 2

STAGE 3 MILD/MODERATE/

SEVERE

STAGE4

A

B

STAGE 5

DESCRIPTIONDemarcation line

Ridge

Ridge with extraretinal fibrovascular proliferation

Subtotal retinal detachment

A.Not involving macula

B.Involving macula

Total retinal detachment

STAGE 1

STAGE 3

STAGE 4ASTAGE 4B

Open opeop

Funnel shaped RD(STAGE 5)

Retrolental fibroplasia

Leukocoria resuting from fibrovascular proliferation and advanced Retinal detachment.

Classification based on location/clock hours

Plus disease

Aggressive posterior(AP-ROP)/RUSH Disease

Rapid progression through the three stages of ROP, with plus disease

STAGE 3 + ROP IN ZONES 1 / 2 OCCUPYING ATLEAST FIVE CONTIGUOUS OR EIGHT NON CONTIGUOUS CLOCK HOURSOF RETINA

THRESHOLD ROP

Early treatment of retinopathy of prematurity(ETROP)Cooperative group classification(Arch,ophthalmology2003-04)TYPE 1 PRETHRESHOLD TYPE 2 PRETHRESHOLD

Zone I ROP(any stage)+ Zone I stage 3 Zone II stage 2/3 +

High risk Immediate treatment

Zone I stage 1/2 - Zone II stage 3-

low risk Observation,treat when

progresses to threshold ROP.

Screening for ROP To detect the babies with treatable disease

in time for treatment to be effective.

Which and when to screen???????

At 31 wks post conceptional age(gestational age+post natal age) or 4-5 wks after birth whichever is later.

Which children to screen?? Screen all premature infants less than

1500 g birth weight. Screen all babies born at less than or equal

to 32wks of gestational age(postmenstrual age).

Selected preterm infants,birth wt between 1500-2000g or gestational age of more than 32 wks with an unstable clinical course(including those requiring cardiorespiratory support, who are believed to be at a higher risk (SICKNESS CRITERIA)

STANDARD SCREENING PROTOCOL Inform neonatology unit nurse regarding time of

examination. Instruct nurse regarding pupillary dilatation of eyes. Avoid feeding of infants until 60 mins after examination. Attending neonatologist should be there, especially in

cases which are unstable. Maintain asepsis. Low light of indirect

ophthalmoscope(+20D/+28Dlens),look for plus disease.

First screen nasal retina. Draw retinal chart.

Aim: To compare the diagnostic accuracy of wide-field digital retinal imaging (WFDRI) with the current “gold standard” of binocular indirect ophthalmoscopy (BIO) for retinopathy of prematurity (ROP) screening examinations.

Methods: A consecutive series of premature infants undergoing ROP screening at Edinburgh Royal Infirmary were eligible for recruitment into this prospective, randomised, comparative study. Infants were screened using both WFDRI (Retcam II with neonatal lens) and BIO by two paediatric ophthalmologists who were randomised to the examination technique. Both examiners documented their clinical findings and management plans in a masked fashion. WFDRI eye findings were compared with those of BIO.

Wide-field digital retinal imaging versus binocular indirect ophthalmoscopy for retinopathy of prematurity screening: a two-observer prospective, randomised comparison

BRITISH JOURNAL OF OPHTHALMOLOGY, MARCH 2009,VOL.93,ISSUE 3;pg355-59

C Dhaliwal,E Wright, C Graham,N Mcintosh,B W Fleck

Results: A total of 81 infants were recruited, and information from 245 eye examinations was analysed. The sensitivity of WFDRI in detecting any stage of ROP, stage 3 ROP and “plus” disease was 60%, 57% and 80%, respectively, and specificity 91%, 98% and 98%, respectively. The proportional agreement between WFDRI and BIO was 0.96 for detecting stage 3 disease and 0.97 for detecting “plus” disease. There was very good agreement on management decisions (kappa 0.85).

Conclusion: When used in a routine ROP screening setting, a randomised comparison of WFDRI and BIO, WFDRI showed relatively poor sensitivity in detecting mild forms of ROP in the retinal periphery. This resulted in difficulty in making decisions to discharge infants from the screening programme. Sensitivity was better for more severe forms of ROP, but at present WFDRI should be regarded as an adjunct to, rather than a replacement for, BIO in routine ROP screening.

AIM: To compare the speed of retinopathy of prematurity (ROP) diagnosis using standard indirect ophthalmoscopy with that of telemedicine.

Three study examiners (2 pediatric retinal specialists [R.V.P.C., T.C.L.] and 1 pediatric ophthalmologist [M.F.C.]) conducted ROP diagnosis via standard indirect ophthalmoscopy and telemedicine. Each examiner performed: 1) standard ophthalmoscopy on 72 to 150 consecutive infants at his respective institution and 2) telemedical diagnosis on 125 consecutive deidentified retinal image sets from infants from an at-risk population. Time for ophthalmoscopic diagnosis was measured in 2 ways: 1) time spent by the examiner at the infant's bedside and 2) mean total time commitment per infant. Time for telemedicine diagnosis was recorded by computer time stamps in the web-based system. For each examiner, nonparametric statistical analysis (Mann–Whitney U test) was used to compare the distribution of times for examination by ophthalmoscopy vs telemedicine

SPEED OF TELEMEDICINE VS OPHTHALMOSCOPY FOR DIAGNOSIS OF ROP

METHODS:

AMERICAN JOURNAL OF OPHTHALMOLOGY JULY 2009, VOL 148,ISSUE 1,pg 136

Mean (± standard deviation [SD]) times for ophthalmoscopic diagnosis ranged from 4.17 (± 1.34) minutes to 6.63 (± 2.28) minutes per infant. Mean (± SD) times for telemedicine diagnosis ranged from 1.02 (± 0.27) minutes to 1.75 (± 0.80) minutes per infant. Telemedicine was significantly faster than ophthalmoscopy (P < .0001). The total time commitment by ophthalmologists performing bedside ophthalmoscopy for ROP diagnosis, including travel and communication with families and hospital staff, was 10.08 (± 2.53) minutes to 14.42 (± 2.64) minutes per infant

The ophthalmologist time requirement for telemedical ROP diagnosis is significantly less than that for ophthalmoscopic diagnosis. Additional time requirements associated with bedside ROP diagnosis increased this disparity. Telemedicine has potential to alleviate the time commitment for ophthalmologists who manage ROP

RESULTS:

CONCLUSION:

Treatment options(available) Ablative therapy(cryotherapy and laser) Scleral buckling surgery Lens sparing vitrectomy Lensectomy +vitrectomy Open sky vitrectomy Anti VEGF injections(controversial)

Guidelines for treatment of ROP(Ablative therapy) Stage 1 or 2 ,progressing to stage 3 All stage 4a cases Extraretinal fibrovascular proliferation

present in more than 3contiguous or 5 cumulative clock hours in zone 1/2

Presence of plus disease

Comparison of ablative therapyCryotherapy Laser

Transscleral Very painful Require ventilation during procedure Substantial lid swelling and

conjunctival edema. Posterior retina difficult to reach. In small pupil ,easy to do. Myopia and retinal detachments are

problems. No risk of damage to iris,and

cataractformation during the procedure.

Low cost Diffuse treatment Shorter time.

Direct ablation Less painful No need for ventilation Less local complications Posterior retina can be reached

more readily. Difficult. less common. Possible risk Expensive More precise Longer time

Fundus showing multiple white cryo burns (black arrows) in avascular retina anterior to ridge (white arrow).

PurposeTo assess the long-term visual outcomes and refractive status in patients with diode laser-treated threshold retinopathy of prematurity (ROP), and to investigate the causes of impaired visual function

MethodA total of 60 eyes of 30 consecutive patients with diode laser-treated threshold ROP were recalled for assessment at the age of 7 years or more.

Yang CS, Wang AG, Sung CS, Hsu WM, Lee FL, Lee SM.

Long-term visual outcomes of laser-treated threshold retinopathy of prematurity: a study of refractive status at 7 years

JOURNAL OF EYE(ONLINE),APRIL, 2009

ResultsThere were 38 eyes (65.5%) achieving 6/12 or better vision, however, an unfavourable visual outcome (6/60 or worse) occurred in four eyes (6.9%). One eye (1.7%) had unfavourable structural outcome. Of these 60 laser-treated eyes, 46 eyes (77.0%) were myopic, the overall mean spherical equivalent was -3.87 D. Anisometropia (>/=1.5 D) was also noted in 14 patients (46.7%). Strabismus was present in nine patients (30.0%). Perinatal neurological events of intraventricular haemorrhage (IVH) were identified in eight children (26.7%), periventricular leucomalacia (PVL) in eight children (26.7%), and cerebral palsy (CP) in four children (13.3%). There was a statistically significant association of the presence of strabismus with PVL (P=0.002). The presence of anisometropia was a significant risk factor associated with poor visual outcome of 6/15 or worse in laser-treated ROP (P=0.002)

ConclusionThe majority of patients with diode laser-treated threshold ROP had favourable anatomical and visual outcomes. However, anisometropia, advanced refractive error, strabismus, and perinatal neurological events remain important causes of impaired visual function. Long-term follow-up is very important for early detection and timely treatment of these ocular morbidities.

To assess the functional and visual outcomes after primary lens-sparing pars plana vitrectomy for Stage 4 ROP.

MATERIALS AND METHODS: In a retrospective, interventional, consecutive case series, the records of 39 eyes of 31 patients presenting with Stage 4 retinal detachment secondary to ROP who underwent primary two or three-port lens-sparing vitrectomy from January 2000 to October 2006 were evaluated. The outcomes studied at the final follow-up visit were the retinal status, lens and medial clarity and visual acuity . Favorable anatomical outcome was defined as the retinal reattachment of the posterior pole at two months after the surgery; and favorable functional outcome was defined as a central, steady and maintained fixation, with the child following light.

Functional and anatomical outcomes after primary lens-sparing pars plana vitrectomy for Stage 4 retinopathy of prematurity.

Bhende P, Gopal L, Sharma T, Verma A, Biswas RK

Indian J Ophthalmol. 2009 Jul-Aug;57(4):267-71

RESULTS: At mean follow-up of 15 months, 74% of the eyes had a favorable anatomical outcome with single procedure. The visual status was favorable in 63% . The lens remained clear in all the eyes at the last follow-up, and the media clarity was maintained in 87%. Intraoperative complications included vitreous hemorrhage, pre-retinal hemorrhage and retinal break formation.

CONCLUSION

Lens-sparing vitrectomy helps to achieve a favorable anatomical and functional outcome in selected cases of Stage 4 ROP.

OBJECTIVE: To assess the effect of early vitrectomy for aggressive posterior retinopathy of prematurity (APROP) using fundus fluorescein angiography.

METHODS: All eyes underwent vitrectomy with lensectomy that removed the vitreous gel around the fibrovascular proliferative tissue, but not the proliferative tissue when fibrovascular proliferation and retinal detachment occurred despite retinal photocoagulation. Fundus fluorescein angiography was performed before and after the early vitreous surgery.

Effect of Early Vitreous Surgery for Aggressive Posterior Retinopathy of Prematurity Detected by Fundus Fluorescein Angiography

Nishina S, Yokoi T, Yokoi T, Kobayashi Y, Hiraoka M, Azuma N.

ONLINE JOURNAL OF OPHTHALMOLOGY,2009,OCTOBER

RESULTS: Nine eyes had severe dye leakage from the fibrovascular tissue and 2 eyes had moderate leakage seen by preoperative fluorescein angiography. Severe dilation and tortuosity of the retinal vessels were detected in 10 eyes and shunt vessels in 7 eyes. Six to 12 days after successful surgery, the retina reattached and dilation and tortuosity of the retinal vessels decreased substantially. Dye leakage diminished markedly in all eyes, resolved completely in 7 eyes, and was still apparent slightly in 4. At the final examination, fibrovascular proliferation and retinal detachment did not progress in any eyes; however, 2 eyes had a dragged or folded retina. Follow-up ranged from 6 to 19 months (mean,9.2)

CONCLUSIONS: Early vitrectomy that removes vitreous gel from around the proliferative tissue promptly reduces vascular activity and may limit progression of retinal detachment in APROP.

To evaluate the short-term efficacy of intravitreal injections of bevacizumab for severe retinopathy of prematurity (ROP).

Methods: A retrospective chart review was conducted of 23 consecutive eyes (stage 3, three eyes; 4A, 18 eyes; 4B, two eyes) of 14 patients with vascularly active ROP considered at high risk for progression or development of tractional retinal detachment despite conventional laser ablation therapy. Patients received an intravitreal injection of bevacizumab (0.5 mg), either as the initial treatment (15 eyes) or at the end of vitrectomy (eight eyes)

Efficacy of intravitreal injection of bevacizumab for severe retinopathy of prematurity: a pilot studyS Kusaka, C Shima, K Wada, H Arahori, H Shimojyo, T Sato, T Fujikado

BRITISH JOURNAL OF OPHTHALMOLOGY,92, 2008,PG 1450-55

Results: After injection of bevacizumab as the initial treatment, reduced neovascular activity was seen on fluorescein angiography in 14 of 15 eyes. In three eyes, a tractional retinal detachment developed or progressed after bevacizumab injection. No other ocular or systemic adverse effects were identified. Vitrectomy was performed in 20 eyes and the retina was reattached after one surgery in 18 eyes. Multiple surgeries were necessary in two eyes, resulting in retinal reattachment.

Conclusion: There results suggest that intravitreal injection of

bevacizumab seems to be associated with reduced neovascularisation without apparent ocular or systemic adverse effects, and is thus beneficial for treating severe ROP that is refractory to conventional laser therapy.

Differential diagnosis

Retinoblastoma Familial exudative vitreoretinopathy Coats’ disease Toxocariasis/toxoplasmosis Persistent primary hyperplastic vitreous Congenital X-linked retinoschisis Incontinentia pigmenti

COMPARISONROP

RETINOBLASTOMA

History of prematurity, low birth wt ,oxygen usage.

Family history negative. Leukocoria may be detected

after 6-8 wks. Clinical findings bilateral. Leukocoria-fibrotic look,a ridge

with cicatricial vessels in periphery.

No significant lesion on X-ray. B-scan-complex pattern of

detachment. CTscan-no specific pattern

Usually negative. Positive(25-30%cases,bilateral) Usual time of presentation is 6-

18 mths. Unilateral usually. Heterogenous mass with

haemorrhages,many vessels on surface.

Calcification(large% of cases) Origin of mass from underlying

retina. Calcification within the mass.

Sequelae of ROP

Spontaneous regression MYOPIA STRABISMUS AMBLYOPIA CATARACT GLAUCOMA RETINAL BREAKS/DETACHMENT

PURPOSE: To determine the incidence and possible causes of a late recurrence of a retinal detachment (RD) in eyes with stages 4B and 5 retinopathy of prematurity (ROP), in which the retina was once reattached by lensectomy and vitrectomy

AMERICAN JOURNAL OF OPHTHALMOLOGY APR 2009,VOL 147, ,ISSUE 4 pg-661-66

Kondo H, Arita N, Osato M, Hayashi H, Oshima K, Uchio E.

METHODS: The medical records of 124 eyes of 99 infants and children <2 years of age at the time of initial vitrectomy, in which the retina had been reattached for at least 1 year, were reviewed. The incidence of a recurrence of the RD >1 year after the initial surgery for eyes at stage 4B ROP (42 eyes) was compared with that in eyes at stage 5 ROP (82 eyes). The onset and symptoms were evaluated.

Late recurrence of retinal detachment following successful vitreous surgery for stages 4B and 5 retinopathy of prematurity.

RESULTS: A recurrent RD occurred in 2 eyes (5%) at stage 4B ROP and 18 eyes (22%) at stage 5 ROP (P = .01). The recurrence developed at 2 to 10 years of age (median, 4 years). Prior to the recurrence, clear signs of traction on the peripheral retina were detected in 10 eyes (50%): localized residual RDs in 8 eyes, and peripheral retinal breaks in 2 eyes. Dense vitreous hemorrhage was present in 5 eyes (25%) at the time of the recurrence.

The retina of eyes at stage 5 ROP is more vulnerable to a recurrence of the RD than in eyes at stage 4B after being attached by vitrectomy. The time of recurrence varies widely, and the presence of traction on the peripheral retina may be a sign of a recurrence.

CONCLUSION:

PREVENTION OF ROP

Judicious oxygen therapy Judicious use of blood transfusions Strict clinical and electronic monitoring Vitamin E supplementation Prenatal steroids

PROGNOSIS

Predicted by the stage of retinopathy of prematurity. 

Patients who did not progress beyond stage I or stage II have a good prognosis. 

Patients with posterior zone I disease or stage III, IV, or V have a guarded prognosis for their vision.

Thank you!!