BEYOGLU EYE JOURNAL 2018-1

ISSN 5989-6587 ISSN 2459 - 1777

BEYOGLU EYE JOURNAL

Volume 3 Issue 1 Year 2018

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YILIN TECRÜBESİ

ZADITEN® % 0.025 Steril Göz Damlası Etkin madde: 1 ml çözeltide 0,345 mg ketotifen hidrojen fumarat’a eşdeğer 0,25 mg ketotifen içerir. Terapötik endikasyonlar: Alerjik konjonktivit semptomlarının tedavisinde endikedir. Pozoloji ve uygulama şekli: Yetişkinler, yaşlılar ve çocuklarda (3 yaş ve üzeri) konjonktival kese içine günde 2 defa 1 damla damlatılır. Özel popülasyonlara ilişkin ek bilgiler: ZADITEN®’in 3 yaşın altındaki çocuklarda etkinlik ve güvenliliği gösterilmemiştir. Kontrendikasyonlar: Ketotifen veya yardımcı maddelerden herhangi birine karşı aşırı duyarlılığı olduğu bilinen hastalarda kontrendikedir. Özel kullanım uyarıları ve önlemleri: ZADITEN® koruyucu olarak yumuşak kontakt lenslerde birikebilen bir madde olan benzalkonyum klorür ihtiva eder; bu nedenle, ilacın damlatılması esnasında gözde kontakt lens bulunmamalıdır. İlaç damlatıldıktan en az 15 dakika sonra kontakt lensler tekrar göze takılabilir. Diğer tıbbi ürünler ile etkileşimler ve diğer etkileşim şekilleri: ZADITEN®’e ek olarak başka göz ilaçları kullanılması gerektiğinde, iki ilaç en az 5 dakika ara ile uygulanmalıdır. Oral yolla ketotifen fumarat kullanımı, santral sinir sistemi depresanlarının, antihistaminiklerin ve alkolün etkisini potansiyalize edebilir. Bu olgunun ketotifen fumarat ihtiva eden göz ürünleri açısından önemi bilinmemektedir. Gebelik ve laktasyon: Gebelik Kategorisi: C. Ketotifenin gebe kadınlara kullanımına ilişkin yeterli veri mevcut değildir. Oral kullanım ve toksik dozlar için yapılmış hayvan çalışmalarında pre ve postnatal mortalitede artış gözlenirken teratojenitede böyle bir durum gözlenmemiştir. Oküler kullanımı takiben sistemik düzeyler genellikle limitlerin altındadır. ZADITEN® gerekli olmadıkça gebelik döneminde kullanılmamalıdır. Laktasyon dönemi: Oral uygulamayı takiben elde edilen hayvan verilerine göre ilacın anne sütüne geçtiği bildirilmiş olmasına rağmen, insanda topikal uygulamayı takiben anne sütünde tespit edilebilir miktarlarda bulunmamıştır. ZADITEN® emzirme döneminde kullanılırken dikkatli olunmalıdır. Araç ve makine kullanımı üzerindeki etkiler: Bulanık gören veya uyku hali olan hastalar araç ve makine kullanmamalıdırlar. İstenmeyen etkiler: Göz bozuklukları: Gözde yanma/batma, noktasal korneal epitel erozyonu, ilacın damlatılması esnasında bulanık görme, kuru göz, göz kapağı rahatsızlığı, konjonktivit, göz ağrısı, fotofobi, subkonjonktival hemoraji; Bağışıklık sistemi bozuklukları: Alerjik reaksiyon, ağız kuruluğu; Sinir sistemi bozuklukları: Baş ağrısı, somnolans; Deri ve deri altı doku bozuklukları: Deride döküntü, egzama, ürtiker. Doz aşımı ve tedavisi: Klinik sonuçlar 20 mg’a kadar ketotifenin oral yolla alımını takiben hiçbir ciddi belirti ya da semptomun gözlenmediğini göstermiştir. Raf ömrü: 24 aydır. Şişe açıldıktan sonra 4 hafta içinde kullanılmalıdır. Saklamaya yönelik özel tedbirler: 25°C’nin altındaki oda sıcaklığında saklayınız. Ambalajın niteliği ve içeriği: 5 ml’lik polietilen şişe. Ruhsat sahibi: Thea Pharma İlaç Tic. Ltd. Şti.

Hakkı Yeten Cad. No:10 K:21 Fulya Beşiktaş - İstanbul Tel: 0 212 310 80 20. Ruhsat tarihi ve no: 22.11.2011 ve 132/36. KDV dahil perakende satış fiyatı: 13,68 TL Geçerlilik tarihi: 19.02.2018 Reçete ile satılır. Prospektüs kodu: 01/22.11.2011/G00.

DAHA GENİŞ BİLGİ İÇİN FİRMAMIZA BAŞVURUNUZ. Théa Pharma İlaç Tic. Ltd. Şti. Hakkı Yeten Cad. Selenium Plaza No.10/C K.21 Fulya-Beşiktaş 34349 İstanbul, Türkiye. Tel: +90 212 310 80 20, faks: +90 212 310 80 22.

www.theapharma.com.tr

ISSN 2459 - 1777

BEYOGLU EYE JOURNAL

EDITOR-IN-CHIEF

MUHITTIN TASKAPILI, MD University of Health Sciences, Beyoglu Eye Training and Research Hospital

ASSOCIATE EDITORS

ALPER AGCA, MD University of Health Sciences, Beyoglu Eye Training and Research Hospital

CIGDEM ALTAN, MD University of Health Sciences, Beyoglu Eye Training and Research Hospital

PINAR CAKAR OZDAL, MD Ankara Ulucanlar Eye Training and Research Hospital

ABDULLAH OZKAYA, MD University of Health Sciences, Beyoglu Eye Training and Research Hospital

IRFAN PERENTE, MD University of Health Sciences, Beyoglu Eye Training and Research Hospital

SCIENTIFIC ADVISORY BOARD NUR ACAR, Istanbul ALPER AGCA, Istanbul ZEYNEP ALKIN, Istanbul NILUFER ALPARSLAN, Istanbul TUGRUL ALTAN, Istanbul TULIN ARAS OGREDEN, Istanbul HALIL OZGUR ARTUNAY, Istanbul MELIKE BALIKOGLU YILMAZ, Izmir FIGEN BATIOGLU, Ankara NILUFER BERKER, Ankara CAGRI G. BESIRLI, Michigan, USA FERDA CIFTCI, Istanbul AHMET DEMIROK, Istanbul MURAT DOGRU, Keio, Japan G. MUSTAFA ERDOGAN, Istanbul KORHAN FAZIL, Istanbul

BIRSEN GOKYIGIT, Istanbul G. IBRAHIM GULKILIK, Istanbul KIVANC GUNGOR, Gaziantep DILEK GUVEN, Istanbul ZIYA KAPRAN, Istanbul SAFAK KARSLIOGLU, Istanbul SULEYMAN KAYNAK, Izmir AHMET KIRGIZ, Istanbul R. BERIL KUCUMEN, Istanbul ORKUN MUFTUOGLU, Istanbul OSMAN BULUT OCAK, Istanbul HALIT OGUZ, Istanbul AYŞE ONER, Kayseri ALTAN ATAKAN OZCAN, Adana FERAH OZCELIK, Istanbul HAKAN OZDEMIR, Istanbul

GAMZE OZTURK KARABULUT, Istanbul AHMET MURAT SARICI, Istanbul BANU SATANA, Istanbul KUBRA SEREFOGLU CABUK, Istanbul DIDEM SERIN, Istanbul ARZU TASKIRAN COMEZ, Canakkale BETUL TUGCU, Istanbul DIDAR UCAR, Istanbul CANAN ASLI UTINE, Istanbul MURAT UYAR, Istanbul NILUFER YALCINDAG, Ankara MELDA NURSAL YENEREL, Istanbul YUSUF YILDIRIM, Istanbul IHSAN YILMAZ, Istanbul PELIN YILMAZBAS, Ankara

VOLUME 3 ISSUE 1 YEAR 2018

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Implantation of foldable posterior chamber intraocular lens in aphakic All submissions to the journal must include full disclosure of all relationships vitrectomized eyes without capsular support. Arq Bras Oftalmol. that could be viewed as presenting a potential conflict of interest. If there 2016;79:159-162. are no conflicts of interest, authors should state that there are none. This Journal article (print, more than six authors): Ozkaya A, Alagoz C, Garip R, must be stated at the point of submission (within the manuscript after the et al. The role of indocyanine angiography imaging in further differential main text under a subheading "Declaration of interest" and where available diagnosis of patients with nAMD who are morphologically poor responders within the appropriate field on the journal’s Manuscript Central site). This to ranibizumab in a real-life setting. Eye (Lond) 2016;30:958-65. may be made available to reviewers and will appear in the published article Book: Bill A, Maepea O. Mechanisms and Routes of Aqueous Humor at the discretion of the Editors or Publisher.

Drainage. Philadelphia: WB Saunders; 1975.

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Cornea. 2nd ed. Boston, MA: Butterworth-Heinemann; 1998.

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EU GMP ve US FDA onaylı Kartepe üretim tesisimizde üretilmektedir.

hayatın değerini görüyor, anlam yüklüyoruz...

Kuru göz, oküler yüzeyde gözyaşı filminin homeostazisinin bozulmasıyla karakterize, oküler semptomların eşlik ettiği, gözyaşı film hiperosmolaritesi ve instabilitesi ile birlikte oküler yüzeyde inflamasyon ve hasara neden olan ve nörosensoryal anomalilerin etiyolojisinde rol oynadığı multifaktöriyel bir hastalıktır.1

18DVA027DPR03

LUC 1480 3/23/2020

BEYOGLU EYE JOURNAL CONTENTS

VOLUME 3 ISSUE 1 YEAR 2018 ISSN 2459 - 1777

INVITED REVIEW

Evaluation and Treatment of Congenital Nasolacrimal Duct Obstruction Ozturk Karabulut G, Fazil K............................................................................................................................................... 1 ORIGINAL ARTICLES

Vertical Retraction Syndrome: Clinical Features and Surgical Outcomes Aygit ED, Celik S, Ocak OB, Inal A, Gurez C, Kepez Yildiz B, Fazil K, Kandemir Besek N, Gokyigit B, Demirok A......................................................................................................................................................... 4 Intravitreal Ranibizumab Therapy for Choroidal Neovascularization Secondary to Pathological Myopia: 3-Year Outcomes Perente I, Artunay O, Sengul A.......................................................................................................................................... 8 Changes in Central Macular Thickness after Uncomplicated Phacoemulsification Surgery in Diabetic and Non-Diabetic Patients Akkaya S, Ozkurt Y.............................................................................................................................................................13 Efficacy of Botulinum Toxin in Patients with Infantile Esotropia: Long-Term Effects with a Single Injection Aygit ED.................................................................................................................................................................................20 CASE REPORTS

Intravitreal Aflibercept Treatment of Anterior Segment Ischemia After Scleral Buckling Surgery Erol MK, Suren E, Gedik B................................................................................................................................................24 Effect of Epiretinal Membrane Peeling on Intravitreal Aflibercept Therapy Response for Polypoidal Choroidal Vasculopathy: A Case Report Kirmaci A, Demircan A, Yasa D, Alkin Z.......................................................................................................................29 Medical Management of Non-Progressive Periorbital Necrotizing Fasciitis Ayhan Z, Yaman A, Soylev Bajiin M.................................................................................................................................34 Management of Open Globe Injuries and Concern About Sympathetic Ophthalmia: A Case Report Ozturker C, Kaynak P, Ozturk Karabulut G, Fazil K, Yildirim Y, Ocak OB..........................................................38

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http://beyoglueye.com

DOI:10.14744/bej.2018.69188 Beyoglu Eye J 2018; 3(1): 1-3

Invited Review

Evaluation and Treatment of Congenital Nasolacrimal Duct Obstruction Gamze Ozturk Karabulut, Korhan Fazil University of Health Sciences, Beyoglu Eye Training and Research Hospital, Istanbul, Turkey

Abstract Congenital nasolacrimal duct obstruction is a common problem in neonates that can result in epiphora, superimposed infection, or amblyopia. The aim of this review was to examine causes and current management of this problem in the pediatric population. Before 1 year of age, a conservative approach with the help of the parents is preferred. Afterwards, an interventional approach is recommended to overcome obstruction of the nasolacrimal duct.

Keywords: Balloon dacryoplasty, congenital nasolacrimal duct obstruction, probing, silicone intubation in children.

Introduction Congenital nasolacrimal duct obstruction (CNLDO) is a common problem in the pediatric population with an incidence of 6% to 20% in newborns, and it is bilateral in approximately one-third of cases (1-5). The problem is usually at the Hasner valve, where the nasolacrimal duct would open into the inferior meatus of the nasal cavity (6). As demonstrated in the study of Weiss et al. the obstruction may be due to a persistent membrane at the distal end of the duct, a bony obstruction, or a narrowing of the inferior meatus (7).

The most common symptoms are epiphora, mattering of lashes with an overflow of tears, chronic or recurrent conjunctivitis caused by bacterial overgrowth in the sac, and maceration of the skin around the eye. Associated preseptal or orbital cellulitis may complicate the problem and require hospitalization and systemic antibiotic treatment. High tear meniscus, distension of the lacrimal sac and expression of mucopurulent material on compression are the signs of CNLDO. A fluorescein dye disappearance test, conducted by administering an anesthetic agent and then applying a fluorescein drop or moistened fluorescein paper strip to the

inferior fornix can confirm the diagnosis. In a patent system, dye should disappear from the conjunctival cul-de-sac after 5 minutes upon examination of the eyes with a cobalt blue filter (8). MacEwen and Young (9) reported that this test had 90% sensitivity and 100% specificity for CNLDO in their preliminary study, and Bowyer et al. (10) postulated that reading the test at 5 minutes demonstrated 76% sensitivity and 76% specificity.

Epiphora caused by excess tear production due to irritation, trichiasis, distichiasis, abnormal eyelid position, a foreign body, or corneal abrasion should be considered in the differential diagnosis of CNLDO. Infantile glaucoma is another condition that should be kept in mind as a cause of epiphora, photophobia with blepharospasm, and corneal edema.

Dacryocystocele, also called amniocele, and mucocele, presents as a blue, non-inflamed mass inferior to the medial canthal area, seen 1 in 3900 live births and 0.1% of infants with CNLDO (3, 6, 11). It is caused by dual obstruction of the nasolacrimal system at the junction of the common canaliculus-lacrimal sac and at the opening of the nasolacrimal

Address for correspondence: Gamze Ozturk Karabulut, MD. University of Health Sciences, Beyoglu Eye Training and Research Hospital, Istanbul, Turkey Phone: +90 212 251 59 00 E-mail: gokarabulut@gmail.com Submitted Date: January 25, 2018 Accepted Date: March 12, 2018 Available Online Date: April 03, 2018 Copyright 2018 by Beyoglu Eye Training and Research Hospital - Available online at www.beyoglueye.com

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duct to the nose (8, 12). Because infants are obligate nasal inhalers, intranasal extension of the dacryocystocele can result in respiratory distress (13, 14).

Management Remission of epiphora with non-surgical treatment was reported in 66% of infants aged 6 to 10 months who were followed up for 6 months (15) and 96% by 1 year of age (3).

Urgent surgical treatment is unnecessary in the first year; education of the parents on conservative treatment is the mainstay of therapy. Lacrimal sac massage, first described by Crigler (16) in 1923, which entails gently compressing the lacrimal sac until the fingertip reaches the inferior medial orbital rim, performed 3 to 5 times, twice daily after cleansing the lashes with cooled boiled water, has been recommended to parents. The administration of antibiotic drops before massage is necessary in cases of purulent discharge. Massaging in a downward fashion increases the hydrostatic pressure inside the nasolacrimal canal and ruptures the membranous Hasner valve and also helps to drain discharge inside that, had it remained, could result in infection (6). Parents should be warned about signs of dacryocystitis and orbital cellulitis.

Systemic antibiotic therapy is necessary in cases of acute dacryocystitis and preseptal or orbital cellulitis. Dacryocystoceles require decompression with massage and urgent probing with or without excision of an intranasal extension of dacryocystocele.

After 1 year of age, probing of the nasolacrimal system is the main approach. Early (6-9 months) vs late (6 months of observation, after 1 year of age) probing was studied prospectively by the Pediatric Eye Disease Investigator Group (PEDIG) (17). Similar success rates were reported; however, 66% of cases in the late group resolved without intervention.

Early probing decreases the risk of fibrosis and the duration of chronic discharge; avoids the risk of complications, such as dacryocystitis, fistula formation, and orbital cellulitis; and can be performed under local anesthesia in an office setting (4, 6, 18). Katowitz et al. (18) reported a success rate of 97% for probing in patients younger than 13 months of age, 54.5% for patients older than 13 months, and 33% for patients older than 24 months, and they recommended conservative therapy until 1 year of age (18). Repeat probing can be performed in patients who still have epiphora despite successful initial probing and patent nasolacrimal lavage (4).

In the PEDIG study, the success rate in a second intervention was 56% for repeat probing, 77% for balloon catheter dilatation, and 84% for intubation (19, 20).

In the event of canalicular stenosis, hypertrophy of the RosenmĂźller valve, a history of dacryocystitis, or an inability to pass the probe into the inferior meatus, lacrimal intubation or balloon dacryoplasty, with or without fracture of an inferior turbinate, is the treatment of choice (4, 6). The

Ozturk Karabulut et al., Congenital nasolacrimal duct obstruction

success rates of monocanalicular and bicanalicular intubation are similar (21). However, performing monocanalicular intubation and removal of the tube is easier and less harmful (6, 12). A simple square knot at the end of bicanalicular stents helps with easy removal from the upper lacrimal system, which is the preferred approach in our clinic. Silicone intubation dilates stenosis in the lacrimal system and prevents the formation of granulation tissue along the lacrimal system following probing (12). Potential complications of tube implantation include corneal abrasion due to tube contact, early extrusion of the tube, slitting of the punctum or the canaliculus, sinusitis, epistaxis, and pyogenic granuloma formation.

The optimal timing of tube removal is 2 to 6 months after insertion (6, 12, 22, 23). Tube removal at 6 weeks is usually effective in children younger than 2 years old. However, 3 months is the recommended time for older children (22).

Another alternative approach for failed probing is balloon dilatation of the distal nasolacrimal duct. In this technique, inflation of a balloon at the end of a probe can be effective in diffusely dilating the lacrimal system and opening adhesions or constrictions due to chronic infection (4) with a reported success rate of 76% to 83% (24).

Nasal endoscopy during all of the procedures discussed above helps with visualization of exit of the instruments from their true location and with the anatomical relationship of the nasal structures, as well as avoiding false passages, which have been reported to occur as often as in 15% of cases (25).

Dacryocystorhinostomy (DCR) is indicated in patients with persistent epiphora despite probing, silicone intubation, or balloon dacryoplasty; with craniofacial abnormalities; and with bony or traumatic obstructions (4, 26). The success rate for DCR in children is between 85% and 95% (12).

Ill-defined anatomy, such as a poorly developed lacrimal crest, shallow lacrimal fossa, or anteriorly placed ethmoidal cells, are among the difficulties of pediatric DCR (4, 27).

It has been demonstrated that risk of amblyopia increases with CNLDO. The incidence of anisometric amblyopia associated with CNLDO is 10% to 12% (28-30). It is important to be alert for amblyopia by performing cycloplegic refraction and examining children periodically until 4 years of age.

Conclusion The initial treatment of a child with CNLDO who is younger than 1 year of age is primarily lacrimal massage of the sac, with or without antibiotics. In a case of persistence of symptoms and obstruction, probing is performed at around 1 year of age. An inferior turbinate can be fractured if the inferior meatus is narrow due to the close apposition of an inferior turbinate to the lateral nasal wall. If the obstruction remains unresolved and if the initial probing was easily performed, a second probing may be attempted. If epiphora still persists

Ozturk Karabulut et al., Congenital nasolacrimal duct obstruction

after interventions, intubation of the nasolacrimal system or balloon dacryoplasty can be performed. Dacryocystorhinostomy is indicated only in intractable conditions, such as anatomical and/or traumatic abnormalities. Amblyopia is a risk factor in children with CNLDO; therefore, they need be examined until 3 to 4 years of age.

Disclosures Peer-review: Externally peer-reviewed.

Conflict of Interest: None declared.

Authorship Contributions: Involved in design and conduct of the study (GOK); preparation and review of the study (GOK, KF); data collection (GOK); and statistical analysis (GOK).

References 1. Guerry D 3rd, Kendig EL Jr. Congenital impatency of the nasolacrimal duct. Arch Ophthal 1948;39:193–204.

2. Ballard EA. Excessive tearing in infancy and early childhood.

The role and treatment of congenital nasolacrimal duct obstruction. Postgrad Med 2000;107:149–54.

3. MacEwen CJ, Young JD. Epiphora during the first year of life.

Eye (Lond) 1991;5:596-600.

4. Tan AD, Rubin PA, Sutula FC, Remulla HD. Congenital nasolacrimal duct obstruction. Int Ophthalmol Clin 2001;41:57–69.

5. Crawford JS, Pashby RC. Lacrimal system disorders. Int Ophthalmol Clin 1984;24:39–53.

6. Schnall BM. Pediatric nasolacrimal duct obstruction. Curr Opin Ophthalmol 2013;24:421–4.

7. Weiss AH, Baran F, Kelly J. Congenital nasolacrimal duct obstruction: delineation of anatomic abnormalities with 3-dimensional reconstruction. Arch Ophthalmol 2012;130:842–8.

8. Ogawa GS, Gonnering RS. Congenital nasolacrimal duct obstruction. J Pediatr 1991;119:12–7.

9. MacEwen CJ, Young JD. The fluorescein disappearance test (FDT): an evaluation of its use in infants. J Pediatr Ophthalmol Strabismus 1991;28:302–5.

10. Bowyer JD, Holroyd C, Chandna A. The use of the fluorescein disappearance test in the management of childhood epiphora.

Orbit 2001;20:181–7.

11. Wong RK, VanderVeen DK. Presentation and management of congenital dacryocystocele. Pediatrics 2008;122:e1108–12.

12. Kapadia MK, Freitag SK, Woog JJ. Evaluation and management of congenital nasolacrimal duct obstruction. Otolaryngol Clin North Am 2006;39:959–77, 13. Mazzara CA, Respler DS, Jahn AF. Neonatal respiratory distress: sequela of bilateral nasolacrimal duct obstruction. Int J Pediatr Otorhinolaryngol 1993;25:209–16.

14. Bernardini FP, Cetinkaya A, Capris P, Rossi A, Kaynak P, Katowitz JA. Orbital and Periorbital Extension of Congenital Dacryocystoceles: Suggested Mechanism and Management. Ophthal Plast Reconstr Surg 2016;32:e101–4.

15. Pediatric Eye Disease Investigator Group. Resolution of congenital nasolacrimal duct obstruction with nonsurgical manage-

3

ment. Arch Ophthalmol 2012;130:730–4.

16. Crigler LW. The treatment of congenital dacryocystitis. JAMA 1923;81: 23–4 17. Pediatric Eye Disease Investigator Group. A randomized trial comparing the cost-effectiveness of 2 approaches for treating unilateral nasolacrimal duct obstruction. Arch Ophthalmol 2012;130:1525–33.

18. Katowitz JA, Welsh MG. Timing of initial probing and irrigation in congenital nasolacrimal duct obstruction. Ophthalmology 1987;94:698–705.

19. Pediatric Eye Disease Investigator Group, Repka MX, Chandler DL, Bremer DL, Collins ML, Lee DH. Repeat probing for treatment of persistent nasolacrimal duct obstruction. J AAPOS 2009;13:306–7.

20. Repka MX, Chandler DL, Holmes JM, Hoover DL, Morse CL, Schloff S, et al; Pediatric Eye Disease Investigator Group. Balloon catheter dilation and nasolacrimal duct intubation for treatment of nasolacrimal duct obstruction after failed probing.

Arch Ophthalmol 2009;127:633–9.

21. Andalib D, Gharabaghi D, Nabai R, Abbaszadeh M. Monocanalicular versus bicanalicular silicone intubation for congenital nasolacrimal duct obstruction. J AAPOS 2010;14:421–4.

22. El-Essawy R. Effect of timing of silicone tube removal on the result of duct intubation in children with congenital nasolacrimal duct obstruction. Ophthal Plast Reconstr Surg 2013;29:48–50.

23. Migliori ME, Putterman AM. Silicone intubation for the treatment of congenital lacrimal duct obstruction: successful results removing the tubes after six weeks. Ophthalmology 1988;95:792–5.

24. Ali MJ, Naik MN, Honavar SG. Balloon dacryoplasty: ushering the new and routine era in minimally invasive lacrimal surgeries.

Int Ophthalmol 2013;33:203–10.

25. MacEwen CJ, Young JD, Barras CW, Ram B, White PS. Value of nasal endoscopy and probing in the diagnosis and management of children with congenital epiphora. Br J Ophthalmol 2001;85:314–8.

26. Forbes BJ, Khazaeni LM. Evaluation and management of an infant with tearing and eye discharge. Pediatr Case Rev 2003;3:40–3.

27. Takahashi Y, Kakizaki H, Chan WO, Selva D. Management of congenital nasolacrimal duct obstruction. Acta Ophthalmol 2010;88:506–13.

28. Matta NS, Singman EL, Silbert DI. Prevalence of amblyopia risk factors in congenital nasolacrimal duct obstruction. J AAPOS 2010;14:386–8.

29. Simon JW, Ngo Y, Ahn E, Khachikian S. Anisometropic amblyopia and nasolacrimal duct obstruction. J Pediatr Ophthalmol Strabismus 2009;46:182–3.

30. Eshraghi B, Akbari MR, Fard MA, Shahsanaei A, Assari R, Mirmohammadsadeghi A. The prevalence of amblyogenic factors in children with persistent congenital nasolacrimal duct obstruction. Graefes Arch Clin Exp Ophthalmol 2014;252:1847–52.

Original Article

DOI:10.14744/bej.2018.76486 Beyoglu Eye J 2018; 3(1): 4-7

Vertical Retraction Syndrome: Clinical Features and Surgical Outcomes Ebru Demet Aygit, Selcen Celik, Osman Bulut Ocak, Asli Inal, Ceren Gurez, Burcin Kepez Yildiz, Korhan Fazil, Nilay Kandemir Besek, Birsen Gokyigit, Ahmet Demirok University of Health Science Beyoglu Eye Training and Research Hospital, Istanbul, Turkey

Abstract Objectives: The aim of this study was to report our clinical observations and the results of the surgical treatment of patients with vertical retraction syndrome (VRS).

Methods: Medical records were analyzed retrospectively and 5 patients with VRS were included in this study. A detailed ophthalmological examination and an orthoptic exam were performed. Superior rectus recession was performed in all cases and all of the patients were followed for at least 6 months.

Results: Analysis indicated that the mean patient age was 26.8 years. (min-max: 4-65 years). There were 3 females and 2 males in the group. Family history of a similar condition was positive in 2 patients. All of the patients had orthophoria following surgical treatment.

Conclusion: VRS is a rare, special form of retraction syndrome in which eye movement is limited by a fibrous band.

Imaging was important to the surgical approach used in this group of patients to successfully treat the syndrome.

Keywords: Extraocular muscles, strabismus, vertical fibrosis syndrome.

Introduction Congenital fibrosis of the extraocular muscles (CFEOM) has genetically defined strabismus syndrome subtypes (CFEOM1A, CFEOM1B, CFEOM2, CFEOM3A, CFEOM3B, CFEOM3C, Tukel syndrome, and CFEOM3 with polymicrogyria). These syndromes are characterized by congenital, non-progressive ophthalmoplegia, with or without ptosis, affecting part or all of the oculomotor nucleus and nerve (cranial nerve III) and muscles (superior, medial, and inferior recti, inferior oblique, and levator palpabrae superioris) innervated by this nerve. The trochlear nucleus, nerve (cranial nerve IV), and its innervated muscle (the superior oblique) may be involved in congenital fibrosis syndrome (CFS) (1).

Recently, CFS was added to those classified as congenital

cranial dysinnervation disorders (2). These syndromes are characterized by the replacement of normal tissue by fibrous tissue, which brings about a limitation of extraocular muscle movement. The clinical presentation is based on the number of affected muscles and the degree of fibrosis (3).

Vertical retraction syndrome (VRS) is a special form of CFS, and it is a rare kind of strabismus that consists of retraction of the globe with narrowing of the lid fissure in attempted elevation or depression. Frequently, elevation deficiency with variable retraction of the globe has been reported in the literature. In this study, the patients had depression deficiency and minimal retraction of the globe. The surgical goals were minimizing of head position, resolution of ptosis, and elimination or reduction of eye misalignment.

Usually, correction of strabismus consisted of fibrotic muscle

Address for correspondence: Ebru Demet Aygit, MD. Department of Ophthalmology, Beyoglu Eye Training and Research Hospital, Istanbul, Turkey Phone: +90 212 251 59 00 E-mail: ebrudemet@hotmail.com Submitted Date: September 19, 2017 Accepted Date: March 03, 2018 Available Online Date: April 03, 2018 Copyright 2018 by Beyoglu Eye Training and Research Hospital - Available online at www.beyoglueye.com

Š

Aygit et al., Atypical strabismus cases

5

recessions, in some cases with ipsilateral muscle resection.

The objective of this study was to report clinical observations and the results of surgical treatment of patients with VRS.

Methods Medical records were analyzed retrospectively, and the following ophthalmological and orthoptic data were recorded: family history of similar conditions, age, sex, laterality, deviation, and restriction (–5)-(0) of eye movement preoperatively and postoperatively. The study was performed in compliance with the principles of the Declaration of Helsinki.

The exclusion criteria of this study were a negative forced duction test (FDT), a history of orbital trauma, and other causes of ptosis: congenital or acquired ptosis, globe retraction with duction movements, myasthenia gravis, and different type of myopathy, and Marcus Gunn jaw-winking phenomenon.

A detailed ophthalmological examination, including a slit-lamp exam and fundoscopy, was performed on patients if possible, and visual acuity, deviation angle, and head turn were also examined. Visual acuity was assessed for each eye using the Snellen Chart. Cycloplegic refraction was performed after the administration of cyclopentolate eye drops.

Patients had limited depression, and in 2 cases, a light retraction of the globe during downward gaze and eyelid lag. Deviation was measured using the Krimsky and the Hirschberg methods for near (33 cm) and distance (6 m) fixation.

A superior rectus (SR) muscle recession was preferred for depression deficiency. The degree of recession varied from 6 to 10 mm, depending on the degree of hypertropia and the tightness of the muscle. Adhesions and fibrotic bands were released. If the treatment of horizontal strabismus was needed, the recession/resection procedures were performed taking the anterior segment circulation into account.

A forced duction test was performed on both eyes to identify restriction of vertical movement. A superior limbal conjunctival incision was used to access the SR muscle. At

this point, the surrounding fascial attachments of the SR muscle were removed. Afterwards, a 6/0 vicryl (Ethicon, Inc., Somerville, NJ, USA) suture was used at each border of the muscle. Scleral reattachment of the SR muscle was performed according to the calculation of the recession. If the patient had a fibrotic band, it was noted. A topical steroid and antibiotic eye drops were used for the first postoperative week.

Examinations were performed on all patients on the postoperative first day, at the first week, first month, third month, and sixth month.

Statistical Analysis The mean (SD) and frequency (percentage) were used to describe the summary data. The statistical analysis was performed using IBM SPSS Statistics for Windows, Version 20.0 (IBM Corp., Armonk, NY, USA). P<0.05 was considered statistically significant.

Results The mean age at presentation was 30.6±23.4 years (range: 4-65 years). The mean length of the follow-up period was 12 months (range: 6-24 months). There was a female dominance in our study, with a total of 3 (60%) female patients.

All of the patients were affected in the left eye. There was a positive family history of a similar condition in 2 patients.

The mean preoperative hypertropia was 42±2.7 PD, characterized by distinct, limited depression in the primary position (PP). After the third postoperative month, all of the patients displayed orthophoria. The primary surgery for all patients was recession of the SR muscle. Table 1 illustrates the demographic features of the study patients. Amblyopia was treated in 2 patients, but their visual acuity did not change.

Frequency doubling technology was performed at the start of the operation and all patients had positive results.

Upon examination, the SR muscle in 1 patient was observed to be fibrotic and calcified. Two fibrotic tissues found in another patient were evaluated as muscle tissue. The SR muscle in the other 3 patients was tight and rigid.

Table 1. Clinical characteristics of the 5 patients Patients

Age

Sex

Affected eye

1

Preoperative

Surgery

Outcome

deviation

14

Male

Left

45

SRR

Orthophoria

2

4

Female

Left

40

SRR

Orthophoria

3

35

Female

Left

40

SRR

Orthophoria

4

16

Female

Left

45

SRR

Orthophoria

5

65

Male

Left

40

SRR

Orthophoria

SRR: Superior rectus recession.

6

Example Case A 14-year-old male presented with complaints of hypertropia from an early age in his left eye. An ophthalmological examination indicated that the right eye was normal and there was hypertropia in the left eye. The best corrected visual acuity was 10/10 in the right eye and hand movement in the left eye. The anterior segment slit-lamp biomicroscopy was normal in the left eye, and the posterior segment was also normal. The decreased visual acuity in the left eye was attributed to deprivation amblyopia. A strabismus examination revealed 45 PD hypertropia and abduction, adduction, and depression deficiency in the left eye. The patient had not undergone any prior strabismus surgery. Recession of the SR muscle was planned. During the surgery, 2 fibrotic tissues were dissected from the area of the SR muscle. Following the operation, noticeable hypotropia in the PP was observed at the first week examination and 2 IU botulinum toxin A (Botox; Allergan plc, Dublin, Ireland) was injected into the inferior rectus muscle. At the postoperative third month, orthophoria in the PP was recorded.

Discussion Gast (4) reported a case of congenital external ophthalmoplegia in 1889 that was likely hereditary extraocular muscles fibrosis (4). In 1912, Bradbourne defined autosomal dominant extraocular muscle fibrosis with ptosis (5). Aebli first described congenital fibrosis of the extraocular muscle in 1933 (6). Brown et al. classified the following 5 types: (1) general fibrosis syndrome, (2) fibrosis of the inferior rectus with blepharoptosis, (3) strabismus fixus, (4) vertical retraction syndrome, and (5) unilateral fibrosis, blepharoptosis, and enophthalmos syndrome (7-9). Vertical retraction in 2 siblings has been well described by Khodadoust and Von Noorden (10).

Congenital fibrosis of the extraocular muscles is characterized by the replacement of normal contractile muscle tissue with fibrous tissue or fibrous bands of varying degrees.

Light and electron microscopy demonstrate the replacement of normal muscle with collagen and dense fibrous tissue with occasional areas of degenerated skeletal muscle. Cases may be unilateral or bilateral, and one or more than one muscle may be affected. Genetic factors may or may not have an impact (11). Zhang et al. (12) revealed that anomalous orbital structures may partially explain the cause of VRS and that it may also lead to atypical strabismus (12).

Magnetic resonance imaging (MRI) can help to identify the presence of unusual eye movements. Yang et al. (13) described the clinical features and MRI findings of 6 children with VRS in their study. They concluded that an anomalous orbital structure was the main cause of VRS and specific unusual eye movement. They added that MRI might assist in

Aygit et al., Atypical strabismus cases

diagnosis. Zhang et al. (12) presented the case of a girl with unilateral retraction in the upgaze and reported the MRI findings associated with retraction (12). In our study, MRI did not indicate any pathology in the study patients.

The presence of an accessory extraocular muscle sometimes gives rise to restrictive strabismus. This only rarely appears in the literature (14). Molinari et al. (15) concluded that the presence of an accessory extraocular muscle should be included in the differential diagnosis of patients with atypical restrictive strabismus and especially when globe retraction is observed. Khitri and Demer (16) evaluated the orbital MRI of 118 orthotropic and 453 strabismic patients, and 12 were noted to have these anomalous structures. In our study, we had 1 patient with an accessory fibrotic superior rectus muscle, which was dissected during surgery.

In these types of diseases, strabismus should be corrected before ptosis. Surgical correction has unpredictable outcomes in CFEOM because of the restrictive nature of the condition (17). The aim of surgical management is to achieve some functional readjustment of the ocular position and abnormal head posture.

Correction of vertical and horizontal strabismus was addressed with large muscle recession. Ptosis repair should aim at achieving a lid level 1 to 2 mm above the pupil in the PP to avoid exposure keratopathy. A rare condition, VRS may affect the SR or the inferior rectus muscle and result in depression or elevation of the eye. Therefore, surgery is performed on the muscle, and the area is examined for fibrotic tissue. In this study, orthophoria was obtained in all of the patients who had SR muscle recession surgery.

In the present study, all of the patients had left eye involvement. However, side dependence in VRS has not been reported in the literature.

There are some limitations to this study. First, we did not use imaging methods in all of the patients, and a genetic assessment was not possible. In addition, the number of patients studied was small, but this condition is very rare and specific. We believe that this study may be very useful to ophthalmologists who are interested in VRS. Correction of vertical and horizontal strabismus is challenging in patients with congenital fibrosis of the extraocular muscles. To the best of our understanding, the surgical decision should be based on the clinical manifestations of the disease and the needs of the patient. Surgical recession of the affected muscle recession can be effective.

Disclosures Acknowledgements: Ege AygÄąt contributed to the revision of the English-language spelling and grammar of this report.

Peer-review: Externally peer-reviewed.

Conflict of Interest: None declared.

Aygit et al., Atypical strabismus cases

Authorship Contributions: Involved in design and conduct of the study (EDA, BG); preparation and review of the study (AD, EDA, SC, AI); data collection (EDA, OBO, CG, BKY, NKB); and statistical analysis (KF, EDA).

References 1. Whitman M, Hunter DG, Engle EC. Congenital Fibrosis of the Extraocular Muscles. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, editors. GeneReviews. Seattle (WA): University of Washington; 1993–2018.

2. Singh A, Pandey PK, Agrawal A, Mittal SK, Rana KM, Bahuguna C. Congenital cranial dysinnervation disorders. Int Ophthalmol 2017;37:1369–81.

3. Harley RD, Rodrigues MM, Crawford JS. Congenital fibrosis of the extraocular muscles. J Pediatr Ophthalmol Strabismus 1978;15:346–58.

4. Peng JH, Huang FS, Liu Y, Chai HY, Li L, Gong SX, et al. A family history of congenital fibrosis of the extraocular muscle with autosomal dominant inheritance. Yi Chuan 2005;27:205–7.

5. Traboulsi EI, Lee BA, Mousawi A, Khamis AR, Engle EC. Evidence of genetic heterogeneity in autosomal recessive congenital fibrosis of the extraocular muscles. Am J Ophthalmol 2000;129:658–62.

6. Hiatt RL, Halle AA. General fibrosis syndrome. Ann Ophthalmol 1983;15:1103–9.

7. Hertle RW, Katowitz JA, Young TL, Quinn GE, Farber MG. Congenital unilateral fibrosis, blepharoptosis, and enophthalmos syndrome. Ophthalmology 1992;99:347–55.

8. Reck AC, Manners R, Hatchwell E. Phenotypic heterogeneity

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may occur in congenital fibrosis of the extraocular muscles. Br J Ophthalmol 1998;82:676–9.

9. Brown H. Congenital structural muscle anomalies. In: Allen J, editor. Strabismus Ophthalmic Symposium. St. Louis: Mosby; 1950. p. 205–36.

10. Hansen E. Congenital general fibrosis of the extraocular muscles. Acta Ophthalmol (Copenh) 1968;46:469–76.

11. Harley RD, Rodrigues MM, Crawford JS. Congenital fibrosis of the extraocular muscles. Trans Am Ophthalmol Soc 1978;76:197–226.

12. Zhang CY, Man FY, Wang ZC, Yu G, Wu Q, Jiao YH, et al.

Magnetic resonance imaging of unilateral vertical retraction syndrome with atypical strabismus. Chin Med J (Engl) 2011;124:3195–7.

13. Yang Q1, Jiao YH, Man FY, Wang ZC, Chang QL, Lu W, et al. Vertical retraction syndrome caused by anomalous orbital structures. Zhonghua Yan Ke Za Zhi 2011;47:983–8.

14. Lueder GT. Anomalous orbital structures resulting in unusual strabismus. Surv Ophthalmol 2002;47:27–35.

15. Molinari A, Plager D, Merino P, Galan MM, Swaminathan M, Ramasuramanian S, et al. Accessory Extraocular Muscle as a Cause of Restrictive Strabismus. Strabismus 2016;24:178–83.

16. Khitri MR, Demer JL. Magnetic resonance imaging of tissues compatible with supernumerary extraocular muscles. Am J Ophthalmol 2010;150:925–31.

17. Mohamad S, Jaafar MD, Traboulsi EI. Clinical strabismus management, principles and surgical techniques. In: Rosenbaum AL, Santiago AP, editors. Congenital fibrosis of the extraocular muscles. Saunders Company; 1999.

DOI:10.14744/bej.2018.88698 Beyoglu Eye J 2018; 3(1): 8-12

Original Article

Intravitreal Ranibizumab Therapy for Choroidal Neovascularization Secondary to Pathological Myopia: 3-Year Outcomes Irfan Perente,1 Ozgur Artunay,1 Alper Sengul2 1 2

Department of Ophthalmology, Beyoglu Eye Training and Research Hospital, Istanbul, Turkey Department of Ophthalmology, T.C. Istanbul Bilim University Faculty of Medicine, Istanbul, Turkey

Abstract Objectives: The purpose of this study was to report the functional and anatomical results of intravitreal ranibizumab (IVR) injections administered for myopic choroidal neovascularization (mCNV) secondary to pathological myopia.

Methods: In this retrospective study, 32 eyes of 32 mCNV patients were evaluated. After a first IVR injection, patients were followed up and treated with an as-needed monthly regime. Best-corrected visual acuity and optic coherence tomography (OCT) findings were evaluated at baseline and then monthly. The reinjection criteria were a reduction in visual acuity and/or an increase in central macular thickness measured with OCT. Results: The mean age of the patients was 57.7±14.6 years, and the mean axial length was 27.8±1.3 mm. The mean visual acuity improved significantly from 46.4±9.7 letters at baseline to 54.1±9.5 letters at the last follow-up visit (p<0.05). The mean central macular thickness decreased from 301.4±11.7 μm at baseline to 258.8±12.5 μm at the last visit (p>0.05). The mean number of injections was 3.5±1.1, 2.3±0.9, and 1.7±0.8, at 12, 24, and 36 months, respectively.

Conclusion: The results of this study indicated that IVR injections provided a significant long-term visual and anatomical benefit in cases of mCNV with few injections.

Keywords: Central macular thickness, intravitreal ranibizumab, myopic choroidal neovascularization.

Introduction High degree myopia is a major cause of legal blindness in many developed countries (1-3). It affects 27% to 33% of all myopic eyes, corresponding to a prevalence of 1.7% to 2% in the general population (4). High myopia is defined as a refractive error of at least -6.00 D or an axial length of 26.5 mm or more. Pathological or degenerative myopia is defined as high myopia with any posterior myopia-specific pathology from axial elongation. A proportion of people with myopia have pathological myopia, which is characterized by excessive and progressive elongation of the globe, and is now

considered to be an important cause of impaired vision and blindness worldwide (3, 4).

Myopic choroidal neovascularization (mCNV) may develop in 5% to 10% of people with pathological myopia, and is mainly characterized by widespread chorioretinal degeneration in the posterior pole of the eye, the growth of new blood vessels from the choroid capillary layer, breaks of Bruch’s membrane, subsequent subretinal hemorrhage, and fibrotic membrane formation under the foveola (5-7). Mechanical, heredodegenerative, and hemodynamic theories have been proposed to explain the development of mCNV (8-12).

Before the era of intravitreal anti-vascular endothe-

Address for correspondence: Alper Sengul, MD. Department of Ophthalmology, T.C. Istanbul Bilim University Faculty of Medicine, Istanbul, Turkey Phone: +90 212 224 49 50 E-mail: ealper_sengul@yahoo.com Submitted Date: January 15, 2018 Accepted Date: March 14, 2018 Available Online Date: April 04, 2018 Copyright 2018 by Beyoglu Eye Training and Research Hospital - Available online at www.beyoglueye.com

©

Perente et al., Intravitreal ranibizumab for myopic choroidal neovascularization

lial growth factor (VEGF) drugs (bevacizumab, pegaptanib sodium, ranibizumab and aflibercept), laser photocoagulation, verteporfin photodynamic therapy, and surgical excision or macular translocation were performed to treat mCNV (13-16). The results of the REPAIR (Phase 2) and the RADIANCE (Phase 3) studies demonstrated good visual gain and anatomical improvement with intravitreal ranibizumab (IVR) (17-18). The efficacy and safety of IVR for mCNV have been demonstrated in several small prospective and retrospective studies (19-22). There are a few reports on longterm outcomes of anti-VEGF therapy in mCNV in the literature (23-25).

The aim of this study was to report the long-term anatomical and visual outcomes of IVR monotherapy in naive CNV caused by myopia.

Methods This study was a retrospective assessment of the records of 32 eyes of 32 consecutive patients who were given IVR. They were all diagnosed with mCNV and followed up for 3 years, with additional treatment provided on an as-needed basis.

The study was approved by the ethics committee of Istanbul Bilim University. Written informed consent was obtained from each patient in accordance with the ethical principles stated in the Declaration of Helsinki.

The inclusion criteria were eyes with a myopic refractive error (spherical equivalent) ≥8.0 D or an axial length ≥26.0 mm, treatment naive mCNV, leakage of fluorescein from the CNV during fluorescein angiography, treated with anti-VEGF monotherapy, and a minimum follow-up period of 3 years after the first IVR treatment. Patients were excluded if they had CNV due to another etiology, any ocular disease other than pathologic myopia, any concurrent ocular disease in the study eye that could be the cause of vision loss; chronic ocular disease (uveitis and optic neuritis); open-angle glaucoma, angle-closure glaucoma, or suspected glaucoma; optic nerve disease (anterior ischemic optic neuropathy); neurological disease (multiple sclerosis); a history of other treatment for CNV; or a follow-up period of fewer than 36 months.

The IVR (Lucentis; Novartis Pharma AG, Basel, Switzerland) was injected at a dose of 0.5 mg/0.05 mL once per month for 3 consecutive months. The decision to administer further injections was made on an as-needed basis. At each visit, the best-corrected visual acuity (BCVA) was measured using the ETDRS scale. Each visit also incorporated a biomicroscopic examination of the anterior segment, measurement of intraocular pressure (IOP), a fundus examination, and a central macular thickness (CMT) measurement using optical coherence tomography (OCT) (Optovue , Inc., Fremont, CA, USA). The decision to administer subsequent injections was based on the BCVA and CMT results for each

9

patient. The following criteria were considered when making a decision about reinjection: persistence or recurrence of subretinal fluid or cystic structures via OCT, an increase in the most recent OCT measurement of CMT of 50 µm or more, incipient CNV, incipient hemorrhage, and a loss of 5 or more letters when compared with the last recorded BCVA. The intraocular injections were carried out under operating theater conditions. Following topical application of proparacaine, the eyelids, lashes, and conjunctiva were cleaned with 5% povidone iodine. After placement of a speculum to keep the eyelids open, IVR was injected at a distance of 4 mm from the superior temporal quadrant. After the injection, the patient was given a topical antibiotic in the quinolone group to use 4 times each day for a period of 7 days.

Biochemical values were measured at the first visit and after every 12 months, and hematology, blood chemistry, and urine were regularly monitored. IOP measurement (before and after each administration, using tonometry) and a standard ophthalmic examination were also performed at every visit.

The values are presented as the mean±SD. The Student’s t-test or the Mann–Whitney U test was used to determine the significance of the differences in the BCVA, and CMT value recorded. A P value <0.05 was considered statistically significant.

Results The mean age of the study patients was 57.7±14.6 years.

Fourteen patients were men and 18 were women. All of the eyes were naive and all of the patients were treated with anti-VEGF monotherapy with IVR. The mean refractive error was -12.8±4.5 and the mean axial length was 27.8±1.3 mm (Table 1).

The mean number of ETDRS letters read was 46.4±9.7 at baseline, 53.2±10.9 at 6 months, 54.4±9.9 at 12 months, 54.3±8.8 at 18 months, 54.4±9.9 at 24 months, 54.2±10.1 at 30 months, and 54.1±9.5 at 36 months (p<0.005; baseline vs 6, 12, 18, 24, and 36 months). A BCVA improvement of ≥15 letters was seen in 9 (28.1%), 10 (31.2%), and 9 (28.1%) eyes at 12, 24, and 36 months, respectively. (Fig. 1) Furthermore, a BCVA improvement of >5 letters was determined in 20 (62.5%), 20 (62.5%), and 17 (53.1%) eyes at 12, 24, and 36 Table 1. Clinical characteristics of study patients Age (years) Sex (male/female) Eye (right/left)

57.7±14.6 14/18 17/15

Spherical equivalent (D)

-12.8±4.5

Axial length (mm)

27.8±1.3

10

Perente et al., Intravitreal ranibizumab for myopic choroidal neovascularization

Visual acuity change (Letters) 56 54 52 50 48 46 44 42 Initial

6. month

12. month

18. month

24. month

30. month

36. month

Figure 1. Change in mean best-corrected visual acuity at month 36 after intravitreal ranibizumab treatment.

Central macular thickness change (μm) 310 300 290 280 270 260 250 240 230 Initial

6. month

12. month

18. month

24. month

30. month

36. month

Figure 2. Change in mean central macular thickness at month 36 after intravitreal ranibizumab treatment.

months, respectively. A BCVA deterioration of >5 letters was observed in 3 (9.3%), 3 (9.3%), and 4 (12.5%) eyes at 12, 24, and 36 months, respectively.

The mean CMT was 301.4±11.7 μm at baseline, 264.7±10.9 μm at 6 months, 260.7±13.9 μm at 12 months, 258.4±11.5 μm at 18 months, 258.6±10.9 μm at 24 months, 258.6±10.1 μm at 30 months, and 258.8±12.5 μm at 36 months (p<0.005; baseline vs 6, 12, 18, 24, and 36 months). (Fig. 2) The mean number of injections administered was 3.5±1.1, 2.3±0.9, and 1.7±0.8 at the first, second, and third year, respectively. (Fig. 3)

Discussion The prevalence of myopia and high myopia has been increasing globally at an alarming rate, with significant increases in terms of the risks for vision impairment due to pathological conditions. High myopia was estimated to affect 2.8% (170

million) of the world population in 2010. Preliminary projections were based on these prevalence data and the corresponding population figures of United Nations. Considering the effects of age and time, we may assume that high myopia will affect 10.0% (925 million) of the world population by 2050 (26).

The reported prevalence of pathological myopia based on population studies is 1% to 3% in adults, and 5% to 11% of those patients with pathological myopia develop mCNV. Several phenotypic features of pathological myopia are associated with an increased risk for mCNV; they include lacquer cracks, patchy atrophy, thinning of the choriocapillaris and choroid, and mCNV in the fellow eye (9, 12, 27). Long-term studies of the natural course of pathological myopia have reported that almost all patients have significant vision loss (28-30). In a 10-year follow-up of 25 patients with mCNV, visual acuity was found to be <20/200 in 89% of the patients

Perente et al., Intravitreal ranibizumab for myopic choroidal neovascularization

Injection numbers

3.5 3 2.5 2 1.5 1 0.5 0 1. year

2. year

3. year

Figure 3. Mean number of intravitreal injections administered over 3 years.

5 years after onset, and in 96% 10 years after the onset of CNV (31).

In a prospective, interventional study of 19 highly myopic eyes of 18 patients with subfoveal and juxtafoveal CNV who were treated with intravitreal bevacizumab on a pro re nata (PRN) regimen after 3 loading injections, Ruiz-Moreno et al. (32) reported that the initial BCVA gain had decreased and was no longer significant by the end of the second year.

However, these results could be related to the relatively small sample size and short follow-up period of the study.

On the other hand, Gharbiya et al. (33) and Nakanishi et al.

(34) demonstrated that intravitreal bevacizumab for mCNV led to a rapid and sustained visual and anatomical improvement over 2 years.

In a phase 3, 12-month, randomized, multicenter study of IVR in patients with mCNV, IVR was administered according to the presence/absence of CNV activity in 1 group and according to visual acuity changes in a second group.

The RADIANCE study demonstrated that IVR treatment based on CNV activity was as effective as ranibizumab treatment based on visual acuity stability at 6 months (17). In the REPAIR study, Tufail et al. (18) reported that OCT-guided retreatment had excellent efficacy with a small number of injections in mCNV patients. Relying on these findings, a re-treatment regime based on functional parameters assessed with BCVA and morphological parameters assessed with SDOCT appears to be a reliable and effective procedure for mCNV patients.

Franqueira et al. (20) retrospectively analyzed the 3-year safety and efficacy of IVR. The change from baseline BCVA was +4.3 letters at 12 months, +6.4 letters at 24 months, and +8.0 letters at 36 months. Twenty-five percent of the patients gained ≥15 letters at 12 months, 30% at 24 months, and 35% at 36 months. A mean of 4.1 injections was administered in the first year, 2.4 in the second year, and 1.1 in the third year. In our study, the BCVA change was +8.0 letters at 12 months, +8.0 letters at 24 months, and +7.7 letters at 36

11

months. The BCVA gain was greater in the first year, and this gain was maintained for 3 years.

In a retrospective, nonrandomized study, Ladaique et al. (35) reported functional results concerning the efficacy of IVR for mCNV with a PRN regimen. The mean BCVA improved significantly from 62.8±13.8 letters at baseline to 72.8±12.9 letters at the last follow-up visit. The mean BCVA improvement of ≥15 letters was 21% at 12 months, 18% at month 24, 20% at month 36, and 22% at month 48 (35). In our study, a BCVA improvement of ≥15 letters was noted in 28.1%, 31.2%, and 28.1% of eyes at 12, 24, and 36 months, respectively. Our relatively greater percentage of patients gaining ≥15 letters could be explained by the greater mean baseline BVCA of our study group. (62.8 vs 46.4) In our study, the mean number of injections administered was 3.5±1.1, 2.3±0.9, and 1.7±0.8 injections at 12, 24, and 36 months, respectively. The percentage of eyes given ≤1 injection was 75% at 12 months, 82% at 24 months, and 88% at 36 months. Also, 81% of eyes received a maximum of 3 injections at 36 months. These findings confirmed that fewer injections were needed to achieve stable visual acuity than for other diseases that respond to anti-VEGF. A retrospective research method and the small number of patients included are limitations of this study. The lack of control group for analysis of treatment decision specificity is also a limitation.

In conclusion, our study reports long-term safety and benefits of IVR monotherapy in the treatment of mCNV on a PRN regimen and confirms an excellent long-term visual prognosis with a small number of injections. However, randomized studies with long-term outcomes and a larger sample size are warranted.

Disclosures Peer-review: Externally peer-reviewed.

Conflict of Interest: None declared.

Authorship Contributions: Involved in design and conduct of the study (IP, OA, AS); preparation and review of the study (AS); data collection (IP, OA, AS); and statistical analysis (OA, AS).

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DOI:10.14744/bej.2018.41636 Beyoglu Eye J 2018; 3(1): 13-19

Original Article

Changes in Central Macular Thickness after Uncomplicated Phacoemulsification Surgery in Diabetic and Non-Diabetic Patients Sezen Akkaya, Yelda Ozkurt Health Sciences University Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey

Abstract Objectives: The aim of this study was to assess changes in central macular thickness following uncomplicated phacoemulsification surgery in diabetic patients with and without retinopathy and in a control group.

Methods: The records of 43 eyes of patients with mild non-proliferative diabetic retinopathy (NPDR), 43 eyes of diabetic patients without diabetic retinopathy (no-DR), and 43 eyes of a control group that also underwent phacoemulsification surgery were prospectively reviewed. Foveal thickness was measured using optical coherence tomography preoperatively and at 1 week and 1, 3, 6, and 12 months postoperatively.

Results: No clinically significant differences in foveal thickness were observed preoperatively between groups. Foveal thickness had increased in the NPDR group at 1 week and 1 and 3 months after surgery, in the no-DR group at 1 week and 1 month, and in the control group at 1 week after surgery. Foveal thickness decreased gradually in the NPDR group after 3 months. When comparing the groups, foveal thickness was significantly greater in the NPDR group than in the noDR group and the control group at postoperative months 1 and 3; however, at month 6, the differences had decreased, and there were no clinically significant differences between groups.

Conclusion: Foveal thickness increased until 3 months after cataract surgery and decreased gradually thereafter in NPDR patients. Foveal thickness had also increased during the first month in the no-DR group. Foveal thickness increased only in the first week in the control group. These changes were more prominent in eyes with NPDR than in eyes with no-DR and those of the control group.

Keywords: Diabetic retinopathy, macular thickness, uncomplicated phacoemulsification surgery.

Introduction Cataract is a common cause of decreased vision worldwide, and the treatment for cataracts is surgical removal (1). Cataracts occur more often in patients with diabetes than in those without diabetes. The worldwide prevalence of diabetes is on the rise; thus increasing the importance of the relationship between diabetes and cataracts (2). Cystoid macular edema (CME) is one of the potential complications following uncomplicated cataract surgery in patients that can cause unwanted visual outcomes (3).

Some processes may underlie pathogenic mechanisms of macular thickening, such as postoperative inflammation caused by surgically damaged tissue, the breakdown of the blood-retinal and blood-aqueous barriers, and the release of prostaglandins and vascular endothelial growth factor (VEGF) (3, 4).

Cataract surgery initiates an inflammatory process in the eye. The risk of macular thickening after uncomplicated phaco surgery may increase in the presence of ocular or systemic inflammatory diseases like uveitis or diabetes (5).

Address for correspondence: Sezen Akkaya, MD. Health Sciences University Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey Phone: +90 216 578 30 00 E-mail: drsezenakkaya@gmail.com Submitted Date: November 29, 2017 Accepted Date: March 01, 2018 Available Online Date: April 04, 2018 Copyright 2018 by Beyoglu Eye Training and Research Hospital - Available online at www.beyoglueye.com

Š

14

Primarily, the status of macular thickness before the cataract surgery determines the visual outcome after surgery (6-8).

Previous studies have described many diabetic patients who developed severe maculopathy, progression of retinopathy, and/or neovascular glaucoma following cataract surgery (9, 10). Progression of diabetic retinopathy (DR) has been demonstrated in approximately 10% to 30% of patients after uncomplicated cataract surgery (11, 12). Some surgeons think that the progression of DR after cataract surgery is due to the natural course of the condition, and that the progression is independent of the surgery (5, 12-14). According to previous studies, the most significant predictive factor for progression of DR is the status of DR before the cataract surgery (15, 16).

Two mechanisms may lead to macular edema after surgery. One is Irvine–Gass syndrome (transient pseudophakic edema), which usually resolves spontaneously, and the other is actual progression of diabetic maculopathy (17-19).

A study reported by Kim et al. (20) revealed a short-term increase in macular thickness after cataract surgery in diabetic patients.

The purpose of this study was to demonstrate changes in macular edema that occurred after uncomplicated phacoemulsification surgery in eyes with and without DR in diabetic patients and in a control group. The foveal thickness was periodically measured using optical coherence tomography (OCT) to quantitatively compare the degree of macular edema before and after surgery. If there was a difference in foveal thickness between the measurements taken before and after surgery of 100 µm or greater, the patient was treated with intravitreal anti-VEGF or micropulse laser.

Methods All diabetic patients scheduled for phacoemulsification surgery and intraocular lens (IOL) implantation between May 2013 and July 2015 were consecutively screened for inclusion in this study. No statistically significant differences were observed between the 3 working groups with respect to average age, gender distribution, cataract grade, or mean phaco time and phaco power. The exclusion criteria were the presence of additional underlying disease other than diabetes and cataract that could affect macular thickness (e.g., uveitis, glaucoma, or epiretinal membrane), uncontrolled blood sugar level (glycated hemoglobin >6%), proliferative DR or preexisting macular edema, incomplete or missing baseline or follow-up data, no aggregate results, unrelated outcome measurements, and any operative complication.

Screening was continued until 43 eyes with DR, 43 eyes without DR, and 43 control eyes could be included in this study. At the time of cataract surgery, all of the patients underwent implantation of a hydrophobic acrylic IOL per-

Akkaya et al., Central macular thickness after phacoemulsification surgery

formed by 2 surgeons. The study protocol was approved by the hospital's institutional review board, and informed consent was obtained from each patient.

All of the surgeries were performed using the same technique. No significant differences were found between the 3 groups in the grade of the nucleus, ultrasound time, or ultrasound power emitted. Following a side port incision, a 3.0-mm superior incision was performed, and the continuous curvilinear capsulorhexis technique was used. Hydrodissection with balanced salt solution and cataract extraction using the bimanual “divide-and-conquer” endocapsular phacoemulsification technique was performed. Sodium hyaluronate 1.4% was injected into the capsular bag. A foldable intraocular lens was implanted (Eyecryl Plus, Biotech Vision Care Pvt. Ltd., Ahmedabad, India) using an injector. After insertion, the viscoelastic material was thoroughly evacuated.

All surgeries included in the analysis were uneventful and the IOLs were implanted accurately within the capsular bag. All patients used the same steroid and antibiotic 4x1 per day for 1 month after the surgery. We did not use a non-steroid anti-inflammatory drug in any patient to avoid any potential effect on the macular thickness.

The central retinal (foveal) thickness of all patients was measured with OCT (RS-3000 Advance; Nidek Co. Ltd., Gamagori, Japan) a day before surgery and 1 week and 1, 3, 6, and 12 months after surgery.

A fundus examination with full pupil dilation was performed before surgery and during each scheduled examination.

Statistical Analysis Statistical analysis was performed using IBM SPSS Statistics for Windows, Version 22.0 (IBM Corp., Armonk, NY, USA) software. The distribution parameters were evaluated using the Shapiro-Wilks test and found to be in accordance with the parameters of normal distribution. Analysis of variance and Tukey’s Honest Significant Difference test were used for inter-group comparisons. For intra-group comparison, a paired sample t-test was used. P<0.05 was considered statistically significant.

Results The mean preoperative foveal thickness in each group is provided in Table 1. The mean foveal thickness of the DR group was significantly lower than that of the control group (p=0.009). However, this small difference was not clinically significant. There were no statistically significant differences between other groups in preoperative mean macular thickness.

No statistically significant differences were observed between the groups in the first week after surgery. Differences

Akkaya et al., Central macular thickness after phacoemulsification surgery

15

Table 1. Distribution of foveal thickness by group Control group

No-DR group

NPDR group

Mean±SD

Mean±SD

Mean±SD

236.28±14.71

233.6±15.53

227.56±8.42 0.009*

1 week

239.4±15.19

236.37±14.52

238.53±13.57

0.608

1 month

235.65±13.59

Foveal thickness Preoperative

1p

Postoperative 237.49±14

256.33±13.64

0.001*

3 months

237.4±9.95

236.93±11.5

257.74±14.01

0.001*

6 months

235.58±11.79

233.49±13.86

224.42±7.14

0.001*

1 year

234.37±12.7

231.77±11.06

225.4±7.39

0.001*

Preoperative 1 week2p

0.001*(increased)

0.030*(increased)

0.001*(increased)

Postoperative1 month2p

0.844

0.009*(increased)

0.001*(increased)

3 months2p

0.510

0.061

0.001*(increased)

6 months2p

0.471

0.938

0.002*(decreased)

1 year2p

0.024*

0.163

0.041*(decreased)

2Paired-sample t-test

*p<0.05

One-way ANOVA Test

ANOVA: Analysis of variance; No-DPR: No diabetic retinopathy; NPDR: Non-proliferative diabetic retinopathy.

in the mean central foveal thickness were observed between the groups at months 1 and 3 (p=0.001). Binary comparisons were performed: the mean foveal thickness level of the NPDR group after 1 and 3 months was significantly higher than that of the control and the no-DR group (p=0.001), and there were no statistically significant differences between the control and no-DR groups at months 1 and 3.

In the control group, a statistically significant increase was seen in the mean foveal thickness in the first week after surgery compared with the preoperative value (p=0.001); however, no significant changes were observed in the first, third, and sixth months. The decline observed in the mean macular thickness in the first year, in comparison with the preoperative value, was statistically significant (p=0.024).

In the no-DR group, in comparison with the mean pre-

operative foveal thickness, there was a statistically significant increase in the first week (p=0.030) and in the first month (p=0.009), but no statistically significant differences were observed at the third and sixth months or the first year.

In a comparison with the mean preoperative foveal thickness in the DR group, there were statistically significant increases in the first week (p=0.001) and the first (p=0.001) and third months (p=0.001). A statistically significant reduction was observed after 6 months (p=0.002) and 1 year (p=0.041).

The percent of change in foveal thickness by group over time from baseline can be seen in Table 2.

A statistically significant difference in the mean foveal thickness was observed at week 1 and months 1 and 3 in comparison with the baseline (p=0.001). Binary comparisons

Table 2. Percent change in foveal thickness by group at the first week; first, third, and sixth months; and first year postoperatively, in comparison with the mean preoperative foveal thickness Foveal thickness

Control group

No-DR group

NPDR group

p

(% change)

Mean±SD

Mean±SD

Mean±SD

1 week

1.33±1.92

1.27±3.42

4.83±4.63

0.001*

1 month

0.12±8.4

1.78±3.93

12.76±6.83

0.001*

3 months

0.67±4.65

1.64±4.83

13.41±7.3

0.001*

6 months

-0.2±2.67

0.08±4.29

-1.33±2.59

0.112

1 year

-0.74±2.24

-0.63±3.57

-0.89±2.92

0.914

One-way ANOVA test

*p<0.05

ANOVA: Analysis of variance; No-DPR: No diabetic retinopathy; NPDR: Non-proliferative diabetic retinopathy.

16

Akkaya et al., Central macular thickness after phacoemulsification surgery

ness decreased 6 months after surgery.

Table 3 illustrates the percent of patients with increased postoperative foveal thickness. Values for the NPDR group in the first and third months were greater than those of the other groups; however, that difference was no longer observed at the sixth month and first year after surgery.

Figures 1 and 2 show changes in foveal thickness over time and the percent of change in foveal thickness in the groups.

Table 3. Percent of patients by group with increased foveal thickness in the first week; first, third, and sixth months; and first year postoperatively

1st 1st 3rd 6th 1st week month month month year

Control 69.8% 46.5% 41.9% 39.5% 32.6% No-DR 65.1% 55.8% 67.4% 34.9% 32.6% NPDR 83.7% 93% 97.7% 30.2% 32.6%

Discussion

No-DPR: No diabetic retinopathy; NPDR: Non-proliferative diabetic retinopathy.

Following phacoemulsification surgery, no visual impairment accompanied the subclinical thickening of the central macula, which could now be visualized using OCT and angiographic examination with fundus fluorescein (21). The application of phacoemulsification can lead to inflammation due to the release of inflammatory substances directly involved in the thickening of macula, including prostaglandins (22). It has been reported that after phacoemulsification without complication, an inflammation response triggered by the surgery led to early edema in the macula (23, 24). Measurement of central macula thickness (CMT) at week 1 and months 1 and 3 indicated a significant change following phacoemulsification surgery that was without complication. The CMT later

were performed. The NPDR group had significantly higher macular thickness measurement results in the first week and at the first and third months than the control and no-DR groups (p=0.001).

No statistically significant differences were observed in the first week and first and third months after surgery between the control and no-DR groups.

There was no statistically significant difference between the groups at the sixth month and first year after surgery.

When comparing group results 3 months after surgery, the percent increase in the DR group was significantly higher than those of the no-DR and control groups. Foveal thick-

No-DR Group Control Group DR Group

Foveal thickness 0.67 0.66 0.65 0.64 Preop

1st week

3rd month

1st month

6th month

1st year

Figure 1. Changes in foveal thickness over time.

Conrol Group

Percent change in foveal thickness

No-DR Group NPDR Group

15 10 5 0 -5 1 st week

1 st month

3 rd month

Figure 2. Percent change in foveal thickness by group.

6 th month

1 st year

Akkaya et al., Central macular thickness after phacoemulsification surgery

showed a gradual decrease in diabetes patients who also had concomitant mild NPDR. This indicates that compared with the control group and with diabetes patients with no DR, the phacoemulsification surgery had a stronger effect on the blood-aqueous barrier of diabetes patients with mild NPDR. Pseudophakic CME that develops following the surgical treatment of cataracts differs in many respects from diabetic edema of the macula, particularly in the immediate postoperative period. Pseudophakic CME is known to show regression within a period of 1 month (when associated with Irvine-Gass syndrome), while diabetic edema can exhibit progression for a period of more than 3 months (25).

It is important for physicians to recognize the distinction between surgical treatment-related pseudophakic CME and diabetic edema of the macula.

Following cataract surgery, patients with diabetes are more likely to experience subclinical thickening or edema in the macula (26). Due largely to its ability to increase blood vessel permeability, VEGF assumes a central role in the development of diabetes-related microangiopathies (27). It is also known that proliferative DR patients have considerably higher VEGF levels in the vitreous humor (28). A number of risk factors are also involved in changing the extent of DR progression following phacoemulsification, such as the administration of insulin treatment to the patient, uncontrolled blood sugar level, and younger age. Some researchers have demonstrated that such factors had no impact on the degree of retinopathy progression (29, 30). In patients both with and without diabetes, CME following surgery is generally caused by prostaglandin-induced intraocular inflammation (31).

A comparison of the control group and diabetes patients without DR with patients with mild NPDR revealed that the NPDR group exhibited a statistically greater likelihood of macular thickening or edema in week 1 and in months 1 and 3 following phacoemulsification surgery.

In the present study, preoperative and postoperative CMT levels in diabetes patients without DR were compared with the level observed in the control group and in diabetes patients with mild NPDR. These comparisons indicated that, relative to the control group, phacoemulsification surgery (without complications) could potentially have a greater impact on the CMT value of diabetes patients than on the CMT value of the control group.

At month 1 following the surgery, it was observed that diabetes patients with mild NPDR exhibited significantly greater CMT values, while diabetes patients without DR demonstrated an almost significant rise in CMT values (p=0.054). The greater CMT level might have been caused by the inflammatory response resulting from the phacoemulsification at 1 month after the surgery; however, it may equally have been associated with Irvine-Gass syndrome, which is

17

induced by growth factors and cytokines (such as VEGF and prostaglandins) passing through the blood-aqueous barrier following phacoemulsification.

Certain researchers have suggested that in patients with a lengthy prior history of edema in the eye and maculopathy, the rapid rise in CMT level due to micro-injuries caused by the phacoemulsification surgery may result in a greater likelihood of postoperative CME (32, 33). The present study excluded patients with a history of severe proliferative or non-proliferative retinopathy, prior cataract surgery with complications, and prior CME. Such exclusion criteria can also be considered a limitation of the present study.

The present study revealed that, compared with the control group, diabetes patients without DR and with NPDR had a notably different CMT level 1 week and 1 and 3 months following phacoemulsification without complications. That is, a diabetes patient with mild NPDR had a greater CMT level at week 1 and months 1 and 3 after surgery. However, the CMT level began to gradually decrease starting from postoperative month 3, and completely returning to a normal level by postoperative month 6. Yet, it must also be noted that in all groups, any increase in CMT level was still subclinical.

Neither the control group nor the diabetes patients without DR exhibited any statistically significantly greater CMT level in months 3 and 6 following surgery. The study findings revealed that phacoemulsification without complications had a minimal impact on the mechanisms and pathology of retinopathy in diabetes patients with mild NPDR â&#x20AC;&#x201C; a group known to be associated with a greater occurrence of subclinical thickening in the macula following phacoemulsification relative to control groups and diabetes patients without retinopathy.

The present study demonstrated that in comparison with the control group and the no-DR group, phacoemulsification surgery without complications and accompanied by the implantation of an intraocular lens is associated with a significantly greater incidence of subclinical macular thickening in a mild NPDR group, specifically at week 1 and months 1 and 3 after surgery.

Disclosures Peer-review: Externally peer-reviewed.

Conflict of Interest: None declared.

Authorship Contributions: Involved in design and conduct of the study (SA, YO); preparation and review of the study (SA, YO); data collection (SA); and statistical analysis (SA).

References 1. Song E, Sun H, Xu Y, Ma Y, Zhu H, Pan CW. Age-related cataract, cataract surgery and subsequent mortality: a systematic review and meta-analysis. PLoS One 2014;9:e112054.

2. Klein BE, Klein R, Moss SE. Incidence of cataract surgery in the

18

Wisconsin Epidemiologic Study of Diabetic Retinopathy. Am J Ophthalmol 1995;119:295–300.

3. Romero-Aroca P. Targeting the pathophysiology of diabetic macular edema. Diabetes Care 2010;33:2484–5.

4. Chae JB, Joe SG, Yang SJ, Lee JY, Sung KR, Kim JY, et al. Effect of combined cataract surgery and ranibizumab injection in postoperative macular edema in nonproliferative diabetic retinopathy. Retina 2014;34:149–56.

5. Krepler K, Biowski R, Schrey S, Jandrasits K, Wedrich A. Cataract surgery in patients with diabetic retinopathy: visual outcome, progression of diabetic retinopathy, and incidence of diabetic macular oedema. Graefes Arch Clin Exp Ophthalmol 2002;240:735–8.

6. Dowler JG, Hykin PG, Lightman SL, Hamilton AM. Visual acuity following extracapsular cataract extraction in diabetes: a meta-analysis. Eye (Lond) 1995;9:313–7.

7. Zaczek A, Olivestedt G, Zetterström C. Visual outcome after phacoemulsification and IOL implantation in diabetic patients.

Br J Ophthalmol 1999;83:1036–41.

8. Chew EY, Benson WE, Remaley NA, Lindley AA, Burton TC, Csaky K, et al. Results after lens extraction in patients with diabetic retinopathy: early treatment diabetic retinopathy study report number 25. Arch Ophthalmol 1999;117:1600–6.

9. Jaffe GJ, Burton TC, Kuhn E, Prescott A, Hartz A. Progression of nonproliferative diabetic retinopathy and visual outcome after extracapsular cataract extraction and intraocular lens implantation. Am J Ophthalmol 1992;114:448–56.

10. Schatz H, Atienza D, McDonald HR, Johnson RN. Severe diabetic retinopathy after cataract surgery. Am J Ophthalmol 1994;117:314–21.

11. Mittra RA, Borrillo JL, Dev S, Mieler WF, Koenig SB. Retinopathy progression and visual outcomes after phacoemulsification in patients with diabetes mellitus. Arch Ophthalmol 2000;118:912–7.

12. Chung J, Kim MY, Kim HS, Yoo JS, Lee YC. Effect of cataract surgery on the progression of diabetic retinopathy. J Cataract Refract Surg 2002;28:626–30.

13. Schrey S, Krepler K, Biowski R, Wedrich A. Midterm visual outcome and progression of diabetic retinopathy following cataract surgery. Midterm outcome of cataract surgery in diabetes.

Ophthalmologica 2002;216:337–40.

14. Romero-Aroca P, Fernández-Ballart J, Almena-Garcia M, Méndez-Marín I, Salvat-Serra M, Buil-Calvo JA. Nonproliferative diabetic retinopathy and macular edema progression after phacoemulsification: prospective study. J Cataract Refract Surg 2006;32:1438–44.

15. Pollack A, Leiba H, Bukelman A, Abrahami S, Oliver M. The course of diabetic retinopathy following cataract surgery in eyes previously treated by laser photocoagulation. Br J Ophthalmol 1992;76:228–31.

16. Somaiya M, Burns JD, Mintz R, Warren RE, Uchida T, God-

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ley BF. Factors affecting visual outcomes after small-incision phacoemulsification in diabetic patients. J Cataract Refract Surg 2002;28:1364–71.

17. Gass JD, Norton EW. Cystoid macular edema and papilledema following cataract extraction. A fluorescein fundoscopic and angiographic study. Arch Ophthalmol 1966;76:646–61.

18. Schepens CL, Avila MP, Jalkh AE, Trempe CL. Role of the vitreous in cystoid macular edema. Surv Ophthalmol 1984;28 Suppl:499–504.

19. Henricsson M, Heijl A, Janzon L. Diabetic retinopathy before and after cataract surgery. Br J Ophthalmol 1996;80:789–93.

20. Kim SJ, Equi R, Bressler NM. Analysis of macular edema after cataract surgery in patients with diabetes using optical coherence tomography. Ophthalmology 2007;114:881–9.

21. Lima-Gómez V, Razo Blanco-Hernández DM. Expected value of foveal thickness in macular edema in Mexican patients with diabetes. Cir Cir 2012;80:109–14.

22. Chen D, Zhu J, Li J, Ding XX, Lu F, Zhao YE. Effect of simulated dynamic intraocular pressure on retinal thickness measured by optical coherence tomography after cataract surgery. Int J Ophthalmol 2012;5:687–93.

23. Miyanaga M, Miyai T, Nejima R, Maruyama Y, Miyata K, Kato S. Effect of bromfenac ophthalmic solution on ocular inflammation following cataract surgery. Acta Ophthalmol 2009;87:300– 5.

24. Bannale SG, Pundarikaksha HP, Sowbhagya HN. A Prospective, Open-label Study to Compare the Efficacy and the Safety of Topical Loteprednol Etabonate and Topical Flurbiprofen Sodium in Patients with Post-Operative Inflammation after Cataract Extraction. J Clin Diagn Res 2012;6:1499–503.

25. Schmier JK, Halpern MT, Covert DW, Matthews GP. Evaluation of costs for cystoid macular edema among patients after cataract surgery. Retina 2007;27:621–8.

26. Oh JH, Chuck RS, Do JR, Park CY. Vitreous hyper-reflective dots in optical coherence tomography and cystoid macular edema after uneventful phacoemulsification surgery. PLoS One 2014;9:e95066.

27. Kuiper EJ, Van Nieuwenhoven FA, de Smet MD, van Meurs JC, Tanck MW, Oliver N, et al. The angio-fibrotic switch of VEGF and CTGF in proliferative diabetic retinopathy. PLoS One 2008;3:e2675.

28. Abu El-Asrar AM, Mohammad G, Nawaz MI, Siddiquei MM, Van den Eynde K, Mousa A, et al. Relationship between vitreous levels of matrix metalloproteinases and vascular endothelial growth factor in proliferative diabetic retinopathy. PLoS One 2013;8(12):e85857.

29. Nascimento MA, Lira RP, Kara-José N, Arieta CE. Predictive value of preoperative fasting glucose test of diabetic patients regarding surgical outcome in cataract surgery. Arq Bras Oftalmol 2005;68:213–7.

30. Suto C, Hori S, Kato S, Muraoka K, Kitano S. Effect of periop-

Akkaya et al., Central macular thickness after phacoemulsification surgery

erative glycemic control in progression of diabetic retinopathy and maculopathy. Arch Ophthalmol 2006;124:38–45.

31. Simó R, Sundstrom JM, Antonetti DA. Ocular Anti-VEGF therapy for diabetic retinopathy: the role of VEGF in the pathogenesis of diabetic retinopathy. Diabetes Care 2014;37:893–9.

32. Hartnett ME, Tinkham N, Paynter L, Geisen P, Rosenberg P, Koch G, et al. Aqueous vascular endothelial growth factor as a

19

predictor of macular thickening following cataract surgery in patients with diabetes mellitus. Am J Ophthalmol 2009;148:895– 901.e1.

33. Lanzagorta-Aresti A, Palacios-Pozo E, Menezo Rozalen JL, Navea-Tejerina A. Prevention of vision loss after cataract surgery in diabetic macular edema with intravitreal bevacizumab: a pilot study. Retina 2009;29:530–5.

Original Article

DOI:10.14744/bej.2018.40085 Beyoglu Eye J 2018; 3(1): 20-23

Efficacy of Botulinum Toxin in Patients with Infantile Esotropia: Long-Term Effects with a Single Injection Ebru Demet Aygit University of Health Science Beyoglu Eye Training and Research Hospital, Istanbul, Turkey

Abstract Objectives: Botulinum toxin A (BTX) can be used for strabismus in cases of congenital esotropia or large-angle horizontal strabismus in adults, as well as acute paretic strabismus when surgical treatment of the ocular muscles is not yet possible. This study investigated the long-term efficacy of BTX in patients with infantile esotropia (IE).

Methods: A single-center, retrospective study was performed. The patients had esotropia onset before 12 months and aged were ≤24 months. A successful outcome was defined as ocular alignment within 8 to 10 prism diopters (PD) of orthotropia.

Results: A record review identified 6 patients: 2 boys and 4 girls. The mean age was 14.3±5.4 months. The mean followup time was 30.5±12.4 months. A BTX injection was effective, achieving results of a change in deviation from 34.2±5.8 PD (range: 25-40 PD) to orthophoria.

Conclusion: BTX injections can be considered as a primary treatment for patients with IE that may have successful longterm results. Further longitudinal studies are required to support this conclusion.

Keywords: Botulinum toxin A, infantile esotropia, strabismus.

Introduction Infantile esotropia (IE) is defined as large-angle convergent deviation. It has an onset in the first 6 months of life. It is often associated with other motor abnormalities, such as inferior oblique overaction, cross fixation, dissociated vertical deviation (DVD), and latent nystagmus. Usually, patients don't have refractive errors.

The US Food and Drug Administration (FDA) approved the use of botulinum toxin A (BTX) for the treatment of strabismus and other ophthalmic disorders, such as blepharospasm and hemifacial spasm in 1989. It is produced from the anaerobic bacteria Clostridium botulinum. BTX inhibits muscle spindles, leading to decreased sensory input and decreased muscle contraction. BTX has not been shown to penetrate the blood–brain barrier in humans. When BTX is injected into the muscle, the peak of the resulting muscle

weakness or paralysis occurs in 3 to 5 days and lasts approximately 8 to 12 weeks (1-3).

BTX is frequently used to manage esotropia in children. It may also be used for congenital or acquired esotropia, during surgery for large-angle horizontal strabismus, and in cases of acute paretic strabismus when surgical treatment of the ocular muscle is not yet possible at any age.

This study is a report of the long-term results of a single dose BTX injection and a review of some of the relevant literature.

Methods This was a retrospective study in conducted by the Strabismus Unit of the University of Health Sciences Beyoglu Eye Training and Research Hospital between January 2014 and December 2017. All of the patients provided written

Address for correspondence: Ebru Demet Aygit, MD. University of Health Science Beyoglu Eye Training and Research Hospital, Istanbul, Turkey Phone: +90 212 251 59 00 E-mail: ebrudemet@hotmail.com Submitted Date: March 20, 2018 Accepted Date: April 03, 2018 Available Online Date: April 04, 2018 Copyright 2018 by Beyoglu Eye Training and Research Hospital - Available online at www.beyoglueye.com

©

Aygit, Botulinum toxin a in infantile esotropia

21

Table 1. Demographic characteristics of the patients Patient

Age

Sex

SD

CM

FH

OT Preoperative Postoperative Postoperative Last visit Follow-up

(months)

(near) (PD)

1 week (PD) 1 month (PD)

(PD)

(months)

1

24

F

No

No

No

No

25

20 Ti

16 Ti

0

27

2

8

F

No

No

No

No

30

30 Ti

16 Ti

0

16

3

15

M

No

Yes

No

Yes

40

25 Ti

20 Ti

0

30

4

12

F

No

No

No

No

40

30 Ti

20 Ti

0

42

5

12

M

No

No

No

No

35

20 Ti

14 Ti

0

20

6

15

F

No

No

No

No

35

20 Ti

14 Ti

0

48

SD: Standard deviation; CM: Consanguineous marriage; F: female; FH: family history; M: male; OT: occlusion therapy; PD: prism diopters; SD: systemic disease.

informed consent and the study adhered to the Declaration of Helsinki. The study was approved by the review board of our institution.

A diagnosis of IE was the basic inclusion criterion in this study. In this clinic, an average of 111 patients with IE receive BTX injections per year. To be included in the study, the patient had not had a previous BTX injection or strabismus surgery, there must have been a minimum follow-up of 6 months, and the patient received only a single injection.

Refraction values were determined using an autorefracter (Retinomax-K; Righton Opthalmic Instruments, Tokyo, Japan) after administration of cyclopentolate hydrochloride drops (Sikloplejin 1%; Abdi İbrahim İlaç San. ve Tic. A.Ş., Istanbul, Turkey) 2 or 3 times, with a 5-minute interval. The best corrected visual acuity was assessed using the Lea Grating Acuity Test (0.25 CPCM-8.0 CPCM, Licensed by Lea-Test Ltd., Helsinki, Finland). Refraction errors were corrected, and after the correction, near and distance deviation angles were measured with an accommodation target using either the prism cover test or the Krimsky test when the patient complied, and the results were measured and recorded in terms of prism diopters (PD). Eye movement in the 9 cardinal gaze positions was examined, and binocular vision function of communicative patients was assessed using the Titmus and Lang I-II tests. A fundus examination was performed using direct ophthalmoscope.

The patients were examined on the first postoperative day and discharged. Steroid and antibiotic eye drops were used 5 times daily for 5 days. All of the patients received 1 injection and were evaluated at 1 month, 3 months, and 6 months after the injection. Surgical success was considered to be alignment within 8 to 10 PD at distance and near.

Technique of injection All of the injections were performed under general anesthesia. The conjunctiva was anesthetized with topical anesthesia (Lidocaine 4%). Injection to the muscle was done via the conjunctiva while holding the muscle with forceps. Electro-

Table 2. Refractive measurements of the patients Patients Spherical equivalent

Right eye

Left eye

1

+1.50

+1.75

2

+1.75

+2.00

3

+0.75

+1.25

4

-1.25

-0.25

5

+2.00

+1.75

6

+1.50

+1.75

myography was not used. The standard dose in this study was 3 IU (1-6 IU) Botox (Allergan Inc., Dublin, Ireland).

The statistical analysis was performed using SPSS for Windows, Version 14.0 (SPSS Inc., Chicago, IL, USA). Mean (SD) and frequency (percentage) were used to describe the summary data. A paired p t-test was used to determine the mean difference. A p value of <0.05 was accepted as significant.

Results In all, 2 male and 4 female patients were enrolled in this study.

The mean age was 14.3±5.4 months. The mean postoperative follow-up period was 30.5±12.4 months. The DVD and cross fixation have not seen in preoperative evaluation. Two patients had -1/-2 abduction restriction. The demographic characteristics of the patients are provided in Table 1.

The mean spherical equivalent was +1.45±0.86 D in the right eye, +1.40±0.76 D in the left eye (Table 2). The mean preoperative angle of esodeviation was 34.2±5.8 PD (range: 25-40 PD) for near vision, and 28.6±10.6 PD (range: 15-85 PD) for distance (compliant patients).

In the early postoperative period, all of the patients demonstrated exotropia. At the 6-month and final exams, the patients displayed orthotropia. The difference between the preoperative and postoperative values was significant (p<0.01). In the final exam, an operation was recommended

22

for bilateral inferior oblique overaction in 1 female patient.

Discussion BTX inhibits the muscle, resulting in lengthening and a reduction of the contraction of the antagonist. Patients’ sensory mechanisms may also play a role in realignment of the eyes.

After the injection, if the patient develops some form of binocular vision, ocular alignment may be maintained throughout life. The development of binocular vision is associated with the patient's age.

Scott (1) was the first to use BTX injections on IE patients. Since then, many studies have reported good effects in strabismus patients and have advocated the use of BTX as an alternative in the treatment of strabismus.

For patients with IE, it is less invasive than muscle surgery, and this treatment is performed under a short anesthetic (3, 4). A BTX injection can be a successful alternative in strabismus management. A Cochrane review found that there was no difference between the use of BTX and surgery in patients requiring retreatment for acquired esotropia or IE. However, BTX injections had poorer results in comparison with surgery in patients who had horizontal strabismus in the absence of binocular vision (2).

According to some reports in the literature, multiple injections are needed for maintained ocular alignment in esotropia patients. De Alba Campomanes et al. (5) injected BTX in 322 children as primary treatment for IE and had a success rate of 45% with a mean number of injections of 1.6 IU. The most important factor for maintaining ocular alignment was the pretreatment magnitude of deviation. In our study, the mean pretreatment magnitude of deviation was 33.8±7.5 PD (range: 25-40 PD) for near vision. This was consistent with the literature. Campos et al. (6) evaluated the results of BTX injections administered to 60 children with essential IE, and the success rate was 88% after a single treatment. The mean age at injection was 6.5 months, in contrast to the age group in our study. Scott et al. (7) suggested that approximately 2.1 injections were required to achieve a 66% success rate. In a prospective report, Gursoy et al. (8) found that after a mean follow-up time of 84 months and an average of 1.4 injections, 68% of the patients had achieved successful alignment.

Early treatment provides a “self-adjusting” sensorimotor mechanism to support stable binocular alignment near orthoposition once the motor system has been suitably modified. In fact, at early ages, the central connections of the sensory and motor visual systems can still be changed (9).

McNeer et al. (10) studied a dose of 2.5 IU of Botox in 2 groups of patients formed according to age at the time of injection. Patients who received the BTX injection before 12 months of age had a success rate of 93%, while patients

Aygit, Botulinum toxin a in infantile esotropia

older than 12 months had a success rate of 86%. The mean age was 25 months and 25% required surgery. In our study, only 1 patient was younger than 12 months of age. This can be explained by the fact that our hospital is a not a general hospital.

The BTX dose used in our study was a standard 3 IU. A meta-analysis study showed that the greater the dose of BTX, the lower the success rate; for every 1 IU increase in the mean dose there was a reduction of 0.10% in the success rate (9).

Tejedor et al. (3) suggested that BTX injections are a rapid and less-invasive alternative to reoperation in children who have been unsuccessfully treated with surgery to correct IE. The motor and sensory results obtained were similar. Wan et al. (4) found that BTX was at least as effective as surgery for the treatment of acute-onset comitant esotropia in children. The authors found no significant difference in the success rate between the chemodenervation group and the surgery group.

A major limitation of this study is its retrospective design and the small number of patients. Another limitation is the lack of electromyographic guidance. The rectus muscles were identified without a conjunctival incision, and the injection was performed transconjunctivally with forceps. We did not use a control group in this study because we wanted to present our BTX results.

BTX injections offer several advantages: the effect can be the equivalent of surgical results, it reduces the contracture of paralytic strabismus, and additional surgery can required small angle of deviation.

We achieved long-term success in treating IE with only a single BTX injection. However, further longitudinal studies are required to support these results.

Disclosures Acknowledgements: Ege Aygıt contributed to the revision of the English-language spelling and grammar of this report.

Peer-review: Externally peer-reviewed.

Conflict of Interest: None declared.

References 1. Scott AB. Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery. Ophthalmology 1980;87:1044–9.

2. Rowe FJ, Noonan CP. Botulinum toxin for the treatment of strabismus. Cochrane Database Syst Rev 2017;3:CD006499.

3. Tejedor J, Rodríguez JM. Early retreatment of infantile esotropia: comparison of reoperation and botulinum toxin. Br J Ophthalmol 1999;83:783–7.

4. Wan MJ, Mantagos IS, Shah AS, Kazlas M, Hunter DG. Comparison of Botulinum Toxin With Surgery for the Treatment of Acute-Onset Comitant Esotropia in Children. Am J Ophthal-

Aygit, Botulinum toxin a in infantile esotropia

mol 2017;176:33–9.

5. de Alba Campomanes AG, Binenbaum G, Campomanes Eguiarte G. Comparison of botulinum toxin with surgery as primary treatment for infantile esotropia. J AAPOS 2010;14:111–6.

6. Campos EC, Schiavi C, Bellusci C. Critical age of botulinum toxin treatment in essential infantile esotropia. J Pediatr Ophthalmol Strabismus 2000;37:328–32.

7. Scott AB, Magoon EH, McNeer KW, Stager DR. Botulinum treatment of strabismus in children. Trans Am Ophthalmol Soc 1989;87:174–80.

8. Gursoy H, Basmak H, Sahin A, Yildirim N, Aydin Y, Colak E.

23

Long-term follow-up of bilateral botulinum toxin injections versus bilateral recessions of the medial rectus muscles for treatment of infantile esotropia. J AAPOS 2012;16:269–73.

9. Issaho DC, Carvalho FRS, Tabuse MKU, Carrijo-Carvalho LC, de Freitas D. The Use of Botulinum Toxin to Treat Infantile Esotropia: A Systematic Review With Meta-Analysis. Invest Ophthalmol Vis Sci 2017;58:5468–5476.

10. McNeer KW1, Tucker MG, Spencer RF. Botulinum toxin management of essential infantile esotropia in children. Arch Ophthalmol 1997;115:1411–8.

DOI:10.14744/bej.2018.64936 Beyoglu Eye J 2018; 3(1): 24-28

Case Report

Intravitreal Aflibercept Treatment of Anterior Segment Ischemia After Scleral Buckling Surgery Muhammet Kazim Erol, Elcin Suren, Birumut Gedik Department of Ophthalmology, Antalya Training and Research Hospital, University of Health Sciences, Antalya, Turkey

Abstract This report describes a case of corneal edema, aqueous flare, rubeosis iridis, and neovascular glaucoma due to anterior segment ischemia after scleral buckling surgery that was treated with intravitreal aflibercept.

Anterior segment ischemia is a complication that may develop after scleral buckling surgery. The signs of anterior segment ischemia include corneal edema, aqueous flare, iris atrophy, photophobia, rubeosis iridis, neovascular glaucoma, and cataract formation. It can be diagnosed with biomicroscopy and carotid Doppler ultrasonography. In the present case, there were signs of corneal edema, aqueous flare, rubeosis iridis, and neovascular glaucoma due to anterior segment ischemia that developed after scleral buckling surgery. No pathology was found in carotid Doppler ultrasonography.

Intravitreal aflibercept treatment was administered to the left eye. At a follow-up 2 weeks later, it was determined that the rubeosis iridis had receded: there were no cells in the anterior chamber, and the left eye intraocular pressure was 16 mmHg. The patient was followed for 2 years. After 1 year, implantation of an Ex-press shunt (Alcon, Hunenberg, Switzerland) was performed for glaucoma. Intravitreal aflibercept treatment was administered to the left eye 4 times over 2 years.

Keywords: Anterior segment ischemia, intravitreal aflibercept, neovascular glaucoma, rubeosis iridis, scleral buckling.

Introduction Anterior segment ischemia (ASI) is a rare but important complication that can develop after posterior segment surgery. Corneal edema, aqueous flare, iris atrophy, photophobia, rubeosis iridis, neovascular glaucoma, and cataract are among the signs of ASI. Presently described is the case of a patient who developed postoperative ASI after pars plana vitrectomy and scleral buckling surgery for total retina detachment, and the treatment provided.

Case Report A 64-year-old male patient who had no disease history presented at the clinic due to vision loss in his left eye. His eye examination indicated that his visual acuity was 10/10 in the right eye, while in the left eye it was hand motion. The intraocular pressure was 15 mmHg in the right eye and 7 mmHg

in the left eye. A fundus examination revealed total retinal detachment with a horseshoe tear in the temporal area of the left eye (Fig. 1). A pars plana vitrectomy and scleral buckling surgery were performed to treat the retinal detachment.

At week 2 of the postoperative follow-up, the retina was reattached and the visual acuity of his left eye was 10/100 (Fig. 2). The intraocular pressure was 13 mmHg in the right eye, and 10 mmHg in the left eye. At postoperative month 4, the retina remained attached, and the visual acuity of the left eye was counting fingers from 1 meter. The intraocular pressure was 15 mmHg in the right eye and 9 mmHg in the left eye. Biomicroscopy revealed edema in the cornea of the left eye and that the anterior chamber was densely populated with cells. It was thought to be anterior uveitis; therefore, topical antibiotic and topical steroid treatment was pursued.

During follow-up 1 week later, the earlier signs persisted, the intraocular pressure of the left eye was 24 mmHg and the

Address for correspondence: Birumut Gedik, MD. Department of Ophthalmology, Antalya Training and Research Hospital, University of Health Sciences, Antalya, Turkey Phone: +90 242 249 44 00 E-mail: birumut.gedik@gmail.com Submitted Date: November 12, 2017 Accepted Date: January 15, 2018 Available Online Date: April 05, 2018 Copyright 2018 by Beyoglu Eye Training and Research Hospital - Available online at www.beyoglueye.com

Š

Erol et al., Treatment of anterior segment ischemia

Figure 1. Fundus view: Total retinal detachment in the left eye.

Figure 2. Fundus view: At the postoperative follow-up at week 2, the retina in the left eye was seen to be attached.

25

26

Erol et al., Treatment of anterior segment ischemia

Figure 3. Anterior segment view: After 2 weeks of intravitreal injection in the left eye, the rubeosis iridis had disappeared.

left eye was also found to have rubeosis iridis. (No image was obtained because the anterior segment camera was inoperative at the time.) Anterior segment angiography was not performed. Bilateral carotid Doppler ultrasonography not reveal any pathology. There was no predisposing factor for anterior segment ischemia about surgical manoeuvres. He was diagnosed with anterior segment ischemia based on the existing signs, panretinal photocoagulation was performed and antiglaucomatous treatment was initiated. At week 1 follow-up, the same signs persisted and the left eye intraocular pressure was 40 mmHg. Antiglaucomatous treatment continued and intravitreal aflibercept treatment was administered to the left eye. Follow-up at week 2 revealed that the visual acuity of the left eye had increased to 3 mps. The left eye intraocular pressure was 16 mmHg. There were no cells in the anterior chamber. Rubeosis iridis had disappeared (Fig. 3). The patient was followed for 2 years. After 1 year, implantation of an Express shunt (Alcon, Hunenberg, Switzerland) was performed for glaucoma. Postoperative follow-up at year 2 revealed that the left eye intraocular pressure was 38 mmHg and that the anterior chamber was densely populated with cells. The left eye was found to have rubeosis iridis (Fig. 4). Intravitreal aflibercept treatment was administered to the left eye. After 2 weeks, the left eye intraocular pressure was 17 mmHg.

There were no cells in the anterior chamber. Rubeosis iridis had resolved (Fig. 5). Intravitreal aflibercept treatment was administered to the left eye 4 times in 2 years.

Discussion Anterior segment ischemia is a complication that may develop after posterior segment surgery. Rubeosis iridis and neovascular glaucoma are among the signs of ASI. Doi et al. (1) found ASI in 3% of 34 patients in their study exploring complications after scleral buckling surgery. The anterior segment is fed by short anterior ciliary arteries and long posterior ciliary arteries. Venous drainage occurs through the vortex veins. Anterior segment ischemia may develop due to various mechanisms, primarily as a result of hypoxia.

Tanaka et al. (2) and Tawara et al. (3) demonstrated that ASI caused neovascularization in the iris in their studies on rabbits. Tanaka et al. (2) also showed that ASI led to VEGF release according to the severity of ocular ischemia. Hayreh et al. (4) reported that ASI developed after scleral buckling surgery due to venous congestion caused by compression of the vortex veins. Another study showed that ASI developed after scleral buckling surgery due to intervention in the long posterior ciliary arteries (5). Furthermore, another study on rabbits demonstrated that scleral buckling surgery

Erol et al., Treatment of anterior segment ischemia

27

Figure 4. Anterior segment view: Postoperative follow-up at year 2 revealed rubeosis iridis (arrows) in the left eye.

Figure 5. Anterior segment view: After 2 weeks of intravitreal injection to the left eye, the rubeosis iridis disappeared.

decreased perfusion in the iris and ciliary body (6).

The signs of ASI include corneal edema, aqueous flare, iris atrophy, photophobia, rubeosis iridis, neovascular glaucoma, and cataract formation. In our case, corneal edema, rubeosis iridis, and neovascular glaucoma were present at the postoperative fourth month. Aqueous flare and cornea edema are also symptoms of anterior uveitis (7). Therefore,

ASI should also be considered for patients who have the preliminary diagnosis of uveitis.

Biomicroscopy and carotid Doppler ultrasonography are useful in the diagnosis of patients with anterior segment ischemia (7). The biomicroscopy results revealed corneal edema, dense cell population in the anterior chamber, and rubeosis iridis. Carotid Doppler ultrasonography did not re-

28

veal any pathology.

Treatment options for patients who develop rubeosis iridis and neovascular glaucoma include antiglaucomatous medications (8), panretinal photocoagulation (9, 10), antiglaucomatous surgery (11), and intravitreal injection (12-14).

In their case report, Janssens et al. (12) reported that they injected intravitreal Bevacizumab into a patient who had developed rubeosis iridis and neovascular glaucoma due to ASI after scleral buckling surgery and 2 months after the injection, rubeosis iridis remained in only a small area. Hung et al. (13) stated in their case report that they administered an intravitreal Bevacizumab injection for rubeosis iridis and it regressed 6 days later (13). Durmaz et al. (14) reported that rubeosis iridis regressed after intravitreal aflibercept and triamcinolone acetonide treatment they administered to a patient who developed rubeosis iridis (14). We applied intravitreal aflibercept treatment in a patient who developed rubeosis iridis and neovascular glaucoma due to ASI after scleral buckling surgery and we found that the rubeosis iridis disappeared. There were no cells in the anterior chamber and intraocular pressure was normal 2 weeks later.

Conclusion This case report is a description of a patient who developed corneal edema, rubeosis iridis, and neovascular glaucoma due to ASI that developed after pars plana vitrectomy and scleral buckling surgery. The patient was treated with intravitreal aflibercept and we found that the rubeosis iridis resolved: there were no cells in the anterior chamber and intraocular pressure was normal 2 weeks later. Intravitreal aflibercept is a fast and effective agent in the treatment of neovascularization due to hypoperfusion in ASI. It should be remembered that ASI may developed in a patient who presents with corneal edema, rubeosis iridis, and high intraocular pressure after scleral buckling surgery, while keeping in mind also that some symptoms of ASI, such as aqueous flare and corneal edema, overlap with those of anterior uveitis.

Disclosures Informed consent: Written informed consent was obtained from the patient for the publication of the case report and the accompanying images.

Peer-review: Externally peer-reviewed.

Conflict of Interest: None declared.

Authorship Contributions: Involved in design and conduct of

Erol et al., Treatment of anterior segment ischemia

the study (MKE, ES, BG); preparation and review of the study (MKE, ES, BG); data collection (MKE, ES, BG).

References 1. Doi N, Uemura A, Nakao K. Complications associated with vortex vein damage in scleral buckling surgery for rhegmatogenous retinal detachment. Jpn J Ophthalmol 1999;43:232–8.

2. Tanaka T, Matsuo T, Ohtsuki H. Aqueous vascular endothelial growth factor increases in anterior segment ischemia in rabbits.

Jpn J Ophthalmol 1998;42:85–9.

3. Tawara A, Kubota T, Hata Y, Sakamoto T, Honda M, Yoshikawa H, et al. Neovascularization in the anterior segment of the rabbit eye by experimental anterior ischemia. Graefes Arch Clin Exp Ophthalmol 2002;240:144–53.

4. Hayreh SS, Baines JA. Occlusion of the vortex veins. An experimental study. Br J Ophthalmol 1973;57:217–38.

5. Lee JP, Olver JM. Anterior segment ischaemia. Eye (Lond) 1990;4:1–6.

6. Bakri SJ, Snyder MR, Reid JM, Pulido JS, Singh RJ. Pharmacokinetics of intravitreal bevacizumab (Avastin). Ophthalmology 2007;114:855–9.

7. Sivakumar RR, Rao NA. Anterior Segment Ischemia in Viper Bite. Ocul Immunol Inflamm 2016;24:49–54.

8. Mendrinos E, Machinis TG, Pournaras CJ. Ocular ischemic syndrome. Surv Ophthalmol 2010;55:2–34.

9. Johnston ME, Gonder JR, Canny CL. Successful treatment of the ocular ischemic syndrome with panretinal photocoagulation and cerebrovascular surgery. Can J Ophthalmol 1988;23:114–9.

10. Chen KJ, Chen SN, Kao LY, Ho CL, Chen TL, Lai CC, et al. Ocular ischemic syndrome. Chang Gung Med J 2001;24:483–91.

11. Sivak-Callcott JA, O'Day DM, Gass JD, Tsai JC. Evidence-based recommendations for the diagnosis and treatment of neovascular glaucoma. Ophthalmology 2001;108:1767–76.

12. Janssens K, Zeyen T, Van Calster J. Anterior segment ischemia with rubeosis iridis after a circular buckling operation treated successfully with an intravitreal bevacizumab injection: a case report and review of the literature. Bull Soc Belge Ophtalmol 2012:5–9.

13.

Hung JH, Chang YS. Ocular ischemic syndrome. CMAJ 2017;189:E804.

14. Durmaz Engin C, Ayhan Z, Men S, Yaman A, Saatci AO. Bilateral Severe Sterile Inflammation with Hypopyon after Simultaneous Intravitreal Triamcinolone Acetonide and Aflibercept Injection in a Patient with Bilateral Marked Rubeosis Associated with Ocular Ischemic Syndrome. Case Rep Ophthalmol Med 2017;2017:5123963.

Case Report

DOI:10.14744/bej.2017.92400 Beyoglu Eye J 2018; 3(1): 29-33

Effect of Epiretinal Membrane Peeling on Intravitreal Aflibercept Therapy Response for Polypoidal Choroidal Vasculopathy: A Case Report Asli Kirmaci, Ali Demircan, Dilek Yasa, Zeynep Alkin University of Health Sciences, Beyoglu Eye Training and Research Hospital, Istanbul, Turkey

Abstract Traction forces in cases of epiretinal membrane (ERM) may antagonize the effects of anti-vascular endothelial growth factors (anti-VEGF) treatments and cause pharmacological resistance in patients with neovascular age-related macular degeneration. Presently described is a case with polypoidal choroidal vasculopathy (PCV) in conjunction with ERM who demonstrated a partial response to intravitreal aflibercept injections. A pars plana vitrectomy with ERM peeling was performed. After surgery, optical coherence tomography showed an improvement in the macular morphology and complete resolution of subretinal fluid. His visual acuity remained stable. Vitrectomy may improve the anti-VEGF response in some patients with ERM who do not respond to anti-VEGF therapy for PCV. Keywords: Aflibercept, epiretinal membrane, polypoidal choroidal vasculopathy.

Introduction Polypoidal choroidal vasculopathy (PCV) is a variant of neovascular age-related macular degeneration (nAMD) characterized by exudative and hemorrhagic changes within the macula leading to visual impairment with a prevalence that increases with age. This subtype of AMD is less responsive to treatment with anti-vascular endothelial growth factors (anti-VEGF) (1). In these refractory cases, aflibercept therapy, a relatively new agent among anti-VEGF treatment alternatives, may be an option (2).

Idiopathic epiretinal membrane (ERM) is another cause of visual acuity deterioration due to traction forces on the retinal surface in the same group of older patients. The coexistence of the aforementioned conditions may cause difficulties in the management of PCV with anti-VEGF therapy (3).

In this case of a patient with both PCV and ERM, there was a response to intravitreal aflibercept injections before

and after a pars plana vitrectomy with ERM peeling. To the best of our knowledge, this is the first report demonstrating the results of ERM peeling in a patient with PCV.

Case Report An otherwise healthy, 68-year-old patient presented with reduced central vision in his left eye in November 2007. Patientâ&#x20AC;&#x2122;s medical and ocular history was unremarkable. At the time of presentation, his best corrected visual acuity (BCVA) was 20/30 in the right eye and 20/66 in the left eye. Intraocular pressure was 13 mmHg in the right eye, and 14 mmHg in the left eye according to Goldmann applanation tonometry measurements. An anterior segment examination of both eyes was normal. A fundus examination revealed hard and soft drusen in the macula in both eyes (Fig. 1a). Fluorescein angiography demonstrated multiple hyperfluorescent spots in the macula due to the presence of drusen in the

Address for correspondence: Asli Kirmaci, MD. University of Health Sciences, Beyoglu Eye Training and Research Hospital, Istanbul, Turkey Phone: +90 212 251 59 00 E-mail: aslikirmaci@gmail.com Submitted Date: October 31, 2017 Accepted Date: December 02, 2017 Available Online Date: April 03, 2018 Copyright 2018 by Beyoglu Eye Training and Research Hospital - Available online at www.beyoglueye.com

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a

Kirmaci et al., ERM peeling in PCV

b

c

Figure 1. (a) Fundus examination of the right and left eye revealing hard and soft drusen. (b) Fluorescein angiography shows multiple hyperfluorescent spots in the macula in the right eye and hyperfluorescence and leakage due to occult choroidal neovascular membrane in the left eye. (c) Optical coherence tomography indicating a thin epiretinal membrane in the right eye and pigment epithelial detachment with subretinal fluid in the left eye.

a

b

Figure 2. (a) Fluorescein angiography demonstrating hyperfluorescence and leakage related to the occult choroidal neovascular membrane in both eyes. (b) Optical coherence tomography illustrating the epiretinal membrane and subretinal fluid in the right eye.

right eye and hyperfluorescence and leakage resulting from occult choroidal neovascular membrane in the left eye (Fig. 1b). Optical coherence tomography (OCT) (Spectralis; Heidelberg Engineering, Heidelberg, Germany) demonstrated a thin ERM in the right eye, and pigment epithelial detachment (PED) and subretinal fluid in the left eye (Fig. 1c). He was diagnosed with dry AMD and ERM in the right eye and neovascular AMD in the left. He was treated with intravitreal

bevacizumab injections in the left eye. In July 2009, his BCVA decreased to 20/50 in the right eye. Fluorescein angiography revealed hyperfluorescence and leakage related to occult choroidal neovascularization in both eyes (Fig. 2a). OCT imaging demonstrated ERM and subretinal fluid in the right eye (Fig. 2b). He was advised to have 3 consecutive intravitreal bevacizumab injections for neovascular AMD in his right eye.

Between July 2009 and August 2015, he underwent 18 bev-

Kirmaci et al., ERM peeling in PCV

31

Figure 3. Optical coherence tomography shows the persistence of subretinal fluid in the right eye and intraretinal fluid in the left eye after bevacizumab injections.

Figure 4. Optical coherence tomography demonstrates partial improvement in the subretinal fluid in the right eye and total resolution of the intraretinal fluid in the left eye.

Figure 5. Indocyanine green angiography reveals a large branching vascular network with multiple polyps in both eyes.

acizumab injections for the right eye and 19 bevacizumab injections for the left eye. His BCVA remained stable at 20/66 in the right eye and 20/50 in the left eye during this period.

Since subretinal fluid in the right eye and intraretinal fluid in the left eye persisted despite the large number of bevacizumab injections, a decision was made to switch to intravitreal aflibercept therapy (Fig. 3). Between August 2015 and June 2016, the patient underwent 3 intravitreal aflibercept injections in each eye. His BCVA dropped to 20/100 in the right eye, while it was stable in the left. OCT imaging demonstrated that the intraretinal fluid totally resolved in the left eye, while the right eye showed partial improvement in subretinal fluid (Fig. 4). Indocyanine green angiography revealed a large branching vascular network with multiple polyps in both

eyes (Fig. 5). The presence of ERM was thought to prevent treatment response in the right eye. Phacoemulsification and intraocular lens implantation together with pars plana vitrectomy and ERM peeling was performed in the right eye. After the surgery, 1 more intravitreal aflibercept injection was administered in the right eye, and 2 additional aflibercept injections were administered in the left eye. The final BCVA was 20/100 in the right eye and 20/50 in the left eye. OCT images illustrated complete resolution of the intraretinal fluid in the right eye at the last visit (Fig. 6).

Conclusion We observed an improvement in macular morphology after the removal of an ERM in a patient with PCV who showed

32

Kirmaci et al., ERM peeling in PCV

Figure 6. Optical coherence tomography shows complete resolution of the intraretinal fluid in the right eye at the last visit.

a partial response to intravitreal aflibercept injections. OCT imaging revealed a complete resolution of subretinal fluid after the surgery, though there was no progress in the functional results, as the BCVA remained stable following the surgery. Previous studies have demonstrated that the presence of an ERM leads to an increase in the number of anti-VEGF injections and a decrease in the injection interval in the management of nAMD (4).

There are several factors regarding idiopathic ERM that may have an effect upon both the progression and the treatment response in the management of PCV. First of all, ERM formation contributes to the already existing chronic inflammation in eyes with PCV. Mechanical traction may cause a deterioration of the retina pigment epithelium (RPE) or Bruchâ&#x20AC;&#x2122;s membrane and induce a release of VEGF and other mediators. While the traction forces created by ERM stimulate the progression of nAMD, several studies have demonstrated that patients with AMD have a greater rate of vitreomacular interface abnormalities, including ERM, compared

with those without AMD (3). Pierro et al. (5) indicated in their study that ERM was present in 26% to 32% of patients with nAMD. The inflammation present in nAMD likely leads to the formation of ERM, and this increased inflammation induces the progression of nAMD (4). Secondly, apart from the inflammatory cytokine-induced pathway, the VEGF concentration in the aqueous humor is also increased by hypoxia due to the closure of small vessels around the macular area as a result of the traction (6). Therefore, a vitrectomy with an ERM peel can be a beneficial procedure for PCV patients with ERM in that it may reduce inflammatory mediators and provide greater oxygen tension in the vitreous cavity (7, 8).

We also performed a pars plana vitrectomy procedure with ERM removal in our case, and observed reduced progression of the disease after the surgery.

The presence of an ERM and the associated traction is thought to be influential in the treatment responsiveness of nAMD patients. Traction forces may lead to a breakdown in the architecture of the RPE, Bruchâ&#x20AC;&#x2122;s membrane, and photore-

Kirmaci et al., ERM peeling in PCV

ceptor layer, which may result in a reduction in the effectiveness of anti-VEGF agents (4). In addition, the presence of a membrane may act as a physical barrier and result in reduced penetration of the anti-VEGF agents through these membranes, leading to pharmacological resistance to anti-VEGF treatment (3, 4). In our case, we continued treatment with intravitreal aflibercept injections after the surgery and observed an improvement in anatomical results, although the BCVA remained the same as before the surgery.

In summary, we speculate that pars plana vitrectomy with ERM peeling seems to have been beneficial in the management of a PCV patient with ERM by both reducing the progression of the disease and increasing the response to treatment. Along with the conventional parameters, such as the presence of intraretinal fluid, hemorrhage, and pigment epithelial detachment, the presence of ERM might be considered at baseline in the treatment of a PCV patient.

33

2.

3.

4.

5.

Disclosures Informed consent: Written informed consent was obtained from the patient for the publication of the case report and the accompanying images.

Peer-review: Externally peer-reviewed.

6.

Conflict of Interest: None declared.

7.

Authorship Contributions: Involved in design and conduct of the study (ZTA, AK); preparation and review of the study (AK); data collection (AD, DY).

8.

References 1. Kokame GT, Lai JC, Wee R, Yanagihara R, Shantha JG, Ayabe J, et al. Prospective clinical trial of Intravitreal aflibercept treatment for PolypoIdal choroidal vasculopathy with hemorrhage

or exudation (EPIC study): 6 month results. BMC Ophthalmol 2016;16:127.

Kawashima Y, Oishi A, Tsujikawa A, Yamashiro K, Miyake M, Ueda-Arakawa N, et al. Effects of aflibercept for ranibizumab-resistant neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. Graefes Arch Clin Exp Ophthalmol 2015;253:1471–7.

Alkin Z, Ozkaya A, Ayranci Osmanbasoglu O, Agca A, Karakucuk Y, Yazici AT, et al. The Role of Epiretinal Membrane on Treatment of Neovascular Age-Related Macular Degeneration with Intravitreal Bevacizumab. ScientificWorldJournal 2013;2013:958724.

Karaca EE, Kepez Yldz B, Çubuk MÖ, Özdek Ş. Epiretinal Mebranes in Neovasculer Age-Related Macular Degeneration: Effect on Outcomes of Anti-vascular Endothelial Growth Factor Therapy. Retina 2015;35:1540–6.

Pierro L, Zampedri E, Milani P, Gagliardi M, Isola V, Pece A. Spectral domain OCT versus time domain OCT in the evaluation of macular features related to wet age-related macular degeneration. Clin Ophthalmol 2012;6:219–23.

Schulze S, Hoerle S, Mennel S, Kroll P. Vitreomacular traction and exudative age-related macular degeneration. Acta Ophthalmol 2008;86:470–81.

Roller AB, Mahajan VB, Boldt HC, Abramoff MD, Russell SR, Folk JC. Effects of vitrectomy on age-related macular degeneration. Ophthalmology 2010;117:1381–6.

Kimura S, Morizane Y, Toshima S, Hosogi M, Kumase F, Hosokawa M, et al. Efficacy of vitrectomy and inner limiting membrane peeling in age-related macular degeneration resistant to anti-vascular endothelial growth factor therapy, with vitreomacular traction or epiretinal membrane. Graefes Arch Clin Exp Ophthalmol 2016;254:1731–6.

Case Report

DOI:10.14744/bej.2017.47966 Beyoglu Eye J 2018; 3(1): 34-37

Medical Management of Non-Progressive Periorbital Necrotizing Fasciitis Ziya Ayhan, Aylin Yaman, Meltem Soylev Bajiin Department of Ophthalmology, Dokuz Eylul University Faculty of Medicine, Izmir, Turkey

Abstract Necrotizing fasciitis (NF) is a serious soft tissue infection with a significant fatality rate. Although the cause may be polymicrobial, the most common microbial agents are Streptococcus pyogenes and Staphylococcus aureus. Early recognition and aggressive surgical debridement are usually required to prevent the rapid spread of infection. Presently described is a case of NF of the eyelids in a patient who had a good response with intravenous antibiotic therapy.

Keywords: Medical treatment, necrotizing fasciitis, non-progressive.

Introduction Necrotizing fasciitis (NF) is a rapidly progressive and serious infection of the subcutaneous tissue and superficial fascia with secondary necrosis of the overlying skin. Although periorbital NF is uncommon, as a result of an excellent blood supply, it can result in visual loss or even death. Early recognition and initiation of treatment is essential to decrease morbidity and mortality (1). Surgical debridement and highdose intravenous antibiotic therapy are usually combined in the treatment of this phenomenon. Though antibiotics may not reach the infected area due to thrombosis, a successful outcome may be obtained in mild cases with antibiotic therapy alone (2).

Presently described is a patient who was treated and cured with intravenous antibiotic therapy and without the need for debridement.

Case Report A 78-year-old woman presented at the clinic with bilateral eyelid swelling, blackened areas of the surrounding periorbital skin, and mild pain. She did not have any history of trauma. She described a history of the right eye and surrounding

area becoming red and swollen first, followed by a similar progression on the left side the next day. Her past medical and ocular history was unremarkable. On examination, black necrotic areas in the periorbital region with mild swelling and redness were observed bilaterally (Fig. 1). The patient’s visual acuity was 2/10 in both eyes. A bilateral grade 3 nuclear cataract was detected in both eyes with slit-lamp examination. Intraocular pressure was measured as 14 mmHg, bilaterally. The optic disc and macula were normal in both eyes on dilated fundus examination. There was no orbital involvement. Relative afferent pupillary defect, diplopia, or gaze palsy was not detected. At the time of examination, the body temperature of the patient was 38.5°C and the patient was oriented. Blood analysis revealed mild leukocytosis (total white cell count: 10.5x103/μL with 90% neutrophilia). The C-reactive protein (CRP) level was 503 mg/mL, and the erythrocyte sedimentation rate (ESR) was >110 mm/ hour. The serum urea and creatinine levels were moderately elevated. After consultation with the departments of infectious diseases, otolaryngology, and plastic surgery, a clinical diagnosis of periorbital NF was confirmed. Intravenous meropenem 1 g every 8 hours, vancomycin 1.5 g every 12

Address for correspondence: Ziya Ayhan, MD. Department of Ophthalmology, Dokuz Eylul University Faculty Of Medicine, Izmir, Turkey Phone: +90 232 412 30 66 E-mail: zyayhan@yahoo.com Submitted Date: November 03, 2017 Accepted Date: November 19, 2017 Available Online Date: March 30, 2018 Copyright 2018 by Beyoglu Eye Training and Research Hospital - Available online at www.beyoglueye.com

©

Ayhan et al., Medical management of periorbital necrotizing fasciitis

35

Figure 1. A photo of the patient taken at presentation. Necrotic areas are evident on both upper eyelids.

Figure 2. Computed tomography scans indicated soft tissue edema in the bilateral preseptal subcutaneous tissue.

hours, and clindamycin 600 mg every 8 hours was initiated as empirical treatment. An emergency computed tomography scan revealed bilateral soft tissue inflammation anterior to the orbital septum (Fig. 2). Analysis of a biopsy specimen indicated the presence of squamous epithelial cells among widespread neutrophils and eosinophiles. Mucormycosis and herpes zoster were not detected. No organism was identified in a wound and blood culture. The patientâ&#x20AC;&#x2122;s temperature was 37.5°C, the CRP level was 151 mg/mL, and the ESR was 75 mm/hour 3 weeks after the initiation of empirical treatment. The patient was followed up for the necrotic tissue in the periorbital area but no surgical debridement was performed as a result of the good response to medical therapy.

After improvement of clinical signs, the patient was released from the hospital with oral amoxicillin-clavulanate antibiotic therapy (Fig. 3).

Discussion NF usually develops secondary to trauma or surgery (1, 3-5).

Some predisposing factors, such as immunosuppression, malignancy, diabetes mellitus, and alcoholism can cause this phenomenon. Periorbital NF has been reported after trauma and surgical operations, such as blepharoplasty and dacryocystorhinostomy (3-5). Suner et al. (4) described a case of a 74-year-old woman with a history of type II diabetes mellitus who underwent bilateral upper eyelid blepharoplasty. Postoperatively, she developed a fever, grayish discoloration of the skin, violaceous bullae, and palsy of the right facial nerve.

NF was diagnosed and treated with intravenous antibiotics, debridement of the necrotic tissue, and hyperbaric oxygen therapy. There was no predisposing factor like trauma, a history of surgery, or a concomitant systemic disorder in our

36

Ayhan et al., Medical management of periorbital necrotizing fasciitis

Figure 3. A photo of the patient taken 2 months after the initiation of treatment. The necrotic areas healed with intravenous antibiotic treatment and debridement was not necessary.

case. The diagnosis of periorbital NF was made clinically. The initial clinical appearance of periorbital NF is usually edema and redness in the region, resembling preseptal cellulitis or erysipelas. After the appearance of the initial signs, the skin then becomes more dusky and grey-blue in color, eventually becoming blackish with a crust forming as a result of the progressive thrombosis of blood vessels (1). Computed tomography and magnetic resonance imaging help in making an early diagnosis and also to differentiate NF from orbital cellulitis and mucormycosis. Imaging scans can be used to guide surgical debridement (6). The most commonly observed causative microorganisms are Streptococcus pyogenes, Staphylococcus aureus, or a combination of facultative and anaerobic organisms, including Group C, G, H Streptococci, Haemophilus influenzae type B, Bacteroides and Clostridia (1).

In our case, the causative microorganism could not be identified, despite repeated microbiological analyses. Early recognition and initiation of intravenous high-dose antibiotics combined with tissue debridement helps to decrease morbidity and mortality. Mild cases may respond to antibiotic therapy alone, as in the present case. The standard initial antibiotic therapy consists of a combination of beta-lactam antibiotics and clindamycin, since multiple microorganisms may be responsible. Surgical debridement decreases the bacterial load and helps with the transmission of antibiotics through the infected area1. Repeated debridement may be necessary if the response to treatment is slow (6). The role of hyperbaric oxygen therapy in the management of NF is controversial. It may help to limit ischemic tissue. Intravenous gamma globulins are also recommended in the management of NF (7). No surgical debridement was undertaken in our case due to the good response to medical therapy. The major morbidity risk is orbital spread and loss of vision. Cos-

metic disfigurement and functional problems of the eyelids may also be seen (8, 9). Raja et al. (8) reported a case of NF initially misdiagnosed as traumatic pre-septal cellulitis following self-puncture of a hordeolum externum in which resistance to aggressive antibiotic therapy resulted in the loss of the lower eyelid. Mortality from periorbital NF is typically caused by the spread of infection to the neck and thorax (10).

Early recognition and effective treatment are the most important factors to reduce the risk of morbidity and mortality. Although surgical debridement and high-dose intravenous antibiotic therapy are usually essential in cases of periorbital NF, a successful outcome may be obtained in mild cases with antibiotic therapy alone, as in our case.

Disclosures Informed consent: Written informed consent was obtained from the patient for the publication of the case report and the accompanying images.

Peer-review: Externally peer-reviewed.

Conflict of Interest: None declared.

Authorship Contributions: Involved in design and conduct of the study (ZA, AY, MSB); preparation and review of the study (ZA); data collection (ZA).

References 1. Amrith S, Hosdurga Pai V, Ling WW. Periorbital necrotizing fasciitis - a review. Acta Ophthalmol 2013;91:596â&#x20AC;&#x201C;603.

2. Luksich JA, Holds JB, Hartstein ME. Conservative management of necrotizing fasciitis of the eyelids. Ophthalmology 2002;109:2118â&#x20AC;&#x201C;22.

3. Balaggan KS, Goolamali SI. Periorbital necrotising fasciitis after minor trauma. Graefes Arch Clin Exp Ophthalmol

Ayhan et al., Medical management of periorbital necrotizing fasciitis

2006;244:268–70.

4. Suñer IJ, Meldrum ML, Johnson TE, Tse DT. Necrotizing fasciitis after cosmetic blepharoplasty. Am J Ophthalmol 1999;128:367–8.

5. Hirschbein MJ, LaBorwit SE, Karesh JW. Streptococcal necrotizing fasciitis complicating a conjunctival dacryocystorhinostomy. Ophthal Plast Reconstr Surg 1998;14:281–5.

6. Saldana M, Gupta D, Khandwala M, Weir R, Beigi B. Periorbital necrotizing fasciitis: outcomes using a CT-guided surgical debridement approach. Eur J Ophthalmol 2010;20:209–14.

7. Seal DV. Necrotizing fasciitis. Curr Opin Infect Dis 2001;14:127–

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8. Raja V, Job R, Hubbard A, Moriarty B. Periorbital necrotising fasciitis: delay in diagnosis results in loss of lower eyelid. Int Ophthalmol 2008;28:67–9.

9. Prendiville KJ, Bath PE. Lateral cantholysis and eyelid necrosis secondary to Pseudomonas aeruginosa. Ann Ophthalmol 1988;20:193–5.

10. Puri P, Innes JR. Necrotising fasciitis of the orbit: early recognition and treatment a key to success. Eur J Ophthalmol 2001;11:180–2.

Case Report

DOI:10.14744/bej.2018.58066 Beyoglu Eye J 2018; 3(1): 38-42

Management of Open Globe Injuries and Concern About Sympathetic Ophthalmia: A Case Report Can Ozturker,1 Pelin Kaynak,2 Gamze Ozturk Karabulut,3 Korhan Fazil,3 Yusuf Yildirim,3 Osman Bulut Ocak3 Department of Ophthalmology, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey Rufus Laser & Ophthalmic Surgery Center, Istanbul, Turkey 3 University of Health Sciences Beyoglu Eye Training and Research Hospital, Istanbul, Turkey 1 2

Abstract An 18-year-old male with an open globe injury, eyelid lacerations, and orbital wall fractures related to severe blunt trauma was referred to the clinic for primary evisceration and eyelid repair. As the patient refused the removal of the eye, the globe, eyelids, and canaliculi were sutured primarily. A month later, the patient accepted the removal of the eye due to progressive phthisis bulbi and underwent evisceration 5 weeks after the injury. He was followed up for 2 years after the second surgery and had an acceptable cosmetic result without any complication. Although very rare, it is very important to remember that there is a risk of sympathetic ophthalmia in severe eye injuries, though prophylaxis by removing the eye remains controversial.

Keywords: Canalicular laceration, enucleation, evisceration, sympathetic ophthalmia, trauma.

Introduction

Case Report

Open globe injuries are one of the main reasons for the removal of an eye in order to avoid sympathetic ophthalmia (SO), which is a devastating, though uncommon, bilateral granulomatous panuveitis following uveal trauma to one eye.

The injured eye is referred to as the inciting eye, while the fellow eye is called the sympathizing eye (1). The prevalence of SO after eye injury is estimated to be between 0.1% and 0.3% (2-4).

Due to its very low incidence, it is controversial whether or not SO can be prevented by removing the eye after trauma (5-7). Even if it occurs, there may be a good prognosis with early diagnosis and the use of modern immunotherapies (8). There is no scientific consensus on the technique and timing of prophylactic surgery (9-12).

The purpose of this case report was to discuss the need for the removal of an injured blind eye after severe trauma and the choice of surgical procedure, considering the risk of SO.

An 18-year-old male with a recent history of a thrown cylindrical metal object having caused trauma to his left eye was referred to the clinic for primary evisceration and eyelid repair. The patient was suffering from open globe injury and multiple upper and lower eyelid lacerations involving both canaliculi (Fig. 1).

The injured eye had no light perception and had a large corneal-scleral rupture, extending vertically from the upper to the lower quadrant on slit-lamp examination. An orbital computed tomography scan revealed multiple fractures of the upper, medial, and lower orbital walls, as well as the maxillary bone (Fig. 2).

Despite being informed about the risk of SO and the unlikelihood of visual recovery, the patient did not give consent for the removal of the eye. Accordingly, the globe and the eyelids were sutured primarily and the canaliculi were repaired using a self-retaining bicanalicular silicone stent on

Address for correspondence: Can Ozturker, MD. Department of Ophthalmology, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey Phone: +90 212 414 20 00 E-mail: canozturker@hotmail.com Submitted Date: August 18, 2017 Accepted Date: March 29, 2018 Available Online Date: April 04, 2018 Copyright 2018 by Beyoglu Eye Training and Research Hospital - Available online at www.beyoglueye.com

Š

Ozturker et al., Open globe injuries and sympathetic ophthalmia

39

Figure 1. The extent of the injury.

Figure 2. Orbital wall fractures seen on a computed tomography scan.

Figure 3. The conclusion of surgery.

the same day of the injury (Fig. 3). Due to a small quantity of prolapsing orbital content, reconstruction of the orbital walls was not planned for the surgery.

One month later, the eye started to develop phthisis and was without any visual recovery (Fig. 4). Concerned about cosmesis, the patient agreed to have the eye removed, and evisceration with a 22-mm acrylic implant was performed 5 weeks after the initial injury.

A silicone stent was removed 3 months after the primary repair and a custom-made prosthetic eye was fitted 3

months after the evisceration. The patient was satisfied with the cosmetic result and had neither epiphora nor SO during 2 years of follow-up. Thereafter, he was discharged from follow-up and recommended to see his ocularist on a yearly basis (Figs. 5, 6).

Discussion There is no clear information about the true prevalence of SO after ocular injury, but it is estimated to be between 0.1% and 0.3%, according to the current literature (2-4). There are

40

Ozturker et al., Open globe injuries and sympathetic ophthalmia

Figure 4. One month after the primary repair, with visible phythisis bulbi.

Figure 5. One year after the primary repair.

2 main questions in the management of severe eye trauma: Should the injured eye be removed as a prophylaxis for SO and what is the ideal surgical technique for this?

In general, it is recommended that a traumatized eye be removed within a time frame of 10 days to 2 weeks following a penetrating injury. Despite that, Savar et al. (10) reported in 2009 that among 660 open globe injuries, only 55 eyes had

undergone enucleation. This review of cases revealed that only 2 patients (0.3%) developed SO. These patients had not undergone enucleation and maintained good vision in the fellow eye after medical treatment. In prospective surveillance for SO in UK and Ireland, Kilmartin et al. (8) found that 75% of cases had a visual acuity of 6/12 or better at 1 year, which was attributed to early diagnosis and modern immunothera-

Ozturker et al., Open globe injuries and sympathetic ophthalmia

41

Figure 6. Movement of the prosthetic eye.

pies by the authors.

This published information brings up the question of how necessary it is to remove an injured eye to prevent SO. Using hypothetical calculations, Bellan (13) proposed that between 908 (assumed SO rate of 3.1%) to 9999 (assumed SO rate of 0.28%) eyes would be enucleated prophylactically to prevent just 1 case of legal blindness.

Although enucleation may be the oldest operation in the history of ophthalmology, going back to 2600 BC, evisceration gained popularity over enucleation among ophthalmologists in the last century due to its cosmetic and functional advantages and its simplicity (12). First described by Bear in 1817, evisceration causes less disturbance to the delicate orbital septal anatomy, preserves the physiological function of the eye muscles, and maintains the sclera as a barrier holding the orbital implant. These features are the keys to a healthy anophthalmic socket, providing good motility for the eye prosthesis and preventing implant exposure (9).

However, reports of SO cases following evisceration, first

by Green at al. (6) in 1972 and then by others (7) led to a distrust in this technique in terms of preventing SO. A survey conducted by Levine et al. (9) among the members of the American Society of Ophthalmic Plastic and Reconstructive Surgery in 1996 revealed that enucleation was the procedure of choice in 72.3% of cases. In the same survey, members of the Uveitis Society and the Eastern Ophthalmic Pathology Society preferred enucleation in more than 90% of cases.

Nevertheless, there are many large published series of evisceration without any postoperative SO during follow-up (9). In their article comparing evisceration and enucleation from the ocularistâ&#x20AC;&#x2122;s perspective, Timothy et al. (11) men-

tioned that their review of the literature did not reveal any published cases of SO following evisceration in the last 25 years.

Unfortunately, in trauma cases it is difficult to know whether SO is a result of the original trauma or the evisceration itself. In 2013, Tseng et al. (5) presented an interesting case of pathologically proven SO following enucleation of a painful phthisical eye with a history of multiple intraocular surgeries. Six weeks after the surgery, a histopathological examination of the enucleated eye revealed findings consistent with SO and the fellow eye was also clinically affected. The authors concluded that SO was related to previous intraocular surgeries rather than the enucleation, but had the eye have been eviscerated in his case, the SO could have been attributed to evisceration itself, due to a lack of pathological evidence.

On the other hand, in a large series of 85 SO cases reported by Galor et al. (14), 19 patients (22%) had a history of enucleation in the inciting eye, suggesting that even enucleation may not be as reliable as it is assumed to be as prophylaxis against SO.

Conclusion The incidence of SO after open globe injury is very low, and the prevention of SO by evisceration or enucleation is controversial. Patients with this condition may need time to accept the loss of their eye. During this period, the risk of SO, surgical and medical treatment options, and possible complications for each scenario must be discussed with the patient in detail, so that they can make the relevant decisions, which will affect them for the rest of their life.

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Disclosures Informed consent: Written informed consent was obtained from the patient for the publication of the case report and the accompanying images.

Peer-review: Externally peer-reviewed.

Conflict of Interest: None declared.

Authorship Contributions: Involved in design and conduct of the study (CO, PK, YY); preparation and review of the study (PK, CO); data collection (GOK, KF, BO).

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