Romanian Journal of Ophthalmologyrjo.ro/wp-content/uploads/2015/10/images_RJO_3_opt.pdfRomanian Journal of Ophthalmology Volume 59, Issue 3, July-September 2015 Contents Editorial

Romanian

Journal of

Ophthalmology

Romanian Society of Ophthalmology

www.rjo.ro

Volume 59, Issue 3, 2015

Romanian Journal of Ophthalmology

EDITOR-IN-CHIEF Mihail Zemba, M.D., Ph.D. Bucharest, Romania

E-mail: [email protected]

ASSOCIATE EDITOR Ovidiu Musat, M.D., Ph.D. Bucharest, Romania


EXECUTIVE EDITOR Victor Lorin Purcarea, Ph.D. Bucharest, Romania


ASSISTANT EDITORS Horia Stanca, M.D., Ph.D. Bucharest, Romania

E-mail: [email protected] Daniel Branisteanu, M.D., Ph.D. Iasi, Romania


INTERNATIONAL EDITORIAL ADVISORY BOARD

Prof. Khaled al Rakhawy, M.D., Ph.D. Cairo, Egipt Daniel Baron M.D., Ph.D. Nantes, France Prof. Zsolt Biro M.D., Ph.D. Pecs, Hungary Prof. Derald Brackmann M.D., Ph.D. Los Angeles, USA Thiery Chazalon M.D., Ph.D. Nantes, France Prof. Gabriel Coscas M.D., Ph.D. Paris, France Prof. J.J. De Laey M.D., Ph.D. Gent, Belgium Prof. Cesare Forlini M.D., Ph.D. Ravenna, Italy

Prof. Fabias Hoehn M.D., Ph.D. Pforzheim, Germany Prof. Christian Paul Jonescu-Cuypers M.D., Ph.D. Berlin, Germany Prof. Slobodanka Latinovic M.D., Ph.D. Novi Sad, Serbia Prof. Dan Milea M.D., Ph.D. Angers, France Gabor Rado M.D., Ph.D. Budapest, Hungary Prof.Gabor Scharioth M.D., Ph.D. Recklinghausen, Germany Prof. Wolfgang Schrader M.D., Ph.D. Wuerzburg, Germany Prof. Fankhauser Franz M.D., Ph.D. Bern, Switzerland

NATIONAL EDITORIAL ADVISORY BOARD

Assoc.Prof. Florian Balta, M.D., Ph.D. Bucharest, Romania Prof. Dorin Chiselita M.D., Ph.D. Iasi, Romania Assoc. Prof. Mircea Filip M.D., Ph.D. Bucharest, Romania Prof. Mihnea Munteanu M.D., Ph.D. Timisoara, Romania Assoc.Prof. Cristina Stan M.D., Ph.D. Cluj Napoca, Romania

Calin Tataru M.D.,Ph.D. Bucharest, Romania Prof.Dr. Cristina Vladutiu M.D., Ph.D. Cluj Napoca, Romania Daniela Selaru M.D., Ph.D. Bucharest, Romania Prof. Adriana Stanila M.D., Ph.D. Sibiu, Romania Cornel Stefan M.D., Ph.D. Bucharest, Romania

NATIONAL EDITORIAL BOARD

Gheorghe Anghel M.D., Ph.D. Bucharest, Romania Eugen Bendelic M.D., Ph.D. Chisinau, Republic of Moldova Camelia Bogdanici M.D., Ph.D. Iasi, Romania Daniel Branisteanu M.D., Ph.D. Iasi, Romania Marian Burcea M.D., Ph.D. Bucharest, Romania Catalina Corbu M.D., Ph.D. Bucharest, Romania Mihaela Coroi M.D., Ph.D. Oradea, Romania Valeria Coviltir M.D., Ph.D. Bucharest, Romania Valeriu Cusnir M.D., Ph.D. Chisinau, Republic of Moldova Danut Costin M.D., Ph.D. Iasi, Romania Monica Gavris M.D., Ph.D. Cluj Napoca, Romania Karin Horvath M.D., Ph.D. Tg. Mures, Romania

Sanda Jurja M.D., Ph.D. Constanta, Romania Carmen Mocanu M.D., Ph.D. Craiova, Romania Cristina Nicula M.D., Ph.D. Cluj Napoca, Romania Monica Pop M.D., Ph.D. Bucharest, Romania Mihai Pop M.D., Ph.D. Bucharest, Romania Alina Popa-Cherecheanu M.D., Ph.D. Bucharest, Romania Vasile Potop M.D., Ph.D. Bucharest, Romania Speranta Schmitzer M.D., Ph.D. Bucharest, Romania Horia Stanca M.D., Ph.D. Bucharest, Romania Ioan Stefaniu M.D., Ph.D. Bucharest, Romania Simona Talu M.D., Ph.D. Cluj Napoca, Romania Liliana Voinea M.D., Ph.D. Bucharest, Romania

PUBLISHING EDITORS

Consuela Madalina Gheorghe, Bucharest, Romania Petrut Radu, Bucharest, Romania Dodu Petrescu, Bucharest, Romania

EDITORIAL OFFICE

"Dr. Carol Davila"Central Military University Emergency Hospital 134 Calea Plevnei Street, District 1, Bucharest, Romania Phone number/Fax: +40.21.3137189 E-mail:[email protected], Typesetting and cover graphic: P. Radu

Volume 59, Issue 3 July-September

2015

© All the rights on the journal belong to the Romanian Society of Ophthalmology. The partial reproduction of the articles or of the figures is possible only with the written consent of the Romanian Society of Ophthalmology. The responsibility of the articles’ originality belongs entirely to the authors.

ISSN 2457 – 4325 ISSN-L 2457 - 4325

mailto:[email protected]




Romanian Journal of Ophthalmology Volume 59, Issue 3, July-September 2015

Contents

Editorial

EBOD – The european standard examination in Ophthalmology Sefan Cornel

127

Reviews Assessment of clinical and imagistic structural progression in glaucoma Alina Popa Cherecheanu, Raluca Iancu, Ana-Maria Dascalu, Dragos Serban, Ruxandra Pirvulescu

129

Diabetic macular edema Ovidiu Musat, Corina Cernat, M. Labib, Andreea Gheorghe, Oana Toma, Madalina Zamfir, Ana Maria Boureanu

133

Anomalous head postures in strabismus and nystagmus- diagnosis and management - Luminita Teodorescu

137

General articles The role of systemic blood pressure in glaucoma progression Silvia Mariana Chiotoroiu, Oana Stefaniu, Monica Noaghi, Alexandra Teodorescu, Lavinia Taina

141

Selective laser trabeculoplasty – short term efficacy and safety profile in open angle glaucoma or ocular hypertension treatment Dorin Chiselita, Alina Cantemir, Anca Delia Pantalon

148

Clinical impact in the management of neovascular glaucoma Halil Ajvazi, Pajtim Lutaj

154

Fuchs endothelial corneal dystrophy: is femtosecond laser – assisted cataract surgery the right approach? Monica Gavriş, Ioan Horge, Elena Avram, Roxana Belicioiu, Ioana Alexandra Olteanu, Hanga Kedves

159

Case reports Anterior chamber synchysis scintillans a case report Ana Banc, Cristina Stan

164

Retinal angiomatous proliferation case report Olaru Andrei., Olaru Denissa-Greta, Nicolcescu Andreea, Olaru Cristian, Popescu Mihaela, Deca Andreea-Gabriela, Mocanu Carmen

167

Nonichemic central retinal vein occlusion associated with hereditary thrombophylia Andreea Dana Fişuş, Doina Suzana Pop, Monica Blanka Rusu, Florina Vultur Karin Ursula Horvath

172

A rarer form of angle-closure glaucoma - diagnosis and treatment Zemba Mihail, Stamate Alina-Cristina, Avram Corina Ioana, Malciolu Radu, Neacsa Raluca, Oprea Stefan, Ivascu Diana Gabriela, Burcea Marian

177

Persistent pupillary membrane or accessory iris membrane? Monica Gavriş, Ioan Horge, Elena Avram, Roxana Belicioiu, Ioana Alexandra Olteanu, Hanga Kedves

184

Plateau iris syndrome – case series Crenguța Ioana Feraru, Anca Delia Pantalon, Dorin Chiselita, Daniel Branisteanu

188

Current options for surgical treatment of glaucoma Ştefan Cornel, Batras Mehdi, Iliescu Daniela Adriana, Timaru Cristina Mihaela, De Simone Algerino, Hosseini-Ramhormozi Jalaladin

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EDITORIAL

127 Romanian Society of Ophthalmology

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EDITORIAL

EBOD – The european standard examination in Ophthalmology

EBOD (European Board of Ophthalmology Diploma) – is organized by the European Board of

Ophthalmology EBO) and it is under the administration (guidance) of the Education Committee of EBO.

This exam is designed to assess the knowledge and clinical requisite skills needed for delivering high standard ophthalmologic care. The focus of the exam is on the harmonization of ophthalmology training across Europe, by the standards set up by Brussels (Respecting the standards that Brussels imposed).

The first EBOD examination was organized in 1995, in Milan. Thereafter, it took place only in Paris, usually in May, hosted by the French Society of Ophthalmology (SFO) and Thea Laboratories. Candidates from all over Europe register for this exam. The pass rate over the past years has been approximately 90%.

The EBOD Examination is not mandatory in most countries of the European Union. However, some countries like Switzerland and Belgium have replaced their National Specialist Examination with this exam.

The number of candidates who can register for the exam is limited. For a candidate to be eligible to take the EBOD Examination, he has to be a certified Specialist in Ophthalmology or in the last year of residency in a country of the European Union, Norway, Switzerland, Croatia or Turkey. Certified specialists or doctors in their last year of residency that come from other countries are eligible to sit the examination if they have completed additional formal training in the countries listed above.

The internationally recognised diploma, the possibility to interact and share opinions and ideas with ophthalmologists from all over Europe, determines the high number of candidates each year.

The exam consists of two parts: a written paper (MCQ-paper) of 52 questions, representing 40% of the final grade, and an oral examination (Viva voce), representing the remaining 60%.

Negative marking has been adopted for the MCQ paper grading since the 2010 Diploma Examination. This means that a negative mark (-0.5) will be applied in the case of an incorrect, double marked answer (when both true and false are ticked; when true and don’t know are ticked; when false and don’t know are ticked) or triple marked answered (when all options are ticked). Choosing the 'don't know' option will result in a score of 0 points. One point can be earned for each correct answer. Studies have shown that this type of grading does not affect the pass rate of the candidates, but reduces the frequency of “wild guessing” of the answers.

The Written Paper (MCQ-paper) There are 52 questions, each containing 5 statements that need to be judged as “true” or “false”.

The questions cover any basic science, medical or surgical topic relevant to the practice of ophthalmology, particularly in the following fields:

1. Optics, Refraction and Contact Lenses 2. Pediatric Ophthalmology and Strabismus 3. External, Corneal and Adnexal disease 4. Glaucoma, Cataract and Refractive Surgery 5. Retina, Vitreous and Uvea 6. Neuro-ophthalmology 7. Orbital Disease and Oculoplastic Surgery 8. General Medicine relevant to Ophthalmology 9. Ophthalmic Pathology, Microbiology and Immunology

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10. Pharmacology and Therapeutics The Oral Examination (Viva voce) Every candidate will sit on 4 separate sessions, of 15 minutes each, conducted by four panels of

two examiners. The debated subjects are:

1. Optics, Refraction, Strabismus, Pediatric ophthalmology and Neuro-ophthalmology 2. Cornea, External Diseases, Orbit and Ocular Adnexa 3. Glaucoma, Cataract and Refractive Surgery 4. Posterior Segment, Ocular Inflammation and Uveitis

Bibliography The recommended reading for the EBOD Examination contains Kanski and the AAO (American

Association of Ophthalmology) series, Spalton, Atlas of Ophthalmology, Wills Eye Manual and Moorfields Eye Hospital Manual.

Candidates have the right to appeal to the EBO Education Committee if they believe that they have been misjudged. They have to send such appeals within three months of the date of examination. The Education Committee will respond to the Candidate in writing within three months of the receipt of the appeal.

The EBOD diplomas are received at a Diploma Award Ceremony. At this ceremony, in the presence of the Executive Committee of EBO and the Board of Examiners, the candidates who passed the EDOB Examination will be presented with their European Board of Ophthalmology Diploma, signed by the President and all Vice-Presidents of the Board. Candidates can, and are encouraged to add the title of Fellow of the European Board of Ophthalmology (FEBO) after their name.

Every year, the Peter Eustace Medal is also awarded. Awarding a Peter Eustace Medal was established by unanimous decision of General Assembly of the European Board of Ophthalmology (EBO) in Tallinn on 20th June 2010 as a token of appreciation of the efforts of Peter Eustace, who established the first EBO diploma examination in Milan in 1995. This award is given to an ophthalmologist who has devoted long term and exceptional efforts towards upgrading education in ophthalmology in Europe. This year, the medal was awarded to Prof. Marie-Jose Tassignon, MD, PhD, FEBO, current Professor and Head of Ophthalmology at the University Hospital in Antwerp, Belgium, who also served as president of EBO and the ESCRS (European Society of Cataract and Refractive Surgeons).

In 2015, over 550 candidates from 28 European countries, met in Paris to take part in the EBOD Examination.

For the first time, this year, the exam also included a subspecialty examination in glaucoma, co-organized by Carlo Traverso, President of the European Glaucoma Society. Successful candidates were awarded a diploma: the Glaucoma Subspecialty EBO Diploma, as an acknowledgement of their knowledge and competence in this field.

From Romania, in the last 6 years, a raising number of candidates set on the EBOD Examination, the pass rate being 100%. However, the number of participants is still below the level of other countries in the area. National Delegates of EBO (Assoc. Prof. Dr. Marian Burcea and Dr. Cornel Stefan) constantly promote the participation of Romanian candidates to this exam.

Romania has a national examiner, so it is possible to facilitate the examination in Romanian. For more information about registration and general information on the EBOD Examination,

visit http://ebo-online.org/newsite/EBODexam.

Stefan Cornel, MD, PhD, FEBO

National Delegate of EBO, National Editorial Advisory Board Member Central Military Emergency University Hospital „Dr. Carol Davila”,

Ophthalmology Department, Bucharest 134 Calea Plevnei Street, District 1, Bucharest

Tel/Fax: +40 21 313 71 89 E-mail: [email protected]

http://ebo-online.org/newsite/EBODexam


REVIEW


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ASSESSMENT OF CLINICAL AND IMAGISTIC STRUCTURAL PROGRESSION IN GLAUCOMA

Alina Popa Cherecheanu, Raluca Iancu, Ana-Maria Dascalu, Dragos Serban, Ruxandra Pirvulescu

“Carol Davila” University of Medicine and Pharmacy

Correspondence to: Alina Popa Cherecheanu 4 bis Berzei Street, Bucharest, Romania Mobile phone: +40723507047, E-mail: [email protected]

Accepted: July 10, 2015

Abstract Glaucoma is a progressive optic neuropathy, characterized by loss of retinal ganglion cells and retinal nerve fiber layer as well as visual field loss. Therefore, in glaucoma, the correlation between structure and function is important, since it can be useful for tracking glaucomatous changes and for following the progression of the disease. Keywords: glaucoma progression, structural progression, optic nerve damages, optical coherence tomography

Glaucoma is a progressive optic neuropathy, characterized by loss of retinal ganglion cells and retinal nerve fiber layer (RNFL) as well as visual field loss [1,2]. Therefore, in glaucoma, the correlation between structure and function is important, since it can be useful for tracking glaucomatous changes and for following the progression of the disease [3].

In everyday practice, spectral domain ocular coherence tomography (SD-OCT) became rapidly one of the most outspreaded technologies, due to the high resolution of the images and to the accuracy of measurements. It is assumed that thickness changes in RNFL usually precede visual field defects [4].

Histological findings show that visual field defects occur only after the loss of an important number of retinal ganglion cells [5,6]. Furthermore, it has been proved that in the initial stages of glaucoma, modifications of the optic nerve are more obvious than those in the visual field, while in more advanced stages, visual field changes are more pronounced comparing to the morphological changes [7].

Assessment of the optic disc and RNFL is an

essential step in detecting glaucoma progression

and consists of: slit lamp examination using

proper lenses (60D, 78D, 90D) or by stereo

photography, when is possible. If stereo

photography is not available, describing

cup/disc ratio and drawing the optic disc

appearance can be useful for quantifying its

aspect at a certain moment. However, the high

interobserver variability makes this method a

limited one, whenever assessment of

progression is necessary. Although stereo

photography of the optic disc offers an objective

documentation, it can be interpreted in a very

subjective way.

While examining serial photographs of the

optic disc, made during time, for spotting the

progression, clinician must look for the following

elements (Fig. 1): - Diffuse or focal enlargement of optic

nerve cup, with the corresponding shrinking of the neuroretinal rim. Usually, the enlargement of the optic nerve cup is vertical, first changes being


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spotted at the inferior or superior sectors of the excavation;

- Displacement of retinal vessels

concomitant with the enlargement of the

excavation, due to the disappearance of the

tissular support. The displacement is mostly

nasal, the typical aspect being “bayonet”-like;

- Peripapillary hemorrhages –with a

“flame”like aspect, usually located in the inferior

sector of the optic disc. Approximately 60% of

the glaucoma patients that have a peripapillary

hemorrhage develop progression of the visual

field defects, corresponding to the location of the

haemorrhage, in the next 16 months.

- Development and widening of the retinal

nerve fiber layer defects.

- Widening of the peripapilary atrophy. A

loss of neuroretinal rim and a correspondent

visual field defect can occur correspondent with

the atrophic area.

One has to remember that poor quality

images and the differences of exposure, focus,

magnification and angle of acquiring the image

scan give a false impression of evidence of

progression. Optical coherence tomography (OCT)

Time Domain OCT (TD OCT) Stratus OCT provides images with an axial

resolution of 8-10 µ and a transverse resolution of about 20 µ. The device can acquire several sections, linear or circular, but the most used to assess glaucoma is "Fast RNFL Scan". This makes a circular scan centered on the optic nerve, with a diameter of 3.4 mm, automatically determining the thickness of the RNFL, which is reported as the average thickness in the 4 quadrants of the 12 hours, a thinning of RNFL being an early sign of glaucoma. Quantitative information about the optic nerve and macular thickness are also provided.

It is shown that OCT has a high reproducibility intra- and interest in detecting diffuse or focal glaucomatous defects. Therefore, little variability in the measurements of RNFL makes OCT to be a useful tool for longitudinal follow-up of patients and to detect progression. In terms of repeatability of data, it is accepted that, in 95% of measurements made in 2 consecutive days in the same eye, to obtain a mean RNFL changed by no more than 8 to 9.5 µ. Values outside this range can suggest progression. Also, the variability is higher in quadrants and sectors compared to those recorded in the average RNFL thickness.

Stratus OCT latest model shave the following three ways of determining the change occurring over time (Fig. 2):

- A summary of the average RNFL

thickness, including upper and lower quadrants

at all visits.

- A graphical representation of RNFL

thickness at all visits.

- A linear regression analysis to determine

the thickness of the RNFL change over time.

Fig.1 Evolution of structural defects after 3years; diffuse thinning of the temporal and inferotemporal rim, evolving localized defect ("notch") after resolution of papillary hemorrhage; C/D ratio has increased from 0.5 (initial) to 0.7 (final).


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The first two methods allow the

identification of changes occurring over time, but do not indicate the significance of this change. Linear regression analysis indicates whether the change is significant only to "zero slope" (no change). In most cases this change may be due to RNFL loss caused by ageing process, which according to studies can vary between 0.16 to 0.31 µ/year. Therefore, this type of analysis can indicate the change because of the physiological loss due to aging and not always due to progression of glaucoma.

Clinical studies that have evaluated the utility of TD-OCT in assessing the progression revealed a higher rate of progression detected with OCT compared with standard automated perimetry, suggesting that OCT might be more sensitive to change. This conclusion can be explained by the fact that structural changes precedes functional loss in glaucoma or it may represent a high false positive rate. Therefore, further longitudinal studies are needed to better understand how to discriminate between the real progression of the disease and the false positive results.

Spectral Domain OCT (SD-OCT)

SD-OCT represents a newer generation of OCT, with a shorter scanning time and increased resolution comparing to TD-OCT (axial resolution of 5-6 µ meters and transverse resolution of 20 µ meters). It also offers 3D images of the scanned areas. Due to these improvements and the very good intra-test and inter-test reproducibility, SD-OCT is a very efficient tool in detection of glaucoma progression. A decrease of 4 µ meters or more of the RNFL thickness may represent a real structural change suggestive for progression. The most important devices that use this technology are: Spectralis OCT (Heidelberg Engineering Carlsbad, California), Cirrus HD-OCT (Carl Zeiss Meditec), RTVue-100 (Optovue,

Fremont, California) and Topcon 3D-OCT 2000 (Topcon, Oakland, New Jersey). Each of these has a different scanning model and different software for glaucoma progression analysis.

Cirrus HD-OCT Guided Progression Analysis (GPA) offers a comparison between the first visit (set as baseline) and the following exams in terms of RNFL thickness measured circumpapillary in a circle of 3.4 mm diameter centered on the optic disk. It also provides a linear regression analysis of the mean RNFL thickness, for the superior and the inferior quadrants and for C/D ratio. The software also reports the change from baseline for every scanned pixel, which also makes possible the analysis of change outside the circumpapillary area, when we suspect the extension of the defects outside the limits of the scan circle (Fig. 3).

In progression analysis using SD-OCT,

artifacts should be carefully detected and corrected. Except for the Spectralis OCT with its eye-tracking technology, motion artifacts can

Fig. 2 Change of average RNFL thickness, statistically insignificant

Fig. 3 GPA showing progression


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occur and interfere with accurate progression analysis.

Media opacity or irregular corneal surface can cause suboptimal OCT image quality that also affects the RNFL or macular thickness measurements. Coexisting posterior segment pathologies including epiretinal membrane and retinoschisis may cause overestimation of RNFL or macular thickness, leading to false-negative results. Additionally, clinicians should also consider age-related decline of RNFL and macular thickness when assessing glaucoma progression [8].

References

1. Quigley HA, Addicks EM, Green WR: Optic nerve damage in human glaucoma. III. Quantitative correlation of nerve fiber loss and visual field defect in glaucoma, ischemic neuropathy, papilledema, and toxic neuropathy. Arch Ophthalmol 1982, 100:135–146.

2. Quigley HA, Dunkelberger GR, Green WR: Retinal

ganglion cell atrophy correlated with automated perimetry in human eyes with glaucoma. Am J Ophthalmol 1989, 107:453–464.

3. Hirooka K et al: Use of the structure-function relationship in detecting glaucoma progression in early glaucoma. BMC Ophthalmology 2014, 14:118

4. Hood DC, Kardon RH: A framework for comparing structural and functional measures of glaucomatous damage. Prog Retina Eye Res 2007, 26:688–710.

5. Kerrigan-Baumrind LA, Quigley HA, Pease ME, et al.: Number of ganglion cells in glaucoma eyes compared with threshold visual field tests in the same persons. Invest Ophthalmol Vis Sci, 2000;41:741–8.

6. Quigley HA, Dunkelberger GR, Green WR: Retinal ganglion cell atrophy correlated with automated perimetry in human eyes with glaucoma. Am J Ophthalmol, 1989;107: 453–64.

7. Bartz-Schmidt KU, Thumann G, Jonescu-Cuypers CP, et al.: Quantitative morphologic and functional evaluation of the optic nerve head in chronic open-angle glaucoma. Surv Ophthalmol, 1999;44:S41–53.

8. Lyu Th, Park SC:How OCT helps monitor glaucoma progression. Ophthalmology Management, Volume: 18 , Issue: July 2014, page(s): 42-45


REVIEW


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DIABETIC MACULAR EDEMA Ovidiu Musat, Corina Cernat, M. Labib, Andreea Gheorghe, Oana Toma, Madalina Zamfir, Ana Maria Boureanu

Correspondence to: Cernat Corina Cristina M.D. 31 Dinicu Golescu Blvd, Floor 4, District 1 Mobile phone: +40721 567 809, E-mail: [email protected] Accepted: July 15, 2015

Abstract Diabetic macular edema (DME) remains the most common cause of vision loss among diabetic patients. New understanding of the underlying pathophysiology has interest in the potential benefits of the specific pharmacologic therapy, such as treatment with intraocular steroids, anti-vascular endothelial growth factor (VEGF), and protein kinase C-beta (PKCβ) inhibition. At the last time, laser photocoagulation, according to the guidelines of the Early Treatment of Diabetic Retinopathy Study (ETDRS), continues to be primary standard care treatment in most communities. Optical coherence tomography (OCT) is very useful in monitoring macular edema progression and response to treatment. Key words: diabetic macular edema, risk factors, clinical presentations, physiopathology

Definition

Diabetic macular edema (DME) is

manifested as retinal thickening caused by the

accumulation of intraretinal fluid, primarily in

the inner and outer plexiform layers. It is

believed to be a result of hyperpermeability of

the retinal vasculature. DME can be present with

any level of diabetic retinopathy.

ETDRS Criteria for Clinically Significant Macular

Edema (CSME)(1):

• Retinal thickening at the center of the

macula

• Retinal thickening and/or adjiacent hard

exudates at or within 500 µ of the center

of the macula ( Fig. 1 )

• An area of retinal thickening greater

than or equal to one disc area, any part of

which is within 1 disc diameter of the

center of the macula

Prevalence and incidence [1] [2]

In USA: The WHO (World Health Organization) estimates 15 million DME half

Fig. 1 CSME


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undiagnosed and 50% of 8 million without eye care, 25-30% risk of vision loss from CSME. International, WHO estimates more than 150 million patients with diabetes worldwide. However, the absolute prevalence of DME might be increasing due to the overall increased prevalence of diabetes in industrialized nations. It is expected that the incidence of DME will decrease as excellent metabolic control is increasingly embraced as a therapeutic goal by patients and health care workers.

Pathology and pathophysiology of dme

Normal retinal circulation is unique: retinal capillaries are non-fenestrated and capillary endothelial cells have tight jonctions; normal capillaries do not leak fluid, blood. There is no lymphatc system in the retina, so in the presence of retinal pathology, leaking fluid can accumulate and cause edema or swelling. Retina responds to ischemia by stimulating growth factors to produce new vessels (called neovascularization).

DME is the result of microvascular changes in diabetes leading to incompetence of vessels, edema. Hypoxic state stimulate VEGF causing more edema.

Thus, 2 key changes occur: • Vessel permeability - Damaged endothelial wall becomes more

porous - Vessel leaks fluid, lipids, erythrocytes - Accumulation of the fluid results in

edema (macular edema if located within the central region of the retina)

• Vessel closure - Supply of oxigen and nutrients are

decreased New fragile growth occurs (secondary to

ischemia)

Clinical associations and risk factors

Macular edema is strongly positively associated with diabetic retinopathy severity. Glycemic control is a conclusively identifies risk factor for retinopathy progression as well as for DME. Duration of diabetes is strongly correlated with prevalence and incidence of macular edema, retinopathy progression, and other diabetic complications. The diagnosis of diabetes in type 2 subjects occasionally occurs sometime after subclinical diabetes has been manifest, which yields a small proportion of patients who may present with macular edema at the time of diagnosis, or even have decreased vision from macular edema at the presenting sign. In contrast, persons with type 1 diabetes are very unlikely to experience advanced retinopathy and macular edema before 5 years of duration.

Clinical Associations with Diabetic Macular Edema Severity: [2] [3]

• Duration of Diabetes – increased risk of diabetic retinopathy

• Glycemic control – The Diabetes Control and Complication Trial (DCCT) clearly demonstrated that tighter control of blood sugar is associated with reduced incidence of diabetic retinopathy (Glycosylated hemoglobin (HbA1c) should be less than 7%)

• Nephropathy – proteinuria is a good marker for development of diabetic retinopathy; thus, patients with diabetic with nephropathy should be observed more closely

• Hypertension – increased risk of retinopathy (diabetic retinopathy with superimposed hypertensive retinopathy)

• Dislipidemia – normalization of lipid levels reduces retinal leakage and exudates deposition

• Pregnancy – diabetic retinopathy can progress rapidly in pregnant women, especially those with preexisting diabetic retinopathy

• Intraocular surgery • Uveitis • Panretinal Photocoagulation

Clinical presentation of diabetic macular edema

Patients with DME present with a range of visual symptoms depending on the degree to

Fig. 2 Photomicrograph of cystoids spaces and subretinal fluid in the retina of a diabetic patient with severe DME


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which the fovea is involved and the chronicity of the edema. If the macula center is not involved patients are rarely symptomatic; only a few very observant individuals may notice relative paracentral scotomas corresponding to focal edema and hard exudates. Some patients with central macular involvement have excellent acuity and no visual complains, presumably because of only recent involvement of the center. Over time, patients experience a gradual progressive vision loss over weeks to month. Patients may complain of loss of color vision, poor night vision and washing-out of vision in bright sunlight with poor dark-light adaptation.

Metamorphopsia is not uncommon. Frequently, patients with center involved DME note fluctuation of vision from day-to-day or even over the course of a day. In some cases, the patient may relate such changes to fluid retention, hyper or hypoglycemia, or ambient lighting.[4][5]

On fundus examination with slit lamp biomicroscopy or contact lens, retinal thickening may present in some commonly identified patterns. Focal edema often occurs associated with a cluster of microaneurysms, sometimes surrounded by an incomplete ring of hard exudates. Diffuse DME may be very difficult to identify clinically if the retina is of uniform thickness, due to the lack of reference landmarks. Clues include the height of the retinal blood vessels over the pigment epithelium, loss of the foveal depression or even cystoids spaces. Other features sometimes seen with macular edema include variable loss of retinal transparency, a large burden of microaneurysms and intraretinal hemorrhages, and dispersed flecks of hard exudates.

Stereoscopic fundus photographs provide an opportunity to evaluate long-term changes in the retina.

Fluoresceine angiography is useful in demonstrating the breakdown of the blood-retinal barrier by delineating retinal capillary leakage and capillary nonperfusion. Fluorescein angiography is not relevant in aiding in the diagnosis of CSME but should be performed if treatment of CMSE is being considered.

Optical coherence tomography (OCT) is able to demonstrate a moderate correlation between retinal thickness and best corrected visual acuity, and it is able to demonstrate 3 basic structural changes of the retina from diabetic macular edema, that is, retinal swelling, cystoid edema, and serous retinal detachment. OCT is not currently required to establish a diagnosis and is not prescribed by current practice guideline; however, OCT has gained widespread acceptance as an additional modality to help identify and evaluate macular pathology. Quantitative measurement of macular thickness and subjective analysis of the foveal architecture allow a precise and reproducible way to monitor macular edema.

Fig.3 Color photograph of a diabetic patient with focal macular edema, with circinate hard exudates roughly circumscribing the area of retinal thickening

Fig. 4 Color photograph of a diabetic patient with diffuse macular edema

Fig. 5 OCT scan demonstrates cystoid edema


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Treatment

Optimizing diabetic, hypertensive, and lipid control has been shown to positively impact diabetic retinopathy.

The ETDRS conclusively demonstrated that focal/grid laser photocoagulation was safe and effective in reducing vision loss due to DME. Significant visual improvement is uncommon; the goal of macular laser treatment is to reduce progression. [6] Photocoagulation reduced the risk of moderate visual loss from diabetic macular edema by 50%, from 24% to 12%, 3 years after initiation of treatment. Laser treatment is most effective when initiated before visual acuity is lost from diabetic macular edema; this emphasizes the need for diligent monitoring and follow-up care. Fluorescein angiography and fundus photos are obtained prior to initiation of laser theraphy. Ophthalmologist views the FA to guide treatment of CSME: for focal leakage, direct laser theraphy using green-only Argon laser is applied to all leaking microaneurysm between 500 and 3000 µm from the center of the macula; for diffuse leakage of capillary nonperfusion adjiacent to the macula, a light-intensity grid pattern using green-only Argon laser is applied to all areas of diffuse leakage more than 500µm from the center of the macula and 500µm from the temporal margin of the optic disc. Multiple sessions spread out over many months are frequently necessary for resolution of DME.

Given the importance of VEGF in vascular permeability and its up regulation in diabetic retinopathy, the rationale for use of anti-VEGF drugs is clear. Current specific anti-VEGF therapy is given intravitreal at frequent intervals, which may temporarily blunt the effects of VEGF and lessen macular edema.

Intravitreal triamcinolone acetonide (IVTA) has been shown to significantly reduce macular edema and to improve visual acuity, particularly when macular edema is pronounced. Some studies advocate IVTA as primary therapy, whereas others label it as adjunctive therapy to macular photocoagulation.[7][8]

A subset of patients with DME has coexistent epiretinal membranes and/or partial posterior vitreous detachment with retinal traction. These patients may benefit from pars

plana vitrectomy to address the mechanical issues contributing to the retinal edema. Even without obvious retinal traction, some clinicians believe that many cases of DME respond to removal of the vitreous, with or without removal of the internal limiting membrane. No large randomized trials have evaluated the treatment to date.[9]

The landscape of DME management is rapidly changing with the advent of research advances leading to better understanding of pathophysiologic mechanisms and discovery of potential therapeutic compounds. There are several challenges that remain in bringing forth new treatments with adequate evidence base to guide clinicians in timely patient care.

References

1. Albert and Jakobiec’s Principles and Practice of Ophthalmology Third edition, second volume2008, Editura SAUNDERS ELSEVIER, Canada, page 1793 - 1996

2. Pr Gabriel Coscas Oedemes maculaires Aspects cliniques et therapeutiques , Editura Springer Science & Business Media, 15 sept. 2011, Spain, page 110 - 196

3. Oct & Retine dr. Marie – Benedicte Rougier, Pr. Marie – Noelle Delyfer, Pr. Jean- Francois Korobelnik Centre Hospitalier Universitaire de Bordeaux, Editura: Laboratoire Thea, 12 Rue Louise Bleriote, France, page 33- 63

4. 4.Miron Yanoff ” Ophtalmology” Fourth Edition, Editura: Elsevier – 2014, London, page: 600 - 715

5. Kanski “Clinical Ophtalmology: a systemic approach” Autor: Brad Bowling, Editura: Elsevier, 2015, page 615-668

6. Abu el Asrar, A. M., & Morse, P. H. (1991). Laser photocoagulation control of diabetic macular oedema without fluorescein angiography. Br J Ophthalmol, 75(2), 97-99, ISSN 0007-1161 (Electronic)

7. Bresnick, G. H. (1983). Diabetic maculopathy. A critical review highlighting diffuse macular edema. Ophthalmology, 90(11), 1301-1317, ISSN 0161-6420 ( Electronic )

8. Klein R, Klein BEK, Moss SE, Cruickshanks K: The Wisconsin Epidemiologic Study of Diabetic Retinopathy, XVII: the 14-year incidence and progression of diabetic retinopathy and associated risk factors in type I diabetes. Ophthalmology105:1801–1815, 1998, Editura: Arch Ophthalmology, San Francisco, page : 1801–1815

9. Medical Retina Essentials in Ophthalmology 2007, pp 131-146 Diabetic Macular Edema: Current Treatments.Florian K. P. Sutter, Mark C. Gillies, Horst Helbig Editura: Springer , Berlin Heidelberg NewYork, page 131-146

http://www.callisto.ro/editura/elsevier--i89

http://www.callisto.ro/editura/elsevier--i89

http://link.springer.com/book/10.1007/978-3-540-33672-3

http://link.springer.com/bookseries/5332

http://link.springer.com/search?facet-author=%22Florian+K.+P.+Sutter%22

http://link.springer.com/search?facet-author=%22Mark+C.+Gillies%22

http://link.springer.com/search?facet-author=%22Horst+Helbig%22

http://link.springer.com/search?facet-author=%22Horst+Helbig%22


REVIEW


© 2015

ANOMALOUS HEAD POSTURES IN STRABISMUS AND NYSTAGMUS

- DIAGNOSIS AND MANAGEMENT -

Luminita Teodorescu OFTALMIX Ophthalmology Clinic Bucharest, Romania:

Correspondence to: Luminita Teodorescu 11 B Turturelelor, Bl A, ap 3, District 3, Cod 030881, Phoenicia Business Center, Bucharest, Romania Mobile phone:+40 722 377 117, Email: [email protected]


Abstract Abnormal head positions are adopted in order to improve visual acuity, to avoid diplopia or to obtain a more comfortable binocular vision. The head can be turned or tilted toward right or left, with the chin rotated up or downwards or combination of these positions. The ophthalmologic examination including the assessment of versions leads to the diagnosis. When versions are free, the cause may be congenital nystagmus or strabismus with large angle. When versions are limited we suspect paralytic or restrictive strabismus. The head tilted to one shoulder suggests cyclotropia (IV Nerve Palsy) or congenital nystagmus. We present few of the above cases. An adequate surgical treatment can improve or correct the ocular deviation, diplopia and the abnormal head posture. Conclusions: The abnormal head posture must be assessed and treated early in order to correct the ocular position and head posture. All patient presenting abnormal head position HAD TO BE investigated by an ophthalmologist. Key words: Anomalous head posture, head turn, head tilt, chin-up, chin-down head posture

Introduction

There is nearly always a significant reason for an abnormal or compensatory head position and the patient often may adopt it unconsciously.

The cause may be an ocular, muscular, skeletal or neurological disease. Very rare it may be a habit, without any reason to adopt it.

The most common cause is an ocular disease. The posture is adopted in order to:

1. Improve visual acuity or obtain a more comfortable binocular vision, like in: unilateral amblyopia, oblique astigmatism, nystagmus.

2. To avoid diplopia – in patients where fusion can be obtained, the deviation and diplopia disappear in the compensatory position. [1].

If the cause is an ocular disease, a simple test can be done: occluding one eye prevents


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diplopia and the compensatory head posture will disappear.

3. To increase the separation of the images when there is no fusion like in a large angle strabismus.

The ophthalmologic examination must emphasize the assessment of ductions and versions:

When versions are free, the cause may be a congenital nystagmus, infantile esotropia, dissociated vertical deviation, large deviation with amblyopia.

In infantile nystagmus, the null zone is the position of gaze in which the nystagmus dampened and the visual acuity (VA) is better.

When the null zone is not in primary position, the patient adopts a face turn, a head tilt, or a chin up or down position, especially during tasks when better vision for distance is required: TV, testing VA, blackboard. VA at near is often better because convergence associated with near vision block the nystagmus and no head turn is needed. [2].

Surgery is aimed to improve the head position, i.e. to shift the null zone toward the primary position. The rule is that eyes should always be shifted in the direction of the head posture.

The most used technique is “Large Anderson” operation: only 2 recessions of the yoke muscles: 7 mm Medial Rectus (MR) recession of the adducted eye 10 mm Lateral Rectus (LR) recession of the abducted eye. For larger face turn the surgery dose may be increased. [3].

Fig. 1 Congenital esotropia with manifest nystagmus, left eye fixing in adduction, head turned towards left, the direction of the left fixing eye – pre-op.

Fig. 2 Post-operative Fig. after bi-lateral medial rectus recession

Fig. 3 Infantile nystagmus with left face turn

Fig. 4 Post-operative after left Medial Rectus recession 7 mm, right lateral rectus recession 10 mm


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When versions are limited we suspect,

according to the clinical features: III or VI Nerve Palsy, Duane syndrome, general fibrosis syndrome, thyroid ophthalmopathy, orbital fractures.

The rule is: “The head moves where the eye cannot”, in order to avoid diplopia.

Fig. 5 Congenital nystagmus with combined vertical and horizontal null zone, chin-up and left face turn position

Fig. 6 Post-operative after left medial rectus recession 8.5 mm, right lateral rectus recession 12 mm, bi-inferior rectus recession 7 mm, bi-superior rectus resection 6 mm.

Fig. 7 (up or in the middle), 8 (left), 9 (right): Right VI nerve palsy after trauma, no abduction in the right eye

Fig. 10(up), 11(left), 12(right): After right medial rectus recession 6,5 mm and half-tendon transfer of the superior and inferior to the lateral rectus insertion.

Fig. 13 (up), 14 (left), 15(right): Right III Nerve Palsy, superior branch, exotropia and hypotropia, left head turn, no adduction


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The head tilted to one shoulder suggests

cyclotropia (IV Nerve Palsy), congenital nystagmus, Brown syndrome or non-ocular causes.

The patient tilts the head to compensate the tilted image.

Conclusions

- The abnormal head posture must be assessed and treated early in order to correct the ocular position and the head posture.

- An adequate surgical treatment improves or corrects the strabic deviation, diplopia and the abnormal head posture.

References

1. Noorden G. K, Helveston E. M, Strabismus. A decision making approach, St. Louis: Mosby;1996, 52-60

2. Helveston E. M. "Strabismus minute" Orbis Cybersight, Anomalous Head Posture and Strabismus, 1999, New York, Lecture 8 of 48

3. Helveston E. M. "Strabismus minute" Orbis Cybersight, Surgery Options for Nystagmus, 1999, New York, Lecture 21 of 48

Fig. 16 (up), 17 (left), 18 (right) Post-op, Right lateral rectus recession 14 mm, right medial rectus resection 9 mm with up-ward insertion

Fig. 19 Left Congenital IV nerve Palsy; Right head tilted, facial asymmetry

Fig. 20 Left hypertropia in primary position

Fig. 21 Bielschowsky head tilted test positive: hypertropia increases in tilting the head towards to side of the palsy

Fig. 22 Post-op, head straight, ortophoria, after left inferior oblique myectomy and left superior rectus recession

Fig. 23 Normal head tilted test


GENERAL ARTICLE


© 2015

THE ROLE OF SYSTEMIC BLOOD PRESSURE IN GLAUCOMA PROGRESSION

Silvia Mariana Chiotoroiu*, Oana Stefaniu**, Monica Noaghi***, Alexandra Teodorescu***, Lavinia Taina*** * “Nicolae Malaxa” Clinical Hospital, Bucharest ** Emergency Hospital of Ophthalmology Bucharest *** University Emergency Hospital Central Militar " Dr. Carol Davila" **** Emergency University Hospital of Bucharest

Correspondence to: Silvia Mariana Chiotoroiu PhD MD 167-177 Giurgiului Bldv., Bl E, 132 Room, District 4 Mobile phone: +40724 261 477, E-mail: [email protected] Accepted: July 18, 2015

Abstract The present paper aims to highlight the role of arterial hypotension in the progression of glaucoma. The data analyzed in this study was collected in a prospective manner for a period of one year, from september 2013 to august 2014. It includes newly diagnosed glaucoma patients treated with prostaglandin analogues and who have presented within normal range values of intraocular pressure during the study. In spite of good control of intraocular pressure, there was recorded a progression of glaucoma lesions documented using the visual field . All patients were evaluated through 24 h outpatient holter monitoring of systemic blood pressure (BP) and were consequently divided into three groups: Group A- non-dipper (within normal range of both diurnal and nocturnal BP values

and no significant drop during the night) Group B- dipper (patients with nocturnal hypotension recording BP drops of more

the X mmHg ) Group C- patients with arterial hypertension (defined as diurnal values of more than

150 mmHg for systolic BP and 110 mmHg for dyastolic BP) After through statistical analysis of the patients data, we noticed that the most important progression of glaucoma changes objectified by visual field and OCT examinations was recorded in group B, which illustrates the importance of careful monitoring and strict control of blood pressure in order to eliminate this risk factor in the progress of glaucoma. Key words: blood pressure, glaucoma, progression, risk factor, dipper, visual field, OCT

Introduction

Although the intraocular pressure is considered firstly the main risk factor in the emerging and evolution of glaucoma and,

secondly, the only parameter which can be treated, there is certain evidence in literature that suggests that glaucoma can advance in spite of normal values of intraocular pressure [1]. An important number of clinical studies conducted on large population groups pointed out the role


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of several risk factors in the patogenesys of glaucoma. One of the most important risk factor is the systemic blood pressure and the ocular perfusion pressure. Although, in clinical practice, the direct blood flow cannot be viewed directly in the eye, clinicians can measure the glaucomatous patients’ blood pressure and their intraocular pressure in order to calculate later the eye’s ocular perfusion pressure and quantify the microvascular modifications.

The main source of vascularization for the optic nerve is the posterior ciliary artery. The temporal region of the optic disk can be vascularized by branches of cilioretinal artery [4]. The prelaminar and laminar regions receive oxygen and nutrients from the short posterior ciliary arteries which have straight branches and form the scleral circulary arterial anastomosis and then the Zinn-Haller arterial ring. The retrolaminar region is vascularized by short posterior ciliary arteries and by branches of the central retinal artery through recurrent pial arteries. The intracranial part of the optic nerve is vascularized by the oftalmic artery and the Calos Body’s artery. The orbital part of the optic nerve is vascularized only by the oftalmic artery. The posterior ciliary artery, posterior short ciliary arteries, the central retinal artery and the cilioretinal artery are branches of the oftalmic artery, the latter being branch of the internal carotid artery [7].

After 24 h continuous recording of the blood pressure for glaucoma patients under correct therapy and without significant intraocular pressure fluctuations, there was observed a progression of lesions on the visual field examinations, especially for patients who presented lower than normal values of nocturnal blood pressure. A higher incidence of optic disk hemorrhages was reported in patients with nocturnal hypotension.

Between the ocular perfusion pressure and open angle glaucoma, it was proven that there is a certain association, due to the fact that intraocular pressure is part of ocular perfusion pressure [3].

The notion of „dipper” is defined as the reduction of blood pressure during night with more than 10% in comparison with the values measured during daytime. Patients who present a reduction of less than 10% of the nocturnal blood pressure are considered nondippers [2].

Objective

The purpose of this study is to review the role of blood pressure in the progression of glaucoma and to highlight the importance of vascular factors (cerebral hypoperfusion and hyperperfusion) in the evolution of glaucoma.

Materials and methods

The present paper consists of a clinical, prospective study, observational and interventional for one year period, that includes newly diagnosed glaucomatous patients in “Nicolae Malaxa” Clinical Hospital. The positive diagnosis was established by clinical and paraclinical examinations and the selected patients had treatment with prostaglandin analogues. In this study, the patients’ blood pressure was evaluated through 24 h outpatient holter monitoring with the help of the cardiology department. There are three groups into discussion:

• Group A- nondipper (without hypotension or hypertension)

• Group B- dipper (patients with nocturnal hypotension)

• Group C- patients with hypertension The patients were all monitorized through

regular checks every 3/6 months by clinical examination (anterior pole, fundus retinoscopy) and laboratory tests (gonioscopy, Goldmann aplanotonometry, pachimetry, retinofotography, computerized perimetry and OCT).

All patients were investigated through Doppler ultrasound velocimetry for cervical arteries to eliminate those who presented significant common carotid artery, internal carotid artery stenosis or stenosis of common carotid artery’s fork, which can represent additional risk factors in the progression of glaucoma (9). This pathology can influence the obtained results.

Results

The clinical study is conducted in a prospective, observational and interventional manner, for a period of one year (from September 2013 to August 2014), held at “Nicolae Malaxa” Clinical Hospital, including 45


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patients (90 eyes) with newly diagnosed open angle glaucoma through clinical and paraclinical examinations and receiving treatment with prostaglandin analogues.

The patients were divided into three homogeneous groups in terms of age and sex, with no other ocular or significant systemic pathologies for the one studied:

• Lot A- 14 patients diagnosed with POAG who do not have hypertension or hypotension (nondipper).

• Lot B- 13 patients diagnosed with glaucoma who have nocturnal hypotension (dipper).

• Lot C- 12 patients diagnosed with glaucoma who have hypertension. (Fig. 1-4)

At the beginning of the study, the visual field analysis, through the parameter called mean deviation (MD) showed the following: the most important visual field modification illustrated by the smallest medium value of the mean deviation was recorded in lot B, followed by lot A and then lot C. (Fig. 5)

Fig. 1 The medium values of systolic blood pressure

Fig. 2 The medium values of diastolic blood pressure

Fig. 3 The evolution of systolic blood pressure

Fig. 4 The evolution of diastolic blood pressure

Fig. 5 The medium value of MD at first examination


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At six months after therapy start, the medium value of MD recorded a much lower decrease than the initial value, especially in lot B. (Fig. 6)

After one year (or at the end of the study), the value of MD decreases continuously in all three lots. The differences between the final and initial values of MD being statistically significant in lot B. (Fig. 7-8)

At the beginning of the study, the analysis of the visual field through the parameter called PSD (Pattern Standard Deviation) showed the following: the most important modifications of visual field, illustrated by the highest medium value of PSD, were recorded in lot B. (Fig. 9)

After six months, the medium value of PSD recorded a more rapid increasing rate than the initial value in all lots, the most important value corresponding to the hypotension patients (lot B) followed by the witness lot (lot A). (Fig. 10)

After one year, the medium value of PSD continues to increase in all three lots, the differences between the final and the initial values being significantly higher in the same lot B and lower in the other two. (Fig. 11-12)

Fig. 6 The medium value of MD at six months

Fig. 7 The medium value of MD at third examination

Fig. 8 The evolution of MD in the three lots

Fig. 9 The medium value of PSD at the first examination

Fig. 10 The medium value of PSD at the second examination


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The structural modifications are highlighted by the vertical cup/disk ratio and its changes during the study, and also by the ganglionar cell loss with decreased thickness of the nerve fiber layer. The highest cup/disk ratio corresponded at the time of diagnosis to lot B, followed by lot A and C. (Fig. 13)

The review on OCT after one year showed

increased values of the C/D ratio in all three

groups, the highest value being recorded to the

hypotensive patients’ group (lot B). (Fig. 14-15)

The glaucomatous pathology affecting

retinal nerve fibers is emphasized by changes in

RNFL. At the beginning of the study, the highest

values of RNFL were recorded for patients in lot

B. Lower levels were recorded in lots A and C.

(Fig. 16)

Fig. 11 The medium value of PSD at the third examination

Fig. 12 The evolution of pattern standard deviation on lots

Fig. 13 The medium value of vertical C/D ratio at first examination

Fig. 14 The medium value of vertical C/D ratio after one year diagnosis

Fig. 15 The evolution of the glaucomatous excavation


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After one year the same distribution of the medium values of RNFL is kept. The biggest loss of nerve fibers is found in lot A, followed by lots C and B. (Fig. 17-18)

Conclusions

It is known that glaucoma is a major cause of irreversible blindness worldwide. This work is one of the more typical glaucomatous pathology, seeking to elucidate the theory of the influence of nocturnal hypotension in the progression of glaucoma.

We have conducted an observational analysis and then compared our data to others found in literature; the results allowed us to formulate the following conclusions:

The main deviation (MD) is the most important parameter for analyzing the progression of glaucomatous damage. According to our findings, it appears that even from the time of diagnosis, values in the dipper group were significantly lower compared to patients who had hypertension and the ones from the nondipper group.

The pattern standard deviation (PSD) is another important parameter in glaucoma progression analysis. Analyzing the average values of the PSD at baseline showed greater values in the dipper group compared to the others. Finally, at the end of the follw-up period, we noticed a higher increase in the PSD value for the same lot, followed by lot A and then C.

The structural changes on the OCT, cuantified by the value of vertical C/D ratio, was highest in lot B.

The glaucomatous pathology affecting nerve fibers was distinguished by changes in RNFL thickness in the same lot B.

Under the influence of risk factors, the nocturnal hypotension recorded major changes in the progression of glaucoma in the dipper lot by analyzing the structural changes highlighted on the OCT and functional analysis of the visual fields.

According to the results obtained in the present study, we can definitively state that nocturnal hypotension is a major risk factor in the progression of glaucoma. The ocular neuroprotection and improved hemodynamics represent future therapeutic options of substantial importance.

Discussions

The paper aims to highlight the role of vascular factors in the development of glaucoma and certify the importance of 24 h continous Holter monitoring of blood pressure for the

Fig. 16 The medium value of RNFL at the establishing of the diagnosis

Fig. 17 The medium value of RNFL at one year of diagnosis

Fig. 18 The evolution of the ganglionar cells layer


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glaucomatous patients. The work opens new premises of research studies with consequent demonstration of the importance of neuroprotection in treatment for glaucoma. The work is consistent with the literature studies like Graham’s who affirmed in one of his studies that nocturnal hypotension can be an additional risk factor in glaucoma [2]. Also, Mary E. Charlson concluded that cumulative nocturnal hypotension predicts visual field loss and that low values of the nocturnal blood pressure, either occurring spontaneously or as a result of medication teraphy, may lead to worsening of visual field defects [13].

References

1. V.P.Costa, E.S.Arcieri, A.Harris. Blood pressure and glaucoma. 2009, Br.J.Ophthalmol, Vol. 93, pg. 1276-1282.

2. Graham S.L., Drance S.M. Nocturnal Hypotension, Role in Glaucoma Progression. 1 June 1999, Survey of Ophthalmology, Vol. 43, pg. S10-S16.

3. Wishal D. Ramdas, Roger C.W.Wolfs, Albert Hofman, Paulus T.V.M. de Jong, Johannes R. Vingerling, Nomdo M. Jansonius. Ocular Perfusion Pressure and the Incidence of Glaucoma: Real Effect or Artifact?: The Rotterdam Study. 2011, Invest Ophthalmol Vis Sci, Vol. 52, pg. 6875-6881.

4. Yingfeng Zheng, Tien Y.Wong, Paul Mitchell, David S.Friedman, Mingguang He, Tin Aung. Distribution of

Ocular Perfusion Pressure and Its Relationship with Open-Angle Glaucoma: The Singapore Malay Eye Study. 7, july 2010, Invest Ophthalmol Vis Sci, Vol. 51, pg. 3399-3404.

5. SM, Drane. The disc and the field in glaucoma. 1978, ophthalmology, Vol. 85, p. 209.

6. Zeyen TG, Caprioli J. Progression of disc and field damage in early glaucoma. 1993, Arch Ophthalmol, Vol. 111, p. 62.

7. Francois J, Neetens A. Vascularization of the optic pathway - lamina cribosa and optic nerve. 1954, Brit J Ophthal, Vol. 38, p. 472.

8. Nicoleta MT, Walman BE, Buckley AR, et al. Ocular hypertention and primary open-angle glaucoma: a comparative study of their retrobulbar blood flow velocity. 1996, J Glaucoma , Vol. 5, p. 308.

9. Butt Z, O'Brein C, McKillop G, et al. Collor Doppler imaging in untreated high-and normal-pressure glaucoma. 1997, Invest Ophthalmol Vis Sci, Vol. 38, p. 690.

10. Kerr J, Nelson P, O'Brein C. A compartion of ocular blood flow in untreated primary open-angle glaucoma and ocular hypertention. 1998, Am J Ophthmol, Vol. 126, p. 42.

11. Karim F. Damji, Sharon Freedman, Sayoko E. Moroi, Douglas Rhee, et al. Shields' Textbook of Glaucoma. s.l. : Lippincott Williams and Wilkins;, 2005. Vol. 5.

12. Dumitrache, Marieta. Tratat de oftalmologie. . Bucuresti : Editura Universitara “Carol Davila” . Vol. 2.

13. Mary E. Charlson , MD Carlos Gustavo de Moraes, MD Alissa Link, MPH Martin T. Wells, PhD, Gregory Harmon, MD Janey C. Peterson, Ed D Robert Ritch, MD Jeffrey M. Liebmann, MD Received: Nocturnal Systemic Hypotension Increases the Risk of Glaucoma Progression December 31, 2013.


GENERAL ARTICLE


© 2015

SELECTIVE LASER TRABECULOPLASTY – SHORT TERM EFFICACY AND SAFETY PROFILE IN

OPEN ANGLE GLAUCOMA OR OCULAR HYPERTENSION TREATMENT

Dorin Chiselita * **, Alina Cantemir **, Anca Delia Pantalon *

*“Gr.T. Popa” University of Medicine and Pharmacy, Iași, Romania Faculty of Medicine Discipline of Ophthalmology, “Sf. Spiridon” University Hospital, Iași, Romania **“Oftaprof” Ophthalmology Clinic, Iași, Romania Correspondence to: Anca Delia Pantalon Ophthalmology Department, “Sf. Spiridon” University Hospital, 1 Piata Independentei , zip code700111, Iasi, Romania Phone/fax: +40232 217 781, Mobile phone: +40740 68 68 65, E-mail:[email protected]


Abstract Selective laser trabeculoplasty – medium term efficacy and safety profile in open anlgle glaucoma or ocular hypertension treatment: SLT effect in reducing the intraocular pressure (IOP) in patients with open angle glaucoma or ocular hypertension. Material and method: 70 eyes from 70 patients were included in the study in 2014 (12 months); the established design for this research was prospective and interventional. Patients received indication for SLT treatment as initial procedure or as adjuvant method in reducing the intraocular pressure when insufficient control with topical medication was noted. A single laser procedure was performed on 360 degrees. The result was verified and compared with baseline values of IOP at 1 month, 3 months respectively. Results: IOP decreased at 1 month with 22.47% vs. baseline IOP and with 26.58% at 3 months. The IOP dynamics showed an additional 5.30% decrease between the intermediate and final values, with statistical significance for all the measured parameters (p=0.001). Conclusion:SLT applied on 360 degrees in a single session represents a safe and efficient procedure. The IOP decrease is marked at 1 month, but the effect continues until later, at 3 months interval after treatment. The higher the initial IOP was, the greater effect SLT has in decreasing the IOP level. Most frequently LST helps control the IOP, but rarely allows reducing or eliminating the glaucoma medication. Key words: glaucoma, slt, efficacy, safety

Glaucoma represents a progressive optical neuropathy that left untreated, leads to blindness. The IOP reduction seems to be the only solution to stop progression in glaucoma and to achieve this goal there are many therapeutic resources: eye drops, laser procedures or surgery [1].

For the glaucoma patient, the clinician will recommend either one of the above-mentioned treatment lines, or a combination between them. The therapeutic options may vary according to the glaucoma type, optic nerve status, symptoms, patient education or compliance [2]. Laser procedures, especially Argon based ones, have



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been utilized in trabeculoplasties for over 30 years. After the introduction of a selective method of laser trabeculoplasty a new possibility in IOP decreasing aroused for the patients with glaucoma or ocular hypertension [3]. Selective laser trabeculoplasty (SLT) proved to be equally efficient in IOP reduction when compared to topical medicine or classic Argon laser trabeculoplasty-ALT [4, 5]. The major advantage is the re-treatment possibility because it doesn’t produce any trabecular meshwork damage as in any ALT procedure, thus allowing a second laser intervention in cases with previously failed ALT. SLT has indications both for primary open angle glaucoma SLT, pseudoexfoliative/pigmentary or normal tension glaucoma and ocular hypertension or secondary afakic glaucoma. Moreover SLT has a special indication in non-compliant or topical therapy intolerant patients and also it doesn’t influence any surgical procedure regarding its potential success. The safety profile includes a transitory inflammatory reaction, ocular pain or certain IOP spikes after treatment. SLT represents a safe and efficient method to lower the IOP in glaucoma patients or subjects with ocular hypertension having a clear indication for treatment due to high risk of glaucoma conversion [6].

Material and method

This interventional and prospective study lasted 12 months in 2014 (January-December). For each patient there were noted demographical data (age, sex) and a complete ophthalmological evaluation that included visual acuity (Snellen chart), IOP (Goldmannaplanotonometer), fundus examination with C/D ratio documentation (Volk lens – 78D) optic nerve status through an OCT exam (Cirrus 6.0 – Carl Zeiss Meditech), gonioscopy (dark room examination, undilated pupil). The anterior chamber angle was classified as open according to the Shaffer system (I-IV) and pigmentation was graded from 0 to 3. Additionally, the investigators performed ultrasonic pachymetry, computerized perimetry (Humphrey perimeter HFA II, SITA-Standard strategy, c24-2); number and type of topical medicine were mentioned for each patient. Pseudo exfoliation syndrome was documented (present/ absent) after mydriasis when anterior segment examination was performed.

IOP measurement and biomicroscopic examination were performed before procedure, after one month and after 3 months. Perimetric evaluation included at least 2 visual field examinations where the defects were constant and compatible with glaucoma damage.

Selective laser trabeculoplasty was indicated as initial treatment in glaucoma patients or in any case with ocular hypertension as adjuvant method in decreasing the intraocular pressure (IOP) when topical therapy was insufficient to control it.

SLT uses Nd-YAG laser with a 532 nm wave length, doubled in frequency. It uses a single pulse (time = 3 nsec) with a spot size around 400 μm. In our study the laser procedure was performed on 360 degrees (100 laser spots). Initially the technique included topical anesthetic (apraclonidine hydrochloride 0.5%) followed by placement of a Latina goniolens on the anterior ocular surface. Initial laser pulse (Ellex - Ellex Medical,Pty Ltd,Australia) was 0.3 mJ, increasing then the power with 0,1mJ/pulse until a small gas bubble was visible in the anterior chamber; at this point the energy got diminishedagain in the same manner (0,1 mJ/ pulse); the impacts were placed on 360 degrees. By the end of the procedure topical NSAIDs drops were instilled in the eye and same treatment was maintained for the next 4-7 days. Neither apraclonidine nor corticosteroids were used in this study related to the SLT procedure. IOP reduction was evaluated at 1 month and 3 months after SLT, along with the safety profile and efficacy check-up.

Population analysis: volunteer patients were enrolled in 2014, according to our inclusion criteria, after signing the informed consent. The present study respected the Helsinki declaration. We included 70 eyes form 70 patients with primary open angle glaucoma, pseudoexfoliative glaucoma or intraocular hypertension (where a clear indication for treatment was compulsory due to the high risk of glaucoma conversion). There were no retributions given to the subjects or any other compensation. The study was analyzed and proved by the Ethics Committee of “Gr.T. Popa” University of Medicine and Pharmacy - Iasi.

Inclusion criteria:

- POAG (primary open angle glaucoma), pseudoexfoliative glaucoma, high risk OHT (ocular hypertension);


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- clear glaucoma diagnosis based on EGS (European Glaucoma Society) guidelines;

- gonioscopy: open anterior chamber angle > grade 2(Schaffer);

Exclusion criteria mentioned any case of non-compliant patient, anterior laser treatment (ALT/ SLT). Lens opacities that interfered with the ophthalmological examination and glaucoma complete evaluation excluded the patient form the study, along with the cases treated with systemic corticosteroids or immunosuppressive drugs, significant eye/general diseases, poor cooperation during laser procedure, any anatomic particularity that prohibited proper SLT treatment (shallow anterior chamber). Subjects priorlytreated with pilocarpine prevented patient recruitment for this study due to a high risk of inflammatory reaction after the procedure. Statistical analysis:

We used for the statistical analysis the SPSS13.0 software (Windows). Descriptive statistics described demographics and baseline parameters (including IOP). IOP dynamics (medium term evaluation) was defined as the mathematical differences between IOP level at baseline and IOP level measured at 3 months after treatment.

The authors evaluated IOP reduction with SLT after 1 month, 3 months respectively ( IOP reduction in percentiles, statistical significance defined for p<0.05 in the final model). Pearson correlation coefficient (r) was calculated to assess the relationship between different IOP parameters. Non-parametric data were analyzed using Kolmogorov-Smirnov distribution test. When calculating the difference between sample frequencies, Student Fisher test was used (t,df,p). Equality between variances was evaluated with Levene test.

Results were compared related to the baseline IOP level; also there were noted any side effects, incidents, accidents, complications during SLT procedure for a proper safety profile assessment. Variables that didn’t reach the statistical significance level (p<0.05), were excluded from the report.

Results

There were included 70 eyes from 70 patients. If the treatment was bilateral, only one

eye was chosen, randomly. All participants remained in the study throughout its entire duration.

Mean age was 64.16 +/- 10.439 years, limits between 40-84 years. Mean baseline IOP level was 22.94 +/- 4.19 mmHg, limits between 15-34 mmHg (Fig. 1).

Fig. 1 IOP – baseline distribution values

Fig. 2 IOP distribution values at 1 month after SLT

Fig. 3 IOP distribution values at 3 months after

SLT


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Patients’distribution within the study group showed 40 cases with primary open angle glaucoma (POAG), 20 cases with pseudoexfoliative glaucoma (PXG) and 10 cases with ocular hypertension (OHT). Each patient had a single SLT procedure, applied on 360 degrees. Before the procedure, each patient received at least one type IOP lowering topical medication.

IOP reduction after SLT at 1 month interval after the procedure was statistically significant, with mean values of 17.79 +/-3.088 mmHg (Fig. 2). 3 months later after SLT the mean IOP was 16.84 +/- 2.301 mmHg (Fig. 3). The IOP lowering effect was 22.47% at 1 month and 26.58% at 3 months when compared to baseline levels.

Procedure safety was noted in both visits (no pain, neither IOP spikes or signs of inflammation), while proven efficacy (IOP reduction) was mostly noted after one month (Fig. 4-5); later the SLT effect continued to be “active” and lower the IOP compared to baseline, but the hypotensive effect was not as much noted as after the first month follow-up (Fig. 6).

IOP – baseline Mean=22.94 mmHg SD=4.191 mmHg N=70

IOP – 1 month Mean=17.79 mmHg SD=3.088 mmHg N=70

IOP – 3 months Mean=16.84 mmHg SD=2.301 mmHg N=70

Statistically, the Student Fisher test detected a negative correlation between the analyzed parameters (IOP level at baseline versus measured IOP/1 month or at 3 months after SLT), which clinically could be translated into a high practical importance: the higher IOP level was at baseline, the greater was the laser effect in IOP reduction; moreover the IOP dynamics maintained the same course both at 1 month and 3 months interval (Fig. 7).

IOP<19 mmHg IOP>19 mmHg

IOP<19 mmHg IOP>19 mmHg

Fig. 4 Mean IOP – baseline

Fig. 5 Mean IOP – 1 month after SLT

Fig. 6 Mean IOP – 3 months after SLT

Differences in meanIOP at baseline vs. 1 month

Differences in meanIOP at baseline

vs. 3 months


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t df p

-3,797 68 .000

t df p

-3,860 68 .000

Pearson correlation = 0.378 Pearson correlation = 0.558

p= 0.001 p = 0.001

SLT efficacy was defined for a maximum IOP of 19 mmHg obtained after the procedure.

Percentile distribution in IOP reduction after the procedure was: 25% decrease with 2 mmHg, 50% with 5 mmHg, and 75% patients drop 7 mmHg from the IOP baseline level; at 3 months interval the same tendency in IOP dynamics was recorded, thus 25% subjects drop 3 mmHg, 50% - 5 mmHg and for 75% patients there was a 8.25 mmHg PIO reduction when compared to baseline. Overall the SLT procedure efficacy for 57 eyes (82%) showed that it was necessary to maintain the same topical glaucoma medication, whereas for 5 patients (7%) it was necessary to supplement the topical medication with an additional drug. In 3 eyes (4%) there was no need to add, but to reduce the number of topical medication and for 5 patients (7%) no topical medication was needed after trabeculoplasty at the 3 months visit.

In percent, the IOP reduction magnitude between baseline and the 1 month visit was 22.47%, while at 3 months there was an IOP decrease of 26.58%; between visits the intermediate IOP reduction value was 5.30% (p<0.05). Safety in this procedure was recorded after the visits by checking if any ocular inflammation, pain, vision decrease, tearing occurred. None of the above mentioned issues occurred in this study.

Discussion

SLT efficacy in open angle glaucoma was earlier described in many studies in ophthalmology literature, but the conclusion widely accepted is that its effect decreases in time (3). Glaucoma Laser Trial [3,4] shows that in 5 years, 32% from the subjects treated with ALT had still an acceptable level of IOP control, with no other methods to decrease the intraocular pressure. Smaller studies conclude

that SLT efficacy is similar to ALT (IOP decreased between 12.1-39.9% vs. baseline) [7-11], but the effect is shorter in time and decreases rapidly on the way [6]. Latina et al. considered that in his experience and practice SLT was still successful at 5 years follow up (50-60%) [1].

Clement et al. (SLT/MED study) reported in 2012 that SLT efficacy, if applied on 360 degrees and compared to prostaglandin analogues (latanoprost) is comparable (82% vs. 90%) after 12 months. Of course, the therapeutic response differed from case to case, but for both methods a drop of more than 20% from the baseline IOP level could be considered efficient [12]. Similarly,McIlraith et al. finds that IOP was reduced equally when used either PGA (prostaglandin analogues) or SLT (83% vs. 84% patients) at 12 months [13].

Theories responsible for losing the SLT effect in time recollected no changes in the trabecular meshwork histology and architecture, offering thus the possibility of re-treatment, which is in complete opposition to the ALT mechanism that produces actual burns in the trabeculum, with no possibility of re-treatment. Different methods of applying the SLT impacts include either 2 sessions, each performed on 180 degrees, or a single session applied on 360 degrees. Hong demonstrated in one of his studies that SLT efficacy at 5 years is higher when applied in sequences, on 180 degrees versus a single sequence on 360 degrees(6). Still, Nagar et al. proved that the most effective SLT regimen was on 360 degrees, in a single laser session [14].

One of the determinant factors responsible for a greater IOP reduction after SLT could be a higher level in the IOP baseline levels [15-16], fact also confirmed by this study.

Conclusion

The present study shows that SLT represents a safe and efficient procedure for

Fig. 7 Differences between mean IOP values at baseline compared to 1 month and 3 months


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mid-term control of IOP (3 months). Additionally, laser treatment (trabeculoplasty) in open angle glaucoma or ocular hypertension could successfully be considered as alternative to topical medication, mostly when thinking costs or compliance.

IOP reduction after SLT was significant at 1 month, but the hypotensive effect continued until later, at 3 months, although not in the same impressive manner. Moreover there was found a negative correlation between the initial IOP level (baseline) and the quantitative aspect of the IOP drop (the higher IOP at baseline was, the greater the reduction was after SLT).

Knowing the fact that most patients (85%) maintained the same topical medication in our study, we can conclude that SLT enhances IOP control, but rarely manages to cut off the patient from medication (7%) and seldom reduces the number of topical active agents (7%) which concurred with the existed and cited literature data [4].It is also highly possible that the IOP reduction induced by SLT could also reduce the amplitude of IOP fluctuation durind 24 hours (glaucoma progression element).

The authors intend to extend the follow up period, increase the number of subjects for having a better view on IOP dynamics and changes in SLT treated patients. In a small prospective data, recent literature data show that after 30 months the SLT failure reaches 16% in POAG and 22% in PXG [17].

Also it would be interesting to establish wether there is a statistical significant relationship between the total energy delivered by SLT and the amount of IOP reduction for a correct and efficient treatment.

In conclusion, SLT applied in a single regimen, on 360 degrees, offers around 25% IOP reduction, both at 1month and 3 months follow-up interval. The higher the IOP baseline level is, the greater the reduction proves to be. The procedure appears safe as no moderate or severe side effects were reported. There is still a need to confirm the present results with longer studies with larger number of patients in order to properly place the SLT in the armentarium used to treat open angle glaucoma.

Contributors: AC ans AP were involved in

manuscript preparation, design and execution of the study, also in data colection process, statistical analysis and manuscript writing. DC was involved in all the steps and mentored the other authors.

Competing/ financial interest: none.

References

1. Latina MA et al. CurrOpinOphthalmol. 2002;13(2):94-96.

2. American Academy of Ophthalmology Glaucoma Panel. Preferred Practice Pattern Guidelines. Primary Open-Angle Glaucoma, 2010:1-32.

3. The Glaucoma Laser Trial Research Group and Glaucoma Laser Trial Follow Up. Am J Ophthalmol. 1995;20(6):718-731.

4. Samples JR et al. Ophthalmology. 2011; 118(11):2296-2302.

5. Katz LJ et al. J Glaucoma. 2011 May 3 [Epub ahead of print]. doi:10.1097/IJG.0b013e 318218287f.

6. Hong BK et al. J Glaucoma. 2009;18(3): 180-183. 7. Lanzetta P, Menchini U, Virgili G. Immediate

intraocular pressure response to selective laser trabeculoplasty. 1999;83 (1):29-32

8. Gracner T, Falez M, Gracner B, Pahor D. Long-term follow-up of selective laser trabeculoplasty in primary open-angle glaucoma.2006;223(9):743-747

9. Cvenkel B. One-year follow-up of selective laser trabeculoplasty in open-angle glaucoma. 2004; 218(1):20-25

10. Weinand FS, Althen F. Long-term clinical results of selective laser trabeculoplasty in the treatment of primary open angle glaucoma.2006;16(1):100-104

11. Song J, Lee PP, Epstein DL, Stinnett SS, Herndon LW Jr, AsraniSG,Allingham RR, Challa P. High failure rate associated with 180 degrees selective laser trabeculoplasty. 2005;14(5):400-408

12. Clement CI. Initial Treatment:Prostaglandin Analog of Selective Laser Trabeculoplasty.J Current GlauPrac 2012;6(3):99-10

13. McIlraith I, Strasfeld M, Colev G, Hutnik CM. Selective laser trabeculoplasty as initial and adjunctive treatment for open-angleglaucoma. J Glaucoma 2006;15:124-3

14. Nagar M, Ogunyomade A, O’Brart DPS, Howes F, Marshall J. A randomized, prospective study comparing selective laser trabeculoplasty with latanoprost for the control of intraocular pressure in ocular hypertension and open angle glaucoma. Br J Ophthalmol 2005;89:1413-17

15. Mao AJ, Pan XJ, McIlraith I, Strasfeld M, Colev G, HutnikC.Development of a prediction rule to estimate the probability ofacceptable intraocular pressure reduction after selective laser trabeculoplasty in open-angle glaucoma and ocular hypertension. J Glaucoma 2008;17:449-54.

16. Ayala M, Chen E. Predictive factors of success in selective laser trabeculoplasty (SLT) treatment. ClinOphthalmol 2011;5: 573-76.

17. Shazly TA, Smith J, Latina MA. Long-term safety and efficacy of selective laser trabeculoplasty as primary therapy for thetreatment of pseudoexfoliation glaucoma compared with primary open-angle glaucoma. Clinical Ophthalmology 2011;5:5-1


GENERAL ARTICLE


© 2015

CLINICAL IMPACT IN THE MANAGEMENT OF NEOVASCULAR GLAUCOMA

Halil Ajvazi*, Pajtim Lutaj** *Regional General Hospital’s in Gjilan, Kosovo **Vision Eye Clinic and Albanian Vision Institut in Tirana, Albany

Correspondence to: Dr.sc. Halil Ajvazi MD - Ophthalmolog Petrovc, Str. n.n., Cod Postal: 62000, Kamenica of Kosovo Mobile phoneȡ + 377 (0) 44 - 777 7 14, E-mail: [email protected]


Abstract Introduction. Neovascular glaucoma (NVG), participates in the group of secondary glaucoma causing the increase of intraocular pressure (IOP) as a result of iridocorneal angle enclosure with the development of neovase derived from the retinal ischemic and other inflamatory diseases. Purpose of the study. Is to show the incidence, etiopathogenesis, clinical development and the management of NVG by comparing the contemporary and referring literature to other clinics. Methods. In this study there were presented the results of NVG treatment for the 2010-2014 interval. The data processing were conducted using statistically package SPSS 22. Results. In this scientific study were included 61 patients with NVG containing 4.3% of all cases with glaucoma and 14% of cases with secondary glaucoma, aged 22-79. The mean age of the patients was 60.9 year (SD + 10.6 year), 39 cases or 63.9% were of masculine gender and 22 cases or 36.1% of feminine gender, as it seems there is a differentiation with a statistical significance (X2=4.74, P=0.03, therefore P˂0.05). The most frequent cause of NVG was PDR in 55 cases or 55.6% of them, then, ischemic CRVO with 11 cases or 11.1%. The most frequent complications to the NVG were hemophthalmos, cataract and absolute glaucoma. Conclusion. In many aspects our results were in line with the results of other authors. Therefore we should focus on the adequate treatment of ocular ischemic in time, as it is only prevention method of NVG. Keywords. Diabetic retinopathy, retina ischemy, neovascular glaucoma.

Introduction

Neovascular glaucoma (NVG) is an eye disease not commonly encountered, but it is a serious disease, as it appears as a result of iris and iridocorneal neovascularization, increased intraocular pressure - IOP, thus causing irreversible sensorineural damage [1]. It takes part in the secondary glaucoma discovered in

1871 [2]. NVG is a consequence of retinal ischemia, resulting from the genetic, inflammatory disease, traumatological, endocrinological, and intraocular tumors complications, all these mentioned complications having a main role in the appearance of new vessels etc. The most frequent diseases causing the NVG are: diabetic retinopathy - DR, central retinal vein occlusion - CRVO and systematically



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inflammatory diseases. [3]. Seldom, glaucoma appears after CRVO, idiopathic retinal periphlebitis - Eales disease, trauma, intraocular tumors, coats syndrome, uveitis, endoftalmite, retinal ablation. Pathogenesis at the NVG retinal ischemia having a main role-capable of causing neovascularization [4]. The positive diagnosis can be determined by biomicroscopic, ophthalmoscopic and gonioscopic examination. The angio-fluorographic examination of the anterior segment can identify in iris and irido-corneal angle neovascularization from its beginning especially when biomicroscopic examination is difficult [5]. Complicated cases of NVG, where the intraocular mediums are less transparent, the treatment effectiveness though the pan-retinal cryo-therapy (PRC) is useful. The filtration surgery is mandatory in these cases through the silicon valvula or with supramid as well as mitomycin - C (MMC) and 5-fluorouracil (5-FU) administration. [6]. Medication treatment: the most important drugs in this stage include the following: cycloplegics like atropine 1%, anti-inflammatory steroids like prednisolone e.g. Pred Forte, Inflamase Forte for lowering the inflammation. The miotics, e.g. sol. Pilocarpine is contraindicated because it may increase inflammation. Existing anti glaucoma drugs to manage the IOP are: beta-blockers, carbonic anhydrase inhibitors, prostaglandins [7]. Timely treatment of proliferative diabetic retinopathy with Pan-retinal photocoagulation (PRP) and Anti-vascular endothelial growth factor (AVEGF) may prevent successfully NVG and its heavy consequences [8, 9, 10].

Purpose of the study

The purpose of the study is to indicate the

incidence of NVG according to age and gender,

researching and analyzing the incidence of NVG

in cases with diabetic retinopathy where only

Partial retinal photocoagulation (P- RP) as well

as in cases where is applied PRP together with

application of therapy with Anti-VEGF

intravitreal injection (e.g. Avastin). On the other

hand, this study indicates the frequency of

diseases with probability of other associated

diseases and complications.

Material and methods

One of retrospective, being conducted between 2010 and 2014 at the HSCUK (Hospital Services and Clinical University of Kosovo), Ophthalmological Department, especially at the eyes wards of Regional Hospital in Gjilan. In this study, 61 patients or 99 eyes, aged between 22 and 79 with NVG were included. The mean age was 60.9 (DS± 10.6 year; SEM ± 1.4 years). The female patients had the newest mean age 58.8 years while the male patients were of aged 62.1%, by the Man-Whitney test we did not get statistically significant differentiations of the mean age according to gender (U=445, P=0.815, well P>0.05).

Results

During this time period 1403 cases with glaucoma have been treated, 66 or 4.7% having congenital glaucoma, 902 or 64.4% primary glaucoma and 435 or 30.9% secondary glaucoma. 61 cases with NVG or 4.3% of all cases with glaucoma and 14.0% of cases with secondary glaucoma were treated in this study (Table 1).

Table 1. Cases treated with glaucoma from 2010-2014

Types of glaucoma

Glaucoma Secondary

all cases glaucoma

N % %

Congenital Total congenital 66 4.7

Primary

Glaucoma simplex 357 25.5

Glaucoma pigmentosa 18 1.3

Glaucoma capsularis 242 17.3

Glaucoma angularis ac. 123 8.8

https://www.google.com/search?biw=1600&bih=799&q=ophthalmoscopic&spell=1&sa=X&ved=0CBkQvwUoAGoVChMIod3Eys7wxgIV4q7bCh0AfAcp


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Glaucoma angularis chr. 162 11.6

Primary glaucoma 902 64.4

Secondary

Glaucoma secundum ac. 126 9.0 29.1 Glaucoma secundum chr. 171 12.2 39.5 Absolute glaucoma 77 5.5 17.9 Neovascular glaucoma 61 4.3 14.0 Secondary glaucoma 435 30.9 100.0

In total 1403 100.0

Table 2. Cases of NVG treated by age-group and gender

Age-group

Gander

In total F M

N % N % N %

<40 3 13.6 1 2.6 4 6.6

40-59 6 27.3 9 23.1 15 24.6

60+ 13 59.1 29 74.4 42 68.9

Total N 22 100.0 39 100.0 61 100.0

% 36.1 - 63.9 - 100.0 -

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Graphic 1. The range of primary disease in

patients with NVG

Graphic 2. Associated disease in patients with NVG

Graphic 3. The structure of complications in patients with NVG

Graphic 4. Scheme of the treatment results


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Table 3. AVGF therapy in cases included in the research

Th: with AVGF

Eye with NVG

Total OD OS

N % N % N %

Avastin ®

(Bevacizumab) 33 67.3 36 72.0 69 69.7

Macugen ®

(Pegaptanib sodium) 5 10.2 4 8.0 9 9.1

Lucentis ® (Ranibizumab) 8 16.3 8 16.0 16 16.2

5 – FU ® (5-fluorouracil) 3 6.1 2 4.0 5 5.1

Total 49 100.0 50 100.0 99 100.0

Discussion

In the time span 2010-2014, 61 cases with NVG, including 4.3% of the cases were with glaucoma, and 14% with secondary glaucoma (Table 1). In our research with NVG, 39 or 63.9% were of male gender and 22 or 36.1% of female gender, noticing statistically significant differentiations (X=4.74, P=00.3, well P>0.05) being in line with the research of other authors. According to age, the NVG is mainly a disease of old people, though, it does not exclude the young people. The youngest patient was aged 22 and the oldest was aged 79, (Table 2).

Primary disease: the most frequent primary disease associated with NVG was proliferative diabetic retinopathy PDR in 55 cases or 55.6% of them, then CRVO in 11 cases or 11.1% of them and uveitis recidivans in 8 cases or 8.1%, (Graphic 1).

Associated diseases: in the group of patients with NVG comprised in the research from 99 examined eyes, 9 or 9.1% have been associated with refraction anomaly as well as 7 or 7.1% with other glaucoma and so on (Graphic 2). Complications: the most frequent complications associated with NVG were hemophthalmos in 20 eyes or 20.2% of cases, then cataract in 15 cases or 15.2% as well as absolute glaucoma in 11 cases or 11.1% (Graphic 3).

Treatment with surgical therapy: 95 eyes

or 96% of the patients have been cured. The

most frequent method was cryotherapy with

20% stabilization and 8% improvement. The

therapy with AVGF, the treatment with AVGF in

cases comprised in the research: the most

frequent was the therapy with Bevacizumab

(avastin) up to 69.7%, then Ranibizumab with

16.2%. Pegaptanib sodium with 9.1% and 5FI-

Uracil with 5.1%, without differentiations

depending on the eyes (Table 3). For the

treatment of NVG For the treatment of NVG,

concerning lowering the level of IOP (intraocular

pressure) the following medical therapy has

been used: betablocators, carbonic anhydrase

inhibitors, prostaglandins eye drops, anti-

inflammatory steroids, and cycloplegic, etc. The

medical therapy in all cases was combined. The

most frequent combination was sol. Timolol, sol.

Lumigan, sol. Pred Forte and sol. Atropine

sulphate with 48.5%, while in the second place

comes therapeutic combination: sol. Lumigan,

tab. Diamox, then sol. Pred Forte and sol

Atropine sulphate with 31.3%. According to

postoperative clinical discourse – POCD ,

following the treatment with PRP 27.3%, Pan-

retinal cryo-therapy (PRC) 8.0% and Pars-plana

vitrectomy (PPV) 57.9% we noticed the

improvement of clinical state, taking into

consideration connection between IOP, PNO and

visual acuity, where we came to this correlation,

X2 = 13.63; Df=4; P<0.01 (Graph. 4).


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Conclusion

According to our analysis results we came to these conclusions: NVG contains 4.3% of all cases with glaucoma and 14.0% of cases with secondary glaucoma. The most affected age by NVG is over 60 years, the mean age being 60.9 (SD±10.6 year; SEM±1.4 year). The most affected gender is the male one with 63.9% and 36.1% of female gender, with a statistically significant differentiation (X2=4.74, P=0.03 well P<0.05). The primary diseases that most frequently disease in cases there was not applied PRP and AVGF. The main complications in patients with NVG are: hemoftalmus, cataract, absolute and other glaucoma. It was proven that the most successful method in preventive and functional aspects of NVG is the therapy with PRP with application of AVGF. The prevention of NVG is the adequate and timely treatment of retinal ischemia.

References

1. Ajvazi H. Neovascular glaucoma treated in the Eye Clinic in Prishtina, Magistrature’s study. Faculty of

Medicine at University of Prishtina /public presentation on – 25.03.2009: 46-53.

2. Mocanu C, Barascu D, Marinescu F. Neovascular glaucoma-Retrospective study. Ophthalmologica 2005; 49: 58-65.

3. Kim D, Singh A, Annapurna S. Neovascular Glaucoma. En: Shaarawy TM. Glaucoma Medical Diagnosis and Therapy. Saint Louis (EEUU): Saunders Elsevier; 2009; I: 409-417.

4. Ajvazi H, Goranci I. et al. Correlations of the changes between the iridocorneal angle and other parametres at the neovascular glaucoma: In the 7th Congress of SEEOS. GLAUCOMA SESSION - 035.20.June.2010, Tiranë.

5. Călugăru D, Călugăru M. Neovascular glaucoma--etipathogeny and diagnosis. Oftalmologia. 2012; 56 (2): 3-14.

6. Ignjatović Z. Neovascular glaucoma. International Symposium on Glaucoma, under auspices: SEEOS and EGS - European Glaucoma Society. Belgrad, April 21-st, 2012.

7. Ajvazi H, Goranci I, Lutaj P. Management of neovascular glaucoma. Oftalmologia. Nr. 4 / 2013. 57 (4): 39-43. [PubMed - indexet for MEDLINE]

8. Masaru I. et al. Management of neovascular glaucoma. Ophthalmology. 2014, Vol. 9, No. 1: P. 33-42.

9. Ajvazi H, Lutaj P, Goranci I. Management of diabetic retinopathy, prevalence and clinical clasification. Oftalmologia. 2014; 58(4):47-50.

10. Ajvazi H. Proliferative diabetic retinopathy-results of the microsurgical and laser treatment. Med Arh. 2010; 64(3):165-7. PMID: 20645511 [PubMed - indexed for MEDLINE]

https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=10&ved=0CE0QFjAJahUKEwjCg8fa7-7GAhXEF9sKHZ-qAG0&url=http%3A%2F%2Fescrs.org%2Fwarsaw2013%2Fprogramme%2Fposters-details.asp%3Fid%3D15634&ei=cJ6vVcKLBcSv7Aaf1YLoBg&usg=AFQjCNEoFewDW6hiNiQyuoU-xVKB3LTOMA&bvm=bv.98197061,d.ZGU

http://www.ncbi.nlm.nih.gov/pubmed/23424756



http://informahealthcare.com/action/doSearch?Contrib=Masaru+Inatani

http://informahealthcare.com/action/doSearch?Contrib=Masaru+Inatani

http://informahealthcare.com/doi/abs/10.1586/17469899.2014.879825






GENERAL ARTICLE


© 2015

FUCHS ENDOTHELIAL CORNEAL DYSTROPHY: IS FEMTOSECOND LASER – ASSISTED CATARACT

SURGERY THE RIGHT APPROACH?

Monica Gavriş* **, Ioan Horge**, Elena Avram*, Roxana Belicioiu*, Ioana Alexandra Olteanu*, Hanga Kedves* * Laser Optisan Clinic, Cluj-Napoca, Romania ** Cluj-Napoca Military Hospital, Cluj-Napoca, Romania Correspondence to: Monica Gavriş 53-55 Traian Moşoiu Street, zip code 400132, Cluj-Napoca, Romania Mobile phone: +400745 65 45 95, E -mail: [email protected]


Abstract Introduction: Femtosecond Laser – assisted cataract surgery represents a modern technology that hopes to lower the risk of complications for patients suffering from Fuchs endothelial dystrophy by using a reduced level of energy that causes less damage to the endothelium, the main concern for patients with Fuchs endothelial dystrophy. The femtosecond laser performs 3 important steps in cataract surgery: corneal incisions, capsulorhexis and nucleus fragmentation without intraocular instrument manipulation. Purpose: The purpose of this study is to determine the efficiency of Femtosecond Laser – assisted cataract surgery in Fuchs endothelial dystrophy. Material and methods: 5 patients with 6 eyes underwent cataract surgery assisted by Femtosecond Laser LensX at Laser Optisan Clinic. Corneal changes before and after surgery and cumulative dissipated energy (CDE) were analyzed. Results: Before surgery, our patients presented BCVA between 0.16 – 0.4, Pachymetry between 450-590 µm, endothelial cells between 789-2008 mm2. The medium cumulative dissipated energy (CDE) used was 4.58 seconds. After surgery, BCVA improved in all patients and none of them developed corneal decompensation so far. Conclusions: Femtosecond Laser – assisted cataract surgery represents a safe alternative in patients with Fuchs endothelial dystrophy and has a low risk of corneal decompensation. Key words: Femtosecond Laser – assisted cataract surgery, Fuchs endothelial dystrophy, Endothelial cell

Introduction

Fuchs Endothelial Corneal Dystrophy (FECD) represents a non-inflammatory dystrophy of the corneal endothelial layer which

involves the presence of guttata – small excrescences on Descemet’s membrane due to abnormal elaborations of basement membrane and fibrillar collagen by the damaged endothelial cells.


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When a patient suffering from mild or moderate FECD undergoes cataract surgery, the main concern of the surgeon is to cause less damage to the already altered corneal endothelium because at densities less than 1,000 endothelial cells/mm2, the risks of significant corneal decompensation with cataract surgery increases in patients with FECD hasting this way the need for DSEK surgery or corneal transplant.

In patients with FECD that are scheduled for cataract surgery it is very important to complete a precise diagnostic workup analyzing existing corneal changes and these patients require additional consideration in choosing the best and safest surgical technique to obtain the best visual outcome.

Anterior segment imaging, by means of specular microscopy, confocal microscopy or optical coherence tomography (OCT) offers the possibility to study corneal changes after cataract surgery by showing a magnified view of the corneal endothelium including measurements of cell density and morphology of the cells and pachymetry. While FECD is characterized by increased polymegethism, decreased hexagonality as well as thickening of the cornea which reveals cell loss and subsequent changings of surrounding cells to fill in the compromised endothelium and also coalescing guttatae, cataract surgery can cause true trauma to the already fragile cornea [1].

Also corneal tomography can show a

pattern compatible with subclinical edema that

implies a straightened or horizontal pachymetric

progression profile [2].

Femtosecond Laser - Assisted Cataract

Surgery represents a modern and safe approach

that hopes to lower the risk of complications in

patients suffering from FECD.

The femtosecond laser performs corneal

incisions, capsulorhexis and nucleus

fragmentation without intraocular instrument

manipulation this way reducing the amount of

ultrasound energy causing less damage to the

endothelium. Fragmentation of the leans with

femtosecond laser has shown to reduce the

average time and energy required by

approximately 50% (Batlle J.F., unpublished

data, [2011]), (Edwards K., unpublished data

[2011]), [3].

In addition, usage of dispersive viscoelastic and performing ”cataract in the bag phacoemulsification” is indicated.

Objective

The purpose of this study is to determine the efficiency of Femtosecond Laser – Assisted Cataract Surgery in patients suffering from mild and moderate FECD with cataract by studying the corneal changes.

Material and methods

Within 2013–2015, 5 patients (6 eyes) with mild-moderate FECD underwent Femtosecond Laser - assisted cataract surgery at Laser Optisan Clinic (Cluj-Napoca).

3 patients (3 eyes) had clinically transparent cornea and 2 patients (3 eyes) had subclinical stromal edema.

Surgery was performed by the same surgeon with LensX Femtosecond laser and Centurion phacoemulsification system (torsional mode). „Cataract in the bag phacoemulsification” was performed. Excessive dispersive viscoelastic devices were used.

Parameters followed were: BCVA before and after surgery; Corneal changes before and after surgery

were made 1 day before and 1 month after surgery:

Measurements of the central corneal thickness and subclinical corneal edema (Allegro Oculyzer Wavelight);

Endothelial cell density (Konan Noncon Robo Specular Microscope);

Cumulative dissipated energy (CDE). After surgery intensive steroids and

antibiotic eye drops (Tobramicinum + Dexametazonum) were applied to minimize the inflammatory damage to the corneal endothelium.

All patients gave their consent for the use of their data in this study.

Results

The average age of the 5 patients enrolled in this study was 69.4 (54-77). 4 patients were female and 1 was male, which attest the higher frequency of women suffering from FECD.


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The preoperative mean BCVA was 0.25 (range 0.1 - 0.4) while 1 month after surgery mean BCVA increased to 0.73 (range 0.4 - 1) (Table 1).

One of the patients was known to have glaucoma (P1) while another mild non-proliferative diabetic retinopathy (P2).

Preoperative data collected revealed: average central corneal thickness was 533 µm (range 450-590 µm), none of the patients having a pachymetry over 600 µm, average endothelial cell density was 1120 cells/mm2 (range 749-2008 cells/mm2) (Fig. 1). None of the patients presented clinical corneal edema, but 2 patients (P1, P3) had subclinical corneal edema (Table 2).

Table 1: Patients’ BCVA evolution

Gender Age Eye

BCVA

Before After 1

month

P1 F 77 OD 0.25 0.4

OS 0.1 0.4

P2 F 72 OD 0.25 1

P3 M 74 OD 0.25 0.7

P4 F 54 OS 0.4 1

P5 F 70 OS 0.2 0.9

Average

= 0.25

Average

= 0.73

Postoperative, a month after surgery we

noticed: decrease in endothelial cell density to an average of 1111.8 cells/mm2 (range 735-2004 cells/mm2) with an average rate of decrease of 0.73% and increse of central corneal thickness to 537.83 µm (range 457-592 µm) with an avarage rate of increase of 0.89% (Fig. 2) (Table 2).

Regarding corneal edeman just 2 of the patients (P1, P3) had moderate edema and corneal folds which has been resolved in a few days, both patients having before surgery an endothelial cell density under 1,000 cells/mm2

(Table 2). During cataract surgery, the average CDE

used varied between 1,95 seconds to 6.98 seconds, with an average of 4.58 seconds (Table 2).

Table 2: Corneal changes before/after surgery and CDE

P1 P2 P3 P4 P5

Average OD OS OD OD OS OS

Endothelial Cells

Density (cells/mm2)

Before 749 848 2008 805 1355 957 1120 ↓ with

0.73% After 1 month 735 843 2004 792 1349 948 1111.8

Pachymetry

(µm)

Before 450 512 590 578 572 499 533 ↑ with

0.89% After 1 month 457 517 592 584 573 504 537.83

Corneal Edema Before S.E. S.E. - S.E. - -

After 1 month S.E. S.E. - S.E. - -

CDE

(seconds) 4.06 4.21 4.81 6.98 1.95 5.47 4.58

S.E. = subclinical edema


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Discussions

Few studies regarding Femtosecond Laser assisted cataract surgery in patients with FECD are mentioned in literature.

Szaflik (Szaflik J.P., unpulished data [2015]), Brundrett (Brundrett A., unpublished data [2015]) and Shukhaev (Shukhaev S., unpublished data [2015]) also reported insignificant changes in corneal thickness and endothelial cell density loss after Femtosecond Laser - Assisted Cataract Surgery in patients with FECD.

In studies regarding Phacoemulsification Cataract Surgery in patients with FECD, Yamazoe (2011) found a loss of 13.5% in Endothelial Cell density, while Hayashi (2011) noticed a loss

from 779 cells/mm2 before surgery to 766 cells/mm2 endothelial cells after surgery [4] [5]. Seitzman (2005) noted an increase in central corneal thickness from 584 µm before surgery to 593 µm after surgery, while Hayashi (2011) noticed an increase of 3.3% µm after surgery [5] [6].

In our study, we obtained similar results in endothelial cell density and pachymetry before and after surgery, this differences being insignificant.

Regarding the amount of CDE used in Phacoemulsification Cataract Surgery differences between longitudinal and torsional phacoemulsification mode were noted. If a CDE of 24.37 ± 16.65 seconds is used in longitudinal phacoemulsification mode, in torsional phacoemulsification mode the CDE decreases to 11.45 ± 6.14 seconds (Doors M., unpublished data [2010]).

Our mean CDE was 4.58 seconds, much lower compared with the ones obtained in Phacoemulsification Cataract Surgery studies.

Conclusions

Insignificant increase in central corneal

thickness and decrease in endothelial cell

density was noticed after Femtosecond – Laser

assisted cataract surgery in patients suffering

from FECD enrolled in this study.

None of the patients developed clinically

significant corneal edema after the surgery, just

2 of the patients had minor or moderate edema

or corneal folds which disappeared in a few days.

Our data suggest that Femtosecond Laser -

assisted cataract surgery can represent a safe

alternative in patients with FECD and has a low

risk of corneal decompensation, allowing

excellent visual rehabilitation.

Although Femtosecond Laser - assisted

cataract surgery seems to be safe in patients

with FECD, a prospective randomized controlled

study on a larger number of patients and with

periodical follow-ups is required for validation of

the results obtained in this analysis.

Discolsureses: none

Fig. 1 Patients with Fuchs Corneal Endothelial Distrophy after Femtosecond laser – Assisted Cataract Surgery (Casuistry LaserOptisan Clinic)


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References

1. Eghrari A.O., Gottsch J.D. Fuchs’ corneal dystrophy. Expert Rev Ophthalmol, 5(2):147–159, 2010.

2. Ambrósio R. Jr., Alonso R.S., Luz A., Coca Velarde L.G. Corneal-thickness spatial profile and corneal-volume distribution: tomographic indices to detect keratoconus. J Cataract Refract Surg. 32(11):1851-9, 2006.

3. Nagy Z., Takacs A., Filkorn T., Sarayba M. Initial clinical evaluation of an intraocular femtosecond laser in cataract surgery. J Refract Surg, 25:1053-60, 2009.

4. Yamazoe K., Yamaguchi T., Hotta K., Satake Y., Konomi K., Den S., Shimazaki J. - Outcomes of cataract surgery in eyes with a low corneal endothelial cell density. Journal of Cataract and Refractive Surgery 37(12): 2130-2136, 2011.

5. Hayashi K., Yoshida M., Manabe S., Hirata A. Cataract surgery in eyes with low corneal endothelial cell density. J Cataract Refract Surg; 37(8):1419-25, 2011.

6. Seitzman G.D., Gottsch J.D., Stark W.J. Cataract surgery in patients with Fuchs’ corneal dystrophy: expanding recommendations for cataract surgery without simultaneous keratoplasty. Ophthalmology, 112(3):441-446, 2005.

http://www.ncbi.nlm.nih.gov/pubmed/?term=Hayashi%20K%5BAuthor%5D&cauthor=true&cauthor_uid=21684110

http://www.ncbi.nlm.nih.gov/pubmed/?term=Yoshida%20M%5BAuthor%5D&cauthor=true&cauthor_uid=21684110

http://www.ncbi.nlm.nih.gov/pubmed/?term=Manabe%20S%5BAuthor%5D&cauthor=true&cauthor_uid=21684110

http://www.ncbi.nlm.nih.gov/pubmed/?term=Hirata%20A%5BAuthor%5D&cauthor=true&cauthor_uid=21684110


CASE REPORT


© 2015

ANTERIOR CHAMBER SYNCHYSIS SCINTILLANS A CASE REPORT

Ana Banc* **, Cristina Stan* **

*Ophthalmology Clinic, Emergency County Hospital Cluj-Napoca, Romania **“Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, Romania

Correspondence to: Cristina Stan Ophthalmology Clinic, Emergency County Hospital Cluj-Napoca 3-5 Clinicilor Street, Cluj-Napoca, Romania, zip code 400006 Fax number:+40264 430 719, Mobile phone: +40745 617 453 E-mail: [email protected]


Abstract Synchysis scintillans is a vitreous condition in which multiple golden brown opacities are formed as a result of chronic vitreous hemorrhage. Anterior chamber synchysis scintillans was described in patients with afakia or lens subluxation. We report a case of a 63-year-old man with a history of left eye trauma and complete loss of vision, who presented for left eye discomfort. The slit lamp examination revealed crystals of synchysis scintillans and rare inflammatory cells in the anterior chamber, stromal iris atrophy, circumferential posterior iris synechiae, and complete lens opacity. Total retinal detachment was observed on ocular ultrasonography. Intraocular pressure value was in normal range. The distinctiveness of this case is the mechanism of vitreous crystals mobilization into the anterior chamber through an atrophic iris while intraocular pressure remains normal. Keywords: synchysis scintillans, anterior chamber, eye trauma

Introduction

Synchysis scintillans is a result of chronic vitreous hemorrhage and is formed of multiple vitreous opacities that are flat, mobile, and golden brown in color [1]. The condition is also known as “cholesterolosis bulbi”, as the presence of cholesterol crystals was demonstrated in these opacities [2].

Synchysis scintillans is usually noted in the vitreous cavity, but there were reported cases of anterior chamber synchysis scintillans due to lens subluxation and anterior mobilization of the vitreous through the pupillary area [3, 4],

although afakia or lens subluxation may not be required [5].

We report a case of anterior chamber synchysis scintillans with normal position of the lens and circumferential posterior iris synechiae.

Case report

A 63-year-old man presented to his family physician with complaints of discomfort in his left eye. The medical history revealed a blunt eye trauma during childhood with complete loss of vision in the left eye. The family physician noted an aspect “similar to hypopyon” and referred the patient to an eye care department.


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The ophthalmological examination revealed best corrected visual acuity of 20/20 in the right eye and no light perception in the left eye. The slit lamp examination showed peripheral corneal opacities consistent with arcus senilis in both eyes. In the left eye there were also noticed mild conjunctival congestion, anterior chamber with mobile sparkling crystals with tendency to accumulate inferiorly and inflammatory cells 1+, stromal iris atrophy, fixed pupil, 360° posterior iris synechiae and complete lens opacity (Fig. 1).

The fundus exam was normal in the right

eye and not visible in the left eye. Ocular ultrasonography revealed complete retinal detachment in the left eye. Intraocular pressure was 14 mmHg in the right eye and 18 mmHg in the left eye.

The patient was treated with topical fixed combination of tobramycin 0.3% - dexamethasone 0.1% q. i. d. for one week, with the remission of inflammatory cells. The patient underwent surgical intervention for the removal of the anterior chamber crystals, as these particles were considered to be the cause of ocular inflammation; bimanual irrigation/ aspiration probes were used. During the surgical intervention a large number of crystals were seen to migrate from posterior into the anterior

chamber through the atrophic iris (Fig. 2), and were also aspired. The intraocular pressure decreased to 16 mmHg on postoperative day one, and intraocular pressure monitoring was recommended.

Discussion

The main feature responsible for the disease course in this case is the presence of the iris atrophy. The presence of the atrophy only in the left eye suggests its traumatic etiology [6]. The atrophic iris explains the absence of iris bombé although circumferential posterior iris synechiae were present. The atrophic iris created a way of communication between the anterior and posterior chambers. Functionally the left eye became a single compartment.

Most probably, the retinal detachment and lens opacity are consequences of the eye trauma the patient reported. The retinal detachment itself could cause the leakage of a cholesterol-rich fluid that contributed to the formation of synchysis scintillans in the absence of other vitreous hemorrhages [5]. The retinal detachment also prevents the ocular hypertension as the aqueous humor can be drained through the subretinal space.

The posterior iris synechiae might have been formed either in the context of eye trauma

Fig. 1 Left eye with synchysis scintillans in the

anterior chamber.

Fig. 2 Intraoperative aspect of the left eye:

vitreous crystals were aspired into the anterior

chamber through the iris.


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or during the inflammatory episode which appeared years later. However at the moment of examination the mechanism which allowed the vitreous particles to migrate into the anterior chamber was the filtering through the atrophic iris and not the passage through the pupillary area. The number and position of the crystals located in the anterior chamber varied with eye position and movements. If the patient was in orthostatism, the crystals had the tendency to form a pseudohypopyon; in dorsal decubitus the crystals were drained through the iris and disappeared from the anterior chamber. Eye movements determined the crystals to move.

Treatment options for anterior chamber synchysis scintillans are limited and address the underlying disease, or the symptoms. In this case the vision loss is irreversible and the patient would not benefit from cataract or retinal surgery because the retinal detachment is more than 40 years old. Periodical ophthalmologic examination is recommended in order to monitor the presence of ocular inflammation or increased intraocular pressure, and consequently prevent painful eye.

In conclusion, synchysis scintillans appears in damaged eyes and iris atrophy contributes to the anterior chamber mobilization of the vitreous crystals.

References

1. Sebag J. Vitreous Anatomy and Pathology. In: Ophthalmology, 4th ed. Yanoff M, Duker JS, editors. Elsevier Saunders 2014:430-6.

2. Andrews JS, Lynn C, Scobey JW, Elliott JH. Cholesterosis bulbi. Case report with modern chemical identification of the ubiquitous crystals. Br J Ophthalmol. 1973;57(11):838-44.

3. Park J, Lee H, Kim YK, Chae JD, Lee HJ. A Case of Cholesterosis Bulbi with Secondary Glaucoma Treated by Vitrectomy and Intravitreal Bevacizumab. Korean J Ophthalmol. 2011;25(5):362-5.

4. Beebe J. Synchysis Scintillans and a Crystal Pseudohypopyion. EyeRounds Online Atlas of Ophthalmology [cited May 2015]. Available from:

5. http://webeye.ophth.uiowa.edu/eyeforum/atlas/pages/Synchysis-scintillans-crystal-pseudohypopion/index.htm

6. Sanmugasunderam S, Giligson A, Choi SB. A “sparkling” eye. Can Med Assoc J. 2003;169(4):319.

7. Edward DP. Degeneration and Atrophy of the Iris. In: Duane’s Ophthalmology on CD-ROM. Tasman W, Jaeger EA, editors. 2006


CASE REPORT


© 2015

RETINAL ANGIOMATOUS PROLIFERATION CASE REPORT

Olaru Andrei.*, Olaru Denissa-Greta*, Nicolcescu Andreea*, Olaru Cristian.*, Popescu Mihaela**, Deca Andreea-Gabriela***, Mocanu Carmen* * Ophthalmology Department, SCJU Craiova, UMF Craiova, Romania ** Endocrinology Department, SCJU Craiova, UMF Craiova, Romania *** Pharmacy Department, SCJU Craiova, UMF Craiova, Romania

Correspondence to: Olaru Denissa-Greta Romul Bl. Romarta Street, Sc. D, App. 67, Craiova, Dolj, Romania Mobile phone: +40766 247 899, E-mail: [email protected]


Abstract The diagnosis of RAP is similar with the diagnosis of the AMD, but PED, exudate and superficial hemorrhages are more common in RAP. A 75-year-old male presented himself at the Ophthalmology Department of the Emergency County Hospital in Craiova in January 2015, with a 4 months history of vision loss. In his right eye the visual acuity was 4/50 eye non-optical correctable and 5/5 with optical correction in the left eye. According to the FA and OCT that were performed in both eyes, in the right eye was found intraretinal neovascularization and sub and intraretinal fluid. A normal aspect was found in the left eye. After the investigations we decided to start the treatment consisting in one single intravitreal injection with Triamcinolone Acetonide (IVTA) in the right eye. The VA improved 1 week after the treatment from 4/50 to 5/30. In comparison with the improved VA, the macular edema gradually resorbed 1 month after the IVTA injection. In spite of the late presentation of the patient in the Ophthalmology Department, the VA and OCT outcome after a single dose of IVTA injection was very good. Key words: Retinal angiomatous proliferation, Triamcinolone acetonide, Age related macular degeneration AMD, Intravitreal injection.

Introduction

Retinal angiomatous proliferation (RAP) is defined as a variant of exudative age related macular degeneration (AMD) in which the retinal-choroidal neovascularization is characterized by intraretinal capillary proliferation or, if the origin of the process is in the choroid, then it is an early retinal-choroidal anastomoses (RCA) without the presence of a neovascular membrane type 1. Although dry AMD represents the majority of all diagnosed cases, wet AMD associated with RAP is responsible for the majority of the severe vision

loss and it can be very difficult to treat. The diagnosis of RAP is similar with the AMD but exudate and superficial and multiple hemorrhages are more common. [1,2,3] We describe the case of a 75-year-old male with unilateral RAP treated successfully with intravitreal triamcinolone acetonide injection (IVTA).

Case presentation

A 75-year-old male presented in the Ophthalmology Department of the Emergency



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County Hospital Craiova in January 2015 with a 4 months history of vision loss in his right eye.

The medical history of the patient revealed in the right eye: a cataract surgery with a posterior chamber pseudofak 2 years ago, a laser YAG iridotomy for closed angle glaucoma 2 years ago and a macular edema; in his left eye a laser YAG iridotomy for closed angle glaucoma 2 years ago and a senile cataract in evolution. He was also diagnosed with essential arterial hypertension 10 years ago and impaired glucose tolerance 8 months ago.

At the admission his visual acuity (VA) was 4/50 in the right eye non-optical correctable and 5/5 with optical correction in the left eye.

The slit lamp examination revealed laser YAG iridotomy in both eyes, posterior chamber pseudofak in the right eye, cortico-nuclear densifications in the left eye.

The indirect ophthalmoscopy examination revealed normal optic disc, a few macular hemorrhages situated in the superior-temporal sector, a white epiretinal membrane and macular edema in the right eye (Fig. 1). The left eye indirect ophthalmoscopy could not be performed due to the miotic pupil.

The angiofluorography (FA) in the right eye

shows intraretinal neovascularization (Fig. 2)

and late hyperfluorence due to staining (Fig. 3).

An optical coherence tomography (OCT-

Fig. 4) was performed to the patient before the

IVTA injection in both eyes as shown below. OCT

revealed sub- and intraretinal fluid in the right

eye with central retinal thickness of 752 µm and

perifoveolar thickness of 549.3 µm and normal

macular aspect with normal thickness in the

center 232 µm and perifoveolar 260.9 µm.

After the investigations we decided to start

the treatment consisting in one single

intravitreal injection with Triamcinolone

Acetonide (IVTA) in the right eye.

The follow-up visits were made at 2 days, 1

week, 4 weeks, 3 months after the IVTA injection.

Two days after the IVTA injection the VA

improved at about 5/40. At the 2nd follow-up

visit the BCVA was 5/30. In comparison with the

improved VA the macular edema gradually

resorbed and 1 months after the IVTA injection

the central retinal thickness was 527µm and

perifoveolar was 417.4 µm.

Fig. 1 Right eye – white epiretinal membrane, macular edema

Fig. 2 intraretinal neovascularisation

Fig. 3 late hyperfluorence due to staining

Fig. 4 3d macula right eye comparing to the left eye


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Discussions

The first author who described the

presence of anastomoses between the retinal

and choroidal circulations in eyes with disciform

scars was Oller over 100 years ago [4].

Chorioretinal anastomoses were later described,

associated with laser photocoagulation [5],

radiotherapy [6], chorioretinal inflammatory

diseases [7] and parafoveal telangiectasias [8]. Later Hartnet et al described in 1992 nine

cases of retinal neovascularization, to which they referred as “deep retinal vascular anomalous complex” [9]. In 2000, Slakter et al. described chorioretinal anastomoses in eyes with pigment epithelial detachment and indocyanine green (ICG) hot spots [10].

In 2001, Yannuzzi et al. described chorioretinal anastomosis as neovascular proliferation with origin in the retina, and proposed the designation of RAP – retinal angiomatous proliferation [2]. Several authors [11-16] maintained the designation of chorioretinal anastomosis, proposing a choroidal origin for this clinical entity. In 2008, Yannuzzi et al. described 5 cases of RAP with the neovascular complex originating in the choroid instead of the retina, and proposed that RAP should be called type 3 neovascularization [17].

According to Yannuzzi et al. [2] classified RAP initial neovascularization process in 3 stages:

1) Stage I– Intraretinal neovascularization. This stage is mainly diagnosed when the second eye is already affected. The presence of associated small retinal hemorrhages constitutes a very useful sign in early RAP diagnosis. A small elevation of the inner/intermediate retina caused by angiomatous tissue may be observed under a slit lamp; this elevation may extend tangentially, assuming telangiectasic appearance. In FA, the angiomatous complex is observed as a hyperfluorescent area in front of the RPE, identical to that occurring in classic choroidal and, more frequently occult neovascularization. Dilated retinal vessels may perfuse and drain the intraretinal neovascularization (IRN) and form retino-retinal anastomoses. ICG may reveal a hot spot with staining and leakage.

2) Stage II– Involvement of the subretinal space with localized neurosensory detachment of the retina, edema and retinal hemorrhages at the edges may already be observed in fundus color photography. The angiomatous formation draining vein becomes visible, originating in the deep retina. PED is observed in 94% of eyes; FA may reveal well-delimited hyperfluorescence in the diffuse leakage area associated with PED, identical to that occurring for a minimally classic

Fig. 5 After 1 week from IVTA injection

Fig. 6 Comparing before and after the IVTA


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choroidal neovascular membrane. ICG clearly establishes stage II diagnosis as the presence of a hot spot with leakage, as well as a hyperfluorescent area associated with serous pigment epithelium detachment (SPED). Leakage might not be revealed by FA, probably because fibrin from retinal exudates cannot be impregnated with fluorescein, contrary to what occurs with ICG [18]. FA is rarely useful in differential diagnosis between classic, occult or minimally classic membranes and stages I and II [2], contrary to ICG, where a slow-growing extra, juxta or subfoveal hot spot, sometimes asymptomatic, is observed in stages I and II. Retino-retinal anastomoses may also be observed in stage II.

3) Stage III– Choroidal neovascularization is clearly visible, sometimes with the appearance of vascularized PED.

According to Gass [19], RAP would progress in 5 stages instead of 3, easily identifiable by FA and ICG:

I) Pre-clinical stage– Atrophy of the outer retina, with retinal capillaries moving closer to a choroidal neovascular complex located below the RPE – type 1 choroidal neovascularization – and no clinical signs of chorioretinal anastomosis. ICG would be necessary to identify type 1 neovascularization.

II) Early clinical signs– Anastomosis between dilated capillaries of the deep retina and the choroidal neovascular complex is associated with small intraretinal haemorrhages, which would constitute the first clinical sign of chorioretinal anastomosis.

This stage may occur weeks or months before stage 3, where subretinal choroidal neovascularization is already observed.

III) Proliferation of choroidal neovascularization over the RPE– subretinal neovascularization – type 2 CNV.

IV) Appearance of serous PED caused by activation of newly formed subepithelial vessels.

V) Mixed neovascularization– piggyback-type neovascularization, with two levels – type 1 and type 2 with cicatricial disciform lesion, making chorioretinal anastomosis visible.

Stage 3 in Gass’s classification corresponds to stage I in Yannuzzi’s classification, with stages 4 and 5 in Gass’s classification corresponding to stages II and III, respectively.

Currently, Yannuzzi’s classification is the most widely used.

In our case, we diagnosed the patient with RAP stage I after Yanuzzi and stage II/III after Gass.

The average and median ages of a series of 108 patients studied by Yannuzzi et al. [2] were 80 and 81 years respectively.

Both eyes were similarly affected in 51.9% of patients, with RAP occurring in the second eye with an average of 15 months after appearing in the first eye.

At 3 years, both eyes were affected in 100% of patients [20,21].

In our case, the patient was diagnosed with RAP in only one eye but we will be monitoring him every six months.

Most of the published studies use intravitreal injection with ranibizumab in treating RAP as a form of exudative AMD. Due to the inflammatory process involved in RAP pathogenesis, recent research has proved the efficacy of IVTA injection in the treatment of this condition.

Saito M et al observed in a retrospective, observational case series over a 3 years period, that the combined therapy intravitreal bevacizumab (IVB) plus PDT was more effective than IVTA plus PDT in the treatment of RAP. [22]

Adnaan Haq et al demonstrated in a case report the successful RAP treatment with combined intravitreal ranibizumab and IVTA. [23]

Conclusions

In spite the patient late presentation in the Ophthalmology Department (4 months after he noticed the vision loss in the right eye) the VA and OCT outcome after a single dose of IVTA injection was very good.

Further studies are required to establish the difference between monotherapy with IVTA or combined therapy IVTA with ranibizumab as the optimal treatment for RAP.

References

1. Jack J. Kanski, Brad Bowling –Clinical Ophthalmology a Systematic Approach Seventh Edition, Elsevier Saunders, 2011 ISBN –13:9780702040931, 627-628


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2. Yannuzzi LA, Negrao S, Iida T, Carvalho C, Rodriguez-Coleman H, Slakter J, Freund KB, Sorenson J, Orlock D, Borodoker N. Retinal angiomatous proliferation in age-related macular degeneration. Retina. 2001;21:416–434. [PubMed]

3. Myron Yanoff, Jay S. Duker – Ophthalmology Thrid edition, Mosby Elsevier, 2009, ISBN 978-0-323-04332-8, 651-663

4. Oeller JN. Atlas of rare ophthalmoscopic conditions and supplementary plates to the atlas of ophthalmoscopy [Snowball T, translation]. Wiesbaden, Germany: JF Bergman; 1904; part C., 61-66

5. Slusher MM, Tyler ME. Choroidoretinal vascular anastomoses. Am J Ophthalmol 1980; 90: 217-22.

6. Boozalis GT, Schachat AP, Green WR. Subretinal neovascularization from the retina in radiation retinopathy. Retina 1987; 7 (3): 156-62.

7. Kennedy JE, Wise GN. Retinochoroidal vascular anastomosis in uveitis. Am J Ophthalmol 1971; 71 (6): 1221-5.

8. Gass JD, Oyakawa RT. Idiopathic juxtafoveolar retinal telangiectasis. Arch Ophthalmol 1982; 100: 769-780

9. Hartnett ME, Weiter JJ, Garsd A, Jalkh AE. Classification of retinal pigment epithelial detachments associated with drusen. Graefes Arch. Clin Exp Ophthalmol 1992; 230:11-19.

10. Slakter JS, Yannuzzi LA, Schneider U, Sorenson JA, Ciardella A, Guyer DR, Spaide RF, Freund B, Orlok DA. Retinal choroidal anastomoses and occult choroidal neovascularization in age-related macular degeneration. Ophthalmology 2000; 107: 742-53.

11. Coscas G. Chorioretinal anastomoses. International Symposium of fluorescein angiography. Toronto. Canada. 1994.

12. Coscas G. Chorioretinal anastomoses. Clinical features and OCT follow-up. In: OCT in AMD. Annual report of the French Ophtalmic Societies. Springer Medelzin Verlag Heidelberg. 2009. 277-300.

13. Kuhn D, Meunier I, Soubrane G, Coscas G. Imaging of chorioretinal anastomoses in vascularized retinal pigment epithelium detachments. Arch Ophthalmol 1995; 113 (11): 1392-8.

14. Gass JD, Agarwal A, Lavina AM, Tawansy KA. Focal inner retinal hemorrhages in patients with drusen: an early sign of occult choroidal neovascularization and chorioretinal anastomosis. Retina 2003; 23 (6): 741-51.

15. Silva RM, Faria de Abreu JR, Travassos A, Cunha-Vaz JG. Stabilization of visual acuity with photodynamic therapy in eyes with chorioretinal anastomoses. Graefes Arch Clin Exp Ophthalmol 2004; 242 (5): 368-76.

16. Silva R, Cachulo ML, Figueira J, Faria de Abreu JR, Cunha-Vaz JG: Chorioretinal anastomoses and photodynamic therapy: a two-year follow-up study. Graefe´s Arch. Clin. Exp. Ophthalmol. 2007; 245:1131-1139.

17. Yannuzzi LA, Freund KB, Takahashi BS. Review of retinal angiomatous proliferation or type 3 neovascularization. Retina 2008; 28 (3): 375-84.

18. Lafaut BA, Aisenbrey S, Vanden Broecke C, Bartz-Schmidt KU. Clinicopathological correlation of deep retinal vascular anomalous complex in age related macular degeneration. Br J Ophthalmol 2000; 84 (11): 1269-74.

19. Gass JD, Agarwal A, Lavina AM, Tawansy KA. Focal inner retinal hemorrhages in patients with drusen: an early sign of occult choroidal neovascularization and chorioretinal anastomosis. Retina 2003; 23 (6): 741-51.

20. Massacesi AL, Sacchi L, Bergamini F, Bottoni F The prevalence of retinal angiomatous proliferation in age-related macular degeneration with occult choroidal neovascularization Graefes Arch Clin Exp Ophthalmol 2008 ; 246 (1): 89-92.

21. Gross NE, Aizman A, Brucker A, Klancnik JM Jr, Yannuzzi LA. Nature and risk of neovascularization in the fellow eye of patients with unilateral retinal angiomatous proliferation. Retina 2005; 25 (6): 713-8.

22. Saito M, Shiragami C, Shiraga F, Kano M, Iida T. Comparison of intravitreal triamcinolone acetonide with photodynamic therapy and intravitreal bevacizumab with photodynamic therapy for retinal angiomatous proliferation. Am J Ophthalmol. 2010;149:472–481.[PubMed]

23. Adnaan Haq, Bharat Kapoor, Maharatnam Logendran and Gopinath Reddy - Successful Treatment of Retinal Angiomatous Proliferation with Intravitreal Triamcinolone and Ranibizumab Injections in a 67-Year-Old Male - Case Rep Ophthalmol. 2014 Sep-Dec; 5(3): 392–399. Published online 2014 Nov 26.doi:10.1159/000369611



http://www.ncbi.nlm.nih.gov/pubmed/?term=Haq%20A%5Bauth%5D

http://www.ncbi.nlm.nih.gov/pubmed/?term=Kapoor%20B%5Bauth%5D

http://www.ncbi.nlm.nih.gov/pubmed/?term=Logendran%20M%5Bauth%5D

http://www.ncbi.nlm.nih.gov/pubmed/?term=Reddy%20G%5Bauth%5D

http://dx.doi.org/10.1159%2F000369611


CASE REPORT


© 2015

NONICHEMIC CENTRAL RETINAL VEIN OCCLUSION ASSOCIATED WITH HEREDITARY

THROMBOPHYLIA

Andreea Dana Fişuş*, Doina Suzana Pop*, Monica Blanka Rusu*, Florina Vultur * Karin Ursula Horvath * ** *Mureş County Hospital, Department of Ophthalmology, Tîrgu Mureş, Romania **University of Medicine and Pharmacy, Tîrgu Mureş, Romania Correspondence to: Fişuş Andreea Mureş County Hospital, Department of Ophthalmology, Tîrgu Mureş, Romania 26 Marton Aron Street, zip code: 540058, Tg Mures, Romania Mobile phone: +40726 136 725, E-mail: [email protected] Accepted: July 10, 2015

Abstract Retinal vein occlusion (RVO) is the second most common retinal vein disease with significant visual loss via thrombus or compression of vein wall. Thrombophilia is the predisposition to vascular thrombosis with the existence of genetic defect that leads to blood hypercoagulability. This report describes the case of a 55 year old male patient, with an active life who presented himself at the emergency room with acute visual lose, insidious and progressive visual field constriction, without any known history of neurological or vascular diseases. The examinations revealed unilateral optic nerve head edema, the fluorescein angiography was specific for nonischemic central retinal vein occlusion CRVO complicated with macular edema. Blood examinations has emphasized the presence of the heterozygous mutation A1298C in the methylenetetrahydrofolate reductase gene (MTHFR), the only one presented from the thrombophilia screen panel and a slightly elevated cholesterol level. During the follow-up period, the patient received anti-VEGF treatment (Bevacizumab, 3x 0.1 ml intravitreal injections) with improved visual acuity and amendment of macular edema. The complex etiology calls for interdisciplinary approach to determine better the cause of this ophthalmological disease. Although studies have found a correlation between some thrombophilia mutations and retinal vein occlusion, more studies that contain a larger number of patients are necessary in order to determine the final role of these gene variants. Keywords: hyperviscosity, hypercoagulable state, (methylenetetrahydrofolate reductase gene) MTHFR, retinal vein occlusion.

Introduction

Retinal vein occlusion (RVO) is one of the most common retinal vein disease, second to diabetic retinopathy.

Central retinal vein thrombosis is typically

a disease of older patients (90% are over 50

years old), rarely occurring in young adults. [1,

2, 3]


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RVO is divided into three types according to Hayreh: BRVO (Branch retinal vein occlusion) is divided further into major BRVO and macular BRVO; CRVO is divided into ischemic and nonischemic types; and hemi-CRVO with involvement of only one half of the retina surface. [1]

Worldwide, approximately 16.4 million adults are affected by RVO and 2.5 million adults suffer of central retinal vein occlusion (CRVO). [4]

Visual acuity is decreased due to one of two conditions macular edema and/or retinal ischemia. Although it was first documented over a century ago, the exact pathogenesis still remains unclear, despite the various systemic and ophthalmic risk factors that have been identified. [1,5]

The condition is due to a combination of three systemic changes known as Virchow's triad:

hemodynamic changes, degenerative changes of the vessel wall,

and blood hypercoagulability. [1] Hypertension, diabetes, vasculitis and high

cholesterol levels are the most frequent factors associated with vascular diseases, therefore retinal occlusions. [6,3]

The common hematological tests performed are: complete blood count, glucose tolerance test, lipid profile, serum protein electrophoresis, chemistry profile and syphilis serology. If the history suggests systemic clotting diathesis, further hematological tests such as lupus anticoagulant level, anticardiolipin antibody, and protein S and protein C levels should be performed. [3,7]

Completely normal-medical laboratory evaluation results and history are found in 25% of patients. [8]

Coagulopathy and thrombophilia should also be considered where the RVO etiology isn't obvious or if the patient is young. [1]

A large number of studies have reported that increased blood viscosity, factor V Leiden mutation, hyperhomocysteinemia, and protein C or S deficiency may play an important role in the etiology of CRVO. [1,9,10]

The role of thrombophilic risk factors in RVO is still controversial. Various studies have

conflicting results, and results should be interpreted with caution. [2,10]

Thrombophilia is the predisposition to vascular thrombosis with the existence of genetic defect that leads to blood hypercoagulability.

Methylene tetrahydrofolate reductase (MTHFR) catalyzes a substrate for homocysteine to methionine. Genetic variation in this gene make individuals susceptibility to occlusive vascular disease, neural tube defects, Alzheimer's disease, colon cancer, and acute leukemia. The enzyme is coded on chromosome 1 location p36.3 in humans. Two of the most investigated nucleotides are C677T and A1298C [11,10]

Homocysteine levels are determined by mutations in the thermolabile gene MTHFR, but also depend on diet, by levels of folic acid, vitamin B6 and vitamin B12. So, for elderly patients there is the theory that the dietary factor is more important than the genetic one. [10]

Case report

A 55-year-old male, former athlete, presented to the emergency room with acutely reduced visual acuity and a central scotoma in the left eye.

The patient's history revealed unknown vascular or neurological diseases. The patient history underlines the absence of vascular comorbidities: a non-smoker patient, with an active life, former athlete.

The current pathology occurred approximately 4 days prior to hospital admission, with the appearance of a central scotoma in the left eye that persisted till the admission day.

From the ophthalmological examination we emphasize on:

Best-corrected visual acuity: RE (right eye) 1.0 with + 1.00 DSph correction

LE (left eye) 0.2 Refraction: RE = +1.50 DSh - -0. 50Dcyl ax

42º LE = + 1.50 DSh

Intraocular pressure (Goldman tonometry): 17-17 mmHg

http://en.wikipedia.org/wiki/Cosubstrate

http://en.wikipedia.org/wiki/Homocysteine

http://en.wikipedia.org/wiki/Methionine

http://en.wikipedia.org/wiki/Peripheral_vascular_disease

http://en.wikipedia.org/wiki/Peripheral_vascular_disease

http://en.wikipedia.org/wiki/Neural_tube_defect

http://en.wikipedia.org/wiki/Alzheimer%27s_disease

http://en.wikipedia.org/wiki/Chromosome_1

http://en.wikipedia.org/wiki/Chromosome_1

http://en.wikipedia.org/wiki/C677T

http://en.wikipedia.org/w/index.php?title=A1298C&action=edit&redlink=1

http://en.wikipedia.org/wiki/Methylenetetrahydrofolate_reductase

http://en.wikipedia.org/wiki/Folic_acid

http://en.wikipedia.org/wiki/Vitamin_B6

http://en.wikipedia.org/wiki/Vitamin_B12


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The anterior segment evaluation was within the normal range, without pupillary defects.

Ophthalmoscopy (Fundus examination) of the - RE showed: normal optic nerve head and stage II angiopathy, (Fig. 1) - LE revealed dot and blot hemorrhages in all quadrants of the retina and blurring of the optic disc, the retinal venules appeared tortuous (Fig. 2);

The patient's history, general and ophthalmic examination point to a vascular retinal pathology, suggested by the means of debut and the fundus imagine.

For the certainty of the diagnosis ancillary tests where performed: (we present only the relevant issues)

1. Computerized perimetry: RE normal aspect, LE multiple central and paracentral scotoma (Fig. 3)

2.Angiofluorgraphy: in the LE revealed normal arterial filling but delayed arteriovenous filling, and there was late disc hyperfluorescence, staining along retinal veins, microaneurysms and dilated optic nerve head capillaries. (Fig. 4)

Fig. 1 Fundus photography RE

Fig. 2 Fundus photography LE

Fig. 3 Computerized perimetry LE

Fig. 4 Fluorescein angiography LE


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3.Paraclinical investigations

o cholesterol 240 mg/dl, o creatinine 1.19 mg/dl, o glucose 87.5mg/dl, o anti-dsDNA antibodies 3.5 U/ml

anti-cardiolipin antibodies IgG 1.73.5 U/ml o uric acid 4.4mg/dl, o ASAT(GOT) 87.5 U/l, ALAT(GPT) 24 U/l

Blood examinations emphasized the

presence of the heterozygous mutation A1298C in the methylenetetrahydrofolate reductase gene (MTHFR), the only one present from the thrombophilia screen panel (factor V Leiden nutation, factor II mutation, MTHFR C677T gene mutation and antibodies from ANA profile were all absent).

Other investigations: Cardiologic consultation: Sinus

Bradycardia, Dental consultation: without infections

pathology ENT consultation: Deviated septum,

Cronic rhinosinusitis, operated basal cell cancer Pulmonology consultation: without acute

pathology Urology consultation: without acute

pathology Neurology consultation: normal Doppler

ultrasound (carotid artery) MRI and angio MRI: without alterations

in the signal sequence T2 and flair to plead for demyelination, without vascular caliber changes of vertebrobasilar and internal carotid.

From the patient's history, ancillary tests

and general examination we established the

following: Nonischemic central retinal vein

occlusion associated with heterozygosity for

the MTHFR A1298C genotype LE, Stage II

angiopathie RE, Hypermetropia BE,

Presbyopia BE, Sinus Bradicardia.

During follow-up period the patient

developed one of CRVO complication, macular

edema, therefore he received anti-VEGF

treatment (Bevacizumab, 3x 0.1 ml intravitreal

injections) with improvement of visual acuity

and amendment of macular edema.

Differential Diagnosis: Ischemic versus nonischemic CRVO-

Ischemic CRVO is usually associated with more extensive 4 quadrant hemorrhage and retinal edema, variable numbers of cotton-wool spots.

Retinopathy due to carotid occlusive disease (ocular ischemic syndrome) - blurred vision in a darker room suggestive of carotid artery disease, not tortoise veins. Hemorrhages are commonly splotchy, located in the midperipheral retina.

Acute hypertensive retinopathy (bilateral) - grade 3/4 with retinal hemorrhages and/or exudate, disc swelling

Papillophlebitis or optic disc vasculitis - an inflammatory optic neuritis or vasculitis

Hyperviscosity syndromes (bilateral retinopathy) - polycytemia vera, leukemia,

Sever anemia with thrombocytopenia - excluded by blood examinations

Discussions

The Central Vein Occlusion Study Group noted that 34% of nonischemic CVRO progressed to ischemic aspect within 3 years. [5]

The prognosis of visual recovery is highly dependent upon the subtype of the occlusion:

1. Less than 10% of the patients who have the nonischemic type may experience a complete recovery of the vision.

2. 7% of patients with CVO develop venous occlusion of the fellow eye within 2 years.

3. The risk of any vascular occlusion in the fellow eye is estimated to be 0.9% per year[5]

Neovascularization of the anterior segment is rare under 2% of cases [12]

Fig. 5 OCT examination LE (macular edema)


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In the present case the prognosis is dismal knowing that thrombophilia induces a higher risk for vascular thrombosis.

The particularities of the case are: occurrence of a vascular pathology in a patient without knows diseases, and the discovery of genetic mutation at an older age.

Conclusions

When dealing with a retinal vein occlusion, the patient should be investigated for hypertension, glaucoma and diabetes mellitus. The estimation of plasma viscosity, a full blood count and lipid levels are cheap investigations and should be performed in every case.

It is mandatory to establish a hypercoagulable state, meaning thrombophilia screen in young patients or to those without other known pathologies.

Thrombophilia screening of these patients poses a particularly difficult diagnostic challenge; it seems likely that several risk factors, both genetic and acquired, need to be present for thrombosis to occur.

The complex pathogenesis and increase in the incidence of occlusion syndrome call for interdisciplinary approach to better determine the etiology.

Although studies have revealed a correlation between some thrombophilia mutations and retinal vein occlusion, more studies that contain a larger number of patients are necessary in order to determine the final role of these gene variants.

Disclosures None

References

1. Kolar P. Risk factors of central and branch vein occlusion A meta-analysis of published clinical data. J Ophthalmol. 2014; 1155(10):724-780

2. Tilleul J., Glacet-Bernard A. Underlying conditions associated with the occurrence of retinal vein occlusions. J Fr Ophtalmol, 2011; 34(5):318-324

3. Salaun N, Delyfer MN, Rougier MB, Korobelnik JF. Assessment of risk factors for retinal vein occlusions in patients under 60 years of age. J Fr Ophtalmol. 2007; 30(9): 918-23

4. Stem MS, Talwar N, Comer GM. A longitudinal analysis of risk factors associated with central retinal vein occlusion. Ophthalmology. 2013; 120(2):362-370

5. Yanoff M, Duker J.S. Venous obstructive disease of the retina. Ophthalmology. Mosby. 2004; 115:862-869

6. Pierre-Filho Pde T, Pierre AM, Nascimento MA, Marcondes AM. Central retinal vein prethrombosisas an initial manifestation of protein S deficiency. Sao Paulo Med J. 2004; 122(3):134-135

7. Muñoz Negrete FJ, Casas-Lleras P, Pérez-López M, Rebolleda G. Hypercoagulable workup in ophtalmology. When and What. Arch Soc Esp Oftalmol. 2009; 84(7):325-332

8. Popa A, Voinea L, Pop M. Sindrom antifosfolipidic primar. Oftalmologia. 2008; 52:13-17

9. Fegan CD. Central retinal vein occlusion and thrombophilia. Eye (Lond). 2002; 16(1):98-106

10. Dan Li, Minwen Zhou, Xiaoyan Peng. Homocysteine, methylenetetrahydrofolate reductase C677T polymorphism and risk of retinal vein occlusion: an update meta-analysis. BMC Ophthalmol. 2014; 14:147

11. Cahill M, Karabatzaki M, Donoghue C, Meleady R, Mynett-Johnson LA, Mooney D. Thermolabile MTFHR genotip and retinal vascular occlusive disease. Br J Ophthalmol. 2001; 85:88–90

12. Scheufele TA, Pieroni CG, Baumal CR. Methylenetetrahydrofolate reductase gene mutation in a 16 year old girl with combined central retinal vein occlusion. Retin Cases Brief Rep. 2007; 1(3):134-137


CASE REPORT


© 2015

A RARER FORM OF ANGLE-CLOSURE GLAUCOMA - DIAGNOSIS AND TREATMENT

Zemba Mihail*,**, Stamate Alina-Cristina*, Avram Corina Ioana*, Malciolu Radu*, Neacsa Raluca*, Oprea Stefan*, Ivascu Diana Gabriela*, Burcea Marian** *Central Military Emergency University Hospital “Dr. Carol Davila” Bucharest, Romania ** “Carol Davila” University of Medicine and Pharmacy Bucharest, Romania

Correspondence to: Zemba Mihail, 5 Adrian Carstea Street, Bl. 33A, App. 38, District 5, Bucharest, Romania Mobile phone: +40722 394 415, Fax: +4021 313 71 89, E-mail: [email protected]


Abstract Purpose: to show how we diagnosed and treated a rarer form of angle-closure glaucoma; the pathogenic mechanism was angle crowding through thick peripheral iris roll. Methods: we show the investigations: biomicroscopy of the fundus, tonometry, pachymetry, gonioscopy, perimetry, ultrasound biomicroscopy, optical coherence tomography of the anterior segment – that helped us to diagnose the angle-closure glaucoma and its pathogenic mechanism; we also show our choice for surgery – lens extraction – and our arguments for this choice. Results: first postoperative day – intraocular pressure was 14 mmHg; a week postoperatively - intraocular pressure was 13 mmHg; three months postoperatively - intraocular pressure was 13 mmHg. Conclusions: lens extraction may be a very good choice in several forms of angle-closure glaucoma. Key Words: angle-closure glaucoma, lens extraction

We present the case of a 40-year-old woman, of Mongoloid race, who was sent to us for an ophthalmological examination.

The history of this case is quite long, but very interesting and instructive.

One year previously, when the patient presented for prescription reading glasses, the ophthalmological examination showed: Visual acuity:

O.D.: 20/20 Snellen (0.0 log MAR) O.S.: 20/20 Snellen (0.0 log MAR)

Intraocular Pressure: O.D.: 30 mmHg. O.S.: 24 mmHg.

An OCT of the optic nerve head was performed and it showed some defects in nerve fiber layer in both eyes.



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An OCT image of the anterior segment of the eye showed a narrow angle in both eyes: O.D. 16⁰, O.S. 16⁰

The diagnosis was: O.U.: Angle-closure

glaucoma and the patient was started on: timolol-dorzolamide drops b.d., with monthly ophthalmological assessments.

Eight months previously, the patient was hospitalized with the diagnosis: O.D. Acute angle-closure glaucoma. She could not specify the medical treatment she was on and she was released on the following treatment: timolol-dorzolamide drops b.d. pilocarpine 2% drops, five times per day

Six months previously, she was hospitalized again. The diagnosis was: O.D.: Acute angle- closure. After three days of medical treatment, peripheral laser iridotomies were performed in both eyes.

One month previously, she was once again hospitalized. Ophthalmological examination showed:

Visual acuity:

O.D.: 20/20 Snellen (0.0 logMAR) O.S.: 20/20 Snellen (0.0 logMAR)

Intraocular Pressure: O.D.: 44 mmHg O.S.: 12 mmHg

The diagnosis was: O.D.: Posner-

Schlossman syndrome. The treatment consisted

of systemic prednisolone 48 mg/day and

acetazolamide 250 mg b.d. and timolol-

dorsolamide b.d. instillations. The evolution was

not very good, with a faint reduction of

intraocular pressure. After three days of

treatment, pilocarpine 2% five times per day was

prescribed and the intraocular pressure

normalized.

The ophthalmological examination in our

clinic was:

Visual acuity:

O.D.: 20/20 Snellen (0.0 log MAR)

O.S.: 20/20 Snellen (0.0 log MAR)

Intraocular Pressure:

O.D.: 20 mmHg

O.S.: 17 mmHg

Ocular refraction:

O.D.: + 2,75/ + 0,25* 90⁰

O.S.: + 3,25/ + 0,75 *95⁰

Biomicroscopy of the anterior segment:

O.D.: shallow anterior chamber, clear

lens, iridotomies at 3 and 9 o’clock

O.S.: shallow anterior chamber, clear

lens, iridotomies at 3 and 9 o’clock

Fig. 1 The OCT image of the optic nerve head

Fig. 2 OCT image of the anterior segment O.D.

Fig. 3 Anterior segment O.D.


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Fundus examination: O.D.: large cup of the optic disc, with

vertical diameter larger than horizontal diameter, cup/disc ratio 0.6, narrow inferior neuroretinal rim.

O.S.: large cup of the optic disc, with vertical diameter larger than horizontal diameter, cup/disc ratio 0.7, narrow inferior neuroretinal rim.

Gonioscopy:

O.D.: Schwalbe line was visible; the upper

part of trabeculum was visible around

180⁰; the peripheral iris configuration

was steep (convex), allowing a very

difficult angle examination.

O.S.: Schwalbe line was visible; the upper

and lower part of trabeculum were

visible around 270⁰; the peripheral iris

configuration was also steep.

A Scheimpflug camera examination of the

anterior segment of the eyes showed:

O.D. angle: 16.9⁰

O.S. angle: 15.6⁰

Fig. 4 Anterior segment O.S.

Fig. 5 Fundus image of the right eye

Fig. 6 Fundus image of the left eye

Fig. 7 Scheimpflug camera image anterior

segment O.D.


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Automated perimetry: O.D.: changes were especially in the

superior hemifield: nasal step, superior arcuate scotoma; the glaucoma hemifield test was outside normal limits; mean deviation: 5.75 dB; pattern standard deviation: 4.34

O.S.: changes were less important; glaucoma hemifield test was outside normal limits; inferior arcuate scotoma; mean deviation: 4.51 dB; pattern standard deviation: 2.84

Our diagnosis was: O.U.: Intermittent angle closure glaucoma.

The reasons for the diagnosis were: aspects of gonioscopy visual field changes optic nerve head changes normal intraocular pressure in many

examinations the prompt efficacy of pilocarpine treatment

Differential diagnosis: open angle glaucoma: the gonioscopy, the

narrow angle (around 15⁰) in Scheimpflug camera imaging and also the sudden response of high intraocular pressure to pilocarpine instillation, contradicted this diagnosis

other forms of angle-closure glaucoma: -with pupillary block: the patient had two patent iridotomies in both eyes -without pupillary block:

Fig. 8 Scheimpflug camera image anterior

segment O.S.

Fig. 9 Automated perimetry O.D. (Humphrey

device)

Fig. 10 Automated perimetry O.S. (Humphrey

device)


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-malignant glaucoma: this form of angle-closure glaucoma appears generally postoperatively; it can appear spontaneously only in case of a very important zonular laxity (this was not our case) -plateau iris configuration -angle crowding

We believe that the last option – angle crowding – was the case in our patient.

Taking this into consideration, we will further discuss about the mechanism of angle-closure in this case. There were more treatment options available: long term pilocarpine instillation surgical iridectomy trabeculectomy clear lens extraction

We chose the clear lens extraction. The surgery was done as usual, with only a change in the routine technique: no pharmacological mydriasis before surgery (use of iris retractors instead).

Postoperative results: Day 1:

Visual acuity O.D.: 20/20 Snellen (0.0 log MAR)

Intraocular pressure O.D.: 14 mmHg Anterior chamber depth: 4 mm

Day 14: Visual acuity O.D.: 20/20 Snellen (0.0 log

MAR) Intraocular pressure O.D.: 12 mmHg Anterior chamber depth: 3.88 mm Angle: 28⁰

Ultrasound biomicroscopy shows a larger angle, a deep anterior chamber and a more flat iris.

Prognosis: we consider that for a short and medium period of time it will be good. One year after the surgery, the visual field had no change and the visual acuity was 17 mmHg, without medication. An unusual situation was that the patient refused the same surgery in O.S. She preferred pilocarpine instillation five times per day; the evolution of this eye was also good.

Discussions

The studies about the epidemiology of glaucoma suggest a much greater rate of open angle glaucoma compared to angle-closure glaucoma in Caucasian population [8,1]. More recent epidemiologic studies in Asia reported that Mongolian and Chinese had significantly higher rates of angle closure glaucoma [3,4]. Our patient, very unusual for Romanian people, was a patient of Mongolian race. The first issue we want to discuss is the mechanism of angle-closure in this patient. It is well known that pupillary block is the commonest mechanism for angle closure. In pupillary block, iridolenticular contact at the pupil limits the flow of aqueous from the posterior chamber to the anterior chamber, resulting in a pressure gradient between posterior and anterior chamber that pushes the iris anteriorly. Anterior bowing of the peripheral iris narrows the angle and may cause iridotrabecular apposition. Laser iridotomy

Fig. 11 Scheimpflug camera imaging of anterior

segment O.D. (postoperatively)

Fig. 12 Ultrasound biomicroscopy O.D.

(postoperatively)


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reestablishes aqueous flow from the posterior to the anterior chamber, allowing the iris to flatten and the angle to widen [10]. The variable efficacy of laser iridotomy in many cases of angle closure or angle-closure glaucoma suggests that pupillary block may not be the only mechanism responsible [5]. Our patient had in both eyes two patent iridotomies. So we looked for other mechanisms for angle-closure. Plateau iris configuration is a condition where the peripheral iris is forced into the angle by anterior rotation of the ciliary body or anteriorly positioned ciliary processes [10]. Plateau iris syndrome is the situation where angle-closure appears spontaneously or after pupil dilatation in an eye with plateau iris configuration, in a patient with patent laser iridotomy [2,9]. Our patient had angle-closure, but she did not have a deep central anterior chamber, as in plateau iris configuration. She also had a different appearance on ultrasound biomicroscopy than the classical image of plateau iris configuration.

In angle crowding the peripheral iris is

thick. Upon iris dilatation the peripheral iris bunches up; if the angle is already narrow, this thick peripheral iris roll becomes opposed to the trabecular meshwork and raises suddenly the intraocular pressure [10]. Our patient had a brown iris with a thick stroma. This aspect, the

presence of a patent iridotomy and the aspect on ultrasound biomicroscopy convinced us to choose this mechanism as the mechanism of angle-closure in our patient.

The second issue to discuss is how to

treat more efficiently this patient. Pilocarpine instillation seems to be

effective; every time the patient used pilocarpine the intraocular pressure became normal. However, we consider that this drug has a lot of adverse reactions in a young person: changes in accommodation, headache, the need to instill the drops five times a day and many others.

Surgical iridectomy – we considered that laser iridotomies were quite large and patent, so that the surgical iridectomy would fail to control the intraocular pressure when the pupil dilate as the iridotomies did.

Trabeculectomy would probably be efficient to control intraocular pressure, but is unclear for how long. Our patient is young and this is a clear risk factor for trabeculectomy failure. Trabeculectomy has also many complications both intraoperatively (choroidal detachment and hemorrhage) and postoperatively (atalamia, malignant glaucoma, intraocular infection). Another argument against trabeculectomy is the fact that the trabeculum seems to work properly - when the patient uses pilocarpine, the intraocular pressure is good.

Clear lens extraction has some advantages: it is a very well known surgery, with very good outcome; the surgery enlarges the angle; the intraocular lens implant is thinner (3-4 times) than the natural lens and its position is clearly more posterior, so the pupillary block is

Fig. 12 Plateau iris configuration – anterior

rotation of ciliary processes [10]

Fig.13 Ultrasound biomicroscopy O.D.


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very improbable; the enlargement of the angle does not permit that the base of the iris (although it is thick) to oppose the trabeculum. If the trabeculum works well – and it does, we showed this previously – clear lens extraction can solve the mechanism of angle closure in our patient. There are also some disadvantages, especially accommodation loss. Our patient cannot afford a multifocal intraocular lens, but she is near the presbyopic age, so she can use near glasses.

Our option seemed to be efficient. One year postoperatively, the pacient showed no increase in intraocular pressure and had a stable visual field. On the other hand, we must specify that the patient’s choice for the left eye – pilocarpine instillation five times per day – seems to be effective as well.

The last issue to discuss is the delay in a proper treatment for this patient. Although the diagnosis was made quickly, she received a treatment that was not very efficient. Part of the initial treatment was suitable for open angle glaucoma, not for angle-closure – timolol instillation for instance. Later, iridotomies were performed, but intraocular pressure kept on raising. A major conclusion of this case is that is very important to discover the mechanism of angle-closure, because otherwise another sudden raise in intraocular pressure is possible.

References

1. Bonomi L., Marchini G., Marraffe M. Epidemiology of angle closure glaucoma: prevalence, clinical types and association with peripheral anterior chamber depth in the Egna Neumarket Glaucoma Study Ophthalmolgy, 2000; 107:998-1003 [2]

2. Druit Z., Freno A., Cronemberg S., Marula R.V., Calixto N. Plateau iris Arq Bras Ophthalmol 2008; 71(5): 752-8 [6]

3. Foster P.J., Baasathu J., Alsbirk P. Glaucoma in Mongolia. A population-based survey in Hovsgol province, northern Mongolia. Arch Ophthalmol. 1996;114:1235-41[3]

4. Foster P.J., Oens F.T.S., Machin D., The prevalence of glaucoma in Chinese residents of Singapore. Arch Ophthalmol 2000; 118: 1105-11 [4]

5. Patel K. Patel S.Angle closure glaucoma Dis. Mon. 2014; 60(^): 254-62[5]

6. Rahat H. Cataract surgery after trabeculectomy. The effect on trabeculectomy function Arch Ophthalmol 2012; 130 (2): 165-70 [9]

7. Tarek M. Shaarawy – Glaucoma – Saunders Elsewier 2009: 277-83 [8]

8. Tielsch J.M., Sommer A., Katz J. Racial variation in the prevalence of primary anle closure glaucoma: The Baltimore Eye Survey J. Am. Med. Assoc. 1991;266:369-74 [1]

9. Yan Y.J., Wu L.L., Wang X., Xiao G.G. Appositional angle closure in Chinese with primary angle closure and primary angle closure glaucoma after laser peripheral iridotomy Invest Ophthalmol Vis. Sci. 2014; 55(12): 8506-12 [7]

10. Yanoff M., Duker J.S. Angle closure glaucoma, Ophthalmology Mosby Elsevier Inc, 2009 1162-72 [10]


CASE REPORT


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PERSISTENT PUPILLARY MEMBRANE OR ACCESSORY IRIS MEMBRANE?

Monica Gavriş* **, Ioan Horge**, Elena Avram*, Roxana Belicioiu*, Ioana Alexandra Olteanu*, Hanga Kedves* * Laser Optisan Clinic, Cluj-Napoca, Romania ** Cluj-Napoca Military Hospital, Cluj-Napoca, Romania

Correspondence to: Monica Gavriş, 53-55 Traian Moşoiu, zip code 400132, Cluj-Napoca, Romania Mobile phone: +40745 654 595, E-mail address: [email protected] Accepted: July 18, 2015

Abstract Frequently, in literature and curent practice, accessory iris membrane (AIM) and persistant pupillary membrane (PPM) are confused. Both AIM and PPM are congenital iris anomalies in which fine or thick iris strands arrise form the collarette and obscure the pupil. AIM, which is also called iris duplication, closely resembles the normal iris tissue in color and thickness and presents a virtual second pseudopupil aperture in the centre while PPM even in its extreme forms presents as a translucent or opaque membranous structure that extends across the pupil and has no pseudopupil. Mydriatiscs, laser treatment or surgery is used to clear the visual axis and optimize visual development. Surgical intervention is reserved for large, dense AIMs and PPMs. Our patient, a 29 year old male, has come with bilateral dense AIM, bilateral compound hyperopic astigmatism, BCVA OD = 0.6, BCVA OS = 0.4, IOP OU = 17 mmHg. To improve the visual acuity of the patient we decided to do a bilateral membranectomy, restoring in this way transparency of the visual axis. After surgery, the visual acuity improved to BCVA OD= 0.8, BCVA OS=0.8. Key words: accessory iris membrane, membranectomy

Introduction

If 95% of newborns and 20% of adults have PPM (persistent pupillary membrane), few cases of AIM have been reported in literature [1]. Levy reported in 1957 a case of bilateral AIM associated with PMM, in 1998 Bhatti reported a case of bilateral AIM associated with microcornea while in 1979 Suh published a paper presenting 2 cases of AIM without other ocular anomaly associated [2] [3] [4].

Accessory iris membrane (AIM) represents a rare congenital ocular anomaly that appears as

iris tissue strands arising from the iris collarette and going along the pupil, which closely resembles the normal iris tissue in color and thickness. It also presents a virtual second pseudopupil aperture in the centre with no muscular activity [2].

Persistent pupillary membrane (PPM) represents a common congenital ocular anomaly that appears as fine iris strands along the pupil, which are remnants of anterior tunica vasculosa lentis that supplies nutrition to the lens in the first six month of fetal life [5].

Frequently, in current practice, AIM is confused with extreme tick PPM [3]. It is true



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that these two conditions have similar origin but the clinical appearance is quite different. PPM even in its extreme forms presents as a translucent or opaque membranous structure that extends across the pupil and has no pseudopupil [2]. PPM can be unilateral or bilateral and can be quite variable in appearance, size, configuration and density while AIM seems to appear always bilateral.

Sometimes this kind of membranes can get attached to the anterior lens capsule creating a small cataract or to the posterior surface of the cornea [6] [7].

Histopathology examination shows that in cases of accessory iris membrane the tissue has an extensive anomalous hyperplasia even when compared with pupillary membrane at the stage in fetal life when it has reached its maximum development [8].

Since a pupillary diameter of only 1.5 mm is necessary for normal retinal image formation rarely this anomaly causes significant decrease in visual acuity but dens AIM can be associated with PPM, amblyopia, anterior polar cataract, coloboma, strabismus and anterior segment abnormalities [9] [10].

Treatment options of this kind of membranes include mydriatics, Nd:YAG laser therapy and surgical excision. If visual acuity is relatively good, a conservative management with mydriatics is recommended, this way preventing the risk of operative complications like traumatic cataract, anterior capsular lens rupture, pigment dispersion and hiphema.

Case report

We report the case of a 29 years old male

patient with bilateral and dense AIM which

presented to Laser Optisan Clinic from Cluj-

Napoca in 2013 complaining of bilateral reduced

visual acuity since birth. The patient was

otherwise healthy. He had no family history of

any ocular pathology and his parents were not

consanguineous.

Examination showed: BCVA OD = 0.6, BCVA

OS = 0.4 and IOP OU = 17 mmHg. The patient had

a regular hyperopic astigmatism: OD +6.00 DSf –

4.50Cyl /1610, OS +4.75 DSf –4.00 Cyl /180, OD:

K1=38.50, K2=42.00, OS: K1=39.00, K2=42.00.

Extraocular muscle movements were normal in both eyes. Slit lamp examination revealed OU clear cornea, normally-reacting pupillary margin and iris, dens strands of tissue attached to the iris collarette along the pupil. In the center of this tissue was a 1 mm diameter pseudo-pupil.

Gonioscopy showed in both eyes a Shaffer

grade III/IV angle with ciliary body band visible,

normal structures and the angle was 36.20 OD

and 37.10 OS. Ophthalmoscopy was impossible to

do due to the dens AIM. Ocular echography was

normal.

Differential diagnosis was done with:

Persistent pupillary membrane (PPM)

even in its extreme forms present as translucent

or opaque membranous structure and extend

across the pupil; also it doesn’t present with a

pseudopupil [2];

Posterior synechiae secondary to

iridocyclitis is characterized by iris strands

attach to the pupil margin while in AIM the iris

strands arise from the iris collarette;

Axenfeld–Rieger syndrome is

associated with presence of microcornea or

megalocornea, anterior displaced Schwalbe’s line

(posterior embryotoxon) with attached iris

strands, smooth and scriptless iris surface with

high iris insertion, corectopia and ectropion

uveae; also implies facial bone and teeth defects,

hypospadias, redundant periumbilical skin [11];

Peters anomaly involves posterior

corneal defect with stromal opacification

(leukoma) that may become vascularized, iris

strands inserting into corneal defect, adhesions

of lens to corneal defect [11];

Iridocorneal endothelium syndrome

(ICE) implies corneal edema, abnormal corneal

endothelium and posterior synechiae with onset

in young adults [1].


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Nd – Yag laser membranectomy was not an

option in this case even if this technique has

been successfully used in older patients with

PMM. Although this approach is preferred

because it avoids intraocular surgery, laser lysis

is difficult in cases of thick membranes [12] [13].

Besides, because the membranes may have

active vasculature, Nd – Yag laser

membranectomy could lead to hyphema and

pigment dispersion. [13] [14].

The patient underwent bilateral AIM

membranectomy on a non-dilated pupil using

lots of viscoelastics for endothelial protection

and microincision surgery instruments to cut the

strands at their origins and get the AIM out of the

anterior chamber. We used 2 side-port incisions

which at the end didn’t need suture. We didn’t

encounter attachments to the anterior lens

capsule. The patient had excellent outcome and

no surgery complications were encountered.

Visual acuity improved to BCVA OD= 0.8,

BCVA OS=0.8 which stands for a deprivation

amblyopia. IOP OU was 15 mmHg. The refractive

error remained the same: OD +6.00DSf –4.50Cyl

/1610, OD +4.75DSf –4.00Cyl /180, OD:

K1=38.50, K2=42.00, OS: K1=39.00, K2=42.00.

Slit lamp examination revealed: clear

cornea, reactive, round and symmetric pupil, free

anterior chamber, iris pigment on the anterior

capsule, clear lens. Ophthalmoscopy showed a

normal retina and optic nerve.

The patient gave his consent for the use of

his data in this study.

Conclusions

Membranectomy done under dispersive viscoelastic protection and with microincision instruments represents the right approach in dense AIM restoring this way transparency of the visual axis. The risk of developing traumatic iatrogenic cataract, if surgical instruments are not carefully manipulated, represents the most important surgery complication that can appear.

Even if AIM and PMM have the same origin and the same treatment, we must differentiate the two conditions and use the right nomenclature.

Discolsureses: none

References

1. Tasman W., Jaeger E., 2007, Duane’s ophthalmology, 2007 Ed., Lippincott Williams & Wilkins, Philadelphia, p.24-258;

2. Bhatti S.M., Kapoor H.K., 1998, Bilateral accessory iris membrane, Indian Journal of Ophthalmology, 46:110-1;

3. Levy W.J., 1957, Congenital iris lesion, British Journal of Ophthalmology, 41:120-23;

4. Suh D.H., 1979, 2 cases of accessory iris membrane, Journal of the Korean Ophthalmology Society, 20(1):107-111;

5. Trattler W.B., Keiser P., Friedman N.J., 2012, Review of ophthalmology, 2nd Ed., Elsevier Inc. p.105-278;

6. Levin A.V., Wilson T.W., 2007, Hospital for Sick Children's - The Atlas of Pediatric Ophthalmology and Strabismus, 1st Ed., Lippincott Williams & Wilkins, p. 77;

7. Mukherjee P.K., 2005, Pediatric Ophtalmology, 1st Ed., New Age International (P) Ltd., Publishers, New Delhi, p.235;

8. Duke-Elder S., 1964, System of Ophthalmology, 1st Ed., Vol. 3, Henry Kimpton, London, p.587-775;

Fig. 1 Anterior segment photographs of bilateral AIM obtained before surgery

Fig. 2 Anterior segment photographs of bilateral AIM obtained during surgery


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9. Levy W.J., 1957, Congenital iris lesion, British Journal of Ophthalmology, 41:120-23;

10. Miller D., Johnson R., 1977, Quantification of the stenopeic effect, Survey of Ophthalmology, 21: 347–350;

11. Strominger M., 2008, Pediatric Ophthalmology and Strabismus, 1st Ed., Elsevier Inc., p.46;

12. Kumar H., Sakhuja N., Sachdev M.S., 1994, Hyperplastic pupillary membrane and laser therapy, Ophthalmic Surgery, 25:189-90;

13. Gupta R., Kumar S., Sonika S.S., 2003, Laser and surgical management of hyperplastic persistent pupillary membrane, Ophthalmic Surgery, 34:136-9;

14. Brusini P., Beltrame G., 1983, Spontaneous hyphaema from persistent remnant of the pupillary membrane: a case report, Acta Ophthalmologica (Copenhagen), 61:1099-103.


CASE REPORT


© 2015

PLATEAU IRIS SYNDROME – CASE SERIES

Crenguța Ioana Feraru, Anca Delia Pantalon, Dorin Chiselita, Daniel Branisteanu “Gr.T. Popa” University of Medicine and Pharmacy, Iași, Romania Faculty of Medicine, Department of Ophthalmology “Sf. Spiridon” University Hospital, Iași, Romania Correspondence to: Anca Delia Pantalon “Sf. Spiridon” University Hospital, Ophthalmology Department 1 Piata Independentei, zip code 700115, Iasi, Romania Mobile phone: +40740 686 865, E-mail: [email protected] Accepted: July 24, 2015

Abstract Plateau iris is characterized by closing the anterior chamber angle due to a large ciliary body or due to its anterior insertion that alters the position of iris periphery in respect to the trabecular meshwork. There are two aspects that need to be differentiated: plateau iris configuration and plateau iris syndrome. The first describes a situation when the iris root is flat and the anterior chamber is not shallow, the latter refers to a post laser iridotomy condition in which a patent iridotomy has removed the relative pupillary block, but goniscopically confirmed angle closure recurs without central shallowing of the anterior chamber. Isolated plateau iris syndrome is rare compared to plateau iris configuration. We hereby present two case reports of plateau iris syndrome in young patients who came to an ophthalmologic consult by chance. Key words: plateau iris configuration, plateau iris syndrome, glaucoma

Introduction

Plateau iris represents one of the most frequent causes of primary angle closure in young patients. It is diagnosed frequently under the age of 50, in patients with narrow anterior chamber angle, after a correct and patent laser peripheral iridotomy was made. There are two aspects that need to be differentiated: plateau iris configuration and plateau iris syndrome [1]. Iris plateau configuration exhibits a flat iris plane with an anterior chamber that is not shallow axially. Plateau iris syndrome refers to a post laser iridotomy condition in which a patent iridotomy has removed the relative pupillary block, but goniscopically confirmed angle closure recurs without central shallowing of the anterior chamber. Isolated plateau iris syndrome is rare

compared to plateau iris configuration. It usually occurs in a younger age group than pupillary block angle closure [2]. The treatment is laser iridoplasty or long term use of pilocarpine postoperatively. This condition must be considered in the differential diagnosis when the intraocular pressure rises unexpectedly following an adequate peripheral iridotomy/ iridectomy procedure for angle closure glaucoma. [3,4]

Case 1

We present the case of a late diagnosed closed angle glaucoma in a young patient who came to an ophthalmologic consult by chance. Mother (43 years old) brought her daughter to our department in April 2015, where the child was diagnosed with retrobulbar optical neuritis.


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At the child’s regular visit at one month after the acute episode of optic neuritis, mother requests a consult for herself as vision became blurry for some time in OD.

Personal history: AO – moderate hyperopia AOVD= 0.5 cc (sph +3.75) AVOS= 1 cc (sph +4.5) Visual field (Humphrey Visual Field

Analyzer II -1200, 3 zones) OD – visual field constriction up to the

central 30 area OS – normal visual field (VF) HFA II, 30-2 central, Full Threshold

Strategy, size III stimulus showed in OD reduced retinal sensitivity (MD = -30.88 dB) and central/ paracentral scotoma (PSD=6.88 dB), see (Fig. 1-2).

Anterior segment: AO shallow anterior chamber in periphery, but normal depth in the center see (Fig. 3-4)

OD – anterior chamber OD – anterior chamber

IOP-OD=70 mmHg IOP-OS=36 mmHg

When fundus exam was performed, it revealed almost total excavation in right eye (C/D=1), whereas C/D ratio in OS was 0.5/0.4.

FOOD – C/D=1(v)/ 0.9(h) FOOS – C/D=0.5/0.4

Goniscopy showed in AO that iris assumed a steep approach at its insertion before flattening centrally (iris drapes over the ciliary body producing the double “hump” aspect on indentation – see Fig. 6).

We diagnosed the patient with plateau iris

syndrome; thus deciding to systemically

prescribe manitol 20% ( iv) and acetazolamide

plus Pilocarpine 2% topically.

When anamnesis was rediscussed, the

patient revealed multiple ophthalmology visits

where she complained of headaches and blurred

vision that were always interpreted as poor optic

correction, but no fundus examination was ever

thoroughly done. When the IOP decreased to a

satisfactory level, a peripheral laser iridotomy

(IP) was done along with an ALPI procedure

Fig. 1-2 HFA II central 30-2 visual field

Fig. 3-4 anterior chamber shallow in periphery, normal depth centrally

Fig. 5 FOAO- C/D ratio

Fig. 6 gonioscopy in plateau iris “double hump” sign (indentation)


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(argon laser peripheral iridoplasty) (see Fig. 7-

8)

OD OS

IOP after laser procedures was 21 mmHg in

OD, thus beta blocker and carbonic anhydrase

inhibitor was prescribed to lower supplementary

the IOP; in OS the IOP was 15 mmHg without any

adjuvant medication. Pilocarpine was prescribed

in both eyes.

At 3 months check-up Pilocarpine 2% was

withdrawn, and the patient remained under

supervision for IOP and gonioscopy each 3

months; last control showed open angle/ 3600

(Schaffer II or III) and IOP in both eyes was 15

mmHg.

Case 2

B.E, female, 29 years old was referred to

our Ophthalmology Clinic for a diagnosis of OU

Juvenile decompensated glaucoma. Major

complaints were ocular pain and bilateral

decreased vision, right eye more than the left

eye.

Last ophthalmological visit stated: AVOD =

0.1 sc; AVOS =0.7sc, IOP-OD=38 mmHg, IOP-

OS=40 mmHg; fundus examination: OU – retinal

degenerescence, C/D ratio OD=0.5, OD=0.6.

Treatment was first initiated with topical beta

blockers, then due to the lack of response,

prostaglandin analogues (PGA) and carbonic

anhydrase inhibitor (CAI) were added topically;

Brimonidine was needed topically only in OS.

Under this treatment IOP was OD=19 mmHg, OS-

28mmHg. A presumed diagnosis of autosomal

recessive bestrophinopathy (ARB) is suspected

by the retina specialist. An electrophysiology testing is mandatory for diagnosis confirmation.

Our current examination found AVOD=0.2

sc; AVOS=0.7 cc (sph +2)

IOP-OD=10 mmHg (PGA+BB+CAI), IOP-

OS=19 mmHg (PGA+BB+CAI+Brimonidine)

Corneal central thickness: OD = 469μm,

OS=474 μm

Slit lamp examination shows shallow

anterior chamber in periphery, but normal axial

depth (see Fig. 9-10).

Gonioscopy reveals convex iris, closed

angle/ 2700 and open inferiorly (Schaffer I); by

indentation the angle opened Schaffer IV/ 3600,

“double hump” sign positive (see Fig. 11-12).

Fig. 7-8 Status post IP+ALPI

Fig. 9 anterior segment OD

Fig. 10 Shallow peripheral AC (OD)


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Visual field (HFA II – central 24-2 SITA Standard) found in OD decreased general retinal sensitivity and paracentral inferior/ central with fixation spot involvement scotoma, MD=-3.69 dB, PSD=5.15 db. In OS there was also a decreased general retinal sensitivity and a superior incomplete arcuate scotoma, with MD=-5.65 dB, PSD=6.26 dB (see Fig. 13-14).

Fundus examination showed asymmetric excavation C/D OD= 0.2, C/D OS=0.5 in small optic disks and in both eyes, diffuse irregularity of retinal pigment epithelium, dispersed punctate flecks and chronic accumulation of fluid beneath the neurosensory retina in the macular region (Fig. 17-18).

Fig. 11 closed angle

Fig. 12 “double hump” sign

Fig. 13 VF – HFA II

c24-2 (OD)

Fig.14 VF – HFA II

c24-2 (OS)

Fig. 15 FOOD presumed autosomal recessive

bestrophinopathy

Fig. 16 FOOS presumed autosomal recessive

bestrophinopathy

Fig. 17 OD- SD OCT


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This patient had initially laser peripheral iridotomies. Her angle depth improved in each eye but there was concern that the angle in the left eye was still occludable. She underwent a bilateral ALPI procedure without complication and repeated gonioscopy that proved improvement in the angle depth OU (see Fig. 19-20).

At the last visit, the angle does not appear to be occludable and we are monitoring her gonioscopically every 3 months.

IOP-OD=16 mmHg; IOP-OS=16 mmHg (BB+CAI)

Discussion

Plateau iris syndrome is a relatively uncommon form of primary angle closure glaucoma that is seen more often in younger adults than pupillary block angle-closure glaucoma5. Patients can come at the hospital presenting angle closure, either spontaneously or after pupillary dilation [6] as one of the cases presented here (case 2), but more commonly, patients are asymptomatic and the diagnosis is made on routine examination (case 1).

Surgical management is the primary treatment modality in patients with plateau iris configuration or syndrome. A patent iridotomy may be therapeutic in reducing risks of angle closure. However, in some patients, laser iridotomy may not significantly alter the anterior chamber depth or anatomy. Even after a successful iridotomy resulting in a well-open angle, periodic gonioscopy remains crucial because these patients may have incomplete plateau iris syndrome or the angle may narrow further with age because of the enlargement of the lens.

Argon laser peripheral iridoplasty (ALPI) is the procedure of choice to effectively open an angle that remains occluded after successful laser iridotomy. It is highly effective, and the effect is maintained for years [7]. Yet, even after successful opening of the angle, regular gonioscopy is mandatory.

Our cases exhibit certain particularities: diagnosis made by chance, advanced glaucoma that passed undiagnosed until advanced stage, thorough history and goniscopy helped getting a correct diagnosis and eliminate other causes of increased IOP in young patients (congenital glaucoma, pigmentary/ inflammatory/ post-traumatic glaucoma, so on); C/D ratio not proportionally increased with the large IOP fluctuations show the intermittent angle closure history; macular associated pathology contributed to additional visual decay.

Fig. 18 OS- SD OCT

Fig. 19 OD-post laser treatment

Fig. 20 OS post laser treatment


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This paper was supported by CERO-POSDRU/159/1.5/S/135760 grant; the project was co-financed by the Social European Fund through the Program for Human Resources Development 2007-2013.

References

1. Cornel Stefan, Daniela Iliescu, Mihail Zemba, Mehdi Batras, Cristina Timaru, Algerino De Simone – Dezbateri clinice despre glaucom, sub redactia Dorin Chiselita, Ed. ‘Gr. T. Popa” Iasi 2015, ISBN 978-606-544-315-0, p.57-73.

2. Terminology Guidelines for Glaucoma - European Glaucoma Society, 4th Ed 2014, p.110-111.

3. Yanoff Myron, Duker Jay S., Ophthalmology – Printbook, Ed. Elsevier 2013, ISBN-9781455739844, p.1162-1167

4. Alward WLM. Glaucoma: The Requisites in Ophthalmology. St Louis: Mosby 2000. Pages 146-7 and 209-213.

5. Kiuchi Y, Kanamoto T, Nakamura T. Double hump sign in indentation gonioscopy is correlated with presence of plateau iris configuration regardless of patent iridotomy. J Glaucoma. 2009; 18(2):161-164.

6. Shukla S, Damji KF, Harasymowycz P, Chialant D, Kent JS, Chevrier R, Buhrmann R, Marshall D, Pan Y, Hodge W. Clinical features distinguishing angle closure from pseudoplateau versus plateau iris. Br J Ophthalmol. 2008; 92(3):340-344.

7. Ritch R, Tham C, Lam D. Long-term success of argon laser peripheral iridoplasty in the management of PIS. Ophthalmology 2004; 111: 104-8.


CASE REPORT


© 2015

CURRENT OPTIONS FOR SURGICAL TREATMENT OF GLAUCOMA

Ştefan Cornel, Batras Mehdi, Iliescu Daniela Adriana, Timaru Cristina Mihaela, De Simone Algerino, Hosseini-Ramhormozi Jalaladin Central Military Emergency University Hospital „Dr. Carol Davila”, Ophthalmology Department, Bucharest, Romania

Correspondence to: Iliescu Daniela Adriana, MD Central Military Emergency University Hospital „Dr. Carol Davila”, Ophthalmology Department 134 Calea Plevnei Street, District 1, Bucharest, Romania Tel/Fax: +400213 137 189, E-mail: [email protected]


Abstract The purpose of this study is to review current surgical treatment and new and better alternatives for patients with glaucoma. Glaucoma refers to a group of related eye disorders that have in common an optic neuropathy associated with visual function loss. It is one of the leading causes of irreversible blindness worldwide. Optic nerve damage and glaucoma-related vision loss can be prevented or limited by early diagnosis and treatment. Surgery offers a better control of the intraocular pressure then medical therapy. Nowadays, research continues for improving current surgical alternatives for treatment. Keywords: glaucoma, surgical treatment, stent, eye implant.

Introduction

The term glaucoma refers to a group of diseases that have in common an optic neuropathy associated with visual function loss. Glaucoma is the second most frequent cause of irreversible blindness in the world.

The number of patients suffering from glaucoma is estimated at 67 million, making this disease a huge public health impact. Filtering surgery

Filtering surgery in glaucoma is indicated when medical treatment and laser therapy are unable to prevent, stop or delay the progression of the disease. It is known that surgery offers a better control of intraocular pressure (IOP) then medical treatment. Even so, the traditional

filtering surgery is a challenge, especially in advanced glaucoma, for it can be accompanied by complications and failure.

Trabeculectomy is considered the “gold standard” of non-penetrating surgery in glaucoma; it is the surgical technique from which all the others are derived, newer procedures, with better efficacy and safety.

Surgical procedures are based on one of the two mechanisms to reduce IOP:

1. Improving drainage of aqueous humor (AH)

2. Reducing production of AH. 1. The first technique is the one usually

used. There are two types of procedures: ab externo and ab interno.

1.1 non-penetrating anterior filtering techniques:


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1.1.1 deep sclerectomy (DS) (simple or assisted by a CO2 laser)

1.1.2 canaloplasty 1.2 penetrating anterior filtering

techniques: 1.2.1 trabectome 1.2.2 Fugo blade 1.2.3 Excimer laser assisted

trabeculectomy. 1.3 penetrating posterior filtering

techniques: 1.1 Non-penetrating anterior filtering techniques

The efficacy of antiglaucoma non-penetrating surgery:

- the rate of success varies between 45% and 69%;

- the rate of complete success is 34.6% for deep sclerectomy and 63.4% for deep sclerectomy with collagen implant, after 48 months [1].

- the qualified success can be up to 69-100%. Indications for non-penetrating anterior filtering techniques:

- primary open angle glaucoma (POAG) - pigmentary glaucoma - pseudoexfoliative glaucoma - non-penetrating deep sclerectomy for :

glaucoma due to high myopia, uveitic glaucoma, primary juvenile glaucoma, glaucoma caused by increased episcleral venous pressure. Contraindications for non-penetrating anterior filtering techniques:

- scares from an anterior trabeculectomy;

- patients with scaring of the Schlemm’s canal caused by laser, surgical procedures or corneo-scleral trauma;

- anomalies of the camerular angle; - primary angle-closure (PAC) (for non-

penetrating deep sclerectomy); - open-angle glaucoma due to ocular

trauma (for non-penetrating deep sclerectomy). Complications of non-penetrating anterior filtering techniques:

- hyphema - early or late elevation of IOP

- suture detachment - Descemet detachment - iris prolapse - hypotonia - inflammation - failure of the procedure

1.1.1 Deep sclerectomy 1.1.1.1 Non-penetrating simple deep sclerectomy

Through this technique the Schlemm’s canal is opened and the partial excision of the external and internal walls and of a part of the trabecular meshwork is made (Fig. 1).

The most frequently used technique is to make two scleral flaps, one superficially situated with the base at the limbus and another, more profound, as a mark for the opening of Schlemm’s canal.

The profound flap is excised, eliminating the internal and external walls of the Schlemm’s canal. The drainage of the aqueous humor is observed. All the anatomical planes are sutured [2].

1.1.1.1 CO2 laser assisted deep sclerectomy

(CLASS) First, the conjunctiva is incised for making

a flap with the ab externo base. A rectangular sclera flap is made (1/3 or 1/2 of the sclera’s thickness), with the base at the limbus (Fig. 2).

The CO2 laser is applied, along with the HENE guidance. The CO2 laser will excise the external wall of the Schlemm’s canal.

Fig. 1 The technique of the deep sclerectomy

Fig. 2 Scleral flap in CO2 laser assisted deep sclerectomy


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A study was conducted on 15 patients to prove the efficacy of this procedure. An average IOP reduction of 13.1±4.3 mm Hg (45.1%) and 11.5±5.5 mm Hg (39.2%) at 6 and 12 months was seen. The complete success rate after 12 months was 45.5%, whereas qualified success was 90.9%. Mitomycin C was used in 76.9% of the CLASS subjects [3].

Trabeculectomy versus deep sclerectomy

There are numerous randomized studies that reveal the superiority of non-penetrating surgery concerning safety; when it comes to efficacy, the results are different in studies.

The trabeculectomy lowers the IOP to greater extent compared to viscocanaloplasty; the rate of complications is higher for the trabeculectomy [4],[5].

Comparing deep sclerectomy with trabeculectomy,using the Kaplan Meier cumulative survival curve, the trabeculectomy patients had a better complete success rate than the non-penetrating deep sclerectomy patients at 18 months post-operatively. There were statistically significantly fewer complications in the non-penetrating deep sclerectomy group [6].

A study conducted on 39 patients revealed there is no significant difference between trabeculectomy and deep sclerectomy for POAG concerning the lowering of IOP, but the rate of complications is lower for the sclerectomy (12 months follow-up) [7].

The sclerectomy with collagen implant has a success rate comparable to trabeculectomy, with a lower complication rate as proven by a study conducted on 100 patients [8].

1.1.1 Canaloplasty

For this type of non-penetrating surgery, a wire is introduced in the Schlemm’s canal, guided by an optic fiber micro catheter (Fig.3).

The wire dilates and keeps tension in

Schlemm’s canal, reestablishing the flow of aqueous humor through the physiological paths.

A viscoelastic product is injected for opening the Schlemm’s canal.

The tension created has a pilocarpin-like effect, improving flow through the trabecular meshwork.

A study conducted on 726 patients concluded that canaloplasty produced a sustained long-term reduction of IOP in black Africans with POAG independent of preoperative IOP. As a bleb-independent procedure, canaloplasty may be a true alternative to classic filtering surgery, in particular in patients with enhanced wound healing and scar formation [9]. Advantages the 360° controlled opening of Schlemm’s

canal the possibility to combine the procedure with

deep sclerectomy for better lowering of the IOP

Disadvantages expensive device unknown long term effect of the implant in Schlemm’s canal

1.2 Penetrating anterior filtering techniques

1.2.1 Trabectome

The trabectome (Fig. 4) is a surgical

instrument used for controlled partial

endoelectro ablation of the trabecular mesh,

under gonioscopic guidance.

This ab interno procedure dissects the

juxtatrabecular region and eliminates the

resistance, creating a direct flow of the aqueous

humor through the Schlemm’s canal and the

collector channels [3].

Indications POAG pigmentary and pseudoexfoliative glaucoma POAG with ineffective filtering.

Fig. 3 Micro catheter used in canaloplasty

Fig. 4 The trabectome


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Contraindications: angle closure, with or without peripheralsynechiae. Complications: hyphema iridodialysis ciclodialysis the abrupt elevation of the IOP. Advantages: creating a large communication between the anterior chamber and the collector channels lack of adjacent tissue damage unaffected conjunctival integrity no filtering bleb. Disadvantages: the opening of the Schlemm’s canal is not circumferential a limited lowering of the IOP caused by the pressure in the aqueous veins expensive procedure

1.2.2 Fugo plasma blade – transciliary filtration

Approved by the FDA in 2004, Fugo plasma blade (Fig. 5) is the first plasma ablation system that can create precise low-energy incisions on the ocular surface without damaging the adjacent elements, with instantaneous hemostasis.

Advantages: posterior drainage no antimetabolites needed

the price is not very high the short duration of the intervention. Disadvantages: the risk of a hyperfiltering hypotonia

The Fugo blade technique can also be ab interno by creating fenestrations in the internal wall of Schlemm’s canal, that allow the AH to flow without resistance.

The procedure was found to be effective and safe [10].

1.2.3 Excimer laser assisted trabeculectomy

The procedure is ab interno; it creates small gaps in the trabecular meshwork which allows the aqueous humor to pass through the Schlemm’s canal without encountering resistance (Fig. 6). An Excimer xenon-chloride laser is used.

Advantages:

the ab interno approach keeps the conjunctiva

intact

control of the ablation, without alternative

tissue damage

can be combined easily with

phacoemulsification

short duration of the intervention.

1.3 Non-penetrating posterior filtering

techniques

Indications:

glaucoma unresponsive to medical treatment

(AqueSys, ExPress)

POAG with moderate IOP (Hydrus microstent,

CyPass),

early onset POAG (EyePass),

Fig. 5 Fugo plasma blade device

Fig. 6 Intraoperatory view during an Excimer laser assisted trabeculectomy


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failure of trabeculectomy (Gold microshunt, iStent) pigmentary glaucoma (iStent) pseudoexfoliative glaucoma (iStent) Sturge-Weber syndrome (ExPress) aphakic glaucoma (ExPress)

Contraindications:

primary angle closure glaucoma (ExPress,

iStent, CyPass, Hydrus microstent, AqueSys)

secondary glaucoma (CyPass, Hydrus

microstent, AqueSys)

acute angle-closure (Gold Microshunt,

EyePass)

uveitic glaucoma, traumatic glaucoma,

neovascular glacoma, iridocorneal endothelial

syndrome (Gold Microshunt, EyePass)

active ocular infection

ocular surgery in the last 12 months (Gold

Microshunt)

active ocular pathologies : uveitis, ocular

infections, dry eye syndrome (ExPress, iStent,

Gold Microshunt)

systemic or ocular disease that can cause

postoperatory complications.

Complications: blockage of the aqueous humor flow (ExPress) possible peripheral anterior synechiae (iStent) hyphema hypotonie (Gold Microshunt, EyePass) supracoroidian hemorrhage (Gold Microshunt) migration of the device discoloration of the Descemet membrane (CyPass)

Advantages: lowered risk of hypotonia (Ex-Press, Gold Microshunt) limited risk of athalamia (Ex-Press) continuous control of filtering reduced inflammation: no iridectomy needed (Ex-Press) fixed and continuous drainage through metallic stent (iStent, Hydrus microstent)

maintaining the integrity of the conjunctiva (iStent, CyPass, Hydrus microstent, AqueSys) possibility of combined surgery (iStent, CyPass, Hydrus microstent, AqueSys) possibility of modulating the IOP by changing parameters of the devices (Gold Micro Shunt) low risk of creating a filtering bleb (Gold Micro Shunt) a permanent communication between the anterior chamber and the supracoroidian space (CyPass) excellent biocompatibility (Hydrus microstent) a permanent communication between the anterior chamber and the subconvunctival space (AqueSys) no adjacent tissue damage (AqueSys)

Disadvantages: the risk of antimetabolites (Ex-Press) the risk of contact with the iris or cornea (Ex-Press) the necessity of multiple stents for obtaining a higher flow (iStent) the risk of device migration difficult procedure expensive device creating a filtering bleb (AqueSys) the possibility of conjunctival damage (AqueSys) risk of fibrosis (AqueSys)

1.3.1 Ex-Press device

It is an alternative to conventional surgery (Fig. 7).

Fig.7 Intraoperatory view after placing an Ex-Press stent


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Studies have proven the superior efficacy of

the Ex-Press stent to the trabeculectomy: IOP

lowering up to 50.9% for the Ex-Press stent and

44.6% for the trabeculectomy after 12 months

[11].

In a study on POAG, Ex-PRESS and

trabeculectomy provided similar IOP control, but

Ex-PRESS was more likely to achieve complete

success, with fewer postoperative interventions.

Complication rates were similar for the two

types of surgery, except for a lower frequency of

hyphema in the Ex-PRESS group [12].

1.1.1 IStent (Glaukos Corp)

The IStent shunt is the first micro-bypass

ab interno implant available for the treatment of

glaucoma (Fig. 8). It was designed for

reestablishing the physiological flow of the AH,

by creating a by-pass through the trabecular

meshwork of the Schlemm’s canal. The IStent is

positioned ab interno through a small incision in

the Schlemm’s canal, in the inferior nasal

quadrant [13].

1.1.1 Gold micro shunt

The Gold micro shunt is a micro gold

plaque of 24 karats that contains 19 canals. It is

used for creating a communication between the

anterior chamber of the eye and the

supracoroidian region (Fig. 9).

The difference of pressure between the

anterior chamber and the supraciliary space

determines a flow of the aqueous humor through

the micro-canals.

The Gold micro shunt is the first implant

that uses natural pressure gradient for creating a

continuous flow of the AH [14][15].

1.3.4 EyePass

EyePass glaucoma implant is a micro tube

shaped as a “Y”; it was developed in order to by-

pass the trabecular meshwork and make a

communication between the Schlemm’s canal

and the anterior chamber (Fig. 10). The

procedure is ab externo; both arms of the device

have to be placed inside the Schlemm’s canal

[16].

Fig. 8 The positioning of the IStent shunt

Fig.9 Gold micro shunt device

Fig. 10 EyePass implant


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1.3.4 CyPass Micro-Stent CyPass Micro- Stent is actually a polyamide

cannula, with a 6.25 mm length and a diameter of 300 µm (Fig.11).

It is placed in the supraciliary space and the aqueous humor drains through the gaps of this tube [17].

In a study conducted on 142 patients, CyPass Micro-Stent implantation resulted in minimal complications and reduced IOP 12 months postoperatively [18].

1.3.6 Hydrus microstent

Hydrus microstent is described as an “intracanalicular scaffolding” (Fig.12).

The procedure is done ab interno; it is actually a micro-by-pass that reestablishes flow through the trabecul - Schlemm’s canal, using a direct communication between the anterior chamber and the Schlemm’s canal.

The device has the size of an eyelash, made of nitinol (nickel-titanium); it is very elastic and biocompatible.

Preliminary data on 28 patients in a study, showed that after 6 months, combined phacoemulsification and Hydrus stent insertion resulted in approximately a 15% decrease in IOP from a baseline of 18 mmHg. The two most common complications were transient hyphema

in 15% and Peripheral Anterior Synechiae (PAS) formation in 10% of patients [19].

1.3.7 AqueSys

The AqueSys system is described as the first procedure with an ab interno subconjunctival approach for lowering the IOP. It creates a direct link between the anterior chamber and the subconjunctival space.

The implant is flexible, with a gel-like structure; its diameter is that of a human strand of hair (65µm) (Fig.13).

Conclusions

Glaucoma is an optic neuropathy characterized by retinal ganglion cell death and axonal loss. It remains a major cause of blindness worldwide. All current modalities of treatment are focused on lowering intraocular pressure.

The surgical treatment for this disease is considered to be a better alternative then medical therapy. There are various types of surgical technique that can be used to treat glaucoma. All of them have proven to be effective and safe.

It is anticipated that the devices developed will pave the way for future discovery, development, and marketing of novel surgical ways to treat glaucoma and thus help save sight for millions of people afflicted with this slow progressive optic neuropathy.

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Fig. 12 Hydrus microstent device

Fig. 13 AqueSys device


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Disclosures In the Disclosures section, authors must disclose any and all relationships that could be perceived as real or apparent conflict(s) of interest. If authors have nothing to disclose, they must state "None." Conflicts of interest pertain to relationships with and/or ownership interests in pharmaceutical companies, biomedical device manufacturers, or other corporations whose products or services are related to the subject matter of the article. Relationships include, but are not limited to, employment by an industrial concern, ownership of stock, membership on a standing advisory council or committee, being on the board of directors, or being publicly associated with the company or its products. Ownership interest includes any stock, stock option, partnership, membership or other equity position in an entity regardless of the form of the entity, or any option or right to acquire such position, and any rights in any patent or other intellectual property. Other areas of real or perceived conflict of interest could include receiving honoraria or consulting fees or receiving grants or funds from such corporations or individuals representing such corporations.

References References must conform to Pubmed requirements. Authors must ensure accuracy of reference data. Verify all entries against original sources. All authors must be listed in each reference. Do not use "et al". Cite references in numerical order according to first mention in the text. Personal communications, unpublished observations, and submitted manuscripts are not legitimate references and must be cited in the text only (not in the reference list) as "(author name, unpublished data, [year])." All submitted manuscripts that are pertinent to the manuscript under consideration must accompany the submission. Personal communications and unpublished observations must be accompanied by a letter from the source approving use of the information. All references will be written in the following order: name (of the author), initial letter of the surname (of the author), title of the article, source (name of the book, magazine, etc), year of publication, volume, issue (if applicable), first page, last page (of the source). Example: Langlois J, Rutland-Brown W, Wald M. The epidemiology and impact of traumatic brain injury: a brief overview.J Head Trauma Rehabil. 2006; 21: 375-378. The references will not contain internet sources. All references which are originally taken from an international database (i.e. Scopus, MedLife, etc.), should respect the same order of the elements mentioned above, but should necessarily contain a “doi” after the year of the publication, instead of the page numbers of the paper. Example: Langlois J, Rutland-Brown W, Wald M. The epidemiology and impact of traumatic brain injury: a

brief overview. 2006; doi:10.1111/j.1464-410X.2009.08495.x. All references which are originally taken from books, should contain the following details in this specific order: name(s) and surname(s) of the author(s), chapter of the book (if applicable), the title of the book, year of publication, the city of publication, the name of the publishing house, first page, last page (of the source). Example: Hojat M. Does empathy predict career choice and professional success? Empathy in Patient Care, 2006, New York, Springer Verlag, 205-209 We recommend you to use only peer-reviewed journals.

Figures Acceptable electronic figure file formats for publication are:

jpg and .tiff

Color figures must be in CMYK mode, not RGB mode.

Color figures and line drawings must be at least 600 dpi

resolution. Grayscale and black/white figures must be at

least 300 dpi resolution.

Combination color, grayscale and line art must be 600 dpi

or higher.

The use of digital media for image acquisition and

processing introduces the potential for inadvertent

distortion of data. To prevent such distortion, data should

neither be added to, nor removed from, an image by digital

manipulation. Figures assembled from multiple images

must indicate the separation of the parts by lines.

Linear adjustment of contrast, brightness or color must be

applied equally to all parts of an image.

Authors must be prepared to submit the original, unaltered

files from which the submitted figures were derived, if

requested by the editorial office.

Graphics downloaded from the Web are not acceptable for

print. Web graphics, usually in GIF or JPEG format, have a

resolution of only 72 dpi, which does not meet the standard

for peer review nor publication.

Figure parts should be clearly labeled. Letters and labels

must be uniform in size and style within each figure and,

when possible, between figures. The font size must be 10

point or higher.

Symbols and abbreviations must be defined in the figure or

its legend.

Avoid headings on the figure. Heading information should

appear in the figure legend.

Provide a short title (in the legend, not on the figure itself)

and an explanation in brief but sufficient detail to make the

figure intelligible without reference to the text (unless a

similar explanation has been given in another figure).

Figure legends are included in the word limit.

Tables Include table(s) in the main manuscript document as text, not as an image. Table(s) are included in the word limit. Number tables using Arabic numerals, and supply a brief, informative title for each table. Table text must be consistent in size and style with main manuscript text. Supply brief column headings. Indicate footnotes in this order: *, †, ‡, §, ||, #, ** Use only horizontal borders above, and below the column headings and at the bottom of the table. Use extra space to delineate rows and columns. Abbreviations/symbols used in a table but not already defined in the main text must be defined in the table or table legend. Do not use colors for tables, use only default .1 black borders. Tables must be placed 1 per page at the end of the manuscript, after the references. Copyright information A letter signed by the main author of the article, which will be sent via mail together with the manuscript, will contain copyright transfer to Romanian Journal of Ophthalmology. The full responsibility for all written information in the article belongs to authors.

Conflict of Interest Policy Authors are responsible for the published materials and other conflicts of interests regarding subjects included in their work. Authors must mention all the funding received for research and other financial or personal connections linked to the article, in their work.

Order of publication The order in which the articles appear in the journal is determined by:

date of arrival

editorial priorities

compliance with the above mentioned recommendations

peer-review recommendations

Priorities can be decided for some articles, requested either by the editors or by being of special interest. For urgent communications (phone, fax, e-mail), the following address may be used as well: " Dr. Carol Davila"Central Military University Emergency Hospital 134 Calea Plevnei Street, District 1, Bucharest, Romania Phone number/Fax: +40.21.3137189, E-mail: [email protected] Please also consider downloading the following documents: Authors' recommendations Authorship responsibility form Copyright transfer agreement

Sponsors of Romanian Journal of Ophthalmology Alcon, Alpha Wassermann, Amaoptimex, AMD – Nobel, Argusoptik, Biosooft, Edyoptic LTT, Essilor, Euromedex France, Expertmed, Farmatin, HOYA, Kemblimed, KRKA, Laboratoire Thea, Menicon, Nova Lenti, Optimed, Pfizer, RECKITT BENCKISER, Romger General, Santen, Sifi, SIFI Medtech, Sover Optica, Unimed Pharma, Valeant Bausch Lomb

http://www.medandlife.ro/assets/files/authors'%20recommendations.pdf

http://www.medandlife.ro/assets/files/authorship%20responsibility%20form.pdf

http://www.medandlife.ro/assets/files/copyright%20transfer%20agreement.pdf

Romanian

Journal of

Ophthalmology


www.rjo.ro

Volume 59, Issue 3, 2015

Documents

Romanian Journal of Ophthalmologyrjo.ro/wp-content/uploads/2015/10/images_RJO_3_opt.pdfRomanian Journal of Ophthalmology Volume 59, Issue 3, July-September 2015 Contents Editorial