July-August, 2022 Vol, 28 No. 4

CONTENTS PAGE NO. TITLE 07 From the DESK of Chief Editor 08 From the DESK of Managing Editor Subspeciality Basic Ophthalmology Tearsheet 09 72 77 74 13 15 24 26 18 36 39 44 47 50 55 60 Humanoptics Customflex Artificial Iris Implant - An Answer to Anterior Segment Rehabilitation!!!! Newer Technology for Myopia Control COVID-19 Vaccine Associated Ocular Adverse Effects Setting up a Ocular microbiology laboratory for an Secondary Center hospital/smaller set ups: Ten step guide for comprehensive ophthalmologists and stand alone Ophthalmic Centers 10 Tips for Managing a Case of Postoperative Endophthalmitis Identifying External Limiting Membrane (ELM) and Ellipsoid Zone (EZ) on SD-OCT A Case of Glaucoma Secondary to Idiopathic Elevated Episcleral Venous Pressure Neovascular Glaucoma Newer Anti-VEGF The First (Awakening) Call… Acanthamoeba Keratitis Sensory Evaluation of Strabismus Acquired Restrictive Esotropia of Ambiguous Etiology in a Two Year Old Child Impact of Strabismus Management on the Retinal Microstructure Visual Outcomes of Secondary Lens Implants in Children with Different Etiologies Kayser Fleischer Ring and Sunflower Cataract in Wilsons Disease 61 64 Surgical Technique of Tenon Patch Graft in Corneal Fistula and Corneal Perforations Peripheral corneal ectatic disorders Surgical Techniques PG Corner 76 Humour in Ophthalmology Beyond Ophthalmology

www.dosonline.org/dos-times DOS Times - Volume 28, Number 4, July-August 2022 DOS EXECUTIVE MEMBERS (2021-2023) 03 Dr. Pawan Goyal Immediate Past President Dr. Om Prakash Anand Prof. Jeewan S. Titiyal Prof. Subhash C. Dadeya Dr. Prafulla Kumar Maharana Dr. Rajendra Prasad Vice President Dr. Gagan Bhatia Prof. M. Vanathi Prof. Namrata Sharma Dr. Amar Pujari Dr. Jatinder Singh Bhalla Secretary Dr. Vivek Gupta Dr. Bhupesh Singh Dr. Sandhya Makhija Joint Secretary Dr. Vivek Kumar Jain Dr. Pankaj Varshney Dr. Alkesh Chaudhary Treasurer Prof. Kirti Singh Editor Dr. Jatinder Bali Library Officer DOS Office Bearers Executive Members DOS Representative to AIOS Ex-Officio Members Dear DOS Members We are sending you DOS TIMES, July-August issue of previous executive tenure. Dr. Rajendra Prasad Dr. Jatinder Singh Bhalla President DOS Secretary DOS

Know Your Editor Managing Editor DOS Times Chief Editor DOS Times Dr. Jatinder Singh Bhalla MS, DNB, MNAMS Hony. General Secretary Delhi Ophthalmological Society DDU Hospital, Hari Nagar Dr. Prafulla Kumar Maharana, MD Associate Professor of Ophthalmology Dr. Rajendra Prasad Centre for Ophthalmic Sciences, AIIMS, New Delhi DOS Times - Volume 28, Number 4, July-August 2022 www.dosonline.org/dos-times 04 Section Editor - Retina & Uvea Prof. (Col) Sanjay Kumar Mishra, HOD, Dept of Ophthalmology (vitreo retina surgeon), Army Hospital (R&R) Section Editor - Retina & Uvea Dr. Alkesh Chaudhary MBBS, MS, FMRF Head Consultant M.D. Eye Care & Laser Centre Section Editor - Uvea & Ocular Inflammatory Disorders Dr. Naginder Vashisht MD, FRCS, FICO Director & Senior Consultant Ophthalmology, Kailash Eye Care, Patel Nagar, New Delhi Senior Consultant Ophthalmology, Artemis Hospitals, Gurugram Section Editor - Retina & Uvea Dr. Raghav Malik, MS Fellowship Cataract & Refractive Surgery Associate Consultant Dept of Cataract, Cornea & Refractive Services, CFS, New Delhi Section Editor - Uvea & Ocular Inflammatory Disorders Dr. Prateek Kakkar (Retina Specialist), MD Ex-Senior Resident (Vitreo-retina, AIIMS, New Delhi) Section Editors - Retina & Uvea Dr. Deepankur Mahajan MBBS, MD (AIIMS), FICO, FAICO (Retina and Vitreous) Consultant Ophthalmologist and Vitreoretina Specialist, New Delhi Section Editor - Uvea & Ocular Inflammatory Disorders Dr. Aman Kumar MD, Senior Resident Vitreo-Retina, Uvea, ROP services Dr. R P Centre for Ophthalmic Sciences, AIIMS, New Delhi Section Editor - Retina & Uvea Dr. Rushil Kumar Saxena Dept of Vitreoretina Dr. Shroff’s Charity Eye Hospital, New Delhi Section Editor - Retina & Uvea Dr. Ankur Singh Assistant professor Dept of Ophthalmology University College of Medical Sciences and GTB Hospital, Delhi Section Editor - Retina & Uvea Dr. Abhishek Jain D.O., D.N.B., FAICO RBM Eye Institute, Delhi ADK Jain eye hospital, Bhagpat Section Editor - Cornea & External Eye Disease Dr. Sameer Kaushal Senior Consultant & Head (Ophthalmology) Artemis Hospital and PL Memorial Eye Clinic, Gurgaon Section Editor - Cornea & External Eye Disease Dr. Abha Gour Senior Consultant Cornea and Anterior Segment Dr. Shroffs Charity Eye Hospital, New Delhi

www.dosonline.org/dos-times DOS Times - Volume 28, Number 4, July-August 2022 05 Section Editor - Ocular Surface Dr. Rajat Jain MBBS, MS (Gold Medalist), FICO (UK) Fellow- Cornea and Anterior Segment- LVPEI Hyderabad Section Editor - Cataract & Comprehensive Ophthalmology Dr. Ritin Goyal Director & Cornea, Cataract and LASIK surgeon at Goyal Eye Group of Eye Centers. Section Editor - Refractive Surgery Dr. Manpreet Kaur MD, Assistant Professor Cornea, Cataract & Refractive Surgery Services Dr. R P Centre for Ophthalmic Sciences AIIMS, New Delhi Section Editor - Ocular Surface Dr. Jaya Gupta Consultant Cornea Cataract & Refractive Surgery The Healing Touch Eye Care Centre, New Delhi Section Editor - Cataract & Comprehensive Ophthalmology Dr. Wangchuk Doma Venu Eye Institute and Research Centre Section Editor - Refractive Surgery Dr. Pranita Sahay, MD (AIIMS), FRCS (Glasgow), DNB, FICO, FICO (Cornea), FAICO (Ref Sx) Consultant, CFS, New Delhi Section Editor - Ocular Surface Dr. Abhishek Dave Consultant Cornea, Cataract & Refractive Surgery - CFS, New Delhi Section Editor - Ocular Surface Dr. Amrita Joshi Assistant Professor Department of Ophthalmology Army Hospital (R&R) Section Editor - Cataract & Comprehensive Ophthalmology Dr. Amit Mehtani MBBS, MS, DNB DDU HOSPITAL Section Editor - Ocular Surface Dr. Neeraj Verma MS (Ophthal) Senior Consultant Centre For Eye Care Kirti Nagar, New Delhi Section Editor - Cornea & External Eye Disease Dr. Ritu Nagpal MD, Senior Research Associate Dr. R P Centre for Ophthalmic Sciences, AIIMS, New Delhi Section Editor - Cornea & External Eye Disease Dr. Parul Jain MBBS, MS, FICO, FAICO, MRCSEd Associate Professor GNEC, Maulana Azad Medical College Dr. Jyoti Batra Consultant, Oculoplasty and Ocular Oncology, ICARE Eye Hospital and Post graduate Institute, Noida Section Editor - Oculoplasty & Asthetics Section Editor - Oculoplasty & Asthetics Dr. Rwituja Thomas Grover Consultant Oculoplastics, Orbit, Ocular Oncology and Aesthetics services, Vision Eye Centres, New Delhi Dr. Anuj mehta Consultant and Professor Vardhman Mahavir Medical College and Safdarjung Hospital Section Editor - Oculoplasty & Asthetics Section Editor - Glaucoma Dr. Kiran Bhanot MS, DNB Senior Consultant & Hod GGS Hospital & Indira Gandhi Hospital, Dwarka, New Delhi Section Editor - Glaucoma Dr. Suneeta Dubey Head - Glaucoma Services Medical Superintendent Chairperson - Quality Assurance Dr. Shroff’s Charity Eye Hospital New Delhi, India Section Editor - Glaucoma Dr. Prathama Sarkar Consultant in Eye7 Chaudhary Eye Centre Section Editor - Glaucoma Dr. Kanika Jain MBBS, MS, DNB Senior Resident, Dept of Ophthalmology, DDU Hospital, Hari Nagar, New Delhi. Section Editor - Glaucoma Dr. Shweta Tripathi DNB, MNAMS, FMRF Senior Consultant Glaucoma Services Indira Gandhi Eye Hospital and Research Centre, Lucknow Dr. Kavita Bhatnagar Professor & Head, Dept of Ophthalmology, AIIMS, Basani Phase-2, Jodhpur Section Editor - Glaucoma

DOS Times - Volume 28, Number 4, July-August 2022 www.dosonline.org/dos-times 06 Prof. Swati Phuljhale Dr. R P Centre for Ophthalmic Sciences, AIIMS, New Delhi Section Editor - Strabismus Dr. Gunjan Saluja Ex SR Strabismus, Oculoplasty and Neuro-Ophthalmology services, Dr. R P Centre, AIIMS, New Delhi Section Editor - Strabismus Dr. Suraj Singh Senjam Community Ophthalmology Dr. R P Centre for Ophthalmic Sciences, AIIMS, New Delhi Section Editor - Community Ophthalmology Dr. V Rajshekhar MS, FICO Professor & Consultant Dept of Ophthalmology VMMC & Safdarjung Hospital, New Delhi Section Editor - Community Ophthalmology Dr. Digvijay Singh Affiliation, Noble Eye Care, Gurugram Section Editor - Residents Corner Dr. Vineet Sehgal MBBS, MD Fellowship in Glaucoma Senior Consultant & Incharge Glaucoma Sharp Sight Eye Hospitals Section Editor - Residents Corner Dr. Sima Das Head, Oculoplasty and Ocular Oncology Services Incharge, Medical Education Dr. Shroff’s Charity Eye Hospital New Delhi Section Editor - Ocular Oncology Prof. Bhavna Chawla Professor of Ophthalmology Dr. R P Centre, AIIMS, New Delhi Section Editor - Ocular Oncology Dr. Paromita Dutta Associate Professor Guru Nanak Eye Centre Maharaja Ranjit Singh Marg New Delhi Section Editor - Strabismus Dr. Sumit Monga, Senior Consultant. Pediatric, Strabismus and Neuro-Ophthalmology Services, CFS group of Eye Hospitals, Delhi-NCR Section Editor - Neuro-Ophthalmology Dr. Amar Pujari Assistant Professor Dr. R P Centre for Ophthalmic Sciences, AIIMS, New Delhi Section Editor - Neuro-Ophthalmology Dr. Rebika Dhiman Assistant Professor Strabismus and NeuroOphthalmology services, Dr. R P Centre, AIIMS, New Delhi Section Editor - Neuro-Ophthalmology Dr. Simi Gulati I/C and Specialist Charak palika hospital (ndmc) Moti bagh, New Delhi Section Editor - Glaucoma

www.dosonline.org/dos-times DOS Times - Volume 28, Number 4, July-August 2022 07 DOS TIMES From the DESK of Chief Editor Dr. J S Bhalla, MS, DNB, MNAMS Secretary Delhi Ophthalmological Society Writing is Human Editing is Divine Overwhelmed by the encouraging response to our previous issues, we promise to fulfil your expectations of enriching the dimensions of ophthalmic knowledge in this as well as forthcoming issues of DOS Times. This issue covers topics from all subspecialities. The articles on Tips for managing endophthalmitis & identifying ELM & EZ on SD OCT, Anti VEGFs from Retina will be of great help.The write ups from Cornea - Peripheral Corneal ecstatic disorders & Tenon patch graft for corneal perforation, The topics on Strabismus like sensory evaluation & Artificial Iris implantation for Anterior segment reconstruction, Myopia control, Neovascular Glaucoma will be very useful. It is really encouraging to see the efforts being put in by Section Editors. Our sincere thanks to them. Last but not the least, I must take the responsibility to express my sincere gratitude to all the contributing experts for their valuable support in bringing out this issue for comprehensive Ophthalmologists. Let the reader find that he cannot afford to omit any line of your writing because you have omitted every word that he can spare- Ralph Waldo Emerson Dr. Jatinder Singh Bhalla, MS, DNB, MNAMS Chief Editor - DOS Times, Consultant & Academic Incharge (Ophthalmology) DDU Hospital, Hari Nagar

DOS Times - Volume 28, Number 4, July-August 2022 www.dosonline.org/dos-times 08 DOS TIMES It’s a great pleasure on my part to bring out this edition of DOS Times. In our previous edition we had focused on Glaucoma. This edition includes articles from all subspecialty. The articles in this volume covers the entire spectrum of ophthalmology. The article on endophthalmitis will be extremely useful to learn the different pearls in prevention and management of endophthalmitis. The articles on strabismus would help the readers in understanding the complex aspects of strabismus. COVID 19 vaccine related ocular side effects have been discussed in a tear sheet for simple understanding by the readers. The article on peripheral corneal thinning disorders in PG corner section will help the post graduate students in preparation of their exam. The article on technique of Tenons patch graft will be useful for the readers to understand the technique and replicate that in their routine practice. A special thanks to all the section editors for helping us in improving the quality of the articles significantly. In the end I would like to repeat my previous words. Change is an essential part of improvement over time. In spite of all our efforts there will definitely be scope for improvement in future. I would request the readers of this edition to convey us through whatever possible means their valuable suggestions and help us improve further. Besides, I would request all the readers to come forward and send their important works for publication in DOS Times. Our next edition will be focused on “Cornea and Ocular Surface” and I encourage the readers to submit articles in this field. Dr. Prafulla Kumar Maharana, MD Managing Editor DOS Times, Associate Professor of Ophthalmology Cornea Cataract & Refractive Services Dr. Rajendra Prasad Centre for Ophthalmic Sciences, AIIMS, New Delhi Email : [email protected] Dr. Prafulla Kumar Maharana, MD From the DESK of Managing Editor

www.dosonline.org/dos-times DOS Times - Volume 28, Number 4, July-August 2022 09 Humanoptics Customflex Artificial Iris Implant-An Answer to Anterior Segment Rehabilitation!!!! Tulika Chauhan, MBBS, MS, FICO, Kanika Bhardwaj, MBBS, DNB Centre For Sight Eye Institute, New Delhi. Introduction There is often pronounced photophobia and cosmetic disfigurement in patients with iris defects such as aniridia, colobomas, traumatic loss or surgical removal, albinism and large colobomas. The iris defects not only cause deterioration of quality of vision but also diminish the quality of life in such patients. To reconstruct iris in such cases, Dr Hans Reinhard Koch together with Dr. Schmidt Intraocularlinsen GmbH, developed an artificial iris implant that has been commercially available since 2007 under the name of CUSTOMFLEX® ARTIFICIALIRIS from Human Optics AG (Erlangen, Germany).[1] The artificial Iris device from Human Optics AG (refer to Figure 1) is a foldable, flexible, biocompatible, customized silicon iris prosthesis used for medical and aesthetic reconstruction of eyes with complete or partial aniridia. The implant is accredited by CE marking and is also FDA (U.S. Food and Drug Administration) approved.[2,3] The FDA approval was granted in 2018, making CUSTOMFLEX® ARTIFICIALIRIS from Human Optics AG a first stand-alone prosthetic iris which received regulatory approval in the United States.[3] This device is however not intended for a cosmetic purpose alone such as change of eye color. It is developed for implantation in the posterior chamber of the eye and is not suitable for placement in the anterior chamber. This iris prosthesis is to be implanted only in aphakic or pseudo phakic patients i.e., after removal of the natural lens and IOL implantation as suggested strongly by the manufacturers. Figure 1: CustomFlex™ Artificial Iris Dimensions. (Reproduced from HumanOptics AG CustomFlex™ Artificial Iris Professional Use Brochure) Figure 2: CustomFlex™ Artificial Iris With Fiber and Fiber-Free Models. (reproduced from HumanOptics AG CustomFlex™ Artificial Iris Professional Use Brochure) What Makes it Special and Different ? The biggest advantage to its use is that the prosthesis is customized and handcrafted in accordance with imaging so that its color matches that of the fellow eye if normal. If the other eye is also anatomically affected, any eye picture can be taken as a template. Using trephines, the prosthesis in the form of silicon diaphragm can be individually customized in adequate shape and size to the respective iris defect thereby providing excellent cosmetic appearance. Though there are no manufacturer advised parameters, most surgeons take horizontal white-towhite diameter as the sizing reference. The Structure The device has a 3-layered silicon structure, with a central core surrounded by silicone on both sides. The middle layer is incorporated with medical grade pigments to match the colour of the iris and based on the core, the iris prosthesis is available in two device forms- CUSTOMFLEX® ARTIFICIALIRIS FIBER and CUSTOMFLEX® ARTIFICIALIRIS FIBER FREE (refer to Figure 2 and Table 1). Both the devices are identical with each other except with respect to their core. The fiber variant has a central layer of fiber mesh to facilitate easy suturing of the implant to the sclera or adjacent remaining iris without cheesewiring of the material thus imparting robust strength.[2] The posterior most layer is colored completely black to block light transmission. The anterior most layer is hand painted to match with pictures of the fellow eye. The implant is both flexible and foldable, and easily inserted through a 3 mm incision. It measures 12.8 mm in diameter with thickness varying from 0.4 mm at pupil margin to 0.25 mm in periphery. The pupil size is fixed at 3.35 mm and features an undulated edge that replicates the pupillary frill of a natural iris (Figure 1). Subspeciality - Anterior Segment and Cataract

DOS Times - Volume 28, Number 4, July-August 2022 www.dosonline.org/dos-times 10 CUSTOMFLEX® ARTIFICIALIRIS- HumanOptics AG Model Description CUSTOMFLEX® ARTIFICIALIRIS Fiber Free CUSTOMFLEX® ARTIFICIALIRIS Fiber Application Developed for cases without suture fixation. Suture fixation possible with appropriate technique. For aniridia cases where suturing is indicated. Material Pigmented silicone elastomer without polymer fiber meshwork Pigmented silicone elastomer with polymer fiber meshwork Diameter Total diameter: 12.8 mm Pupil diameter: 3.35 mm Total diameter: 12.8 mm Pupil diameter: 3.35 mm Specifics The design is based on the labelled photo printout (hard copy) serving as color target for the individual production and resembling the natural iris. The diameter of the implant can be individually trephined. The design is based on the labelled photo printout (hard copy) serving as color target for the individual production and resembling the natural iris. The diameter of the implant can be individually trephined. Table 1: Comparison between the two types of artificial iris devices available. Surgical Tips The aim is to make the implant fit snugly in the sulcus to keep it stable during saccadic eye movements and to block all incoming light from coming around its periphery. The implant is cut to adequate size (if horizontal white to white diameter is less than 11.8mm) using a trephine. Using a sclerocorneal approach, the implant is folded, and inserted into the ciliary sulcus through a mere 3.0 mm incision and IOL injector systems. Additional procedures such as penetrating keratoplasty (PK), cataract extraction, iridoplasty, glaucoma tube shunt revision, IOL removal or implantation, and anterior vitrectomy can be performed as needed.[4] The prosthesis can also be placed Indications The CUSTOMFLEX® ARTIFICIALIRIS represents an ideal treatment option for patients with complete and partial aniridia (both congenital as well as acquired). Aniridia not only reduces optical quality due to photophobia, aberration errors, glare, and the loss of depth of field, but it also has a negative effect on the appearance and thus on the quality of life of the patient. The foldable iris implant provides both medical and aesthetic rehabilitation in such patients. Contraindications[3] 1. Uncontrolled or severe chronic inflammation (uveitis). 2. Abnormally small eye size (microphthalmos). 3. Untreated retinal detachment. 4. Untreated chronic glaucoma. 5. Cataract caused by rubella virus. 6. Abnormal blood vessels on the iris (rubeosis) through the open sky during penetrating keratoplasty. It can be implanted into ciliary sulcus and suture-fixated to sclera or even a small portion can be sutured to the remaining iris tissue in cases with iris defects (refer to Figure 3). It can also be implanted into the capsular bag with the help of capsular tension rings.[5] Anterior chamber implantation is strongly discouraged. A report by Mayer et al., also described very good clinical outcome with monofocal IOL sutured to custom made artificial iris implant in a patient of aniridia undergoing cataract surgery.[6] Authors showed that suturing of the IOL to the AI can be performed in a reliable and reproducible manner without deteriorating optical quality.[6] Figure 3: Rehabilitation with CUSTOMFLEX® ARTIFICIALIRIS. (Pictures courtesy of Kevin M. Miller, MD, Jules Stein Institute, University of California, Los Angeles, USA) Subspeciality - Anterior Segment and Cataract

www.dosonline.org/dos-times DOS Times - Volume 28, Number 4, July-August 2022 11 7. Intraocular infections. 8. It is also contraindicated for patients who are pregnant. Advantages[2] 1. Biocompatible silicon polymer. 2. CE accredited and USFDA approved. 3. Customizable 4. Foldable, Can be placed through small incisions. 5. Can be combined with cataract and other surgical procedures. 6. Two models available- Fiber and Fiber Free. Fiber core suitable for suturing. 7. Excellent therapeutic as well as esthetic rehabilitation. Disadvantages 1. Not suitable for phakic eyes. 2. Not advised to be placed in anterior chamber. 3. Lack of proper sizing recommendations. 4. Availability – takes 6-8 weeks for customization. 5. Cost issues - less popular in third world countries. 6. Risk of elevated IOP and Endothelial Cell Loss. 7. Subjective difficulty in Retina evaluation due to fixed pupillary aperture size. 8. Not safe for patients undergoing MRI> Complications As iris defects can be of various etiologies, including traumatic, post- uveitis or congenital, the patient collective is heterogenous. That being the case, the risk for complications varies among patients, depending on their associated comorbidities. There are reports of complications associated with artificial iris implantation, including CDVA decrease, hemorrhage of the remnant iris, elevated intraocular pressure (IOP), AI dislocation or decentration, corneal decompensation, retinal detachment and macular oedema.[7–9] Patients with pre-existing glaucoma have a higher risk of IOP elevation after AI implantation. In patients with a low endothelial cell density, the risk of corneal decompensation is increased and can lead to further surgical interventions. In patients with residual iris tissue, a darkening of the remaining iris observed.[7] The cause for this is unknown, but it can lead to a color mismatch between the AI and the natural iris tissue. Another complication associated with remaining iris tissue is the residual iris retraction syndrome (RITS).[10–12] In Patients with RITS, the original pupillary aperture gradually enlarges. The underlying mechanism is still unknown, but it has been reported that RITS can lead to severe complications like angle closure glaucoma and chronic inflammation.[10–12] Discussion In patients with severe photic symptoms associated with aniridia, artificial iris devices not just provide visual rehabilitation but additionally impact the psyche of the patient in a positive manner, imparting renewed confidence. The CustomFlex Artificial Iris was a poignant step in this direction. It was never intended to be used for cosmetic purposes alone. The CustomFlex Artificial Iris was approved through a premarket approval application (PMA), which is the most stringent type of device marketing application and generally required for high-risk devices.[3] CustomFlex Artificial Iris was also granted Breakthrough Device designation, meaning the FDA provided intensive interaction and guidance to the company on efficient device development, to expedite evidence generation and the agency’s review.[3] The safety and effectiveness of the CustomFlex Artificial Iris was demonstrated primarily in a non-randomized clinical trial of 389 adult and pediatric patients with aniridia or other iris defects. The study measured patients’ self-reported decrease in severe sensitivity to light and glare post-procedure, health-related quality of life, and satisfaction with the cosmetic improvement or appearance of the prosthesis. More than 70 percent of patients reported significant decreases in light sensitivity and glare as well as an improvement in health-related quality of life following the procedure. In addition, 94 percent of patients were satisfied with the artificial iris’ appearance.[13] Literature search has also concluded upon the safety and efficacy of this device in patients of partial or complete aniridia. Forlini et al. reported a case of bilateral traumatic aniridia who underwent simultaneous implantation of the CUSTOMFLEX ArtificialIris in both eyes with a good functional and aesthetic outcome.[12] Fernandez-Lopez et al. reported a case of a 15-yearold girl with congenital bilateral partial aniridia, cataracts, and intense photophobia, successfully treated with the same implant and even touted the device as a promising device for treating photophobia in cases of congenital aniridia.[14] More recently, Mayer et al reported good outcomes in a series of 3 patients with bilateral iris defects who underwent ArtificialIris implantation.[15] Unlike cosmetic iris implants, these are sulcus or bag-fixated devices and not reported to cause uveitis. The risk of IOP increase and corneal decompensation is higher in those with pre-existing glaucoma and poor endothelial cell density, just like any other intraocular surgery. The importance of careful pre op assessments should not be underestimated when dealing with combinations of comorbidities in such patients with iris defects. Conclusion Until now, iris reconstruction was a challenging surgical procedure requiring large sclerocorneal incisions and often resulting in poor cosmetic outcomes. With the advent of HumanOptics AG CustomFlex™ Artificial Iris device, anterior segment disfigurement correction is possible through small self-sealing incisions, enabling fast visual recovery and excellent cosmetic outcomes. The device may be used for complete or partial iris reconstruction considering all the indications and contraindications to its use. The artificial iris prosthesis sets a new standard in the reconstruction of complex anterior segment pathologies with partial or complete aniridia. Patients benefit Subspeciality - Anterior Segment and Cataract

DOS Times - Volume 28, Number 4, July-August 2022 www.dosonline.org/dos-times 12 from improved visual function, reduced glare, and a satisfactory cosmetic appearance. The latter is important and legitimate, considering that trauma patients are mostly young and invariably desire for a cosmetically acceptable outcome. References 1. Koch KR, Heindl LM, Cursiefen C, Koch HR. Artificial iris devices: Benefits, limitations, and management of complications. Journal of Cataract & Refractive Surgery 2014;40(3):376–82. 2. The ARTIFICIALIRIS for your patients with aniridia | HumanOptics AG [Internet]. 2018 [cited 2022 Sep 20];Available from: https://www. humanoptics.com/en/physicians/artificialiris/ 3. Commissioner O of the. FDA approves first artificial iris [Internet]. FDA2020 [cited 2022 Sep 20];Available from: https://www.fda.gov/ news-events/press-announcements/fda-approves-first-artificial-iris 4. Bonnet C, Miller KM. Safety and efficacy of custom foldable silicone artificial iris implantation: prospective compassionate-use case series. Journal of Cataract & Refractive Surgery 2020;46(6):893–901. 5. Snyder ME, Osterholzer E. Capsular tension segments in repositioning capsular bag complex containing an intraocular lens and iris prosthesis. Journal of Cataract & Refractive Surgery 2012;38(3):551–2. 6. Mayer C, Son HS, Łabuz G, Yildirim TM, Auffarth GU, Khoramnia R. In vitro optical quality assessment of a monofocal IOL sutured to an artificial iris. Journal of Cataract & Refractive Surgery 2020;46(8):1184–8. 7. Rickmann A, Szurman P, Januschowski K, Waizel M, Spitzer MS, Boden KT, et al. Long-term results after artificial iris implantation in patients with aniridia. Graefes Arch Clin Exp Ophthalmol 2016;254(7):1419–24. 8. Spitzer MS, Nessmann A, Wagner J, Yoeruek E, Bartz-Schmidt KU, Szurman P, et al. Customized humanoptics silicone iris prosthesis in eyes with posttraumatic iris loss: outcomes and complications. Acta Ophthalmol 2016;94(3):301–6. 9. Mayer CS, Laubichler AE, Khoramnia R, Tandogan T, Prahs P, Zapp D, et al. Challenges and Complication Management in Novel Artificial Iris Implantation. J Ophthalmol 2018;2018:3262068. 10. Mayer CS, Laubichler AE, Masyk M, Prahs P, Zapp D, Khoramnia R. Residual Iris Retraction Syndrome After Artificial Iris Implantation. Am J Ophthalmol 2019;199:159–66. 11. Mayer C, Tandogan T, Hoffmann AE, Khoramnia R. Artificial iris implantation in various iris defects and lens conditions. J Cataract Refract Surg 2017;43(6):724–31. 12. Forlini M, Date P, Gruber B, Forlini C. Bilateral simultaneous artificial iris implantation for post-traumatic aniridia: a case report. Can J Ophthalmol 2018;53(1):e24–7. 13. Clinical Research Consultants, Inc. Safety and Effectiveness of the CustomFlex Artificial Iris Prosthesis for the Treatment of Iris Defects [Internet]. clinicaltrials.gov; 2018 [cited 2022 Sep 18]. Available from: https://clinicaltrials.gov/ct2/show/NCT01860612 14. Fernández-López E, Pascual FP, Pérez-López M, Quevedo AM, Martínez CP. Sutureless artificial iris after phacoemulsification in congenital aniridia. Optom Vis Sci 2015;92(4 Suppl 1):S36-39. 15. Mayer CS, Baur ID, Storr J, Khoramnia R. Bilateral Artificial Iris implantation in patients with bilateral iris defects. Am J Ophthalmol Case Rep 2021;22:101108. Dr. Tulika Chauhan, MBBS, MS, FICO Centre For Sight Eye Institute, New Delhi. Corresponding Author: Subspeciality - Anterior Segment and Cataract

www.dosonline.org/dos-times DOS Times - Volume 28, Number 4, July-August 2022 13 10 Tips for Managing a Case of Postoperative Endophthalmitis Lalit Verma, MD, Yusra Asad, MS, Anuja Patil, MD, Avnindra Gupta, MS Centre for Sight, New Delhi. Suspect Any unusual post-operative reaction (out of proportion to surgical trauma) should be suspected for Endophthalmitis. Differentiate from TASS All unusual post-operative reactions may not be infective; Pointers towards Toxic Anterior Segment Syndrome could include: Early onset of Limbus to limbus corneal edema with good fundus glow and no exudates in vitreous cavity. Presence of Lid edema, chemosis, marked reduction in vision, vitreous exudates and low intraocular pressure should alert one for Infective Endophthalmitis. Talk Most difficult part is how to tell the patient about this. This is very sensitive issue because in Today`s time.. no patient is willing to take any negative news (Thanks to Trivilisation of eye surgery/googlisation etc etc) and there is always a potential for medicolegal issue cropping up. Talking requires some degree of compassion. It is advisable to take a picture of anterior segment & fundus, even if hazy. Take patient & relatives to a separate room– Explain to all.. what the picture looks like & how should the normal be. Discuss with patient & all relatives that any cut/any surgery has potential to have infection, despite best precautions. This can happen in best of set ups, anywhere in the world. Talk & Talk Also explain that all is not lost & it is possible to have recovery in most of these patients. This can have a calming effect on patient, who was expecting to join back his work, with full vision. Tell him & family that you will make best possible efforts to help him recover and you won`t be charging additional fee for your services. Peer Review If you are a VR surgeon, shouldn’t be much of a challenge, although it may be better if a senior surgeon in your setup, if any, also sees the patient & is kept in the loop–this will assure the patient & more importantly his relatives that the best possible is being done for the patient. If you are an Anterior segment surgeon, you can have an opinion from a VR colleague within your set up. If however VR help is not there in your setup.. best is, if you are confident (which all ophthalmologist should be) to give an intravitreal antibiotic injection & seek an urgent VR opinion. Prompt Intravitreal Injection If diagnosis of Endophthalmitis is confirmed/there is high index of suspicion, prompt intravitreal Antibiotic Injection should be given without delay (even if it is a holiday). It is always better to give 2 antiobiotics, one for Gram positive organisms & other for Gram Negative organisms. Usual recommendation is Vancomycin + Ceftezidime; If suspicion for Gram Negative is high: Can give Vanco + Amikacin (taking care of dilution errrors); For a very severe Endoph, Can give Tazobactum & Piperacillin. If clinical picture/KOH smear suggests Fungal Endophthalmitis, could add Voriconazole in the intravitreal injection. Regular/Daily Review If the clinical diagnosis is TASS and patient has been put on intensive steroids, cycloplegics etc.. it is imperitive to review the patient in the evening.. if improvement–can continue medical treatment & review next day, then daily. If intravitreal antibiotics have been given, then you can see next day for signs of improvement/stabilization. Culture Report Once it has been decided to give intravitreal antibiotics/take up the patient for Vitrectomy, it is desirable to take samples Subspeciality - Retina

DOS Times - Volume 28, Number 4, July-August 2022 www.dosonline.org/dos-times 14 for culture & sensitivity. Best yield is with vitreous biopsy. Alternatively aqueous paracentesis can be done. Inoculation of samples should be done in the operation theatre itself. Early Vitrectomy If patient doesn`t respond at all to intravitreal antibiotics in 24- 48 hours or if endophthalmitis is very severe with PL vision, pars plana vitrectomy should be done. Other indications of Vitrectomy could include: Retained Intraocular Foreign body, Recurrent Endophthalmitis, Retinal detachment on Ultrasound. Referral to Higher Centre If patient is not responding adequately your treatment/If surgeon is not confident of doing a Vitrectomy (whenever needed)/ if facilities for Vitrectomy are not available, patient should be reffered to a higher centre urgently. Document & Document Whatever are the findings, please write them in the case sheet, preferably with a drawing and phtographs. Also very important is to write down your plan of action & the discussion you had with the patient & relatives. The details of every treatment given, smears made, cultures sent should all be recorded with date & time. Remember it is this documentation which is going to help you in court of law (if litigation issues arise). Also remember, what matters in court of law is that you have tried your best & Dr. Lalit Verma, M.D Director - Retina Services, Centre for Sight, New Delhi. Corresponding Author: given the best possible treatment and not the result. If there is an issue of Cluster Infecions, review all the the patients operated on same day(s), review all sterility factors for any breach in protocol & Inform health authorities & AIOS, apart from treating/ referring all patients. Subspeciality - Retina

www.dosonline.org/dos-times DOS Times - Volume 28, Number 4, July-August 2022 15 Identifying External Limiting Membrane (ELM) and Ellipsoid Zone (EZ) on SD-OCT Anupriya, MS, Sandeep Saxena, MS, Ph.D., FRCSEd, FRCS, FRCO, FACS, FAICO Department of Ophthalmology, King George’s Medical University, Lucknow, UP. Abstract: Spectral Domain Optical Coherence Tomography (SD-OCT) has emerged as a vital tool for in-vivo retinal imaging providing layer-by-layer detailed analysis of the retina. External limiting membrane (ELM) and photoreceptor ellipsoid zone (EZ) have a very crucial role to play in different retinal disorders and their integrity is essential for maintaining the visual function of the eye. In this article, we have described the features helping in identifying these outer layers of the retina as well as the effect on ELM and EZ in retinal pathologies like diabetic macular edema, age-related macular degeneration, and degenerative disorders. Introduction Over the years, retinal imaging has enhanced immensely aiding in the diagnosis of various retinal diseases. Out of all, Optical coherent tomography (OCT) which uses low-coherence interferometry to determine the echo time delay and magnitude of backscattered light reflected off an object of interest has emerged at the forefront. OCT which is non-invasive imaging provides high resolution and 3-dimensional data acquisition along with delineation of the retinal anatomy. SD-OCT is the most widely used OCT technology. It uses 820 to 880nm probing light with a scan rate of 52,000 Hz or greater providing excellent imaging of all the layers of retina.[1] Human retina comprises of ten layers. On OCT cross-sectional imaging they are broadly classified into inner retinal layers and outer retinal layers. SD-OCT resolves mainly three bands in the outer retina as hyperreflective bands which are of great importance as they are responsible for retinal functions and correlate with visual acuity. The external limiting membrane (ELM) and ellipsoid zone (EZ) can be observed intricately by SD-OCT. External Limiting Membrane (ELM): The innermost hyperreflective band is the ELM. It is a linear confluence of junctional complexes between Muller cells and photoreceptors. This band typically is thinner and much fainter than the others. The ELM separates the layers of rods and cones from the overlying outer nuclear layer and is a linear confluence of junctional complexes between muller cells and photoreceptors. It serves as a barrier against macromolecules.[2] Ellipsoid Zone (EZ): The second hyperreflective band is the ellipsoid zone, which represents the boundary between the inner and outer segments of the photoreceptors, aligned with the ellipsoid portion of the inner segments. The photoreceptors include an outer segment that absorbs light and converts it into electrical signals and an inner segment that has the metabolic functions of generating energy and proteins.[3] The origin of the EZ and ELM has been found to be associated with the biological activities of the photoreceptor cells. The ELM and EZ integrity is indispensable for the maintenance of vision.[4] (Figure 1) Figure 1: SD-OCT macula depicting External Limiting Membrane (ELM) (white arrow) and Ellipsoid Zone (EZ) (white arrowhead) in normal individuals. Subspeciality - Retina

DOS Times - Volume 28, Number 4, July-August 2022 www.dosonline.org/dos-times 16 Figure 2: SD-OCT macula depicting disruption of external limiting membrane (ELM) and ellipsoid zone (EZ) in patient with DME. Figure 3: SD-OCT macula depicting disruption of external limiting membrane (ELM) and ellipsoid zone (EZ) in patient with AMD. Status of ELM EZ in Diabetic Macular EDEMA In diabetic retinopathy alterations in the blood-retinal barrier causes seepage of fluid into extracellular space, especially in the macular area, and affect the visual acuity severely. initiation of the breach in the blood-retinal barrier has been found to be contributed by increased VEGF levels.[5] DME causes disruption of ELM and EZ, which was described by Jain et al. Increased Anti-VEGFs are the mainstay of the treatment of DME. De et al discovered the mechanism of ELM and EZ restoration after anti-VEGF therapy in DME. Anti-VEGF therapy led to the restoration of the barrier effect of ELM. The ELM was found to restore first followed by EZ restoration. Restoration of ELM and EZ led to improvement in visual acuity.[7] Status of ELM And EZ in Age-Related Macular Degeneration Age-related macular degeneration (AMD) is a condition that is VEGF levels are directly proportional to ELM EZ disruption. (Figure 2) Disruption of ELM and EZ was graded as follows: grade 0–no disruption of ELM and EZ; grade 1–ELM disrupted, EZ intact; grade 2–both ELM and EZ disrupted. This disruption scale correlated with logMAR visual acuity.[6] characterized by abnormal choroidal neovascularization (CNV). This CNV causes hemorrhage and exudation, either of which can lead to photoreceptor cell death. Disruption of the ELM and EZ is seen and intraretinal cystic spaces are often observed. Anti-VEGFs are the first choice of treatment. They have helped in the restoration of ELM-EZ which helped in the enhancement of visual acuity.[8] (Figure 3) Subspeciality - Retina

www.dosonline.org/dos-times DOS Times - Volume 28, Number 4, July-August 2022 17 Dr. Anupriya, MS Department of Ophthalmology, King George’s Medical University, Lucknow, UP. Corresponding Author: Status of ELM AND EZ in Degenerative Disorders OCT of retinal degenerative diseases over time has demonstrated that ELM, EZ lengths are highly correlated with each other and disorganization seems to occur in a stepwise order: first at the EZ followed by the ELM. The hypothesis is that the photoreceptor outer segment layer is the first one to be affected in degenerative conditions, followed by damage of photoreceptor cell bodies occurring later in the process.[9,10] Conclusion SD-OCT has revolutionized the retinal imaging enabling us to provide better visualization of retinal layers in various retinal pathologies. Integrity of ELM and EZ is important for visual acuity. Understanding among the physicians regarding integral retinal layers is important for better patient management. References 1. Barteselli G, Bartsch DU, Weinreb R et al. Real-time full-depth visualisation of Posterior ocular structures: Comparison Between Full-Depth Imaging Spectral Domain Optical Coherence Tomography and Swept-Source Optical Coherence Tomography. Retina. 2016 Jun;36(6):1153-61. 2. Drexler W, Sattmann H, Hermann B, et al. Enhanced visualization of macular pathology with the use of ultrahigh-resolution optical coherence tomography. Arch Ophthalmol. 2003;121:695–706. 3. Srinivasan VJ, Ko TH, Wojtkowski M, et al. Noninvasive volumetric imaging and morphometry of the rodent retina with high-speed, ultrahigh-resolution optical coherence tomography. Invest Ophthalmol Vis Sci. 2006;47:5522–5528. 4. Saxena S, Ruia S, Prasad S, et al. Increased serum levels of urea and creatinine are surrogate markers for disruption of retinal photoreceptor external limiting membrane and inner segment ellipsoid zone in type 2 diabetes mellitus. Retina 2017; 37: 344–349 5. Meleth AD, Agrón E, Chan CC, et al. Serum inflammatory markers in diabetic retinopathy. Invest Ophthalmol Vis Sci 2005; 46: 4295– 4301. 6. Jain A, Saxena S, Khanna VK, et al. Status of serum VEGF and ICAM-1 and its association with external limiting membrane and inner segment-outer segment junction disruption in type 2 diabetes mellitus. Mol Vis 2013; 19: 1760–1768 7. De S, Saxena S, Kaur A, et al. Sequential restoration of external limiting membrane and ellipsoid zone after intravitreal anti-VEGF therapy in diabetic macular oedema. Eye (Lond) 2021; 35: 1490–1495. 8. Kwon Y, Lee D, Kim H, Kwon O. Predictive findings of visual outcome in spectral domain optical coherence tomography after ranibizumab treatment in age-related macular degeneration. Korean J Ophthalmol 2014;28(5):386-92. 9. Hagiwara A, Mitamura Y, Kumagai K, et al. Photoreceptor impairment on optical coherence tomographic images in patients with retinitis pigmentosa. Br J Ophthalmol 2013;97(2):237-8. 10. Aizawa S, Mitamura Y, Hagiwara A, et al. Changes of fundus autofluorescence, photoreceptor inner and outer segment junction line, and visual function in patients with retinitis pigmentosa. Clin Experiment Ophthalmol 2010;38(6):597-604. Subspeciality - Retina

DOS Times - Volume 28, Number 4, July-August 2022 www.dosonline.org/dos-times 18 Newer Anti-VEGFs Jatinder Singh Bhalla[1], MS, DNB, MNAMS, Neha Yadav[2], MBBS, Ridhima Sakhuja[3], MBBS, MS, DNB, FPOS Yogesh Kumar[4], MBBS, Ashish Kumar Sain[5], MBBS, DO Department of Ophthalmology, DDU Hospital, Hari Nagar, New Delhi. Introduction Ocular angiogenesis is a cause of severe worldwide visual loss and ocular morbidity. However, the development of anti vascular endothelial growth factor (Anti-VEGF) has revolutionised the treatment of a plethora of ocular angiogenic disease processes. History IN 1948 Michaelson proposed a factor responsible for iris and retinal neovascularisation seen in ischaemic retinopathies and named it “factor X”. Endothelial mitogen was isolated from pituitary follicular cells and was termed as vascular endothelial growth factor (VEGF) by Leung et al in 1989. At the same time, a tumour-derived factor named vascular permeability factor (VPF) was discovered by Keck et al., which was responsible for inducing vascular permeability.[1] In a further study, retinal ischaemic was induced by laser photocoagulation of the vessels. Neovascularisation of the iris was seen because of presence of VEGF mRNA.[2] There were elevated levels of VEGF in ocular fluids from patients with active neovascular ocular disease when compared with ocular fluids with no vascularisation.[3] Aiello  et al. in 1994 found a direct correlation between intraocular VEGF concentrations and active proliferative retinopathy in patients with diabetes and ischemic central retinal vein occlusion.[4] Adamis  et al. also reported that concentrations of VEGF was increased in the vitreous of patients with diabetic retinopathy.[5] Phase 1 trials was initiated by Genetech for the development of an Anti-VEGF molecule named Avastin (bevacizumab) in 1997. Bevacizumab got FDA approval in February 2004 for the treatment of colon cancer in combination with chemotherapy.[6] FDA approved pegaptanib (Macugen) was developed for treatment of Age related Macular Degeneration, which makes it the first antiangiogenic therapy for ocular neovascularisation.[7] Genetech generated Ranibizumab (Lucentis) which was proven effective by two phase 3 pivotal trials: the MARINA (minimally classic/occult trial of the anti-VEGF antibody ranibizumab in the treatment of neovascular AMD) and ANCHOR (AntiVEGF antibody for the treatment of predominantly classic choroidal neovascularisation in AMD) trials. These trials proved ranibizumab to be effective in improving visual outcomes for all forms of choroidal neovascularisation and was given FDA approval in 2006.[8,9] To improve the pharmacokinetics of VEGF binding with reduced frequency of dosing, Aflibercept was developed. Aflibercept was approved by the FDA in November 2011 based on the VIEW study.[10] EGF Family Type Function VEGF-A • Angiogenesis • ↑ Migration of endothelial cells • ↑ Mitosis of endothelial cells • ↑ Matrix metalloproteinase activity • ↑ αvβ3 activity • ↑ Migration and proliferation of Astrocytes • Creation of blood vessel lumen • Creates fenestrations • Chemotactic for macrophages and granulocytes • Vasodilation (indirectly by NO release) VEGF-B Embryonic angiogenesis (myocardial tissue, to be specific) VEGF-C Lymphangiogenesis VEGF-D Needed for the development of lymphatic vasculature surrounding lung bronchioles PlGF Important for Vasculogenesis, also needed for angiogenesis during ischemia, inflammation, wound healing, and cancer. Subspeciality - Retina

www.dosonline.org/dos-times DOS Times - Volume 28, Number 4, July-August 2022 19 Indications of ANTI-VEGF Use[19] 1. Wet Age-Related Macular Degeneration 2. Diabetic Macular Edema 3. Proliferative Diabetic Retinopathy 4. Retinal Vein Occlusion (RVO) 5. Myopic Choroidal Neovascularisation (MCNV) 6. Retinopathy Of Prematurity (ROP) 7. Neovascular Glaucoma (NVG) 8. Central Serous Retinopathy (CSR) 9. Ocular Tumors 10. Corneal Neovascularization In Use ANTIVEGF Agents Sr. No. ANTI-VEGF Dose Mechanism of Action Structure 1. PEGAPTANIB SODIUM 0.3 mg, 6 weekly injections Binds to VEGF-165 of VEGF-A family Aptamer 2. BEVACIZUMAB 1.25 mg in 0.05 ml Bind to all forms of VEGF-A Humanized, monoclonal antibody 3. RANIBIZUMAB 0.5 mg in 0.05 ml Bind to all forms of VEGF-A Humanized, monoclonal antibody fragment 4. AFLIBERCEPT 2 mg in 0.5 ml Binds to VEGF-A, VEGF- B and PGF Recombinant fusion protein Next-Generation Therapeutics Conbercept Conbercept is a homodimeric protein which is genetically engineered and used for the treatment of wet AMD. It inhibits the activity of all VEGF isoforms and PlGF.[20,21] Conbercept (also named KH902;23,24 Chengdu Kanghong Biotech Co., Ltd., Sichuan, China) is a recombinant VEGF-receptor protein which is composed of the second Ig domain of VEGFR-1, and the third and fourth Ig domains of VEGFR-2, and the constant region (Fc) of the human IgG1. PANDA-1 and PANDA-2 are the phase III trials which compared 0.5 mg conbercept, 1 mg conbercept, and 2 mg aflibercept. The primary aim of the study was to study mean change in BVCA at the end of 36 weeks with conbercept given every 12 weeks compared to aflibercept given every 8 weeks.[22] However the study could not meet its primary aim. A study done by Cui and Lu[23] compared conbercept with ranibizumab, traditional transpupillary thermotherapy (TTT), bevacizumab and triamcinolone for AMD treatment. Best corrected visual acuity (BCVA) and central retinal thickness were measured. It was concluded that conbercept shows more effects on the long-term BCVA improvement in AMD patients than triamcinolone (after 3 months) and TTT (after 6 months). Although the therapeutic effect of conbercept is similar to that of ranibizumab. Conbercept also reduces the concentration of serum VEGF during the period of treatment (1 month). A Phase 3 PHOENIX study by Liu  et al.[24] with 0.5 mg of conbercept once monthly for the first 3 months, then once quarterly until 12th  month in the conbercept group and 3 monthly sham injections followed by 0.5 mg of conbercept quarterly in the sham group was done. At 3 months, BCVA improved in the conbercept group in comparison to sham group. It was concluded that 3 monthly dose of conbercept followed by quarterly dosage is highly effective in AMD. Brolucizumab Brolucizumab (RTH258, also previously known as ESBA1008) is a humanized single chain antibody fragment that inhibits all isoforms of VEGF-A. It is the smallest Anti-VEGF with a molecular weight of only 26 kDa. Thus a much higher molar dose in the same volume can be delivered. The small size leads to fast systemic clearance, a 4-fold lower systemic exposure, and better tissue penetration.[22,23] Because of its high stability and solubility, it is possible to concentrate up to 120 mg/ml, allowing the administration of 6 mg in a single 50-ml intravitreal injection.[25,26] HAWK and HARRIER[27,28] study are 2-years, randomized studies. AIM- Compared the efficacy and safety of brolucizumab versus aflibercept in neovascular AMD. DOSING- HAWK : Two doses of brolucizumab (3 mg and 6 mg) versus aflibercept 2 mg, HARRIER : Brolucizumab 6 mg to aflibercept 2 mg. PRIMARY ENDPOINT: Mean BCVA change at week 48. Subspeciality - Retina

DOS Times - Volume 28, Number 4, July-August 2022 www.dosonline.org/dos-times 20 SECONDARY ENDPOINTS: Average change in BCVA from baseline for 36–48 weeks, change in BCVA and Central Sub Field Thickness (CSFT) from baseline at each postbaseline visit, Sub retinal fluid and Intra retinal fluid (SRF and IRF) at each postbaseline visit, and disease activity status at week 16. Results- In both HAWK and HARRIER, brolucizumab demonstrated noninferiority with respect to its primary endpoint (BCVA at week 48). In HAWK, with respect to the secondary endpoint of change in BCVA over 36–48 weeks, broluicizumab was also found to be noninferior. Also, fewer brolucizumab 6 milligrams-treated eyes had decreased disease activity versus aflibercept (24% versus 34.5%, P = 0.0001) at week 16. In HARRIER, fewer brolucizumab 6 mg-treated eyes had decreased disease activity than aflibercept (22.7% versus 32.2%, P = 0.002) at week 16. BCVA gains achieved in both HAWK and HARRIER study were maintained through 2 years. Thus, it can be concluded that brolucizumab appears to offer the potential for less frequent intravitreal injections in eyes treated for neovascular AMD without sacrificing efficacy. Abicipar Pegol It is a ankyrin repeat protein (mono-DARPin). It inhibit all isoforms of VEGF-A Half life- 13 days (ranibizumab’s half-life of approximately 3 days.) The phase III SEQUOIA and CEDAR studies- Patients with neovascular AMD divided in three groups: • Three monthly abicipar 2 mg injections followed by an injection every 8 weeks • Two monthly abicipar 2 mg injections followed by an injection after 8 weeks and every 12 weeks thereafter. • Monthly ranibizumab injections. Overall abicipar demonstrated noninferiority compared with ranibizumab, with less frequent injections in terms of improving VA. The MAPLE study- Modified formulation of 2 mg abicipar was used in this study. 123 neovascular AMD patients were randomized to treatment by the abicipar 2 mg or sham. Modification of abicipar decreased the rate of inflammation to 8.9%. The REACH study[29]- It was a phase II multicenter RCT which compared abicipar 1 mg, abicipar 2 mg, and ranibizumab in patients with newly diagnosed neovascular AMD. BCVA and CRT improvements were similar in abicipar groups when compared with ranibizumab. The BAMBOO and CYPRESS studies[30]- 25 patients were included in each study which were divided into the same three treatments arms and injection schedules as in REACH between Japanese and non-Japanese patients. The results with both dosages of abicipar were comparable between studies, indicating that its efficacy is similar in Japanese and non-Japanese patients. Faricimab (Vabysmo, Genentech) It is a bispecific antibody for intravitreal administration which targets two factors: VEGF and angiopoietin-2 (Ang-2)[31] Phase I Clinical Trial- 24 patients of neovascular age-related macular degeneration (nAMD) refractory to 3 or more AntiVEGF injections in the past 6 months were included in this study. There was an overall favorable safety profile with evidence of BCVA and anatomical improvement.[32,33] The AVENUE Trial- A phase 2 with 273-patient study, compared ranibizumab 0.5 mg every 4 weeks, faricimab 1.5 mg every 4 weeks, faricimab 6 mg every 4 weeks, faricimab 6 mg every 8 weeks, and faricimab 6 mg/ranibizumab 0.5 mg combination therapy (three ranibizumab injections every 4 weeks, followed by faricimab every 4 weeks) in newly diagnosed nAMD.[32,34] BOULEVARD Trials- A 36-week, randomized trial with 229 patients of DME. Newly diagnosed patients (168) were randomized into three groups1. 6.0 mg of faricimab, 2. 1.5 mg of faricimab, 3. 0.3 mg of ranibizumab. Previously treated patients (61) were randomized into1. 6.0 mg of faricimab 2. 0.3 mg of ranibizumab. Result- 6.0 mg faricimab was superior to 0.3 mg ranibizumab arm in terms of letter gains in VA, greater central subfoveal thickness (CST) reduction and diabetic retinopathy severity score improvement. It has also shown to have better durability in terms of less requirement of injections during the follow-up period. STAIRWAY Trial[35]- Evaluated two extended dosing regimens of faricimab in patients of nAMD. A total of 6.0 mg of faricimab was given in four weekly loading doses followed by two different dosing schedules of q16w and q12w dosing and compared to 0.5 mg of ranibizumab. Both Phase II trials of faricimab (STAIRWAY and BOULEVARD) have shown to be safe and effective option for treating DME and nAMD. RHINE and YOSEMITE Phase III trials will evaluate its effect for DME, whereas its effect on nAMD will be evaluated in TENAYA and LUCERNE trial. Phase III will evaluate the Antiinflammatory properties of the drug. Subspeciality - Retina

www.dosonline.org/dos-times DOS Times - Volume 28, Number 4, July-August 2022 21 KSI-301 KSI-301 (Kodiak Sciences, Palo Alto, CA) is a humanized AntiVEGF antibody (similar to ranibizumab) It is a phosphorylcholine-based polymer with ultra–high molecular weight, thus increasing its intraocular stability and drug durability.[36] It is by far the largest anti-VEGF drug. Its size and clinical dose (5 mg, or an equivalent dose of 3.5 M) creates an equivalent molar dose seven times that of ranibizumab.[37,38] Currently, DAZZLE STUDY a phase IIB/III study is investigating the efficacy and safety of repeated KSI-301 injections in 368 patients with nAMD given at 12-, 16-, or 20-week intervals following an initial three loading doses, while being compared to aflibercept at 8-week intervals following the three initial monthly loading doses.[39] OPT 302 OPT-302 (Opthea) targets VEGF-C and VEGF-D, which may play role in nAMD pathogenesis. A phase 1/2a study showed that in newly diagnosed patients, intra-vitreal injections of both OPT-302 2 mg and ranibizumab 0.5 mg administered every 4 weeks resulted in meaningful additional VA gain and reduction in macular thickness compared to ranibizumab alone at 12-week follow up. Phase 2B trials comparing ranibizumab monotherapy with OPT-302 2 mg/ranibizumab 0.5 mg, and OPT-302 0.5 mg/ ranibizumab 0.5 mg in 351 newly diagnosed patients over 6 months are awaiting results.[40] X-82 X-82 (Tyrogenex) is an oral anti-PDGF and VEGF-A inhibitor. The most common adverse effects seen are diarrhea, nausea, fatigue, and elevated transaminase enzymes that reversed with cessation of X-82. The Phase 2 APEX study tested X-82 at doses of 50 mg, 100 mg, and 200 mg compared to placebo and as- needed Anti-VEGF. Change in VA from baseline to 52 weeks was the primary outcome. Participants in the 200 mg arm gained a mean of 1.7 letters while those in the placebo arm lost a mean of 0.3 letters.[41] Ranibizumab Port-Delivery System The ranibizumab port-delivery system (PDS; Genentech) is a permanent, surgically implanted intraocular device which may be refilled.[42,43] It is currently approved for wet AMD and has ongoing clinical trials for DME and DR.[22]   It Contain a high- concentration ranibizumab formulation (up to 100 mg/ mL) which slowly diffuses into the vitreous, the ranibizumab PDS is designed to continuously release ranibizumab directly into the vitreous cavity at appropriate intervals and extend treatment duration.[44] In the phase II LADDER trial, visual and anatomic results were comparable between the ranibizumab PDS and traditional intravitreal injections.[43] The phase III trial ARCHWAY has shown noninferior with the use of the 100 mg/mL surgical implant compared to monthly ranibizumab injections.[44] The ARCHWAY trial is being continued in the ongoing PORTAL study. The most common concerning complication is rates of vitreous hemorrhage, for which modifications in the delivery technique are being done.[45] Gene Therapy Delivery There are many active gene therapy trials going on in the field of Anti-VEGF. RegenxBio has multiple gene therapy trials underway for wet macular degeneration. it is a modified adenoviral vector containing a genetic package that, through the process of transfection, enables retinal pigment epithelial cells to produce a modified ranibizumab- like molecule that then dramatically reduces the number of intravitreal injections a patient requires.[46,47] The company Adverum Biotechnologies is using a viral vector intravitreally for expression of aflibercept with positive Phase I results, now moving into Phase II.[48] References 1. Arroyo J. G. Towards a rational approach to combination therapy for neovascular age related macular degeneration. The British Journal of Ophthalmology. 2007;91(2):130–131. 2. Miller J. W., Adamis A. P., Shima D. T., et al. Vascular endothelial growth factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model. American Journal of Pathology. 1994;145(3):574–584.  3. Aiello L. P., Avery R. L., Arrigg P. G., et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders.  The New England Journal of Medicine. 1994;331(22):1480–1487.  4. Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 1994;331:1480-7. 5. Adamis AP, Miller JW, Bernal MT, D'Amico DJ, Folkman J, Yeo TK, et al. Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy. Am J Ophthalmol 1994;118:445-50.  6. M. S. Gordon, K. Margolin, M. Talpaz et al., “Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer,” Journal of Clinical Oncology, vol. 19, no. 3, pp. 843–850, 2001. 7. E. S. Gragoudas, A. P. Adamis, E. T. Cunningham Jr., M. Feinsod, and D. R. Guyer, “Pegaptanib for neovascular age-related macular degeneration,” The New England Journal of Medicine, vol. 351, no. 27, pp. 2805–2816, 2004. 8. P. J. Rosenfeld, D. M. Brown, J. S. Heier et al., “Ranibizumab for neovascular age-related macular degeneration,” The New England Journal of Medicine, vol. 355, no. 14, pp. 1419–1431, 2006. 9. D. M. Brown, P. K. Kaiser, M. Michels et al., “Ranibizumab versus Subspeciality - Retina

DOS Times - Volume 28, Number 4, July-August 2022 www.dosonline.org/dos-times 22 verteporfin for neovascular age-related macular degeneration,”  The New England Journal of Medicine, vol. 355, no. 14, pp. 1432–1444, 2006. 10. M. W. Stewart, P. J. Rosenfeld, F. M. Penha et al., “Pharmacokinetic rationale for dosing every 2 weeks versus 4 weeks with intravitreal ranibizumab, bevacizumab, and aflibercept (vascular endothelial growth factor Trap- eye),” Retina, vol. 32, no. 3, pp. 434–457, 2012. 11. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med 2003;9:669-76. 12. Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 1983;219:983-5. 13. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 1989;246:1306-9. 14. Ferrara N, Henzel WJ. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun 1989;161:851-8. angiogenic mitogen. Science 1989;246:1306-9. 15. Olofsson B, Korpelainen E, Pepper MS, Mandriota SJ, Aase K, Kumar V, et al. Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells. Proc Natl Acad Sci U S A 1998;95:11709-14. 16. Bauer SM, Bauer RJ, Liu ZJ, Chen H, Goldstein L, Velazquez OC. Vascular endothelial growth factor-C promotes vasculogenesis, angiogenesis, and collagen constriction in threedimensional collagen gels. J Vasc Surg 2005;41:699-707. 17. Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M, et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 1996;380:435-9. 18. Ferrara N. Role of vascular endothelial growth factor in physiologic and pathologic angiogenesis: Therapeutic implications. Semin Oncol 2002;29:10-4. 19. Cornel S, Adriana ID, Mihaela TC, Speranta S, Algerino S, Mehdi B, Jalaladin HR. Anti-vascular endothelial growth factor indications in ocular disease. Rom J Ophthalmol. 2015 Oct-Dec;59(4):235-242. PMID: 29450313; PMCID: PMC5712945. 20. Li X, Xu G, Wang Y, Xu X, Liu X, Tang S, et al. Safety and efficacy of conbercept in neovascular age- related macular degeneration: Results from a 12-month randomized phase 2 study: AURORA study. Ophthalmology 2014;121:1740-7. 21. Zhang M, Zhang J, Yan M, Luo D, Zhu W, Kaiser PK, et al. A phase 1 study of KH902, a vascular endothelial growth factor receptor decoy, for exudative age-related macular degeneration. Ophthalmology 2011;118:672-8. 22. Efficacy and safety trial of conbercept intravitreal injection for neovascular age-related macular degeneration (PANDA-1) - full text view- ClinicalTrials.gov. Clinicaltrialsgov 2020; https://clinicaltrials. gov/ct2/show/NCT03577899. 23. Cui C, Lu H. Clinical observations on the use of new anti-VEGF drug, conbercept, in age-related macular degeneration therapy: A meta-analysis. Clin Interv Aging 2018;13:51-62. 24. Liu K, Song Y, Xu G, Ye J, Wu Z, Liu X, et al. Conbercept for treatment of neovascular age-related macular degeneration: results of the randomized phase 3 PHOENIX study. Am J Ophthalmol 2019;197:156- 67. 25. Tietz J, Spohn G, Schmid G, Konrad J, Jampen S, Maurer P,  et al. Affinity and potency of RTH258 (ESBA1008), a novel inhibitor of vascular endothelial growth factor a for the treatment of retinal disorders. Invest Ophthalmol Vis Sci 2015;56:1501. 26. Gaudreault J, Gunde T, Floyd HS, Ellis J, Tietz J, Binggeli D, et al. Preclinical pharmacology and safety of ESBA1008, a single-chain antibody fragment, investigated as potential treatment for age related macular degeneration. Invest Ophthalmol Vis Sci 2012;53:3025.   27. Dugel PU, Koh A, Ogura Y, Jaffe GJ, Schmidt-Erfurth U, Brown DM, et al. HAWK and HARRIER: phase 3, multicenter, randomized, double-masked trials of brolucizumab for neovascular age-related macular degeneration. Ophthalmology 2020;127:72-84. 28. Dugel P. Brolucizumab for neovascular AMD: The 2 year HAWK and HARRIER results. Presentation at the American Academy of Ophthalmology, Chicago, IL., October 27, 2018. 29. Callanan D, Kunimoto D, Maturi RK, Patel SS, Staurenghi G, Wolf S, et al. Double-masked, randomized, phase 2 evaluation of abicipar pegol (an Anti-VEGF DARPin therapeutic) in neovascular age-related macular degeneration. J Ocul Pharmacol Ther 2018;34:700-9. 30. Kunimoto D, Ohji M, Maturi RK, Sekiryu T, Wang Y, Pan G, et al. Evaluation of abicipar pegol (an Anti- VEGF DARPin therapeutic) in patients with neovascular age-related macular degeneration: studies in Japan and the United States. Ophthalmic Surg Lasers Imaging Retina 2019;50:e10-22. 31. Sharma A, Kumar N, Kuppermann BD, Bandello F, Loewenstein A. Faricimab: Expanding horizon beyond VEGF, Eye 2020;34:802-4. 32. Iwata D, von Leithner PL, Ng YS, Hartmann G, Shima DT. Anti-VEGF/Ang2 bi-specific antibody ameliorates endotoxin-induced uveitis in mice. Invest Ophthalmol Vis Sci 2014;55:2354. 33. Chakravarthy U, Bailey C, Brown D, Campochiaro P, Chittum M, Csaky K, et al. Phase I trial of anti-vascular endothelial growth factor/anti-angiopoietin 2 bispecific antibody RG7716 for neovascular age-related macular degeneration. Ophthalmol Retina 2017;1:474- 85. 34. Helzner J. Faricimab shows potential for 16-week dosing. Retina Physician 2018. Available from: https://www.retinalphysician.com/ issues/2018/september-2018/faricimab-shows-potential-for-16-weekdosing. 35. Khanani AM. Simultaneous inhibition of VEGF and Ang-2 with faricimab in neovascular AMD: STAIRWAY phase 2 results. Presented at the 2018 American Academy of Ophthalmology (AAO) Annual Meeting; 26 October, 2018; Chicago, United States. 36. Al-Khersan H, Hussain RM, Ciulla TA, Dugel PU. Innovative therapies for neovascular age-related macular degeneration. Expert Opin Pharmacother. 2019;20(15):1879–1891. 37. Nguyen QD, Das A, Do DV, et al. Brolucizumab: evolution through preclinical and clinical studies and the implications for the management of neovascular age-related macular degeneration. Ophthalmology. 2020;127(7):963–976. 38. Barakat MR. One-year and beyond: results of phase 1b study of KSI301, an antiVEGF antibody biopolymer conjugate with extended durability, in wAMD, DME, and RVO. Presented at: American Society of Retina Specialists Annual Meeting; July 26th, 2020; Seattle, WA. 39. Kodiak sciences completes enrollment of DAZZLE Phase 2b/3 pivotal study of KSI-301 in patients with wet age-related macular degeneration; 2020. Available from: https://www.prnewswire.com/ news-releases/kodiak-sciences-completes-enrollment-of-dazzle-phase Subspeciality - Retina

www.dosonline.org/dos-times DOS Times - Volume 28, Number 4, July-August 2022 23 -2b3-pivotal-study-of-ksi-301-in-patients-with-wet-age-relatedmacular-degeneration-301173275.html. Accessed September 6, 2021. 40. Al-Khersan H, Hussain RM, Ciulla TA, Dugel PU. Innovative therapies for neovascular age-related macular degeneration. Expert Opin Pharmacother 2019;20:1879-91. 41. Jackson TL, Boyer D, Brown DM, Chaudhry N, Elman M, Liang C, et al. Oral tyrosine kinase inhibitor for neovascular age-related macular degeneration: A Phase 1 dose-escalation study. JAMA Ophthalmol 2017;135:761-7. 42. Campochiaro PA, Brown DM, Awh CC, et al. Sustained benefits from ranibizumab for macular edema following central retinal vein occlusion: twelve-month outcomes of a phase III study. Ophthalmology. 2011;118(10):2041–2049. doi:10.1016/j.ophtha.2011.02.038. 43. Campochiaro PA, Marcus DM, Awh CC, et al. The port delivery system with ranibizumab for neovascular age-related macular degeneration: results from the randomized phase 2 ladder clinical trial. Ophthalmology. 2019;126(8):1141–1154. doi:10.1016/j.ophtha.2019. 03.036. 44. Chen ER, Kaiser PK. Therapeutic potential of the ranibizumab port delivery system in the treatment of AMD: evidence to date. Clin Ophthalmol. 2020;14:1349–1355. doi:10.2147/OPTH.S194234. 45. Genetech. Phase III data show port delivery system with ranibizumab enabled over 98% of patients to go six months between treatments for neovascular age-related macular degeneration; 2020. Available from: https://www.biospace.com/article/releases/phase-iii-data-show-portdelivery-system-with-ranibizumab-enabled-over- 98-percent-of- p tients-to-go-six-months-between-treatments-for-neovascular-agerelated-macular-degeneration/. Accessed September 6, 2021. 46. Loewenstein A, Laganovska G, Bressler NM, et al. Phase 1 clinical study of the port delivery system with ranibizumab for continuous treatment of neovascular age-related macular degeneration. Invest Ophthalmol Vis Sci. 2020;61(7):4201. 47. Holekamp NM, Campochiaro PA, Chang MA, et al. Archway Randomized Phase 3 Trial of the Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration. Ophthalmology. 2022;129(3):295-307. 48. RegenxBio announces additional positive long-term and interim Phase I/IIa trial update for RGX-314 for the treatment of wet AMD [news release]. Rockville, MD: RegenxBio; April 22, 2020. regenxbio. gcs-web.com/news-releases/news-release-details/regenxbio-announces-additional-positive-long-term-and-interim. Accessed December 29, 2021. 49. Koponen S, Kokki E, Kinnunen K, Ylä-Herttuala S. Viral-vector-delivered anti-angiogenic therapies to the eye. Pharmaceutics. 2021;13(2):219. Dr. Neha Yadav, MBBS DNB Resident, DDU Hospital, New Delhi. Corresponding Author: Subspeciality - Retina

DOS Times - Volume 28, Number 4, July-August 2022 www.dosonline.org/dos-times 24 A Case of Glaucoma Secondary to Idiopathic Elevated Episcleral Venous Pressure Rinal Pandit, MS Department of Glaucoma, Choithram Netralaya, Shriram Talawali, Dhar Road, Indore, MP. Abstract: Persistently elevated episcleral venous pressure (EVP) is a known cause of open-angle glaucoma as it can lead to obstruction of the aqueous drainage into the orbital venous system. Idiopathic elevated episcleral venous pressure (IEEVP) refers to a clinical entity defined as elevated EVP without an underlying cause. IEEVP is an uncommon cause of secondary open angle glaucoma and numerous causes leading to raised EVP need to be ruled out before establishing the diagnosis. We report a case of a middle aged female with advanced open angle glaucoma secondary to IEEVP and discuss the approach to management. Case Report A 53-year-old female presented with progressive and painless diminution of vision in right eye (RE) for 6 months. On evaluation, her best-corrected visual acuity (BCVA) in RE was 20/200 and in left eye (LE) was 20/20. Intraocular pressure (IOP) was 46 mmHg in RE and 12 mmHg in LE measured by Goldman applanation tonometry. Gonioscopy revealed open angles in both eyes with blood in Schlemm’s canal in RE. RE was noted to have dilated and tortuous episcleral vessels (Figure1), relative afferent pupillary defect, early nuclear sclerosis, and fundus examination revealed CDR of 0.9 (Figure 2). There was no proptosis or audible bruit; extraocular movements were full in all gazes. RE Humphrey visual field analysis 10-2 showed severely depressed field (Figure 3). LE examination was within normal limits. The systemic evaluation was unremarkable. Based on the clinical examination a provisional diagnosis of RE open angle glaucoma secondary to raised episcleral venous pressure (EVP) was made and the patient was advised Magnetic resonance imaging (MRI) of the brain and orbit and MR angiography of brain to determine the cause of raised EVP. We started topical Brimonidine 0.2%+ timolol maleate 0.5% twice a day and Bimatoprost 0.03 % at night in RE along with systemic acetazolamide 250 mg twice a day. At 2-week follow, IOP in RE was 34mmHg and the neuro-imaging reports did not reveal any abnormality. A final diagnosis of glaucoma secondary to idiopathic raised EVP in RE was made. Patient was advised Trabeculectomy in RE in view of failure to achieve target IOP with anti-glaucoma medications and advanced disease. She underwent trabeculectomy with prophylactic sclerostomies to minimize the chance of post-operative uveal effusion. Post-operatively, the anterior chamber was well formed with a good functioning bleb maintaining the IOP in low teens in the immediate post-operative period as well at the 6 weeks follow-up without any anti-glaucoma medication. Figure 1: Slit lamp photograph of Right eye showing dilated and tortuous episcleral vessels. Figure 2: Fundus photo of right eye showing advanced glaucomatous cupping. Subspeciality - Glaucoma

www.dosonline.org/dos-times DOS Times - Volume 28, Number 4, July-August 2022 25 Figure 3: Humphrey visual field analysis 10-2 of Right eye showing severe depression. Discussion Persistently elevated EVP is a known cause of open-angle glaucoma as it can lead to obstruction of the aqueous drainage into the orbital venous system. Idiopathic elevated episcleral venous pressure (IEEVP) refers to a clinical entity defined as elevated episcleral venous pressure without an underlying cause. IEEVP is an uncommon cause of secondary open angle glaucoma, first described by Minas and Podos.[1] It is also popularly known as Radius–Maumenee syndrome after the two ophthalmologists who presented a report of four cases of IEEVP with secondary glaucoma in 1978.[2] IEEVP is said to be caused due to a congenital abnormality in vasculature or localized venous obstruction in the region of the extraocular muscles.[3,4] It can occur as a unilateral or a bilateral condition.[5] It can occur at any age, the most common age of onset being the third and the fourth decade.[1] There is no known sex predilection, but the majority of cases reported are among women.[3] There is familial predisposition in IEEVP.[1] IEEVP is a diagnosis of exclusion and numerous causes leading to raised EVP like retrobulbar tumor, thyroid ophthalmopathy, jugular vein obstruction, congestive heart failure, thrombosis of cavernous sinus or orbital vein, vasculitis involving episcleral vein or orbital vein, superior vena cava syndrome (mediastinal tumour), carotid-cavernous sinus fistula, orbital varix, Sturge–Weber syndrome, orbital–meningeal shunts, carotid–jugular venous shunts, intraocular vascular shunts need to be ruled out before establishing the diagnosis. Dural arteriovenous shunts or fistulas, a sub-type of arteriovenous fistulas, also termed indirect cavernous-sinus fistula, is the most common misdiagnosis for IEEVP, as the flow through this fistula is so minute that it cannot be detected by neuro-radiologic examination. In diagnosing an arterio-venous fistula, cerebral angiography is the gold standard, and orbital colour Doppler ultrasound is also helpful as non-invasive method to confirm dilation of the superior ophthalmic vein or other veins when arterial blood flow is reversed. The treatment of IEEVP differs slightly from POAG. Owing to elevated EVP, medications or procedures that increase aqueous humor outflow through trabecular drainage pathway, such as pilocarpine and Rho-kinase inhibitors, and selective laser trabeculoplasty (SLT) are of low-efficacy. Majority of the cases are refractory to medical management and warrant a surgical intervention eventually. Trabeculectomy is the procedure of choice. It has been reported that eyes under-going filtering surgery are at high risk for postoperative uveal effusion. Measures such as prophylactic sclerostomies, anterior chamber maintainer, injection of viscoelastic in AC, pre-placed scleral flap sutures, tight closure of scleral flap and delayed and step wise removal of the releasable sutures can be adopted to prevent choroidal effusion. Conclusion All glaucoma patients with co-existing dilated episcleral vessels need thorough evaluation. This case report highlights the importance of arriving at the diagnosis by careful exclusion of other grave etiologies and the approach to management. References 1. Minas TF, Podos SM. Familial glaucoma associated with elevated episcleral venous pressure. Arch Ophthalmol 1968;80:202-8. 2. Radius RL, Maumenee AE. Dilated episcleral vessels and open-angle glaucoma. Am J Ophthalmol 1978;86:31-5. 3. Jørgensen JS, Guthoff R. The role of episcleral venous pressure in the development of secondary glaucomas. Klin Monbl Augenheilkd 1988;193:471-5. 4. Foroozan R, Buono LM, Savino PJ, Sergott RC. Idiopathic dilated episcleral veins and increased intraocular pressure. Br J Ophthalmol 2003;87:652-4. 5. Rhee DJ, Gupta M, Moncavage MB, Moster ML, Moster MR. Idiopathic elevated episcleral venous pressure and open-angle glaucoma. Br J Ophthalmol 2009;93:231-4. Dr. Rinal Pandit, MS Department of Glaucoma Choithram Netralaya, Shriram Talawali, Dhar Road, Indore, MP. Corresponding Author: Subspeciality - Glaucoma

DOS Times - Volume 28, Number 4, July-August 2022 www.dosonline.org/dos-times 26 Neovascular Glaucoma Faisal Thattaruthody[1], MS, Parul Chawla Gupta[1], MS, Surinder Singh Pandav[2], MS 1. Associate Professor, Advanced Eye Centre, Postgraduate Institute of Medical Education and Research, Chandigarh. 2. Professor, Advanced Eye Centre, Postgraduate Institute of Medical Education and Research, Chandigarh. Abstract: Neovascular glaucoma (NVG) is a potentially blinding secondary glaucoma represented by the formation of new vessels over the iris and anterior chamber angles and the proliferation of fibrovascular tissue in the anterior chamber angles. The iris new vessels and fibrovascular proliferation can hamper the aqueous outflow and lead to increased intraocular pressure (IOP). In most cases, retinal ischemia is the triggering factor, and the most frequent causes are ischemic central retinal vein occlusion, proliferative diabetic retinopathy and ocular ischemic syndrome. The incidence of NVG is increasing due to the increased incidence of diabetes mellitus. Early diagnosis of iris new vessels and angle new vessels by slit lamp biomicroscopy can aid in preventing the formation of peripheral anterior synechiae and obstruction of aqueous outflow, and consequent rise in IOP. Aggressive management is crucial, and systematic strategies are aimed to turn down the underlying retinal ischemia and control IOP. Introduction Neovascular glaucoma (NVG) is a potentially devastating secondary glaucoma which is characterized by neovascularization (NV) of the iris (rubeosis iridis) and elevated intraocular pressure (IOP). It is often associated with poor prognosis.[1] Coats, in 1906, first described rubeosis iridis in eyes with central retinal vein occlusion (CRVO).[2] Earlier synonyms used for NVG were hemorrhagic, congestive, rubeotic, thrombotic, or diabetic retinopathy glaucoma.[3,4] Weiss et al. coined the term NVG as increased IOP was shown with NV and connective tissue growth of the anterior segment.[5] Rubeosis iridis and NVG are secondary to an array of ocular pathologies, and in the majority of cases, the posterior segment hypoxia/ischemia is the crucial driving factor.[4] Epidemiology The prevalence of NVG varies in different populations and depends upon the prevalence of various etiologies for NVG.[6] In a hospital-based study in China, the incidence was 5.8% over 11 years.[7] In Singapore, the prevalence of NVG in migrant Indians was 0.12%.[8] The Hoogly-River Study, a population-based study in West Bengal, India, reported a prevalence of 0.01%.[9] In the diabetes control complication trial (DCCT), the reported incidence was 24% among the standard treatment group compared to 8% in the intensive treatment group.[10] Etiology and Pathogenesis The inciting factor for NVG is the posterior segment ischemia, which could result from many ocular and systemic disorders[11] (table 1). All these causes share a common mechanism, i.e. retinal hypoxia and ischemia leading to the evolution of NV of the iris (NVI) and anterior chamber angle (NVA).[11] Among various etiologies, around 75% of cases are produced by three entitiesDiabetic retinopathy (DR) (33%), Ischemic-CRVO (33%), and Ocular ischemic syndrome (OIS) (13%).[4] Neovascularisation can develop in ischemic-CRVO eyes even up to 60% within a few weeks to years after the onset of vascular occlusion.[12] Eyes with non-ischemic CRVO usually do not develop NVI or NVG, and conversion to ischemic CRVO is 3.3% by four months.[13] Differentiation of ischemic CRVO from non-ischemic CRVO is crucial. NVI occurs in 1%-17% of the eyes of diabetic patients[14,15] and the incidence is higher in proliferative diabetic retinopathy (PDR).[16] The reported incidence of NVI in PDR patients is as high as 65%, and the fellow eye has a 33% higher risk for developing NVG.[17] Ocular ischemic syndrome (OIS) is usually unilateral, with 20% of cases being bilateral. The reduction of anterior and posterior circulation causes anterior and posterior segment ischemia.[4] Ischemic retinal diseases Proliferative diabetic retinopathy Central retinal vein occlusion (mainly ischemic variety) Central retinal artery occlusion Branch retinal vein occlusion Branch retinal artery occlusion Retinopathy of prematurity Sickle cell retinopathy Familial exudative vitreoretinopathy Persistent hyperplastic primary Vitreous Inflammatory retinal diseases Chronic anterior or posterior uveitis Eales’s disease Behcet disease Vogt-Koyanagi-Harada syndrome Sympathetic ophthalmia Idiopathic retinal vascultis, aneurysm and neuro-retinitis (IRVAN) syndrome Endophthalmitis Subspeciality - Glaucoma

www.dosonline.org/dos-times DOS Times - Volume 28, Number 4, July-August 2022 27 Panophthalmitis Crohn disease Trauma Tumors Choroidal melanoma Iris melanoma Ciliary body melanoma Choroidal metastasis Retinoblastoma Myeloproliferative disorders Retinal detachments Long-standing retinal detachment Proliferative vitreo-retinopathy Coats disease Retinoschisis Detachment associated with intraocular tumors Irradiation Photo-radiation External beam radiation Charged particle radiation: Proton, helium ion Plaque brachytherapy Systemic disorders Leukemia Systemic lupus erythematosus Juvenile xanthogranuloma Cryoglobulinemia type-1 Neurofibromatosis type-1 Internal carotid artery obstruction, Carotid cavernous fistula Ischemic retinal diseases Diabetic retinopathy Central retinal vein occlusion Central retinal artery occlusion Branch retinal vein occlusion Branch retinal artery occlusion Retinopathy of prematurity Sickle cell retinopathy Familial exudative vitreoretinopathy Persistent hyperplastic primary Vitreous Inflammatory retinal diseases Chronic uveitis Chronic iridocyclitis Behcet disease Vogt-Koyanagi-Harada syndrome Sympathetic ophthalmia Endophthalmitis Panophthalmitis Crohn disease Trauma Tumors Choroidal melanoma Iris melanoma Ciliary body melanoma Retinoblastoma Hyperviscosity syndromes Myeloproliferative disorders Retinal detachments Long-standing retinal detachment Proliferative vitreo-retinopathy Coats disease Retinoschisis Detachment associated with intraocular tumours Irradiation Photo-radiation External beam radiation Charged particle radiation: Proton, helium ion Plaque brachytherapy Systemic disorders Juvenile myelomonocytic leukemia Systemic lupus erythematosus Juvenile xanthogranuloma Cryoglobulinemia type-1 Neurofibromatosis type-1 Internal carotid artery obstruction, Carotid cavernous fistula Table 1: Various causes of Neovascular glaucoma[4,14,15] The entire primary disease event, which results from retinal ischemia and hypoxia, leads to a disproportion between proangiogenic and antiangiogenic factors, and the former predominates.[4] NV is a multi-step process requiring interaction between various angiogenic factors. Retinal hypoxia, ischemia, and consequent events (disproportion between proangiogenic and antiangiogenic factors) result in new leaky vessels at angles and iris. Vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), tumour necrosis factor (TNF), hepatocyte growth factor, and inflammatory cytokines, mainly interleukin-6 (IL-6), are the major proangiogenic factors. While pigment epithelium-derived factor (PEDF), somatostatin, transforming growth factor-beta (TGF-β), and thrombospondin are the major antiangiogenic factors.[18-22] The VEGF is secreted mainly by mullers cells, retinal pigment epithelium, retinal capillary pericytes, retinal ganglion cells, and non-pigmented epithelium of ciliary processes.[23] The VEGF is a strong vasopermeable and cell mitogen factor. Besides cell migration, it enhances the leukocyte adhesion to the capillary endothelium and breaks the blood-retinal barrier.[18,19] The TGF-β provokes fibroblast proliferation and fibrovascular membrane (FVM) formation. The results of these ischemic events on the retina are the formation of leaky new vessels in the AC and blockages of the TM (Rubeosis iridis stage). This leads to increased IOP Subspeciality - Glaucoma

DOS Times - Volume 28, Number 4, July-August 2022 www.dosonline.org/dos-times 28 Figure 1: Flow charts showing the pathogenesis of NVG. Figure 2: Neovascularisation of iris at the pupillary margin (white arrows) and glaucomatous optic neuropathy (figure 1). It has also been hypothesized that posterior diffusion of oxygen from aqueous humor to the hypoxic retina causes hypoxia to the iris and ciliary body.[17] This successively causes the liberation of VEGF from the non-pigmented epithelium and results in the formation of NVIs. This could elucidate the high risk of NVIs in vitrectomized and aphakic eyes as the oxygen can quickly reach the hypoxic retina and lead to rapid and severe iris and ciliary body ischemia. The FVM contains proliferated myofibroblasts, and this membrane can cover the iris and AC and block the passage of aqueous through the TM and increase the IOP (secondary open-angle stage). On further progression, this membrane shrinks or contracts, pull the iris and causes closure of the anterior chamber angle (secondary angle-closure stage). Ischemia of the optic nerve head and retina has a detrimental outcome on the visual acuity of the NVG eyes. Low perfusion pressure could aggregate cascade events of ischemia in the retina and optic nerve head. Hence, systemic hypotension should be avoided while treating NVG.[4] History and Physical Evaluation The history and evaluation must disclose all the detailed characteristics of the disorder, as the etiology of NVG is multifactorial. Patients with CRVO might be asked and evaluated for various thrombogenic events. The systemic diseases include hypertension, hyperlipidemia, diabetes mellitus, hyperviscosity syndromes, protein S or protein C deficiency, smoking, myeloproliferative disorders, pregnancy oral contraceptive pills, and glaucoma. Patients with diabetic retinopathy should be evaluated for glycemic control and other co-morbidities like hypertension, anaemia, hyperlipidemia, and nephropathy. History of transient ischemic attacks and strokes is relevant in the case of OIS, and a thorough neurological evaluation is necessary. Patients with uveitis are evaluated for chronicity, frequency and remissions, and relapses. Pediatric patients with NVG should be asked for prematurity, birth weight, septicemia, trauma, and laterality. The previous history of any ocular tumour like melanoma or retinoblastoma should be elicited. The prior history of any ocular surgeries like pars plana vitrectomy, lensectomy, and filtration surgeries are relevant in NVG. Symptoms NVG eyes typically present with redness and pain associated with profound vision loss. NVG can be asymptomatic in the initial stage of the disease.[24] Blurring of vision may be the earliest symptom in some patients, depending upon the underlying primary disorders. Some patients report decreased vision for weeks to months before the onset of typical pain and redness. Signs The first sign of NVI is the increased permeability of the blood vessels at the pupillary margin, as identified by fluorescein angiography (FA). The following signs are seen; • Clinically the NVIs are first detected as small tufts at the pupillary margins (Figure 2) • At times new vessels are first visible at the anterior chamber angle (Figure 3) Subspeciality - Glaucoma

www.dosonline.org/dos-times DOS Times - Volume 28, Number 4, July-August 2022 29 • The NV then progresses over the iris surface onto the angle, then extends from the root of the iris across the ciliary body band, scleral spur, and arborizes over the TM. • Elevated IOP with or without corneal haziness. • On gonioscopy, NVA with or without angle–closure depends upon the stage of the disease (Figure 4). • On posterior segment examination, features of underlying diseases like DR, CRVO, OIS etc. Figure 3: Neovascularisation angle (tiny branching vessels over the TM). Figure 4: Gonioscopy of left eye showed A; Open angle inferior quadrant, B Partially opened angle at temporal quadrant. C&D; Closed angles of same eye at nasal and superior quadrant respectively. NVG can be divided into four stages 1). The Pre-rubeotic stage: In this stage, the NVI/NVA is clinically not seen but can be found on FA by the leakage of dye from the pupillary margin. 2). The Rubeotic stage: NVI and NVA are clinically visible. On slitlamp evaluation, NVI presents as fine, tortuous, and irregularly oriented vessels over the iris near the pupillary border. At the same time, it can be challenging to differentiate from aberrant vessels originating from iris vessels, especially in eyes with pupillary atrophy. The clinical stages of NVI and NVA are described in Table 2. These aberrant vessels have a more uniform size, are more radial, arise from the iris root, and do not branch until they disappear into the stroma at the mid periphery. 3). In the stage of secondary open-angle glaucoma (Figure 4) occurs a FVM which covers the iris, and TM obscures the aqueous Subspeciality - Glaucoma

DOS Times - Volume 28, Number 4, July-August 2022 www.dosonline.org/dos-times 30 Table 2: Weiss and Golden Classifications of neovascularisation of iris and anterior chamber angle[54] outflow. 4). The stage of secondary angle closure (Figure 4) where contraction of the FVM causes peripheral anterior synechiae and angle closure. In advanced stages, there can be ectropion uvea (Figure 5). Various stages of NVG are described in Table 3. Grade-1 Grade-2 Grade-3 Grade-4 NVI Neovascularisation at pupillary border < 2 quadrants Neovascularisation at pupillary border> 2 quadrants Neovascularisation at the ciliary zone and/or ectropion uvea 1-3 quadrants Neovascularisation at the ciliary zone and/ or ectropion uvea ≥3 quadrants NVA New vessels cross SS and ramify over TM <2 quadrants New vessels cross SS and ramify over TM >2 quadrants New vessels at TM, and PAS 1-3 quadrants PAS ≥3 quadrants NVI= Neovasculirisation of iris, NVA= Neovasculrisation of Angle, SS= Scleral Spur, TM= Trabecular meshwork, PAS= Peripheral anterior synechiae. Stage Rubeotic iridis SOAG SACG Clinical characteristic Fine tufts of new vessels grow over the pupillary margin and less commonly at the anterior chamber angle New vessels grow irregularly over the iris The formation of a thin fibrovascular membrane over the iris creeps into the anterior chamber angle blocks TM and obscure the aqueous outflow Pulling of iris over TM and form PAS due to contraction of fibrovascular membrane NVI Present Prominent Prominent with ectropion uvea Gonioscopy Open-angle, NVA with or without NVI may be present Open-angle with or without NVA Closes angles IOP Normal High High Prognosis Good Good with timely detection and treatment Guarded SOAG= Secondary open-angle glaucoma, SACG= Secondary angle closure glaucoma, NVI= Neovasculirisation of iris, NVA= Neovasculrisation of Angle, TM= Trabecular meshwork, PAS= Peripheral anterior synechiae, IOP=Intraocular pressure. Figure 5: 360 degrees ectropion uvea in an eye with advanced NVG. Table 3: Various clinical stages of NVG[4] Subspeciality - Glaucoma

www.dosonline.org/dos-times DOS Times - Volume 28, Number 4, July-August 2022 31 Investigations Investigations can be predominantly divided into Ophthalmic and Systemic. Ophthalmic Investigation Slit-lamp microscopy and gonioscopy are indispensable for diagnosing NVG. Tiny NV can be appreciated over the iris, especially near the pupillary margin. Hyphema can also be appreciated in some cases. Gonioscopy is more dynamic, preferably done in an undilated pupil. Fundus fluorescence angiography (FFA) is an invasive procedure and is the gold standard for detecting neovascularization elsewhere (NVE), neovascularisation of the disc (NVD), and Capillary non-perfusion (CNP) area.[4] Recently, ultra wide-field FFA (figure 6) can acquire the retinal image up to 200o of the retina and thus identify peripheral NVE and CNP areas better than conventional FFA (Figure 6 A&B).[4] The most recent technique is optical coherence tomography angiography (OCTA) (Figure 6C), which is a noninvasive technique; it can define the extent and depth of NV as compared to FFA.4 It can be used as a follow-up tool to document the regression of NV.[4] Ultrasound B Scan helps to detect the underlying pathology in many cases. It can detect vitreous hemorrhage, retinal detachment, and mass lesions like choroidal melanoma, ciliary body melanoma, metastasis, and retinoblastoma. Figure 6: A wide field fundus photo, blue arrowed showed the occluded vessels, B FFA showed Capillary non perfusion area and new vessels. C OCTA showed capillary drop out and new vessels. Systemic Investigations Neovascular glaucoma is a secondary illness, and many systemic diseases could be associated with NVG. These investigations rely upon the specific underlying etiology of NVG. The investigations for various systemic diseases are as follow. 1. Diabetes Mellitus: blood sugar level and HbA1C. 2. Hypertension: blood pressure. 3. Ocular Ischemic Syndrome: Carotid Doppler, Magnetic resonance/computed tomography angiography, and Carotid digital subtraction angiography. 4. Uveitis: HLA B27, VDRL, TPHA, Mantoux test (TB), Serum ACE level, and HRCT Chest (Sarcoid). 5. Blood Dyscrasias: Complete hemogram, ESR, CRP, ANCA, and plasma electrophoresis. Differential Diagnosis The differential diagnosis of NVG includes entities with similar presentation or etiologies that are predisposed to NVG.[4,11, 24-31] 1. Acute angle closure glaucoma. The presentation closely mimics the presentation of NVG, and the engorgement of iris vessels may be mistaken as NVI. The corneal edema often obscures the detailed evaluation of the iris. Evaluation of the fellow eye for narrow angles is often the only differentiating character in eyes where the media is poor. 2. Uveitic glaucoma: The presence of Keratic Precipitates (KP), iris atrophy, and engorged iris vessels (rather than tiny and branching) are differentiating features. 3. Chronic angle closure glaucoma. Iris atrophy and prominent iris vessels may be mistaken as rubeosis. Examination of the fundus for evidence of ischemia and fellow eye for angle closure will help differentiate both conditions. 4. Intraocular tumour. Eyes with posterior segments can present with engorged vessels. The tumour should be promptly diagnosed by fundoscopy, USG B scan, UBM, or MRI Scan. 5. Carotid cavernous fistula. A carotid cavernous fistula can have dilated vessels on the iris with normal or high IOP. Gonioscopy (blood in the Schlemn canal), MRA, or CTA will help diagnose the condition. 6. Anterior segment dysgenesis, like essential iris atrophy, can have prominent iris vessels. Correctopia, polycoria, and iris atrophy can help differentiate this entity. 7. Pseudoexfoliation glaucoma can also present with prominent iris vessels with high IOP. Deposition of pseudoexfoliative material on the pupillary border, crystalline lens, and anterior chamber angle are some differentiating features of pseudoexfoliation. 8. Fuchs heterochromic uveitis (FHU) can have high IOP with NVA. Stellate KPs and the presence of a vitreous membrane are features of FHU. Subspeciality - Glaucoma

DOS Times - Volume 28, Number 4, July-August 2022 www.dosonline.org/dos-times 32 Treatment of NVG The treatment principle[24] can be categorized into 1. Treatment of the primary disease which causes retinal ischemia. 2. Control of IOP. 3. Treatment of underlying systemic diseases (diabetes, hypertension, carotid artery obstruction, etc.) improves blood flow. 4. Control of inflammation. The treatment of underlying retinal ischemia comprises laser (pan-retinal photocoagulation -PRP) and anti-VEGF. PRP is the treatment of choice whenever the posterior segment is visible.[32,33] PRP has indicated not only the initial stages of NVG but also in late stage.[1] The treatment parameters include 1200-1600 burns, 500-micron size, and one spot size apart. It is completed in 2-3 sittings 5-7 days apart.[34] Though PRP does not immediately reduce the new vessels but has prolonged treatment effects compared to bevacizumab. Sufficient treatment of underlying posterior segment ischemia can stabilize the IOP and reduce the NVI/ NVA.[35] In NVG secondary to PDR 1200- 1600 burns cause regression of NVI in 70.4% of cases.[36] The presence of NVI itself is a risk for intraoperative bleeding. An adequate PRP 2-3 weeks before surgery can reduce the risk of hyphaema and bleb failure.[4] Anti-VEGF like bevacizumab and ranibizumab are widely used Figure 7: Flow chart shows the management algorithm of NVG. DLCP=Diode laser cyclophotocoagulation. ECP=Endocyclophotocoagulation. GDD=Glaucoma drainage device. ARC= Anterior retinal Cryotherapy. PPV=Pars plana vitrectomy. LIO=Laser indirect Ophthalmoscopy. Anti-VEFG=anti-Vascular Endothelial Growth Factor. Trab=trabeculectomy. nowadays for the management of NVG, and their role has been extensively studied.[37,38] They lead to regression of anterior segment and posterior segment new vessels and reduction of IOP. Intravitreal injections of anti-VEGF cause regression of NVA/NVI within 24-48 hours in contrast to PRP, which usually takes 2-3 weeks. A combination of intravitreal antiVEGF and PRP is widely accepted and recommended in clinical practice nowadays as anti-VEGF-induced regression of NV is temporary and often recurs. At the same time, lasers (PRP) offer a more permanent reduction of retinal ischemia. When PRP is impossible due to poor media clarity, intravitreal anti-VEGF can be injected before trabeculectomy or glaucoma drainage implant surgery. Medical Management The NVI/NVA with normal IOP is managed by treating the underlying cause of the ischemia and careful monitoring of IOP. Treatment selection of hypotensive medications depends on the stage of NVG. The figure-7 depicts the management of NVG. Aqueous suppressants like topical beta-blockers, carbonicanhydrase inhibitors (topical and systemic), and α-2 agonists may be effective in NVG when combined. Prostaglandin analogues are only used when other drugs are ineffective, as they may aggravate inflammation. Miotics should be avoided as they may cause PAS formation and aggravate inflammation.[4] Supportive treatments like topical steroids and cycloplegics like atropine or homatropine are advocated for treating inflammation and pain. Subspeciality - Glaucoma

www.dosonline.org/dos-times DOS Times - Volume 28, Number 4, July-August 2022 33 Surgical Management The main indications for surgery are inadequate IOP control even with maximum tolerable medications and extensive PAS formation that obscure the angle and prevents the aqueous outflow. Surgical modalities for NVG include trabeculectomy, glaucoma drainage implant surgery, and cyclo-destructive procedures. Trabeculectomy Conventional trabeculectomy has a high failure rate, possibly due to severe inflammation and hyphema.[39,40] However, the adjuvant use of anti-metabolites, like Mitomycin C (MMC) or 5-Fluorouracil (5 FU), has improved outcomes of trabeculectomy.[41] Other factors which better the outcome are prior PRP, prior anterior retinal cryotherapy, and intravitreal anti-VEGF.[4] High doses (0.04%) and long MMC application duration (3-4 minutes) can be beneficial. Postoperatively subconjunctival injection of 5FU should be considered in eyes that show early signs of bleb failure or aggressive vascularization. The success rate of trabeculectomy MMC varies between 62.8% to 81.2% at 1 year and 51.3% at 5 years.[41,42] Adjutant use of preoperative bevacizumab, the success rate may increase to 95%.[43] Therefore, it has been suggested that adequate PRP and or anti-VEGF injection should be given before filtration surgeries. Glaucoma Drainage Device Glaucoma drainage devices (GDD) were previously contemplated as a last resort in NVG. Today, GDD is widely used as a primary surgical modality in NVG as an alternative to trabeculectomy. The commonly used implants are valved (Ahmed Glaucoma Valve-AGV) and non-valved (Baerveldts, Molteno, and Aaurolab Aqueous Drainage Implant-AADI), and in high-pressure NVG, the AGV is preferred. GDD implantation may be technically challenging in NVG due to the presence of NVI, and extensive PAS and the tube should be placed as far posterior (ciliary sulcus for pseudophakic eyes or pars plana for vitrectomized eyes) to prevent tube occlusion by a fibrous membrane. The success rates of GDD in eyes with NVG are lower than other indications.[44-46] Studies found that the success rate did not increase with prior PRP[47] or concurrent use of antimetabolites.[48] Various studies have compared the outcome of trabeculectomy and glaucoma drainage implants in NVG eyes. Shen et al.[49], in a retrospective study, documented a similar success rate for trabeculectomy (with MMC) and AGV (55% and 60%, p=0.474) over 2 years. Wang et al.[50] reported a more significant IOP reduction with AGV than trabeculectomy in NVG eyes with vitreous haemorrhage (glaucoma surgery was done after pars plana vitrectomy for vitreous haemorrhage) at 12 months, but no significant difference in absolute success probability. Various complications of glaucoma surgeries in NVG include hyphema, shallow anterior chamber, serous choroidal detachment, supra-choroidal haemorrhage, and late complications related to MMC. The most frequent complication is hyphema, and the incidence can be reduced by preoperative intravitreal bevacizumab to reduce the NVI and avoid intraoperative and postoperative hypotony. Cyclodestructive Procedure Cyclodestructive procedures destroy or ablate the ciliary body and reduce the aqueous production. Currently, the trans scleral diode laser cyclophotocoagultion (DLCP) is widely popular; however, endoscopic cyclophotocoagulation (ECP) is gaining popularity.[51] Previously, this procedure was reserved for painful blind eyes or patients who were poor candidates for surgery. Nowadays, this procedure is indicated even in functional eyes with advanced glaucoma like NVG with high IOP on maximal medical therapy or failed trabeculectomy/glaucoma drainage implant surgery.[52] Recently, micropulsediode cyclophotocoagulation has come into practice, but the capability to reduce the IOP is not much different from DLCP.[4] Advantage of ECP is that it can be combined with pars plana vitrectomy, and retinal endolaser is reported to have better IOP reduction in NVG with high IOP.[53] Complications of cyclodestructive procedures include hyphema, corneal edema, iritis, suprachoroidal haemorrhage, and phthisis bulbi.[4] Conclusions NVG is a potentially blinding secondary glaucoma and is often refractory to all available treatments. Timely diagnosis and a systematic approach are crucial to preventing or reducing vision loss. Appropriate treatment of the primary etiology for ischemia and controlling the IOP are critical to successfully managing this challenging entity. Financial Disclosure No financial interest to any of the author . Acknowledgement Acknowledges Dr. Mohit Dogra for contributing the fundus picture, FFA and OCTA images. References 1. Rodrigues GB, Abe RY, Zangalli C, et al. Neovascular glaucoma: a review. Int J Retina Vitreous. 2016;2:26. Published 2016 Nov 14. doi:10.1186/s40942-016-0051-x. 2. Coats G., Further cases of thrombosis of the central vein. Roy LondOphthal Hosp Rep 1906; 16:516. 3. Salus R. Rubeosis iridis diabetica, einebisherunbekanntediabetischeIrisveränderung. Med Klin1928;24:256-8. 4. Senthil S, Dada T, Das T, et al. Neovascular glaucoma - A review. Indian J Ophthalmol. 2021;69(3):525-534. 5. Weiss DI, Shaffer RN, Nehrenberg TR. Neovascular glaucoma complicating Carotid-cavernous fistula. Arch Ophthalmol. 1963;69(3):304– 307. 6. Mishra C, Meyer JJ. Neovascular Glaucoma. [Updated 2022 Jun 12]. In: Stat Pearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/ NBK576393/. 7. Liao, N., Li, C., Jiang, H. et al. Neovascular glaucoma: a retrospective review from a tertiary center in China. BMC Ophthalmol 16, 14 (2016). https://doi.org/10.1186/s12886-016-0190-8. Subspeciality - Glaucoma

DOS Times - Volume 28, Number 4, July-August 2022 www.dosonline.org/dos-times 34 8. Narayanaswamy A, Baskaran M, Zheng Y, et al. The prevalence and types of glaucoma in an urban Indian population: the Singapore Indian Eye Study. Invest Ophthalmol Vis Sci. 2013;54(7):4621-4627. 9. Paul C, Sengupta S, Choudhury S, Banerjee S, Sleath BL. Prevalence of glaucoma in Eastern India: The Hooghly River Glaucoma Study. Indian J Ophthalmol. 2016;64(8):578-583. 10. Progression of retinopathy with intensive versus conventional treatment in the Diabetes Control and Complications Trial. Diabetes Control and Complications Trial Research Group. Ophthalmology. 1995 Apr;102(4):647-61. 11. Sivak-Callcott JA, O’Day DM, Gass JD, Tsai JC. Evidence-based recommendations for the diagnosis and treatment of neovascular glaucoma. Ophthalmology. 2001 Oct;108(10):1767-76. 12. Mocanu C, Barăscu D, Marinescu F, Lăcrăţeanu M, Iliuşi F, Simionescu C. [Neovascular glaucoma--retrospective study]. Oftalmologia. 2005;49(4):58-65. 13. Baseline and early natural history report. The Central Vein Occlusion Study. Arch Ophthalmol. 1993 Aug;111(8):1087-95 14. Hayreh SS, Rojas P, Podhajsky P, Montague P, Woolson RF. Ocular neovascularization with retinal vascular occlusion-III: Incidence of ocular neovascularization with retinal vein occlusion.Ophthalmology 1983;90:488-506. 15. Armaly MF, Baloglou PJ. Diabetes mellitus and the eye: I. Changes in the anterior segment. Arch Ophthalmol1967;77:485-92. 16. Madsen P. Haemorrhagic glaucoma. Comparative study in diabetic and nondiabetic patients. Br J Ophthalmol1971;55:444-50. 17. Lee P, Wang CC, Adamis AP. Ocular neovascularization: An epidemiologic review. SurvOphthalmol1998;43:245-69. 18. Chalam KV, Brar VS, Murthy RK. Human ciliary epithelium as a source of synthesis and secretion of vascular endothelial growth factor in neovascular glaucoma. JAMA Ophthalmol2014;132:1350-4. 19. Tolentino MJ, Miller JW, Gragoudas ES, Chatzistefanou K, Ferrara N, Adamis AP. Vascular endothelial growth factor is sufficient to produce iris neovascularization and neovascular glaucoma in a nonhuman primate. Arch Ophthalmol1996;114:964-70. 20. 25. Yu XB, Sun XH, Dahan E, Guo WY, Qian SH, Meng FR, et al. Increased levels of transforming growth factor-beta1 and-beta2 in the aqueous humor of patients with neovascular glaucoma. Ophthalmic Surg Lasers Imaging Retina 2007;38:6-14. 21. Chen K-H, Wu C-C, Roy S, Lee S-M, Liu J-H. Increased interleukin-6 in aqueous humor of neovascular glaucoma. Invest Ophthalmol Vis Sci 1999;40:2627-32. 22. Simo R, Carrasco E, Garcia-Ramirez M, Hernandez C. Angiogenic and antiangiogenic factors in proliferative diabetic retinopathy. Curr Diabetes Rev 2006;2:71-98. 23. Senger DR, Perruzzi CA, Streit M, Koteliansky VE, de Fougerolles AR, Detmar M. The α1β 1 and α2β 1 integrins provide critical support for vascular endothelial growth factor signaling, endothelial cell migration, and tumor angiogenesis. Am J Pathol2002;160:195-204. 24. Shazly TA, Latina MA. Neovascular glaucoma: Etiology, diagnosis and prognosis. Paper presented at: Seminars in ophthalmology. 2009. 25. Hayreh SS. Neovascular glaucoma. Prog Retin Eye Res 2007;26:470-85. 26. Luo J, Yan Z, Jia Y, Luo R. Clinical analysis of 42 cases of ocular ischemic syndrome. J Ophthalmol 2018;2018: 2606147. doi:10.1155/2018/2606147. 27. Sivak-Callcott JA, O’Day DM, Gass JDM, Tsai JC. Evidence-based recommendations for the diagnosis and treatment of Neovascular glaucoma. Ophthalmology 2001;108:1767-76. 28. Brown GC, Magargal LE, Schachat A, Shah H. Neovascular glaucoma: Etiologic considerations. Ophthalmology 1984;91:315-20. 29. Morrison JC, Pollack IP. Glaucoma: Science and practice. Thieme New York; 2003. 30. Havens SJ, Gulati V. Neovascular glaucoma. In: Retinal Pharmacotherapeutics. Vol 55. Karger Publishers; 2016. p. 196-204. 31. Barac IR, Pop MD, Gheorghe AI, Taban C. Neovascular secondary glaucoma, etiology and pathogenesis. Rom J Ophthalmol2015;59:24-8. 32. Callahan MA. Photocoagulation and rubeosis iridis. Am J Ophthalmol1974;78:873-4. 33. Laatikainen L. Preliminary report on effect of retinal panphotocoagulation on rubeosis iridis and neovascular glaucoma. Br J Ophthalmol1977;61:278-84. 34. Bressler NM, Beck RW, Ferris FL 3rd Panretinal photocoagulation for proliferative diabetic retinopathy. N Engl J Med 2011;365: 1520-1526. 35. Fujioka S, Karashima K, Saito Y (2009) Differences of ocular circulation in eyes with proliferative diabetic retinopathy after panretinal photocoagulation with and without rubeosisiridis. Nihon Ganka Gakkai Zasshi113:11-15. 36. Ohnishi Y, Ishibashi T, Sagawa T Fluorescein gonioangiography in diabetic neovascularisation. Graefes Arch Clin Exp Ophthalmol 1994;232: 199-204. 37. Horsley MB, Kahook MY. Anti-VEGF therapy for glaucoma. CurrOpinOphthalmol2010;21:112-7. 38. Grisanti S, Biester S, Peters S, Tatar O, Ziemssen F, Bartz-Schmidt KU, et al. Intracameral bevacizumab for iris rubeosis. Am J Ophthalmol2006;142:158-60. 39. Olmos LC, Lee RK. Medical and surgical treatment of Neovascular glaucoma. Int Ophthalmol Clin 2011;51:27-36. 40. Nakatake S, Yoshida S, Nakao S, Arita R, Yasuda M, Kita T, et al. Hyphema is a risk factor for failure of trabeculectomy in neovascular glaucoma: A retrospective analysis. BMC Ophthalmol2014;14:55. 41. Takihara Y1, Inatani M, Fukushima M, Iwao K, Iwao M, et al. (2009) Trabeculectomy with mitomycin C for neovascular glaucoma: prognostic factors for surgical failure. Am J Ophthalmol.2009;147: 912- 918, 918. 42. Higashide T, Ohkubo S, Sugiyama K. Long-term outcomes and prognostic factors of trabeculectomy following intraocular bevacizumab injection for neovascular glaucoma. PLoS One 2015;10:e0135766. 43. Saito Y, Higashide T, Takeda H, Ohkubo S, Sugiyama K. Beneficial effects of preoperative intravitreal bevacizumab on trabeculectomy outcomes in neovascular glaucoma. Acta Ophthalmol2010;88:96 102. 44. Christakis PG, Kalenak JW, Tsai JC, Zurakowski D, Kammer JA, Harasymowycz PJ, et al. The Ahmed versus Baerveldt study: Five-year treatment outcomes. Ophthalmol2016;123:2093-102. 45. Netland PA, Ishida K, Boyle JW. The Ahmed Glaucoma Valve in patients with and without neovascular glaucoma. J Glaucoma 2010;19:581-6. 46. Netland PA. The Ahmed glaucoma valve in Neovascular glaucoma (An AOS Thesis). Trans Am Ophthalmol Soc 2009;107:325-42. 47. Yalvac I, Eksioglu U, Satana B, Duman S. Long-term results of Ahmed glaucoma valve and Molteno implant in Neovascular glaucoma. Eye 2007;21:65-70. Subspeciality - Glaucoma

www.dosonline.org/dos-times DOS Times - Volume 28, Number 4, July-August 2022 35 48. Kang JY, Nam KY, Lee SJ, Lee SU. The effect of intravitreal bevacizumab injection before Ahmed valve implantation in patients with neovascular glaucoma. Int Ophthalmol2014;34:793-9. 49. Shen CC, Salim S, Du H, Netland PA. Trabeculectomy versus Ahmed Glaucoma Valve implantation in neovascular glaucoma. Clin Ophthalmol. 2011;5:281-6. 50. Wang MH, Li QM, Dong HT, Dong SQ, Li Y, Zheng CY. Ahmed valves vs trabeculectomy combined with pans plana vitrectomy for neovascular glaucoma with vitreous hemorrhage. Eur J Ophthalmol2017;27:774-80. 51. Pastor SA, Singh K, Lee DA, Juzych MS, Lin SC, et al. (2001) Cyclophotocoagulation: a report by the American Academy of Ophthalmology. Ophthalmology. 2001;108: 2130-2138. 52. Rotchford AP, Jayasawal R, Madhusudhan S, Ho S, King AJ, et al. Transscleral diode laser cycloablation in patients with good vision. Br J Ophthalmol . 2010;94: 1180-1183. 53. Marra KV, Wagley S, Omar A, Kinoshita T, Kovacs KD, Silva P, et al. Case-matched comparison of vitrectomy, peripheral retinal endolaser, and endocyclophotocoagulation versus standard care in neovascular glaucoma. Retina 2015;35:1072-83. 54. Weiss D, Gold D. Neofibrovascularization of iris and anterior chamber angle: A clinical classification. Ann Ophthalmol1978;10:488-91. Dr. Parul Chawla Gupta, MS Associate Professor, Advanced Eye Centre, Postgraduate Institute of Medical Education and Research, Chandigarh. Corresponding Author: Subspeciality - Glaucoma

DOS Times - Volume 28, Number 4, July-August 2022 www.dosonline.org/dos-times 36 The First (Awakening) Call… Mukta Sharma, MS, Anil Verma, MS Department of Ophthalmology, Dr. RKGMC, Hamirpur (HP). Abstract: History of Eye Banking in India dates back to 1970s. Preservation of cornea was then a rather very complicated affair. But even in present scenario, not every Medical College is well equipped with the basic essentials of an Eye Bank. Even collection of donated eyes is a tedious affair with limited manpower and material. Hopefully things will improve in near future so that the donated eyes be collected within the stipulated time frame and the cornea gets transplanted to the suitable recipients. It was the first call for home retrieval that we received at our budding Medical College, that woke me from slumber and daily routine and made me pen this article. Introduction Someone has rightly said that, “The beginning is the most important part of the work”. Though we all are very well versed with the thick and thin of eye donation in India and utilisation of the cornea thereafter, still it is a never ending tale to be written in the ongoing Eye donation fortnight with theme, “Eye never die, donate eye.” Eye Banking in India In early days the main reason why Eye Banks were not very successful in India was because of the lack of awareness. Cornea transplant in the late 1970s and 1980s in India was a rather complicated affair. Preservation techniques were not very advanced, the ratio of donors to recipients was very poor and modest transport connections between places added to the woes. Many eye banks had been set up but owing to logistic and other inconveniences, these ideas were abandoned almost soon after they had begun.[1] The late Dr. RES Muthiah started the very first eye bank in India and the first corneal transplantation took place successfully by him in India in 1948. From then on a movement started for donation of eyes. The prime concept of Eye Bank Association of India (EBAI) is to motivate the people for eye donation. Eye donation fortnight in India is celebrated from August 25th to September 8th every year. These are the days when the general public is made aware of the need for eye donation after death. The national fortnight on eye donation is under the Control of National program. Doubtless, the gift of sight is invaluable and the most delicate of all sense organs. And the most profound disability considered is the impairment of vision. It is heartening to point out that not all people are blessed with this gift of sight. In most cases, blindness is irreversible. However, today, medical science has made such progress that it can even restore eyesight for many blind patients, who struggle daily to live because of vision damage.[2] The purpose of the eye donation fortnight is to create social awareness and to fill the gap between the demand and supply of cornea. Lakhs of people in India are in the wait for a corneal transplant in order to restore their vision. But unfortunately, only a few thousands of such patients benefit, while most people suffer blindness due to a lack of eye donation by people after they pass away. Most blind patients are young people who lost their eyesight due to injuries, malnutrition, infections, congenital or other factors. Their eyesight can be revived through corneal transplantation only. The national eye donation fortnight aims to make the public participate in this charitable act of eye donation wherein they pledge to donate their eyes after death. However, people generally hesitate to donate their eyes as many myths and rumors are circulated among them regarding eye donating.[3] According to the World Health Organisation, in India, nearly 40 million people are sightless or visually impaired, out of which 1.6 million are children. It is also estimated that 12 million people in the country have corneal blindness, which can be cured through corneal transplantation. With these striking figures, some proposals of compulsion to eye donation after death are also coming up. National eye donation considers this a significant health concern as many people don’t even know that they can cure corneal blindness by replacing the damaged or diseased corneal tissue with a donor. Though the skills and infrastructure required for corneal transplantation are readily available in India, lack of awareness and fear act as critical obstacles to eye donation. And so, national eye donation fortnight is celebrated in the country to encourage eye donation to the people who need corneal transplantation.[4] To contribute to the national eye donation fortnight 2022, you need to pledge to donate your eyes. Pledging for eye donation is an impressive strategy to create awareness among your social groups. It can be done in any of the nearest registered eye banks, wherein you will be required to fill a form with all the crucial details such as name, address, age, blood group, and other personal specifics and sign the pledge. The eye bank then registers you as an official eye donor and provides you with an Eye Donor Card. You can also register your eye donation pledge on the Eye Bank Association of India website. By pledging, you are aware of the need for eye donation and other facets concerned with it. As you have to get a consent signature from any of your family members for pledging, the awareness Subspeciality - Cornea

www.dosonline.org/dos-times DOS Times - Volume 28, Number 4, July-August 2022 37 regarding national eye donation further spreads to family and friends. Since you can donate eyes only after death, you must convey your decision to your family, as at the time of your death; they will be required to inform the eye bank of your pledge so that they can collect your eyes at the earliest. The heroic deed of donating eyes is done free of cost to offer the gift of vision to another individual and enrich their life.[5] It is a common myth that eye donation disfigures the face of the donor. And this has become the most prominent barrier to eye donation as it can be seen in many cases that after the death of a registered eye donor, their family members refuse the eye bank to donate the eyes of the departed soul. So it is why national eye donation fortnight is celebrated to spread awareness against such misconceptions. Some important things which the family of prospective donor ought to know are that: • Call the team as soon as possible • Keep both eyes of deceased closed and covered with moist cotton • Switch off the overhead fan • Raise the head end of the body by about 6 inches, if possible, to lessen the incidence of bleeding during the removal of the eyes[6] The reality is that not the whole eye is removed, but cornea and removal of the cornea do not alter the appearance of the face. Also, after the cornea is removed, an apparent plastic prosthetic eye cap is positioned in the eye and gently closes the eyelids. So, it is to remember that the process of eyeball removal takes only 15- 20 minutes, and neither will cause any huudisfigurement of the dead body nor will it cause any delay in the funeral arrangement. Everyone can contribute to eye donation fortnight by pledging to become an eye donor, irrespective of their caste, creed, religion, age, sex, or blood group. People with eyesight problems like short or long-sightedness who use contact lenses or wear glasses can also pledge eye donations. In addition, people who have endured eye surgery can also become eye donors by simply endorsing the national eye donation fortnight 2022. • However, checking a donor’s medical history is crucial as some conditions disallow eye donation. These conditions include diseases like severe infectious problems such as active sepsis or hepatitis, HIV positive, or AIDS. Also, the advanced stages of diabetes that assign insulin deter a patient from being an eye donor. Therefore, patients suffering from severe forms of diabetes should avoid donating their eyes. Additionally, those with infectious diseases are not eligible to donate their eyes. A model eye banking system in India can be achieved only when it is linked with the targeted infrastructure proposed under ‘Vision 2020: Right to Sight-India’. Considering these targets, there is a requirement of at least 20 eye bank training centres, 200 eye banks with corneal transplant facility (collection of nearly 500 corneas per year) and 2000 eye donation centres in the country. This would become a reality if the Hospital Cornea Retrieval Programme is strengthened at all private and government hospitals. Uniform medical standards are made mandatory for all eye banks and eye donation centres and the process of registration and eye donation is simplified to enhance community participation.[8] One survey globally quantified the considerable shortage of corneal graft tissue, with only 1 cornea available for 70 needed. Efforts to encourage cornea donation must continue in all countries. The study reveals a dynamic development of the eye bank over the last 30 years and emphasizes the importance of an active quality management in coping with the challenges of modern eye banking. The increasing trend of cornea collection and transplantation is a reflection of the needs and efforts towards treating and eliminating corneal blindness. Traditionally, barriers to increased corneal transplantation have been daunting, with limited tissue availability and lack of trained corneal surgeons making widespread keratoplasty services cost prohibitive and logistically unfeasible. The two key factors are the development of professional eye bank managers and the establishment of Hospital Cornea Recovery Program.[9] The present study has spotted a considerable pool of potential eye donors. The realisation and pursuit of implementing cornea retrieval from this potential donor pool is necessary to bridge the gap between the donors and those waiting for corneal transplantation. Hospital cornea retrieval programme can immensely contribute to fill the deficiency of donor corneal tissue. The present study concluded that upto 74.8% of corneas could have been potentially retrieved and indicates a vast potential to reduce the deficit of corneal tissues.[10] An Awakening Call Having said that all, I would like to highlight the present scenario in our budding medical College in Hamirpur District of Himachal Pradesh. Although it has been credited with the establishment of an Eye Collection Centre, but so far no eye collection call had been received. Lately we got a call for home retrieval , past midnight, with ongoing heavy rainfall and that too at about 1 hour drive from the college. We were caught unaware. In no time we got our instruments ready and rushed to the spot which was about 25kms away. As compared to hospital retrieval, going to somebody’s home at such an hour and environment is quite an experience. But with the efforts of my whole team I could finally make it. And our sincere efforts made it possible for two corneal blind patients to get vision. Although we were quite appreciated for our act but it somehow left a feeling of unfullfillment in our hearts. But at the same time we learned a lot from this experience and now I can say that we are better prepared for this noble but exihalarating deed, after this First Call at our upcoming Medical College. I would further like to state that we should work together as a team to make our workplace better equipped for this noble deed every single day Apart from taking a pledge for eye donation, we should also take a pledge to make more and more people aware of the concept of eye donation so that getting such calls and working on it thereafter becomes a routine for us. Lastly a big thanks to the Subspeciality - Cornea

DOS Times - Volume 28, Number 4, July-August 2022 www.dosonline.org/dos-times 38 family who took this decision and had faith in us and made us shoulder the responsibility of home retrieval. I hope many more will now give us a chance so that cornea blind people could finally see the light of the day once again. References 1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6798607/ 2. https://www.hindawi.com/journals/tswj/2022/5206043/ 3. Eye donation movement in India.K A Kannan. J Indian Med Assoc. 1999 Aug. 4. Eye donation and eye banking in India.Noopur Gupta et al. Natl Med J India. 2018 Sep-Oct. 5. Global Survey of Corneal Transplantation and Eye Banking.Philippe Gain et al. JAMA Ophthalmol. 2016 Feb. 6. Thirty years of eye bank experience at a single centre in India.Sunita Chaurasia et al. Int Ophthalmol. Jan 2020. 7. Turning the tide of corneal blindness. Matthew S Oliva et al. Indian J Ophthalmol. 2012 Sep-Oct. 8. Lost Opportunities for Cornea Retrieval: A Cross-sectional Study from District Hospital, Tumakuru, Karnataka https://doi.org/10.7860/ JCDR/2022/52721.15926. Dr. Mukta Sharma, MS Senior Resident, Department of Ophthalmology, Dr. RKGMC, Hamirpur (HP). Corresponding Author: 9. Ministry of Health & Family Welfare Government of India. The National Blindness and Visual Impairment Survey 2015-2019- A Summary Report. Nation Programme for Control of Blindness.Pg.01- 15.;2019. 10. A study of knowledge and attitude about eye donation among 1st-year medical students. Gotekar R., K. Joshi etal https://doi.org/10.17511/ jooo.2020.i02. Subspeciality - Cornea

www.dosonline.org/dos-times DOS Times - Volume 28, Number 4, July-August 2022 39 Acanthamoeba Keratitis Parul Lokwani, MBBS, DNB (Oph), PGDHA ADEH (Arunodaya Deseret Eye Hospital), Gurgaon, Haryana, India. Abstract: Acanthamoeba keratitis is a rare sight-threatening disease which, in the United States and Europe, is found predominantly among contact lens wearers.[1,2] It is caused by infection of the protozoa Acanthamoeba and is commonly misidentified as one of the more common fungal or viral forms of keratitis.[3] The primary risk factors being accidental corneal trauma, which is more common in developing countries, and contact lens wear in developed countries. Key words: Keratitis, Acanthamoeba, Contact Lens, Protozoa. Case Report A 30-year-old male presented with chief complaints of pain, redness, diminution of vision and photophobia in the right eye since last 20 days. There was no history of trauma or any significant systemic disorder. On asking further he revealed the history of taking bath in stagnant pond water number of times back in his village 1 month back. At the time of presentation his visual acuity was 1/60 in the right eye. Left eye visual acuity was 6/6. On slit lamp examination of the right eye he had almost central geographical corneal ulceration about 6mmX4mm along with circumcorneal congestion and lid edema. (Figure 1, 2) Pupil and lens details were hazy. Dull fundal glow was seen. Left eye was unremarkable. Intraocular pressure was not recordable in the right eye and 11 mm of Hg in the left eye. Corneal sensations were diminished in the right eye. 1A 1B Figure 1: (A) External photograph of Right eye at presentation. (B) External photograph of Right eye at presentation. Figure 3: At 3rd day follow up. Figure 2: (A) Right eye at presentation showing geographical corneal ulceration. (B) Right eye at presentation showing corresponding flourescein staining. 2A 2B A provisional diagnosis of viral keratitis with superadded bacterial infection was made and patient was started on Acivir eye ointment (3%) 5 Times a day, Moxifloxacin eye drops (0.5%) 6 times a day, Homatropine eye drops (2%) 3 times a day, tablet Acyclovir (800 mg) 5 times a day, Neosporin eye ointment 2 times a day and Carboxymethylcellulose (0.5%) 6 times a day. Corneal scrapping was taken and sent for Microbiological evaluation. On 3rd follow u6666p day patient was only symptomatically better. Eye was less congested. (Figure 3) The report as of now Gram stain revealed few gram-positive cocci in clusters suggestive of staphylococcus. KOH mount gave a picture of ?fungal hyphae ?Yeast cells. Neosporin eye ointment was increased to 3 times a day. In next 5 days the visual acuity improved to 2/60 in the right eye. Patient was even better symptomatically and size of the defect had reduced to almost 3mmX3mm. (Figure 4A) . Fluorescein Subspeciality - Cornea

DOS Times - Volume 28, Number 4, July-August 2022 www.dosonline.org/dos-times 40 staining also reduced during this period. (Figure 4B). 4A 4B Figure 4: (A) Next 5 days follow up: Right eye showing resolving keratitis. (B) Right eye showing corresponding decreasing Fluorescein staining. Figure 5: Culture report depicting acanthamoeba growth on Non Nutrient Agar. Figure 7: Right eye showing nearly resolved keratitis with corneal scarring. Figure 6: (A) Right eye showing healing acanthamoeba keratitis. (B) Right eye showing healing acanthamoeba keratitis. The Culture report arrived stating growth of Acanthamoeba on non-nutrient agar. (Figure 5) The patient was prescribed PHMB 0.02% eye drops 1 hourly along with atropine 1% eye drops 3 times a day. Frequency of Neosporin eye ointment was also increased to 6 times a day. The keratitis started to heal further with corneal scarring in the right eye and stain was negative in next 5 days. (Figure 6 A, B) Although he could not procure PHMB eye drops. Within 2 weeks the ulceration had healed completely with corneal scarring (Figure 7). 6A 6B Discussion Acanthamoeba Ecology Acanthamoeba is an abundant protozoon on earth. Members of the genus Acanthamoeba are almost ubiquitous and have been isolated from soil, dust, air, treated and untreated tap water, swimming pools, air-conditioning units and numerous other domestic and outdoor environments.[4] The life cycle consists of an active feeding trophozoite phase and dormant cyst phase, which is activated by unfavourable conditions, such as exposure to extreme temperature, high or low pH, dryness or starvation.[4] Resilience through adverse conditions due to which the cysts can remain viable for 24 years or longer[5] allows acanthamoeba a broad ecological range and also makes it a formidable parasite in humans. Pathogenesis and Risk Factors The contact lens can introduce the pathogen through an abrasion previously caused by its wear. This trauma contributes to the onset and development of an amoebic infection, although this mode of infection is not solely responsible for Acanthamoeba keratitis, because persons who do not wear contact lenses have also been affected.[6] The results of in vitro binding studies by Alizadeth H et al.[7] have shown that abrasions increased the binding of the parasite to the cornea. The first step in the infection involves adhesion of Subspeciality - Cornea

www.dosonline.org/dos-times DOS Times - Volume 28, Number 4, July-August 2022 41 the trophozoite to the corneal epithelium. The trophozoites are species specific; they appear to bind only to corneal epithelial cells from humans, pigs, rabbits, and Chinese hamsters, whereas the majority of corneas in the animals are resistant to infection. Pathogenic strains of Acanthamoeba Castellani produce a variety of proteases, termed Acanthamoeba plasminogen activators which facilitate corneal invasion.[8-10] The stromal disease occurs later. Corneal trauma, ocular surgery and contact lens use are all risk factors for the development of infectious keratitis.[11] When the epithelial layer of the cornea is damaged, it is left susceptible to infection by fungi, bacteria or protozoa.[12] Prior to the widespread use of contact lenses, corneal abrasions and exposure to contaminated water or soil are the most distinguishable risk factors for AK. Contact lenses can help Acanthamoeba reach the cornea and exacerbate the progression of the disease. The lenses serve as a physical route of passage from a contaminated source (i.e., lens storage case or tap water) directly to the cornea. Lenses, especially when worn improperly or for longer than recommended, erode the corneal epithelium, allowing microbial entry.[13] Lens wear is also associated with upregulation of mannosylated receptor proteins on the epithelial surface that augment Acanthamoeba’s ability to eat away the corneal tissue. Biofilms and deposits of mannosylated proteins that build up on the lens surface cause trophozoites to produce increased amounts of epithelial apoptosis mediators and proteases that degrade the corneal stroma’s matrix.[13] Susceptibility to Acanthamoeba infection also depends on what type of contact lens is used. Overnight lenses put users at a drastically greater risk of developing AK, as one review by Mitro K at al. found a 30-percent prevalence of the disease among users.[14] While daily disposable lenses are the type of lens least likely to lead to infection,[15] individuals who wear rigid lenses are less prone to AK than users of soft lenses.[16] Approximately 88 percent of contact lens-related AK cases occur in soft contact lens wearers and 12 percent in rigid lens wearers.[17] Increasingly popular continuous-wear silicon hydrogel lenses are also an easier target for Acanthamoeba attachment than conventional hydrogels.[15] Clinical Symptoms of Acanthamoeba Keratitis The clinical features of the disease were reviewed in a study of 11 patients by Wang et al.[18] with culture-proven Acanthamoeba keratitis who were assessed during a 7-year period. The combination of clinical signs includes excessive pain, radial keratoneuritis and, in a later phase, a stromal ring infiltrate. Patients often have a history of contact lens use or contact with polluted water.[19] Acanthamoeba keratitis can occur in 2 separate forms. In the first form, the pathogen is restricted to the epithelium, and there is a good chance of recovery. In the second form, the parasite has entered the stroma, where it causes necrosis and intense inflammation.[20-21] Diagnosis Proper early stage diagnosis is essential before the Acanthamoeba invades more deeply into the cornea and causes permanent tissue damage. Unfortunately, at the initial visit the disease is more commonly diagnosed as herpes simplex keratitis than AK. Acanthamoeba is often considered as a cause of infection when corneal ulcers are unresponsive to antibiotics. This delay can allow the parasite to progress further into the eye.[19] The first step towards proper diagnosis is accurate slit-lamp examination. The slit lamp can show evidence of Acanthamoeba either through its direct presence or by the associated immune response.[23] The lack of bulbous dendrites typical in herpes patients is a good indicator a patient might have AK. Early and accurate slit-lamp examination is important in corneal ulcer patients, since disease stage at the time of AK diagnosis is a strong predictor of final visual outcome.[23] When available, direct in-vivo diagnosis can be performed using an advanced tandem scanning confocal microscope and Heidelberg retina tomograph II (HRT-II) with cornea module. Confocal Microscopy may reveal bright trophozoites with pseudopodia in the basal epithelium and double-walled cyst forms.[23] Polymerase chain reaction can also be used as a diagnostic tool when too few cells are available for an accurate visual determination. If in-vivo examination and PCR aren’t feasible, culturing corneal scrapings can be an invaluable tool in diagnosis of Acanthamoeba and differentiating it from ocular herpes. Histopathology: The double-walled cysts can be recognised with practice on an H&E. Other stains for Acanthamoeba include calcofluor white, acridic orange, Giemsa-Wright, Wheatly trichrome or periodic acid-Schiff.[23] Corneal scraping with a potassium hydroxide wet-mount preparation should be used if microscopic examination is possible. Sufficient scrapings must be taken using sterile equipment for culture plates. Samples are incubated at approximately 37°C on a non-nutrient agar plate coated with Escherichia coli. Within days, a positive culture will be covered with Acanthamoeba feeding on the bacterial overlay. Current Therapeutic Approaches The treatment consists of topical antimicrobial agents, which can achieve high concentrations at the site of infection. Since the cystic form of Acanthamoeba is highly resistant to therapy, a combination of agents is used. Most of the currently used topical agents are effective against trophozoites and cysts of Acanthamoeba such as biguanides, (i) PHMB[25-27] Polyhexamethylene Biguanide which is effective at low concentrations (0.02%), but is somewhat toxic to human corneal cells.[25, 26] (ii) Chlorhexidine, which is effective against both amoebic forms, and at minimal concentrations is not toxic to corneal epithelial cells.[25,26] Chlorhexidine 0.02% is often used in combination with aromatic diamidines. Subspeciality - Cornea

DOS Times - Volume 28, Number 4, July-August 2022 www.dosonline.org/dos-times 42 (iii)Aromatic Diamidines such as 0.1% propamidine isethionate: Brolene®, 0.15% dibromopropamidine, hexamidine 0.1% Desomedine show good results if the treatment is applied in the early stages of the infection.[26] Unfortunately, propamidine and hexamidine are not available in all countries. (iv) Neomycin an aminoglycoside antibiotic is readily available in combination with polymyxin B and Bacitracin Zinc as ophthalmic ointment and eyedrops. It is quite effective and easily available. (v) Imidazole and triazole antifungals topically and/or orally (miconazole, ketoconazole, itraconazole)[23] (vi) Steroid therapy (oral or topical) may help control inflammation if used judiciously only after control of the infection has been achieved.[23] These topical antimicrobials are administered every hourly initially for few days and after corneal debridement. These agents are then continued at least 2 hourly for 3 days depending on clinical response. The frequency is then reduced gradually. Two weeks may be required before a response is observed, and the total duration of therapy is a minimum of 3–4 weeks. Penetrating Keratoplasty (PKP) may be required in cases of impending perforation or for visual rehabilitation after scarring. Recurrence with peripheral limbal cyst reactivation and infection of the graft must be looked for. Topical anti-amoebic therapy must be continued after PKP.[23] Therapeutic keratoplasty retains a role for therapy of some severe complications of AK but not for initial treatment. With modern management, 90% of patients can expect to retain visual acuity of 6/12 or better and fewer than 2% become blind, although treatment may take 6 months or more.[23] Conclusion In this case the patient responded very aptly to Neosporin eye ointment which was started rather timely along with cycloplegics and antibiotic cover. On confirmation with culture reporting its dosage was increased and the ulcer healed within days. The key to diagnosis being good history taking, high degree of suspicion and strong clinical judgement which could guide us to confirm the organism using the right laboratory technique. Early initiation of organism specific therapy will lead to better clinical outcomes and better vision retainment. It may not always be necessary to use the more expensive of laboratory diagnostics and rarer and more difficult to procure drugs unless actually required! Declaration of Patient Consent In authors certify that they have obtained all appropriate patient consent forms. In the form patient has given his consent for his images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial Support and Sponsorship Nil. Conflicts of Interest There are no conflicts of interest. References 1. Moore MB, McCulley JP, Luckenbach M, Gelender H, Newton C, McDonald MB, Visvesvara GS. Acanthamoeba keratitis associated with soft contact lenses. Am J Ophthalmol 1985; 100:3:396. 2. Meier PA, Mathers WD, Sutphin JE, Folberg R, Hwang T, Wenzel RP. An epidemic of presumed Acanthamoeba keratitis that followed regional flooding. Arch Ophthalmol 1998; 116:8:1090-4. 3. Visvesvara GS, Moura H, Schuster FL. Pathogenic and opportunistic free-living amoebae: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea. FEMS Immunol Med Microbiol 2007; 50:1-26. 4. Marciano-Cabral F, Cabral G. Acanthamoeba spp. as agents of disease in humans. Clin Microbiol Rev 2003; 16:2:273-307. 5. Kilvington S, Gray T, Dart J, Morlet N, Beeching JR, Frazer DG, Matheson M. Acanthamoeba keratitis: The role of domestic tap water in the United Kingdom. IOVS 2004; 45:1:165-169. 6. Thomas PA, Geraldine P. Infectious keratitis. Curr Opin Infect Dis 2007; 20:2:129-41. 7. Alizadeth H, Neelam S, Hurt M, Niederkorn JY. Role of contact lens wear, bacterial flora, and mannose-induced pathogenic protease in the pathogenesis of amoebic keratitis. Infect Immun 2005; 73:2:1061- 8. 8. Watt K, Swarbrick HA. Microbial keratitis in overnight orthokeratology: Review of the first 50 cases. Eye Contact Lens 2005; 31:5:201-8. 9. Hammersmith KM. Diagnosis and management of Acanthamoeba keratitis. Curr Opin Ophthalmol 2006; 17:4:327-31. 10. Lorenzo-Morales J, Khan NA & Walochnik J: An update on Acanthamoeba keratitis: diagnosis, pathogenesis and treatment. 2015;22, 10. 11. McCully JP, Alizadeh H, NiederkornJY. The diagnosis and management of Acanthamoeba keratitis, CLAO J, 2000; 26:47-51. 12. Kunimoto DY, Sharma S, Garg P, Gopinathan U, Miller D, RaoGN. Corneal ulcerations in the elderly in Hyderabad, south India, Br J Ophthalmol , 2000;84:54-9. 13. Niederkorn JY, Ubelakar JE, McCullyJP, et al. Susceptibility of corneas from various animal species to in vitro binding and invasion by Acanthamoeba castellani, Invest Ophthalmol Vis Sci, 1992;33:104-12. 14. Mitro K, Bagvathiamai A, Zhou OM, et al. Partial characterization of the proteolytic secretions of Acanthamoeba polyphaga, Exp Parasitol, 1995;78:377-85. 15. Alfieri SC, Correia CE, Motegi SA, PralEM. Proteinase activities in total extracts and in medium conditioned by Acanthamoeba polyphaga trophozoites, J Parasitol , 2000;86:220-7. 16. Kong HH, Kim TH, ChungDI. Purification and characterization of a secretory serine proteinase of Acanthamoeba healyi isolated from GAE, J Parasitol, 2000;86:12-7. 17. He YG, Niederkorn JY, McCully JP, et al. In vivo and in vitro collagenolytic activity of Acanthamoeba castellani, Invest Ophthalmol Vis Sci, 1990; 31:2235-40. Subspeciality - Cornea

www.dosonline.org/dos-times DOS Times - Volume 28, Number 4, July-August 2022 43 18. Wang IJ, Hong JP, Hu FR. Clinical features and outcomes of Acanthamoeba keratitis, J Formos Med Assoc, 1997;96:895-900. 19. Kanski JJ, Nischal KK., Ophthalmology: clinical signs and differential diagnosis, LondonMosby International, 1999; 140-1. 20. Claerhout I, Kestelyn P. Acanthamoeba keratitis: a review, Bull Soc Belge Ophtalmol, 1991;274: 71-82. 21. Garner A. Pathology of Acanthamoeba infection, Cornea, 1998;17:535. 22. Mietz H, Font RL. Acanthamoeba keratitis with granulomatous reaction involving the stroma and anterior chamber, Arch Ophthalmol, 1997;115:259-63. 23. Tu EY, Joslin CE, Sugar J, Booton GC, Shoff ME, Fuerst PA. The relative value of confocal microscopy and superficial corneal scrapings in the diagnosis of Acanthamoeba keratitis. Cornea 2008; 27:7:764-72. 24. Graff JM, Goins KM, Syed NA, Sutphin JE. Acanthamoeba Keratitis: 39-year-old contact lens wearer with persisting keratitis and pain. EyeRounds.org. December 4, 2006. 25. Lim N, Goh D, Bunce C, Xing W, Fraenkel G, Poole TR, Ficker L. Comparison of polyhexamethylene biguanide and chlorhexidine as monotherapy agents in the treatment of Acanthamoeba keratitis. American Journal of Ophthalmology, 2008;145:130–135. 26. Lorenzo-Morales J, Martín-Navarro CM, López-Arencibia A, Arnalich-Montiel F, Piñero JE, Valladares B. Acanthamoeba keratitis: an emerging disease gathering importance worldwide? Trends in Parasitology, 2013;29(4): 181–187. 27. Martín-Navarro CM, Lorenzo-Morales J, López-Arencibia A, Reyes-Batlle M, Piñero JE, Valladares B, Maciver SK. Evaluation of Acanthamoeba myosin-IC as a therapeutic target. Antimicrobial Agents and Chemotherapy, 2014;58(4):2150–2155. 28. John K.G. DartValerie P.J. SawSimon Kilvington. Acanthamoeba Keratitis: Diagnosis and Treatment Update 2009. American Journal of Ophthalmology. October 2009;148(4):487–499. Dr. Parul Lokwani, MBBS, DNB (Oph), PGDHA ADEH (Arunodaya Deseret Eye Hospital), Gurgaon, Haryana, India. Corresponding Author: Subspeciality - Cornea

DOS Times - Volume 28, Number 4, July-August 2022 www.dosonline.org/dos-times 44 Sensory Evaluation of Strabismus Gunjan Saluja[1], MD, DNB, FICO, FAICO, Asha Samdani[2], MD, DNB, FICO 1. Consultant Strabismus, Oculoplasty and Neuro-Ophthalmology Services, Bhatia Netralaya Bhilai, Chhattisgarh. 2. Consultant Strabismus, Oculoplasty and Neuro-Ophthalmology Services Virinchi Hospitals, Hyderabad. Figure 1: Bagolini’s striated glasses. Strabismus examination is incomplete without the sensory evaluation which is an integral part of evaluation and determines binocularity and fusional status of the patient. The various tests target to determine the presence of a sensory adaptation; suppression or anomalous retinal correspondence in a patient of strabismus. The target of strabismus surgeries is beyond cosmesis and involves the improvement in the functional outcomes in the form of improved stereopsis and binocularity. Thus, making a careful examination of sensory status absolutely essential. Sensory examination includes the test for suppression, test for anomalous retinal correspondence and test for stereopsis. Test for Suppression Suppression is a sensory adaptation phenomenon. It can be facultative or obligatory, central or peripheral, and unilateral or alternating. The commonly performed tests for suppression include: Bagolini Striated glasses Bagolini Striated glass test is the most physiological test for dissociation. The test is performed using a pair of striated glasses, the axis of striations are kept at right angle to each other, 45 degree and 135 degree. Patient is shown a point source of light. When viewed through glasses the point source of light is seen as a line which is at right angle to striation. (Figure1) Interpretation In case of suppression the patient may see only one line. In patients with central suppression scotoma a cross response with a central gap is observed by the patient.[1] Worth Four Dot Test Worth four dot test is a less physiological test as in this test red green goggles are used to cause dissociation. In this test the patient is made to wear red green glass, such that red lens lies in front of right eye and green lens lies in front of left eye. The red lens filters all color except red and green lens filters all colors except green. The patient then views a box of four lights which has 1 red, 2 green and 1 white light. The test is performed at a distance of 6 meter and subtends an angle of 1.2 degree. If the patient sees only three green dots, it suggests suppression of right eye. On the other hand, if the patient can see only two red dots, then it suggests suppression of left eye.[2] Tests for Anomalous Retinal Correspondence Anomalous retinal correspondence (ARC), is a sensory adaptation for strabismus and develops in early onset, small angle constant deviations. Bagolini’s Striated Glasses for ARC A symmetrical cross response seen in the presence of manifest squint is indicative of harmonious anomalous correspondence. An asymmetrical cross response with manifest squint such that the two lines are seen intersecting each other at some point other than midline, to form A or V instead of X response is indicative of normal retinal correspondence. The power of prism added to get a symmetric cross response gives the subjective angle of squint.[3] Worth Four Dot Test for ARC If a patient with manifest squint can see four dots, then it is suggestive of harmonious anomalous retinal correspondence, and if the patient sees five dots 2 red and 3 green, then this indicates normal retinal correspondence. The uncrossed pattern i.e. red on right is suggestive of esodeviation and the crossed pattern with red on left is suggestive of exodeviation. This test can also be used to measure subjective angle by adding prisms till patient sees normal four dot response. After image test After image test is a highly dissociative test and demonstrates visual direction of two fovea and eccentric fixation point. In this test the right eye is flashed with vertical bright flash of light and left eye is flashed with horizontal bright flash of light. Patient is then asked to draw relative positions of after image. If patient sees two after images as cross, it is indicative of normal retinal correspondence. In asymmetrical crossing, horizontal and vertical lines have their centers separated and is suggestive of anomalous retinal correspondence. The amount of separation is directly proportional to angle of anomaly.[4] Tests for Stereo Acuity Stereopsis is the ability to fuse images that have horizontally Subspeciality - Pediatric Ophthalmology & Strabismus

www.dosonline.org/dos-times DOS Times - Volume 28, Number 4, July-August 2022 45 disparate retinal elements within Panum’s fusional area resulting in depth perception, i.e. third dimensional image. Test for Near Stereo-Acuity The Netherlands Organization/TNO test The TNO test for stereo-acuity assessment is a simple test based on anaglyph principle, in which dissociation of image is produced by using color. The anaglyph consists of stereo paired object formed by using conjugate colors, these objects when viewed through red green glasses gives appearance of threedimensional scene. The test can be easily done in children above 3 years of age. The patient is made to wear red green glass, and TNO plates are shown serially at 40 cm distance in well illuminated room. TNO test consist of 7 plates, the initial three plates enable the examiner to establish gross stereopsis, plate IV is a suppression test and plates V- VII are for qualitative estimation.[5] (Figure 2) Figure 2: TNO test with red green glass. Figure 3: Randot stereo-acuity test with polaroid glasses. Titmus Stereo Test This test is based on the vectographic principle, the vectograph permits two stereo paired pictures being developed in a pattern such that light passing through one picture is polarized in one direction and light passing through second picture is polarized in other direction and a three-dimensional image can be appreciated by observer by wearing special glasses with Polaroid filters. In Titmus stereo test, the stereograms has contour patterns which uses Polaroid filters located at axis of 45 and 135. The test is used for screening of gross stereopsis and fine depth perception especially in strabismus. The test has minimal monocular clues and hence reduces the chances of false results. However, patients may point out images which look different from others and not because of stereopsis.[5] Stereo Butterfly test Similar to Titmus fly test but has a configuration of butterfly hidden within the dots. Randot Stereotest Based on vectographic principle, similar to Titmus fly test and Stereo Butterfly test, but uses random dots instead of contour patterns that removes the lateral displacement cue found in Titmus fly test. (Figure 3) Lang Test Based on panographic principle, Lang test incorporates a grid of cylinders with random dots in its pattern, causing deviation of image to give real time depth perception. Glasses are not needed and a separate image is provided to each eye through cylindrical lenses imprinted of surface lamination of test card. Two versions of the Lang stereo test are available, Lang-Stereotest I that displays a star, a cat and a car. Lang-Stereo test II has a moon, a truck and an elephant, in addition the test also contains a star which can be seen by one eye also. All the three patterns are visualized at different level. The test is especially useful in children who refuse to wear Polaroid or red-green glasses. In a study done by Ancona et al, Lang I stereo-test was found to have highest sensitivity, specificity, positive predictive value, and negative predictive value.[6] Stereopsis Testing with Synaptophore Two slide types are available to test stereopsis with synaptophore, one slide type has a paratrooper and plane. Patient is asked whether paratrooper is in front of plane or not. Second slide available consist of four stars when seen binocularly each star appears in front of other. Lang Two Pencil Test Horizontal Lang two pencil test can be used as a screening test for gross stereopsis and has a 100% sensitivity.[7] The examiner holds a pencil horizontally and the child is asked to touch the tip of pencil with the tip of another pencil rapidly, coming from one side. Care should be taken to avoid the end view of pencil as that can be accomplished even monocularly, horizontal pencils are therefore better. The test is simple and can be done even in the absence of fine stereo-tests. Stereo Test for Distance Distance stereo-test are highly sensitive for small refractive error and heterophorias. Normal distance stereo-acuity indicates good fusion. Frisby Davis Distance (FD2) test is the most commonly used distance stereo-acuity test. FD2 test is based on the principle of real depth perception. The test is performed at a distance of 6 meter. The test consist of a box with four back illuminated and differently shaped plastic objects mounted on plastic Subspeciality - Pediatric Ophthalmology & Strabismus

DOS Times - Volume 28, Number 4, July-August 2022 www.dosonline.org/dos-times 46 rods, the plastic objects are usually geometric shapes which are set in a transparent frame pointing towards observer, shapes although being translucent are sufficient to hide the plastic rods. (Figure 4) Thus, the shapes appear to be free floating. Repeated testing is possible and the test does not require any special glasses.[8] Normal stereo-acuity on FD 2 test is 10-20 arc second.[9] Figure 4: Frisby Davis Distance (FD2) distance stereoacuity test. Distance Randot Test The test is based on the vectographic principle, and is performed at a distance of 3m. Patient is asked to identify the objects hidden in the random dot pattern. The test offers no monocular clues and deterioration of distance stereo acuity indicates poor fusional control.[10] The test measures stereo-acuity between range of 400-60 arc sec. Other tests described for distance stereo-acuity measurement include AO Vectographic Project-O-Chart Slide test,[11] and the Mentor II-SG B-VAT (Baylor Video Acuity Test-Mentor system).[12] References 1. Bagolini B. Scientific essay: Bagolini’s Striated Glasses: a reappraisal. Binocul Vis Strabismus Q. 1999;14(4):266-71. 2. Roper-Hall G. The ‘‘worth’’ of the worth four dot test. Am Orthopt J 2004;54:112Y9. 3. Bagolini. Sensorio-motorial anomalies in strabismus: (anomalous movements). Doc Ophthalmol 1976;41:23Y41. 4. Hansen Ak. “After-Image Transfer Test” In Anomalous Retinal Correspondence. Ama Arch Ophthalmol. 1954;52(3):369–374. 5. Walraven J, Janzen P. TNO stereopsis test as an aid to the prevention of amblyopia. Ophthalmic Physiol Opt. 1993 Oct;13(4):350-6. 6. Ancona C, Stoppani M, Odazio V, La Spina C, Corradetti G, Bandello F. Stereo tests as a screening tool for strabismus: which is the best choice? Clin Ophthalmol. 2014 Nov 12;8:2221-7. 7. Nongpiur ME, Sharma P. Horizontal Lang two-pencil test as a screening test for stereopsis and binocularity. Indian J Ophthalmol. 2010 Jul-Aug;58(4):287-90. 8. Adams WE, Hrisos S, Richardson S, Davis H, Frisby JP, Clarke MP. Frisby Davis distance stereoacuity values in visually normal children. Br J Ophthalmol. 2005 Nov;89(11):1438-41. 9. Bohr I, Read JC. Stereoacuity with Frisby and revised FD2 stereo tests. PLoS One. 2013 Dec 12;8(12):e82999. 10. Wang J, Hatt SR, O’Connor AR, Drover JR, Adams R, Birch EE, Holmes JM. Final version of the Distance Randot Stereotest: normative data, reliability, and validity. J AAPOS. 2010 Apr;14(2):142-6. 11. Rosenberg S, Sherman A. Vectographic project-o-chart slides. J Am Optom Assoc. 1968 Nov;39(11):1002-6. 12. Instruction manuals:. B-VAT II-SG Video Acuity Tester. Norwell, MA: Mentor O&O, 1987. Dr. Gunjan Saluja, MD, DNB, FICO, FAICO Pediatric Ophthalmology and Strabismus Consultant Strabismus, Oculoplasty and Neuro-Ophthalmology Services Bhatia Netralaya, Bhilai, Chhattisgarh. Corresponding Author: Subspeciality - Pediatric Ophthalmology & Strabismus

www.dosonline.org/dos-times DOS Times - Volume 28, Number 4, July-August 2022 47 Acquired Restrictive Esotropia of Ambiguous Etiology in A Two-Year-Old Child Sandra C Ganesh, DNB, Cinnam Shailaja, MS, Murali Krishnan Srinivasan, MS Department of Pediatric Ophthalmology and Strabismus, Aravind Eye Hospital, Coimbatore , India. Abstract: This reports a rare case of large angle restrictive esotropia secondary to presumed subacute myositis of medial rectus (MR). A two-year-old child came with progressive inward deviation of right eye since nine months of age. She had right sided face turn, esotropia in right eye with loss of abduction. Intraoperatively two fibrotic bands were found beneath MR which were released close to sclera and medial rectus recession was performed, with negative forced duction test at the end. Post operatively, there was minimal esophoria, abolition of face turn and improved abduction. The results were maintained at six months follow-up visit. Introduction Orbital myositis is a non-specific, localised orbital inflammation involving extraocular muscles and presents with sudden painful eye movements, proptosis, ptosis, strabismus and diplopia. While in adults it is characterised by pain, children may have subacute and atypical presentation without pain or proptosis.[1,2] Here one such rare clinically suspected toddler is presented. Case A two-year-old girl presented to us with the complaint of inward deviation of her right eye noted since nine months of age. Her parents stated that she who had normal ocular alignment and motility previously, was suddenly unable to move her right eye outwards and had a face turn to her right side. This was not preceded by any form of illness or vaccination. Her unaided visual acuity and refraction were age appropriate. Anterior segment and dilated fundi examination were normal. She had a right face turn of 30 degrees. In primary gaze her right eye was 30ET with severely limited abduction (-5) with downshoot on attempted abduction. Photographs before 9 months of age seemed normal (Figure 1). MRI of he brain was reported to be normal. MRI of her orbit revealed atrophy of the Figure 1: (A) Orthophoria before 9 months of age (B) Esotropia of right eye at 1 year of age right lateral rectus muscle and mild thickening of right medial rectus (MR) muscle likely due to compensatory hypertrophy. We diagnosed her to have acquired right sided sixth cranial nerve palsy of uncertain etiology. In view of significant face turn and large angle ET, surgery under general anesthesia was planned with the aim of recessing the MR and a split tendon (Hummelshiem’s) transposition to increase the abducting vector force. Intraoperative forced duction testing (FDT) showed extreme tightness of the MR which was hooked with great difficulty (Figure 2A) and secured with 6-0 polyglactin sutures. After carefully cutting the muscle from its insertion it was noted that the restriction to abduction was still present. On further exploration, two bands of fibrotic tissue were noted, one below (Figure 2B) and the other above the muscle (Figure 2C) which were pulling the eyeball medially. They were released by carefully cutting close to their scleral attachment (Figure 2 B). Following this the FDT became negative. A hemi-hangback recession of 7 mm of the muscle was done (Figure 2D). The initial plan of Hummelshiems transposition was aborted due to the disparate intraoperative findings. Postoperatively, the child had good ocular alignment in primary gaze with esophoria. Subspeciality - Pediatric Ophthalmology & Strabismus

DOS Times - Volume 28, Number 4, July-August 2022 www.dosonline.org/dos-times 48 Figure 2: (A) Medial rectus muscle hooked (B) Fibrotic band below the MR muscle released by cutting its attachment close to the sclera (C) Another band of tissue above the insertion if medial rectus muscle (D) Hemi hangback recession of medial rectus muscle Figure 3: (A) Pre operative picture showing gross face turn to the right (B) Post operative picture showing abolition of face turn (C) Preoperative picture showing esotropia with abduction limitation of right eye (D) Post operative picture showing improved abduction of right eye Abduction had improved considerably (-2) and the child’s face turn had decreased to 10 degrees to right (Figure 3). Her condition remaines stable at 1 year follow up (Figure 4). In view of the intraoperative findings, we requested the radiologist to review the preoperative orbital MRI again who re-reported thickening of medial rectus muscle and presence of small fibrous bands adjacent to the muscle with associated fat strands, possibly being sequelae of inflammatory myositis. Comments In this cae the child had no prior pain/redness/proptosis or illness before the onset of esotropia and motility limitation, pointing towards subacute myositis. Definitive diagnosis by pathological examination could not be done in our case as we did not excise any muscle tissue or fibrotic bands in this surgery. A case series by Dias et al[3] describes three similar cases of severely restricted ocular motility and large angle strabismus acquired rapidly during the first months of life in children who had normal eye alignment and movements at birth managed surgically. A case report by Gil et al[4] describes a six-year-old child diagnosed with orbital myositis associated with Coxsackie virus. Another case report[5] describes a nine-year-old girl diagnosed with idiopathic orbital myositis who responded well to oral corticosteroid treatment. As our patient presented late, we did not give a trial of steroids. As she had normal ocular alignment and motility prior to the development of a progressive esotropia that stabilised at a large angle, we considered the etiology of CCDD or Duane’s syndrome unlikely. To conclude, subacute orbital myositis should be included in the differential diagnosis in paediatric patients with sudden onset of ocular motility restriction and strabismus presenting even without significant pain, proptosis and/or ptosis. Figure 4: 1 year post operative picture showing stable condition Subspeciality - Pediatric Ophthalmology & Strabismus

www.dosonline.org/dos-times DOS Times - Volume 28, Number 4, July-August 2022 49 References 1. Belanger C, Zhang KS, Reddy AK, Yen MT, Yen KG. Inflammatory disorders of the orbit in childhood: a case series. Am J Ophthalmol. 2010;150(4):460–3. 2. Chakor RT, Santhosh N S. Painless orbital myosotis. Ann Indian Acad Neurol 2012; 15: 224-6. 3. Souza-Dias C, Scott AB, Wang A Progressive restrictive strabismus acquired in infancy. British Journal of Ophthalmology 2005;89:986- 987. 4. Gil P, Gil J, Paiva C, Castela G, Castela R. Medical and Surgical Treatment in Pediatric Orbital Myositis Associated with Coxsackie Virus. Case Rep Ophthalmol Med. 2015;2015:917275. doi: 10.1155/2015/917275. Epub 2015 Oct 15. PMID: 26550508; PMCID: PMC4624886. 5. Yazicioglu T, Kutluturk I. Idiopathic Orbital Myositis in a 9-YearOld Girl: A Case Report. Iran J Pediatr. 2015 Jun;25(3):e371. doi: 10.5812/ijp.25(3)2015.371. Epub 2015 Jun 27. PMID: 26199706; PMCID: PMC4505988. Dr. Sandra C Ganesh, DNB Consultant, Department of Pediatric Ophthalmology and Strabismus, Aravind Eye Hospital, Coimbatore, India. Corresponding Author: Subspeciality - Pediatric Ophthalmology & Strabismus

DOS Times - Volume 28, Number 4, July-August 2022 www.dosonline.org/dos-times 50 Impact of Strabismus Management on the Retinal Microstructure Shreya Shah[1], DOMS, ORBIS fellow, Mehul Shah[2], MS, Deeksha Thorat[2], MBBS 1. Drashti Netralaya, Dahod, Gujarat, India. 2. Vitreo Retinal Fellow Sankara Nethralaya. Abstract: Aim: To examine whether change in retinal structure can improve vision and stereoacuity following strabismus management. Methods: We recruited patients who presented with strabismus from 2017 to 2019. Information on demographics, posterior and anterior segment findings, and strabismus surgery was collected using a pretested online form. Patients’ stereoacuity was examined by employing the Titmus test. The central macular thickness and retinal nerve fiber layer (RNFL) thickness of all the eyes were evaluated through SD-OCT. Stereoacuity examination and OCT were performed again 3 months postoperatively. Result: We recruited 54 patients (mean age: 19.74 ± 9.2 years). Stereoacuity and vision exhibited significant improvements after treatment. Both eyes showed improvement in RNFL thickness but not CMT. Conclusion: Functional stereoacuity changes and structural RNFL changes were noted following appropriate treatment for strabismus. Introduction A crucial dimension of vision is stereoacuity.[1, 2, 3] It is a vital type of binocular vision responsible for depth perception.[2] In aniseikonia, stereoacuity is affected.[4] Stereopsis is absent in strabismus[5, 6] and refractive errors.[7, 8] Numerous factors affect stereopsis including literacy, poor vision, age, amblyopia, and deprivation.[9, 10] Stereoacuity can be improved by treating its cause including refraction, strabismus, or cataract.[11, 12, 13] This study explored whether strabismus management can improve alignment. The aligned eye may exhibit improved stereopsis and thus binocular vision (ref). We explored the association of functional improvement with retina structure changes. We evaluated whether functional improvement leads neuroanabolism. Materials and Methods Both the study protocol and informed consent form were approved by the Hospital Ethical Committee of Drashti Netralaya and were according to the guidelines of the Helsinki Declaration. We obtained written informed consent from the legal guardian or parents of each child, and each patient provided consent before study participation. This prospective cohort study recruited patients visiting the motility department who were diagnosed as having strabismus requiring surgical correction from 2018 to 2020. We excluded those with other pathology or neurological diseases that can affect the retinal nerve fiber layer (RNFL), optic nerve head (ONH), or central macular thickness (CMT). All patients received comprehensive eye assessments, which included slit lamp biomicroscope or handheld slit lamp evaluation for ocular alignment, A-scan ultrasound biometry, and tests for refraction and visual acuity (VA). Assessments were conducted under anesthesia in younger children who were unable to cooperate. We examined intraocular pressure by employing Perkins applanation tonometer. For children aged <3 years, monocular distance VA was tested. For nonverbal children, VA was examined based on a child’s ability to fix and follow objects. Fixation was determined by examining each eye’s ability to fixate on an object, maintain the fixation, and subsequently follow the object through varying gaze positions. Children aged 3–6 years were shown wall charts containing Snellen letters and numbers and subjected to the tumbling E test and HOTV as per the standard VA assessment. For children, single optotypes of ETDRS acuity charts with surrounding bars were presented. We examined cycloplegic refraction for all children. An indirect ophthalmoscope with +20 D lens was employed to examine the posterior segment. We assessed near stereopsis using the Titmus circle (Titmus, Optical Co, Inc., Chicago, IL, USA) and the Randot circle (Stereo Optical Co). We examined distance stereopsis by employing the B-VAT II BVS contour circle of the Mentor B VAT II video acuity tester (Mentor O & O, Inc., Norwell, MA, USA). Motor and sensory adoption were assessed using various tests for all patients. All patients underwent surgery. We measured distance stereopsis after strabismus and refractive error correction. An arc of 240 s was used with patients wearing liquid-crystal shutter glasses at a 6-m distance. A correct result indicated a successful test. However, for an incorrect result, Subspeciality - Pediatric Ophthalmology & Strabismus