January-February 2024 DOS Times

CONTENTS PAGE NO. TITLE 05 08 10 12 Outgoing Presidential Address Incoming Presidential Address Secretary's Report From the DESK of Chief Editor Subspecialities 16 50 29 62 23 59 21 57 35 68 38 75 43 78 84 Posterior Polar Cataract: Management NittyGritties Ptosis: A to Z Cross Linking in Thin Cornea - A Mini Review Trials in Management of Diabetic Retinopathy and complications: A Comprehensive Review Overview of Amblyopia- Clinical Features and Treatment Combination of Cyclosporine and Tacrolimus in Treatment of Vernal Keratoconjunctivitis The Effectiveness of Prophylactic Intracameral Moxifloxacin Use During Cataract Surgery Congenital Eyelid Imbrication Syndrome Newer Treatment Modalities in the Management of Keratoconus Overview of Laser Photocoagulation in Diabetic Retinopathy Corneal Collagen Crosslinking: Then and Now Ocular Decompression Retinopathy: A Rare Complication After Trabeculactomy Pediatric Keratoplasty Photodynamic Therapy Pachychoroid Spectrum of Disorders Lens/Cataract Oculoplasty Cornea Retina Squint Ocular Surface Case Report Beyond Ophthalmology Tearsheet 91 93 95 98 Bilateral Corneal Ulcer in Young Diabetic Male Shakespeare and Ophthalmology Perilous Prescription: Dangers of Misleading Advertisements in Medicine Roth Spots: Risk Factors

www.dosonline.org/dos-times DOS Times Volume 29, Number 7, January-February 2024 DOS EXECUTIVE MEMBERS (2021-2023) 01 Dr. Om Prakash Anand Dr. Prafulla Kumar Maharana Dr. Rajendra Prasad President Prof. Rohit Saxena Vice President Dr. Gagan Bhatia 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 Dr. Pawan Goyal Prof. Namrata Sharma Ex-Officio Members

Know Your Editor Editor 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 29, Number 7, January-February 2024 www.dosonline.org/dos-times 02 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 29, Number 7, January-February 2024 03 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 Consultant, Eye7 Hospitals, Lajpat Nagar, 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 Section Editor - Oculoplasty and Orbit Dr. Sanjiv Gupta Lotus Eye Center, Naraina Vihar, 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

DOS Times Volume 29, Number 7, January-February 2024 www.dosonline.org/dos-times 04 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 Dr. Arpan Gandhi Dr. Shroff’s Charity Eye Hospital New Delhi Section Editor - Ocular Pathology and Microbiology 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 Dr. Dewang Angmo MD, FRCS, FICO Dr R P Centre for Ophthalmic Sciences AIIMS Section Editor - Glaucoma Dr. Kavita Bhatnagar Professor & Head, Dept of Ophthalmology, AIIMS, Basani Phase-2, Jodhpur Section Editor - Glaucoma

www.dosonline.org/dos-times DOS Times Volume 29, Number 7, January-February 2024 05 Outgoing Presidential Address DOS TIMES Dr. Rajendra Prasad MBBS, MD Dear friends, my senior colleagues, teachers, ladies and gentlemen. I feel extremely glad to welcome every one of you to the final issue of DOS TIMES of our tenure. Ladies and Gentlemen, as I approach to the completion of my presidency of the DOS I will take the opportunity to reflect on what it has meant to me to be DOS president. But before I start I would like to express my gratitude towards all of you who have sincerely contributed to teaching and learning program of all the DOS scientific events in order to make them a grand success. This wouldn’t have been possible without the support of each and every one of you. I am proud to have been given the opportunity to serve as your president for the last one and halfyears. There are many wonderful people in this society with great energy, helping to create a better life for those in need around the world. Over the years I have been involved with, and on the board of, many other community members, but nowhere have I met better people than the members of our own Delhi Ophthalmological Society. This has been a rewarding and interesting experience. These past one and half years have been some of the most rewarding and at the same time challenging experiences of my professional career. I knew it was a significant commitment, but I was prepared to confront the obstacles in the way to achieve the goals I had in my mind. We confronted many challenges during our tenure, mainly difficult financial constraints, we were facing due to some unwarranted situation that affected our ability to achieve our potential and also due to an amplification of the threats regularly posed by misinformation, interference and individualism undermining the core values of society. During the one and half years we also confronted with many surprises. Most of you know about misinformation being spread about the society as a whole. We were surprised by the ferocity of the unfair attacks on office bearers by some of our senior DOS members. We were also surprised at the attempts to defame the society and subject us with unfair process in contravention of the constitution. Throughout all this, we remained steadfast with our commitment to the Rule of Law. We gave priority to our core values and followed as the primary guide to everything we did: that is excellence and professionalism; inclusivity and diversity and transparency and integrity. We did our best to keep the faith of our members to build and preserve the image of DOS that will last forever. Through the great work of our treasurer, we restricted our spending initiatives and adhered to stringent spending guidelines. We brought large scale, functions of the society back to life with least spending. We carried out our programs of education, training and resources that strengthened our professionalism, retained our commitment to solidarity. We had a strategic priority to have a good quality scientific programs, administrative and financial transparency and democratic accountability. We influenced and ensured that all the decisions are taken in a proper account of the constitutional value. Our vision was very clear “advancing science” and serving society with inclusive culture and work for the betterment of society and to ensure that member’s voices are heard and create more opportunities for them. I am not going to highlight all our accomplishments for the year, but this is important to mention

DOS Times Volume 29, Number 7, January-February 2024 www.dosonline.org/dos-times 06 that we could push through all the plans we had promised to you with the strong support from our executive team and of course help from our seniors and colleagues. I tried my best to fulfill the responsibility given to me and worked for the betterment of the society. It was due to the mutual passion of our members for a common goal helped us to organize many highly successful scientific events during our tenure, which included 9 monthly clinical meets, 10 subspecialty global webinars, 7 subspecialty evening CMEs, one full day cataract meet, one international DOS conference with international Ophthalmic society, a full day PG teaching program at RPC and highly successful DOS midterm and DOS annual conference with record number of registration and record amount of profit, all these with top notch host, national and international speakers. Both midterm and annual conferences were a phenomenal success, with better execution of conference management and scientific program, that it has become the envy of all the members of DOS. The theme of the conference “Unlocking Innovations & trends” inspired all the attendees to have some serious, honest and stimulating conversations among themselves. We hosted over 80 regular subspecialty sessions and more than 30 break out sessions with industry experts to raise funds for the society. This year we had re-cord overall registration, submission and attendance with outstanding full house live surgery sessions; fantastic featured speakers; very informative presentations and discussion; most of the sessions having great discussion with full attendance, phenomenal success of our wet lab training sections, great participation of delegates in each and every session, wonderful inaugural ceremony with the best possible chief guest the chief of RP Centre prof J S Titiyal, excellent gala dinner and musical time with Bollywood singer Neha Bhasin followed by delicious meals; superb DOS members entertainment program...! And the best possible venue selected the Ashoka. The very positive feedback from the attendees, showing that most of the sessions/events, were highly appreciated and rated. Great sponsors and trade satisfaction with huge numbers of footfall and superb sales. Although last moment glitches were quite challenging in both expected and unexpected ways, but with the cumulative efforts put in by our executive committee members and office bearers took up the very challenge, overcoming the hurdles and made the annual conference a big success and most memorable. Ofcourse there were some shortcomings due to the last minute absentees, although we took care of by replacing the talks with suitable speakers, but this has become a common problem in most of the conferences and I think this needs to be discussed and sorted out in the upcoming conferences. We also organized many public awareness programs for the prevention of eye diseases as to prevention of blindness through public awareness walks and seminars, radio, television, and many other means of communication media. We organized glaucoma awareness walk in association of GNEC and Shroff charity Daryaganj. We also lended our support to the organizations like Eye Bank Association of India in eye donation movement and organised walk for eye donation campaign in collaboration with RP Center. We organized special activities like DOS sports with full day cricket match in the month of march 23, again full day cricket match in the month of February 24, hands on Golf training session at Sri fort sports complex, was only possible with the active contribution of our treasurer and chair sports organising committee Dr Alkesh Chaudhary. Our library officer, Dr Bali have also been very active in the upliftment of DOS library. He personally added numerous journals, eBooks and articles to provide on demand to all the members. He also initiated to form a sub committee to formulate a code of ethics for practicing Ophthalmologist in Delhi NCR to ensure academic and administrative quality of higher education, through combining self and external quality evaluation, promotion and sustenance initiatives. Since our complete focus was on improving the profile of a scientific discipline and professional development through conferences, seminars, webinars, skill transfer courses, wet labs, live surgical courses, PG teaching programs, monthly clinical rounds, evening CMEs and networking events our two very important section have been publications through DOS Times and Delhi Journal of Ophthalmology. We could bring out all the issues of DOS times and DJO within the given time frame. My special thanks and appreciation goes to our secretary Dr J S Bhalla and our DJO Editor Dr Kirti Singh, who handled wonderfully both DOS Times and DJO. I would also like to thank all of you those who played special roles in handling to ensure that DOS succeeds and grow. I would like to congratulate all our vibrant executive members and those hidden skills of our volunteers because all this has only been possible with their cooperation and assist in bringing solutions to issues that we seriously dislike in the running of DOS. They have also been instrumental in bringing all of us together in the realization of these goals, whether on an individual level or at a group. Our accomplishments are entirely due to the executive members, including our teachers and seniors, who have worked with me throughout the year. Nothing could have been achieved without their outstanding abilities and dedicated efforts. In fact, only the accumulated efforts of successive executives and our members have allowed DOS to reach the place we stand today. I hope our actions over the past one and half years have carried out a grand tradition and have contributed, to laying the ground work for our leap into the future. I hope the progress report secretary and president led in the GBM has succeeded to indicate to you the amount of work that has been done during the last one year in our tenure within DOS. The funds raised allowed us to hold the conference at a greater level and support the organizations those in need in so many different areas. Our vendors delivering their best, at most competitive pricing, which will set a baseline price on their performance for future conferences. DOS TIMES

www.dosonline.org/dos-times DOS Times Volume 29, Number 7, January-February 2024 07 This year during annual conference DOS elections were held to elect the members of executive team. The entire process of election was conducted by a team of election commissioners Dr Deven Tuli, Dr Sushil Kumar and headed by chief election commissioner Dr Subhash Dadeya a man of integrity, with good social repute, conducted onsite ballot paper elections very competently, with utmost transparency and within constitutional provision’s. Congratulations to the whole team for positive thinking and hard work. You truly embraced the meaning of teamwork.The appellate committee members Dr S Khokhar, Dr Kamlesh and headed by Dr Rajender Khanna managed the post election matter very efficiently and to the satisfaction of all the contestants. On behalf of the DOS I want to send you all my deepest thankyou for completing the election process and helping the organization reach a new milestone. DOS has also grown in membership number and scope of responsibility with the new status of the highly looked after professional body. More has to be done and needs to be done to build on the reputation and glory of our society. Requesting all the members to maintain the professional values that make DOS unique, don’t spread negative news, which degrade the name of our society, because pointing fingers has never yielded solutions, while we should be positive to incorporate new ideas, approaches and suggestions from members to improve the quality and functioning of our society. I look forward to the next executive team’s capable steps toward building our society’s new, grand future and work to improve on the areas where we may have missed the mark and overcome the shortcomings if any in the upcoming events. I would like to thank our executive members for their commitment to the society, the time donated for the society, and for all their hard work to ensure we had a successful tenure. Our committee members and committee chairs for their, ongoing support and initiatives in carrying out the proceedings of society. Our senior colleagues and teachers for their, guidance, positive attitude and encouragement. I would congratulate Dr Rohit Saxena who is succeeding me and wish him well in his new role of DOS President. I wish him well in all his future endeavors. I pledge my support and wish him all the best. I also wanted to take a moment to recognize all our DOS office staff specifically Megha our graphic designer, Praveen our office incharge, Sandeep our accountant, Babu and Harshpal for everything you all have contributed to our account over the last one and half year. Thank you for your hard work, creativity, commitment, and for being a joy to work with every day. With this, friends I thank you again profusely for giving me the opportunity to serve as your president. My main personal goal in this role was for us all to have fun together while supporting the things that matter to our members. I think we came pretty close and almost all the goals what we set out to do was looked after carefully and carried out successfully. I wish you all a happy, prosperous and fruitful year ahead. "It always seems impossible until it's done" Thank you so much Jai Hind Dr. Rajendra Prasad President DOS DOS TIMES

DOS Times Volume 29, Number 7, January-February 2024 www.dosonline.org/dos-times 08 Incoming Presidential Address Prof Rohit Saxena MD, PhD Respected Dr. Rajendra Prasad, outgoing President, Dr. J S Bhalla Secretary, Dr. Alkesh Chaudhry Treasurer, all members of the executive committee; past Presidents and past Secretaries of this esteemed association; my teachers, senior colleagues, friends, ladies and gentlemen, it is indeed an honour for me to be addressing this august gathering as the President of this Society. With humility and enthusiasm, I step into this role, committed to advancing the field of ophthalmology and serving the needs of our members. At the outset, I wish to thank each member of the society for unanimously electing me as your Vice President in 2022. It is indeed humbling to become the President of a society I joined as a Junior Resident from Dr R P Centre, nearly 30 years ago. This society has seen some great past Presidents, Secretaries, office bearers and executive members, all of whom have contributed in making this the largest state society of ophthalmologists and one the best Ophthalmic societies in the World. Today, we look tall because we stand on the shoulders of giants. Alone I know I can achieve little, but with all your support I know we will not only continue to build on our strengths, but also reach new heights. As we embark on this journey together, I wish to share with you some of our proposed agenda and initiatives for the year ahead: Our focus would be on improving the participation of every member of the society and plan to hold events in different parts of the city. We will ensure enhanced education and professional development through conferences, seminars, webinars, skill transfer courses, wet labs, surgical training sessions, PG teaching programs, monthly clinical rounds, networking events and publications through DOS Times and Delhi Journal of Ophthalmology. These will be a series of online specialty courses to reach wider range of residents, trainee and professionals. Use our collective strength to work for the benefit of the common ophthalmologist including issues regarding registration of Eye Centre as day care centre, Insurance, TPA standardized price system and the daily challenges faced in running a clinic. Ophthalmology is a unique speciality which provides extensive yeoman service unfortunately without due recognition and acknowledgement by the public and those in power. We had launched the DOS Community Program when I was the Secretary, I plan to strengthen it, increase screening services and try to bring together all those doing community work individually so that we can showcase the valuable input we are making to the health of the nation. We need to bring to the national consciousness, eye related problems like visual impairment due to cataract, uncorrected refractive error, childhood myopia, corneal blindness and the challenges in the eye donation program, glaucoma blindness and our extensive contributions in ameliorating these issues. tog tog tog tog 1. Strengthen the Ongoing Activities and Make Them More Inclusive 2. Increase Webinars, Start A DOS Blog 4. Advocacy 3. Strengthen DOS Community Program DOS TIMES

www.dosonline.org/dos-times DOS Times Volume 29, Number 7, January-February 2024 09 DOS TIMES Creating a forum for Young ophthalmologist in DOS. An event where residents, fellows and ophthalmologists fresh into clinical practice can meet and dicsuss about the unique challenges and problems they face and look for solutions. We will have sessions on future avenues and prospects and career counselling. These will be one-on-one interactions with experts and counselors in the field. The DOS website will collate information and become a one-stop-shop for information on fellowship and job opportunities in and around Delhi. A program to develop the leaders of tomorrow. This program will help build an individual's leadership skill and capacity to excel, both personally and professionally and become future leaders of DOS. We will create an environment for reaserch and development so that new and innovative techniques and ideas developed by our members get the exposure they need. We also hope that we can put in place an Independent Ethics Committee that can help individual practioners and institutions in Delhi not having an Ethics committee to be a part of this revolution. We will play more than just cricket, games for everyone. Have a day out with friends. I have always been blessed with the love and affection of a huge number of DOS members and I pray for their continued support and encouragement so that we can bring about a lasting change in our society. Finally, I wish to acknowledge my family my wife Dr. Pikee and my son Dr. Abhyuday who have always stood with me and permitted me to spend time with my larger DOS family sometimes at the cost of their time. Thank you everyone for being a part of this momentous occasion for me and I look forward to a year of enjoyment, interaction and the opportunity to do good work for our organisation, our community and our patients. Long live DOS! Jai Hind. Prof. Rohit Saxena President, DOS tog tog tog tog tog 5. DOS-YO Forum 6. DOS Crystal Ball Program 7. DOS Leadership Development Program 8. Encouraging Research and Innovation 9. DOS Sports Day

DOS Times Volume 29, Number 7, January-February 2024 www.dosonline.org/dos-times 10 DOS TIMES Secretary's Report Dr. Jatinder Singh Bhalla, MS, DNB, MNAMS Secretary Delhi Ophthalmological Society Honorable President, Dr. Rajendra Prasad, Incoming President Dr. Rohit Saxena, respected Senior Members of the society and my dear friends I welcome you all to this General Body Meeting of the Delhi Ophthalmological Society for the year 2022-2024. On behalf of the executive committee, it is my pleasure and privilege to extend a warm welcome to everyone in this General Body Meeting. We are informed to house that our tenure was finish in October, 2023 but special GBM was held on 15-11-2023 at Army hospital, new delhi, the president were announced the final decision in special GBM that we will hold the annual DOS conference in February month on depend on availability of venue. I wish to express my sincere gratitude and appreciation to all the members of the entire executive committee and all the members of DOS for extending overwhelming support and encouragement throughout this current academic year. The DOS Executive has been constantly striving hard to take DOS to greater heights and set higher standards in all its activities. DOS Membership: DOS is the world’s largest state ophthalmological society with a current membership of 10590 members. 2022-2024 Delhi : 62 Outside : 428 Total : 490 DOS Monthly Clinical Meeting was held No Event Date Hospital 1. November, 2022 27th November, 2022 (Sunday) Safdarjung Hospital 2. December, 2022 18th December, 2022 (Sunday) Dr. RML Hospital 3. January, 2023 5th February, 2023 (Sunday) Centre For Sight 4. February, 2023 5th March, 2023 (Sunday) DDU Hospital 5. March, 2023 2nd April, 2023 (Sunday) Lady Hardinge Medical College 6. April, 2023 30th April, 2023 (Sunday) Dr. Shroff ’s Charity Eye Hospital 7. July, 2023 30th July, 2023 (Sunday) Dr. R.P. Centre for Ophthalmic Sciences 8. August, 2023 27th August, 2023 (Sunday) Army Hospital (R&R) 9. September, 2023 24th September, 2023 (Sunday) Guru Nanak Eye Centre • Got shortage of Pilocarpine sorted out by intervention of PMO in letter dated 2nd June, 2022 • Regular publication & mailing of all issues of DOS TIMES • For the first time, International faculty talk (Dr Boris Malyugin) in the monthly meeting was held at Dr R.P.C AIIMS, New Delhi on 26th June, 2022 • World Wide DOS Physical CME Series on Cataract Didactics & Dietetics - 28th January, 2023, Ashok Hotel, New Delhi • Global DOS We Series on Managing Common Corneal Diseases on 9th February, 2023 at Virtual Platform DOS Subspecialty Meetings & Other Events

www.dosonline.org/dos-times DOS Times Volume 29, Number 7, January-February 2024 11 DOS TIMES • Glaucoma Awareness Walk on 12th March, 2023 at Dr. Shroff ’s Charity Eye Hospital, New Delhi • Global DOS Web Series on Retina at India Habitat Centre, New Delhi at Virtual Platform • International DOS Conference was held from 8th to 11th April, 2023 at Phuket, Thailand • Global DOS Webinar on Squint on 20th April, 2023 at Virtual Platform • DOS World Wide CME on Cataract & Cornea on 11th June, 2023 at India Habitat Centre, New Delhi • DOS Entod virtual Quiz on Comprehensive Ophthalmology on 9th June, 2023 at Virtual Platform • Walk for Vision on Eye Donation program on 29th August, 2023, Dr R.P.C AIIMS, New Delhi • DOS Mid Term Conference on Focus on Future from 2nd to 3rd September, 2023 at Ashok Hotel, New Delhi • DOS National Level CME on “Innovations in Ophthalmology” from 8th to 9th September, 2023 at Army Hospital, New Delhi • World Sight Day Walk was held on 12th October, 2023 at India Gate New Delhi • World Wide DOS Evening CME on Tackling Challenging Scenarios in Cataract Surgery and Clinical Application of Contact lenses in Ophthalmic Practice was held on 4th November, 2023 at India Habitat Centre, New Delhi • DOS PG Teaching Programme was held at Dr. R.P. Centre for Ophthalmic Sciences from 17th to 19th November, 2023 • DOS CME on latest updates in Ophthalmology was held at NRCH, New Delhi on 26th November, 2023 • DOS Cricket Match was held on 11th December, 2023 at Sirifort National Cricket Ground, New Delhi • World Wide DOS Evening CME on Advances in Cataract, Refractive and Corneal Surgery on 7th January, 2024 at Bharti Eye Hospital • Dos World wide CME on Cataract & Cornea on 25th February, 2024 at India Habitat Centre, New Delhi DOS Times were sent hard copies were sent by speed posts all issues published were on a subspecialty: 1. DOS Times on - (Vol. 29 No. 1) Cataract 2. DOS Times on - (Vol. 29 No. 2) General Issue 3. DOS Times on - (Vol. 29 No. 3) Strabismus & Neuro Ophthalmology 4. DOS Times on - (Vol. 29 No. 4) General Issue 5. DOS Times on - (Vol. 29 No. 5) Cornea 6. DOS Times on - (Vol. 29 No. 6) Retina 7. DOS Times on - (Vol. 29 No. 7) General Issue (Unlocking Innovations & Trends) has been successfully held from 29th to 31st March, 2024 at Annual Conference. The highlights were as follows : • A full day dedicated Live Surgeries - 22 • Dr. A C Agarwal Trophy - 08 • Dr. Arjun Narang Trophy - 14 • Dr. T P Agarwal Trophy - 08 • Video Presentation - 32 • Interesting Cases - 175 • Thesis - • Free Papers - 262 • E-Posters - 194 • 2500+ plus Registrations The detailed report will be read by Dr. Kirti Singh– Editor - DJO. DOS Times 2022 - 2023 74th Annual DOS Conference 2024 DJO

DOS Times Volume 29, Number 7, January-February 2024 www.dosonline.org/dos-times 12 DOS TIMES Mid Term Conference 2023 was organized on 2nd & 3rd September, 2023. This was inaugurated by Ms. Meenakshi Lekhi of Delhi Ophthalmological Society on 2nd September, 2023. • 1200 Plus Registrations • 300 Plus Faculties • Free Paper, Interesting cases, Eposter • A full day dedicated Live Surgeries • DOS Scientific Quiz and DOS Quiz Life Time Achievement Award : Dr. Rajender Khanna Life Time Achievement Award : Prof. S. Bharti Dr. Om Prakash Oration : Dr. Jodhbir Mehta Dr. Sadhu Ram Gupta Oration : Brig. Sanjay Kumar Mishra AVSM, SM**, VSM** Dr. Hari Mohan Oration : Dr. Noshir M. Shroff Dr. B.N. Khanna oration : Dr. Lalit Verma Dr. P.K. Jain Oration : Dr. Rajesh Sinha Dr. S.N. Mitter Oration : Dr. Radhika Tandon Mid Term Conference 2023 Orations • Around 700 Faculties • DOS Scientific Quiz and DOS Quiz I acknowledge the tremendous amount of support extended to DOS by DDU Hospital, all the faculty and residents for all academic activities of DOS. I am blessed to be working under the able guidance of our most humble president Dr. Rajendra Prasad, who has always stood by me and has been very encouraging and supportive and advised me timely on various issues, thank you for always being there. Our Treasurer Dr. Alkesh Chaudhary, has been most cooperative and has worked shoulder to shoulder with me in all endeavors. He has been a pillar of strength and always been there. I thank all the members of the executive, who have stood by me and supported me in all the activities and all the members of DOS who have provided invaluable inputs to improve the working culture of the society and participated in in all the academic initiatives of this executive. The diligence and hard work of the DOS office staff particularly Mr. Parveen Kumar is remarkable. His meticulous execution and mastery in secretarial assistance skills deserves a special mention. Mr. Sandeep is our hard working and committed accountant, who has worked tirelessly under the able guidance of Dr. Alkesh Chaudhary our treasurer to keep all accounts in order. Mr. Manish, our editorial assistant helps in typesetting of DJO and assists Editor DJO Dr. Kriti Singh. Mr. Babu our library staff, assists Dr. Jatinder Bali in DOS library maintenance with dedication. Ms. Megha, our creative designer is our hard working and specialty in designing & who helps to bring out the DOS Times & design the flyers. Mr. Harshpal our office attendant, is multipurpose worker and is diligent about his duties. We are thankful to team of IT scenario are led by Mr. Bagheshwar, Rohit, Sharik who have really worked hard to make the scientific programme and make last minutes changes. We are also grateful to team of Ravi Grover for excellent for audio visual services the seamless smooth transmission of live surgery which was appreciated by one and all I would also like to express with thanks to Harbansh Nagpal for the and fabrication at the venue great area which was well appreciated and admired by the delegates I would express my thanks to the team of Ashok Hotel for the excellent services all throughout the three days of the conference. I would like to thank all the members of the executive who have stood by me and supported me in all the activities and all the members of DOS who have provided invaluable inputs to improve the working of the society. Acknowledgements

www.dosonline.org/dos-times DOS Times Volume 29, Number 7, January-February 2024 13 DOS TIMES I would be failing in my duty, if I do not thank my family members for allowing me time away from them to pursue my endeavors. Let us work together for taking DOS to glorious heights with sincerity, dedication and commitments. Thanking you once again Yours sincerely Dr. Jatinder Singh Bhalla Secretary, DOS

DOS Times Volume 29, Number 7, January-February 2024 www.dosonline.org/dos-times 14 DOS TIMES From the DESK of Chief Editor Dr. Jatinder Singh Bhalla, MS, DNB, MNAMS Secretary Delhi Ophthalmological Society Respected Seniors & Dear Friends The Delhi Ophthalmological Society is one of the oldest ophthalmic societies in India successfully running DOS Times as its publication since years. As we come to the end of our eventful tenure, It is my great pleasure to share with you the last issue of the DOS Times from our team. The last issue on Retina was very well received. The field of Ophthalmology is on a fast pace of revolution, in almost every subspecialty. It’s important for the ophthalmologists to be well versed with the upcoming technologies and advancements, apart from being focussed and skilled in their own sub-specialty. This issue has been designed with important topics in various sub-specialties of ophthalmology. We have informative articles in this issue on Pan Ophthalmology: Cross linking in thin cornea-A mini review, Ptosis: A to Z, Posterior polar cataract: Management Nitty-gritties, Combination of cyclosporine and tacrolimus in treatment of vernal keratoconjunctivitis, Ocular decompression retinopathy: A rare complication after trabeculactomy, Overview of amblyopia-Clinical features and treatment, Roth spots: risk factor, Corneal collagen crosslinking then and now, Paediatric keratoplasty, Photodynamic therapy, Congenital eyelid imbrication syndrome, Overview of laser photocoagulation in diabetic retinopathy, The effectiveness of prophylactic intracameral moxifloxacin use during cataract surgery, Trials in management of diabetic retinopathy and complications: A Comprehensive Review, Pachychoroid spectrum of disorders and Newer Treatment Modalities in the Management of Keratoconus. The article by Dr KV Babu on his persistent crusade against the menace of misleading advertisements with false claims of medicinal value and treatment efficiency is a critical reminder of our collective responsibility to ensure that the health information and products that are endorsed are grounded in truth and scientific evidence. 74th Annual DOS Conference was held on 29th – 31st March, 2024. I wish to sincerely express my gratitude to all for attending & contributing to it’s success Your support meant a lot to us. Some of you are aware of the difficulties and problems that were encountered during organisation of this conference. Situations were created that led to question mark over venue, dates, trade participation & whether this conference would be held or not. This led to many faculty, delegates and Trade people backing out. This conference was held in difficult, unpredictable & adverse circumstances. Ignoring the negativity, maintaining positive attitude and with guidance/ blessings of seniors and support of executive, we went ahead. “You never know how strong you are until being strong is the only choice you have.” – Bob Marley Almighty helped us & conference became a great success. Some of the highlights of annual conference were 1. Unprecedented 22 credit hours granted by DMC. Never before DMC has granted DOS

www.dosonline.org/dos-times DOS Times Volume 29, Number 7, January-February 2024 15 DOS TIMES these many Credit hours. 2. 2500 + registrations 3. 22 live surgery from five centres 4. 137 free papers, 84 interesting cases, 106 E posters 5. Participation of reputed faculty from all over the country and abroad 6. Orations, OPL, Court martial, Quiz and Film Festival 7. Trade participation with much persuasion became an astounding success. I really wish to thank each one of you my friends for your support and also my critics whose criticism motivated me to do better than my best. "It is easy to shine in the light but it takes effort to glow in the dark." Sometimes you face difficulties not because, you are doing anything wrong, but because you are doing something right. There were avoidable errors and short comings during the event for which I seek your forgiveness. “You may not control all the events that happen to you, but you can decide not to be reduced by them.” – Maya Angelou "It’s time to say goodbye, but I think goodbyes are sad and I’d much rather say hello. Hello to a new beginning. As I begin my new assignment as DOS Representative to AIOS, I wish to thank my whole Editorial team & my Assistant Megha for giving a new face to DOS TIMES. Wishing all the best to new team. Wish you all a pleasant reading. Signing off. Humble Regards Dr. Jatinder Singh Bhalla, MS, DNB, MNAMS Chief Editor - DOS Times, Consultant & Academic Incharge (Ophthalmology) DDU Hospital, Hari Nagar

DOS Times Volume 29, Number 7, January-February 2024 www.dosonline.org/dos-times 16 Posterior Polar Cataract: Management Nitty-Gritties Rajesh S.Joshi, MS, DNB, Pradeep Tekade, MS, Nilesh Gaddewar, MS, Riya Rajesh Joshi, MBBS Department of Ophthalmology, GMC, Nagpur. Posterior polar cataract (PPC) is a rare developmental form of cataract, accounting for only 0.5% to 2% of all cataracts. It poses a challenge for cataract surgeons due to its thin posterior capsule and strong adherence to opacity, which increases the risk of posterior capsular rent (PCR) and nucleus drop during surgery.[1,2] The incidence of posterior capsular dehiscence has been reported to be between 26% to 36%, while the incidence of PPC is estimated to be between 3 to 5 out of 1000 cases.[3] Bilateral occurrence is common, with 65% to 80% of cases affected on both eyes.[2] There is no gender preference for this condition. Inheritance PPC is usually inherited through autosomal dominant inheritance, but there have been some cases of it occurring sporadically.[4] Sporadic cases usually involve a unilateral cataract associated with remnants of the tunica vasculosa lentis, while autosomal dominant cases are typically bilateral. Pathogenesis Posterior polar cataracts may be caused by the persistence of the hyaloid artery or invasion of the lens by mesoblastic tissue during embryonic life or early infancy.[5,6] Although it typically becomes symptomatic 30-50 years later, the exact pathogenesis of posterior polar cataract is still unknown. However, gene mutation has been identified as a possible cause. In particular, PITX 3 gene mutation can cause the formation of a central opacity in the posterior capsule due to the abnormal drift of dysplastic lens fibers.[4] These fibers become adherent to the opacity, resulting in a weakened central area of the posterior capsule that may rupture during cataract surgery.[7] Classification 1. Duke and Elders Classification[8] Stationary- Circular well defined opacity with central concentric ring on posterior capsule, giving a bull’s eye appearance onion peel appearance. It may or may not be associated with a satellite rosette lesion or nuclear sclerosis. The stationary type is compatible with good visual acuity. Progressive- Characterised by radiating rider type of opacity in posterior cortex. Symptoms are more in this type of posterior polar cataract. 2. Singhs Classification[9] Type 1: The posterior polar opacity is associated with posterior subcapsular cataract. Type 2: Sharply defined round or oval opacity with ringed appearance like an onion with or without grayish spots at the edge. Type 3: Sharply defined round or oval white opacity with dense white spots at the edge often associated with thin or absent posterior capsule. These dense white spots are a diagnostic sign (Daljit Singh sign) of posterior capsule leakage with or without repair and extreme fragility, the incidence of this type in Indian adult cataract patient population was found to be about one in 300. Type 4: Combination of the above 3 types with nuclear sclerosis. 3. Schroeders Classification This classification grades posterior polar cataract in pediatric patients according to its effect in pupillary obstruction in the red reflex testing as follows: Grade 1: A small opacity without any effect on the optical quality of the clear part of the lens. Grade 2: A two-thirds obstruction without other effect. Grade 3: The disc-like opacity in the posterior capsule is surrounded by an area of further optical distortion. Only the dilated pupil shows a clear red reflex surrounding this zone. Grade 4: The opacity is totally occlusive; no sufficient red reflex is obtained by dilation of the pupil. Diagnosis Clinically on slit-lamp examination PPCs have a distinct morphology, and present with a white, central opacity on the posterior capsule with multiple concentric layers, is bulls eye appearance. (Figure-1 and 2) Examination of the anterior vitreous may reveal oil-like droplets or particles[10] and the presence of these should raise the possibility of pre-existing posterior capsular opening. Grade 3 PPCs (sings classification) were associated with a higher incidence of PCR and patients with intraoperative PCR had a significantly poor postoperative visual outcome on the first postoperative day that improved well by postoperative day 30.[21] It can be associated with other ocular features like microphthalmia, microcornea, anterior polar cataract. The typical symptoms are increasing glare while driving at night and difficulty in reading fine prints. Other symptoms include intolerance to light. The cause of glare, reduced Subspeciality - Cataract

www.dosonline.org/dos-times DOS Times Volume 29, Number 7, January-February 2024 17 contrast sensitivity, and decreased visual acuity is forward light scattering (light scattering toward the retina). The reasons for delayed presentation might be increasing density of the opacity, age-related papillary miosis, or increased functional needs or visual expectations. If it is visually significant since childhood, it might present with strabismus or amblyopia indicating poor visual function in that eye. Figure 1: Posterior Polar Cataract Figure 2: PPC with Pre-Existing Posterior Capsular Dehiscence When to Operate? Most of the surgeons opine that surgery should be delayed as long as possible and undertaken only when patients find difficulty in performing routine activities. However, when it is visually significant in childhood, it is considered amblyogenic which warrants an early intervention in these cases. An important point of consideration in these patients is the lower surgical complications and easier technique if surgery is done while the nucleus is soft. Another point is the possibility of the formation of capsular defects over time in patients with initially intact capsules.[9] Counseling It is important for the surgeon to inform the patient about the potential risks during the surgery, such as the nucleus dropping due to a posterior capsular rupture, longer operation time, and delayed visual recovery. Additionally, the surgeon should discuss the option of Nd:YAG capsulotomy for any remaining plaque.[1,2,10] Genetic counseling and screening for family members should also be considered. Surgical Technique According to a study by Das et al., phacoemulsification is a better option than conventional ECCE for treating posterior polar cataracts due to higher complication rates with ECCE.[11] They discovered that posterior capsule rupture commonly happens during nucleus emulsification in phacoemulsification and during nucleus expression in ECCE. However, another study by Osher et al. showed no difference in the rate of posterior capsule rupture between phacoemulsification and ECCE.[1] According to Vasavada and Singh, the most common time for rupture to occur during phacoemulsification is during the removal of the epinucleus.[2] Meanwhile, Osher et al. discovered that it can happen during the removal of the posterior polar opacity or when cleaning the posterior capsule after plaque removal.[1] It’s been found that performing phacoemulsification on eyes with larger polar opacities (>4mm) poses a significant risk for posterior capsule rupture.[20] Anaesthesia For surgical cases involving posterior polar cataract, local and topical anesthesia can be used. However, peribulbar anesthesia is preferred by Vasavada and Singh because it has a longer lasting effect and reduces pressure on the vitreous.[2] Topical anesthesia involves squeezing the lids with a speculum, which can distort the globe and increase eye movement, leading to more forward movement of the posterior capsule. To reduce intraoperative posterior pressure, Osher et al. recommend preoperative gentle ocular pressure.[1] In cases where the patient is young or uncooperative, general anesthesia may be necessary. Phacoemulcification The Incision Starting with the side port incision followed by the injection of viscoelastic material might be better than starting with the main incision. This will avoid the possible chamber collapse that might predispose to premature rupture of the capsule. The incision of the phacoemulsification surgery can be a usual coaxial one, whether corneal or scleral, or it can be microincisional for bimanual technique. Subspeciality - Cataract

DOS Times Volume 29, Number 7, January-February 2024 www.dosonline.org/dos-times 18 The Capsulorhesis It is important to avoid overpressurising the anterior chamber with viscoelastic material. The use of a heavy viscoelastic might be advantageous in the young patients whose scleral elasticity contributes to the tendency toward anterior chamber shallowing. Starting the rhexis should be by pinching the capsule by the forceps or by the cystotome rather by downward movement of the forceps which might lead to posterior capsule rupture or enlarging an existing one. Ideally, the capsulorhexis should be no larger than 5 - 5.5mm because a larger opening may not leave adequate support for sulcus fixated intraocular lens in case the posterior capsule is compromised. During hydrodelineation, excess fluid is released into the anterior chamber, reducing intralenticular pressure. Additionally, if a posterior capsule rupture occurs as a result of accidental hydrodissection, the nucleus will be more likely to prolapse into the anterior chamber than drop into the vitreous.[12] Hydroprocedure Most of the authors considered the cortical-cleaving hydrodissection as an absolute contraindication in posterior polar cataract cases, as it can lead to hydraulic rupture & can precipitate an instant nucleus drop. While Fine et al. did hydrodissection in multiple quadrants with tiny amount of fluid without allowing the wave to transmit across the posterior capsule.[13] Hydrodelineation is the most preferred hydro procedure. It helps to separate the endonucleus from the epinucleus & prevents directly disturbing the posterior capsule. It also creates a mechanical cushion of epinucleus which acts as a safeguard. It is worth mentioning that the surgeon should avoid vigorous decompression of the capsular bag after the delineation. Vasavada and Raj described a technique that was described for dense and posterior polar cataract called inside-out delineation. In this technique, a trench is first sculpted and a right-angled cannula is used to subsequently direct fluid perpendicularly to the lens fibers in the desired plane through one wall of the trench. This would avoid the possibility of inadvertent subcapsular injection and overcome the difficulty of introducing cannula to a significant depth in a dense cataract.[14] However phacoemulsification without hydroprocedure is described in cases of PPC with an excellent visual outcome.[22] Phacoemulsification with hydrodelineation and OVD hydrodissection for removal of the epinucleus was described as an effective treatment for PPCs.[25] Rotation It best to be avoided as rotation may lead to posterior capsular dehiscence.[2] Parameters for Phacoemulcification Slow motion phacoemulsification with low parameters should be used in cases with posterior polar cataract the power should be 60%, bottle height 55–70 cm, aspiration rate 15–25 mL/min, vacuum 30–100mm Hg. The low vacuum and aspiration rates maintain a very stable chamber and the reduced infusion drives less fluid around the lens.[1,2] Nucleotomy Techniques If the nucleus is soft, it can be removed through a procedure called phacoaspiration. However, it's crucial to be cautious during the process to prevent the collapse of the anterior chamber, which could cause the anterior tenting of the posterior capsule and ultimately result in its spontaneous rupture. To avoid this, it's recommended to inject a dispersive viscoelastic through the side port incision before removing the phacoemulsification tip. Additionally, it's best to avoid nuclear rotation and aggressive nuclear cracking techniques with wide separation of fragments. Salahuddin has shared a technique named "inverse horse-shoe". This involves dividing the distal end of the nucleus after sculpting and injecting viscoelastic to lift the two limbs of the nucleus. A visco shell is thus formed around the nucleus, allowing it to be divided into two halves without any harm to the posterior capsule. The two segments can then be chopped, emulsified, and brought to the center separately.[15] Lee and Lee used the "λ technique" to sculpt the nucleus into the shape of the Greek letter lambda. They then removed the distal central piece by cracking along both arms. This technique is advantageous because it allows for gentle removal of the quadrants without stretching the capsule, particularly the first quadrant.[16] Epinucleus Removal After hydrodelineation, the nucleus is sculpted and cracked into halves gently which is then aspirated with low parameter. Then epinucleus is aspirated layer after layer by automated bimanual irrigation and aspiration cannula. The penultimate layer was carefully aspirated leaving thin layer of cortex adherent to the capsule. The most posterior layer along with the plaque was then viscodissected and aspirated using bimanual irrigation and aspiration cannula. It is important to remember to leave the central area attached until the last stage of cortical aspiration.[9,17] Fine et al. used minimal hydrodissection and hydrodelinealtion, nuclear emulsification from within the epinuclear shell and gentle viscodissection of the epinucleus and cortex to avoid unnecessary pressure on the posterior capsule and to protect the region of the greatest potential weakness throughout the procedure.[18] Some surgeons have suggested performing viscodissection of the epinucleus by injecting viscoelastic under the capsular edge to mobilize rim of epinucleus. If posterior plaque firmly adherent to capsule is uncovered it is left behind which can be dealt with ND:YAG laser capsulotomy post operatively. Although few surgeons prefer primary posterior capsulorhexis before lens implantation.[14] Posterior Capsular Dehiscence Recognising the early signs of posterior capsule rupture during cataract surgery and its early management can lead to good visual outcomes. ・ Signs of an early posterior capsular dehiscence or zonular dehiscence includes sudden deepening of the anterior Subspeciality - Cataract

www.dosonline.org/dos-times DOS Times Volume 29, Number 7, January-February 2024 19 chamber with momentarily expansion of pupil ・ Sudden transient appearance of clear red reflex peripherally; ・ Newly apparent inability to rotate previously mobile nucleus; ・ Excessive lateral displacement of nucleus and partial descent of nucleus into anterior vitreous face. Cortex Aspiration It should be done with low bottle height (15–25 cc/min). The usual pulling of the cortex should be minimized as possible. Instead, the aspiration tip should remain at the equatorial angle in the periphery, and the surgeon should wait until suction increases and the cortex is aspirated. Furthermore, it is better to pull the cortex tangentially rather than centrally to mobilize it. This maneuver of mechanical separation from the central plaque avoids traction or pull, which might otherwise be generated from attempting to directly aspirate the cortical matter. Alternatively, the posterior chamber can be filled with viscoelastic material and cortex removed using a “dry” (syringe stripping) technique. It is important to remember to avoid polishing the capsule in such patients as it is usually very thin and may rupture to minimal trauma. Removal of Posterior Polar Opacity To prevent early rupture of the posterior capsule, it's advisable to delay removing the opacity until the final stage of cortical aspiration. You can use viscodissection to remove it, and then aspirate it using either the phaco tip or the irrigation aspiration tip.[19] IOL Implantation If the posterior capsular rupture is small or can be converted to a round shape, a low-diameter single-piece IOL can be safely implanted in the bag. When inserting the IOL, it is important to avoid touching the capsule to prevent further tearing. To minimize the risk of extending the tear, it may be safer to compress the trailing haptic instead of subjecting the capsular bag to rotational forces. However, if the rupture is large or cannot be converted to a round shape, a multipiece IOL must be placed in the ciliary sulcus, with or without rhexis capture. Capturing the optic by the rhexis stabilizes the IOL and reduces contact with the iris, which is an advantage. Posterior Approach Vitrectomy and lensectomy can be performed through the pars plana approach, but using a scleral-fixated, iris-fixated, or anglesupported lens for visual rehabilitation is not a practical option in cases where the capsular barrier can be preserved. Hidden PPC 1. The PPC is not visible during an examination when there is a dense or mature cataract. However, there are clues that can suggest the presence of a hidden PPC. These include a family history of PPC, PPC in the other phakic eye, or a Posterior capsular rent in the other pseudophakic eye. Additionally, a dense cataract that was previously documented as PPC may also be an indication of its presence. Recent Advances 1. Optical Coherence Tomography The use of optical coherence tomography (OCT) has significantly improved patient management before, during, and after surgery. Surgeons are now able to see the condition of the posterior capsule, which helps them plan the surgery and inform patients of any additional risks. In fact, some studies, like the one by Chan et al., have even used OCT to grade posterior polar cataracts and determine if posterior capsule rupture is present or not. 2. B Scan Ultrasonography Guo Y et al show that 25 MHzB can be used to clearly visualize the status of the PC in PPC. These results, in turn, could be used to select the appropriate treatment and to thereby avoid further complications during PPC surgery.[24] 3. Femtosecond Laser-Assisted Cataract Surgery in Posterior Polar Cataracts Titiyal JS et al described technique of femtosecond laserassisted cataract surgery with a hybrid pattern of cylinder and chop is safe and effective in managing cases of posterior polar cataract, specifically for higher grades of nuclear sclerosis.[23] Conclusion Treating PPCs is difficult because of the high risk of PCR. Therefore, it is crucial to conduct a thorough pre-operative evaluation and counseling for these cases. Fortunately, advances in imaging technology such as AS-OCT can help predict the likelihood of PCR in PPCs. References 1. Osher, R.H., Yu, B.C. and Koch, D.D. (1990) Posterior Polar Cataracts: A Predisposition to Intraoperative Posterior Capsular Rupture. Journal of Cataract Refractive Surgery, 16, 157-162. 2. Vasavada, A.R. and Singh, R. (1999) Phacoemulsification with Posterior Polar Cataract. Journal of Cataract Refractive Surgery, 25, 238-245. 3. Vogt, G., Horvath-Puho, E. and Czeizel, E. (2006) A PopulationBased Case-Control Study of Isolated Congenital Cataract. Orv Hetil, 147, 1077-1084. 4. Addison, P.K., Berry, V., Ionides, A.C., Francis, P.J., Bhattacharya, S.S. and Moore, A.T. (2005) Posterior Polar Cataract Is the Predominant Consequence of a Recurrent Mutation in the PITX3 Gene. British Journal of Ophthalmology, 89, 138-141. 5. Gifford S.R. Congenital anomalies of the lens as seen with the slit lamp. Am J Ophthalmol. 1924;7:678–685. 6. Cordes FC. Types of congenital and juvenile cataracts. In GM, editor. Symposium on Diseases and Surgery of the lens. St. Louis, CV Mosby; 1957. p. 43–50. 7. Eshaghian, J. and Streeten, B.W. (1980) Human Posterior Subcapsular Cataract: An Ultrastructural Study of the Posterioly Migrating Cells. Archives of Ophthalmology, 98, 134-143. 8. Duke-Elder, S. (1964) Posterior Polar Cataract, System of Ophthalmology, Vol. iii, pt. 2: Normal and Abnormal Development, Congenital Deformities. MO, CV Mosby, St. Louis, 723-726. Subspeciality - Cataract

DOS Times Volume 29, Number 7, January-February 2024 www.dosonline.org/dos-times 20 9. Masket, S. (1997) Consultation Section: Cataract Surgical Problem. Journal of Cataract and Refractive Surgery, 23, 819-824.Congenital Anomalies of the Lens as Seen with the Slit Lamp. American Journal of Ophthalmology, 7, 678-680. 10. Hayashi K., Hayashi H., Nakao F. Outcomes of surgery for posterior polar cataract. J Cataract Refract Surg. 2003;29:45–49. 11. Das S., Khanna R., Mohiuddin S.M., Ramamurthy B. Surgical and visual outcomes for posterior polar cataract. Br J Ophthalmol. 2008;92(11):1476–1478. 12. Pong J., Lai J. Managing the hard posterior polar cataract. J Cat Refract Surg. 2008;34:530–531. 13. Fine, I.H., Packer, M. and Hoffman, R.S. (2003) Management of Posterior Polar Cataract. Journal of Cataract & Refractive Surgery, 29, 16-19. 14. Vasavada, A.R. and Raj, S.M. (2004) Inside-Out Delineation. Journal of Cataract & Refractive Surgery, 30, 1167-1169. 15. Salahuddin Inverse horse-shoe technique for the phacoemulsification of posterior polar cataract. Can J Ophthalmol. 2010;Apr 45(2):154– 156. 16. Lee M.W., Lee Y.C. Phacoemulsification of posterior polar cataracts—a surgical challenge. Br J Ophthalmol. 2003;87:1426–1427. 17. Vajpayee R.B., Sinha R., Singhvi A., Sharma N., Titiyal J.S., Tandon R. ‘Layer by layer’ phacoemulsification in posterior polar cataract with pre-existing posterior capsular rent. Eye (Lond) 2008;22(8):1008– 1010. 18. Fine I.H., Packer M., Hoffman R.S. Management of posterior polar cataract. J Cataract Refract Surg. 2003;29:16–19. 19. Taskapili M., Gulkilik G., Kocabora M.S., Ozsutcu M. Phacoemulsification with viscodissection in posterior polar cataract: minimizing risk of posterior capsule tear. Ann Ophthalmol (Skokie) 2007;39(2):145–149. 20. Kumar S, Ram J, Sukhija J, Severia S. Phacoemulsification in posterior polar cataract: Does size of lens opacity affect surgical outcome? Clin Exp Ophthalmol 2010;38:857‐61. 21. Ashwin PR, Harika K, Shekhar M, Sankarananthan R, Shah A, Lakshmanan P, et al. Morphological variations influencing the outcomes in posterior polar cataract. Indian J Ophthalmol 2022;70:2426-31. 22. Bardoloi N, Sarkar S, Das H, Burgute PS. Phacoemulsification without hydroprocedure: A novel technique to deal with posterior polar cataracts. Saudi J Ophthalmol 2022;36:218‐23. 23. Titiyal JS, Kaur M, Sharma N. Femtosecond Laser-assisted Cataract Surgery Technique to Enhance Safety in Posterior Polar Cataract. J Refract Surg. 2015 Dec;31(12) 24. Guo Y, Lu C, Wu B, Gao J, Li J, Yuan X, Tang X. Application of 25MHz B-Scan Ultrasonography to Determine the Integrity of the Posterior Capsule in Posterior Polar Cataract. J Ophthalmol. 2018 Mar 26;2018:9635289. 25. Hua X, Dong Y, Du J, Yang J, Yuan X. Phacoemulsification with hydrodelineation and OVD-assisted hydrodissection in posterior polar cataract. BMC Ophthalmol. 2018 Jul 9;18(1):165. Dr. Rajesh S.Joshi, MS, DNB Professor and Head Department of Ophthalmology, GMC, Akola, Maharashtra. Corresponding Author: Subspeciality - Cataract

www.dosonline.org/dos-times DOS Times Volume 29, Number 7, January-February 2024 21 The Effectiveness of Prophylactic Intracameral Moxifloxacin Use During Cataract Surgery Anurag Narula, MS Department of Ophthalmology, Safdarjung Hospital and Vardhman Mahavir Medical College, Delhi. Abstract: Endophthalmitis is a rare, serious infection of the eye that can lead to permanent loss of vision. Topical antibiotic eye drops are often prescribed to prevent endophthalmitis after cataract surgery. However, many times there are concerns about patient’s adherence to regular use of drops in the postsurgical period. In contrast to topical drops, intracameral antibiotics are administered only once and in the last decade, several studies have suggested that intracameral use of Moxifloxacin may reduce endophthalmitis risk. Here we report our surgical experience with Moxifoxacin eye drops. Manuscript Endophthalmitis is rare yet severe eye infection characterized by inflammation and potential vision impairment, with the possibility of permanent vision loss.[1] The primary contributor to endophthalmitis is cataract surgery, where bacteria may infiltrate the eye through patients' eyelids, surgical instruments, or healthcare personnel during the surgical procedure.[2] Despite the relatively low incidence of endophthalmitis following cataract surgery in India, the sheer volume of such surgeries conducted in the country, coupled with the unfavorable visual outcomes associated with endophthalmitis, underscores the gravity of the concern.[3,4] Treatment of endophthalmitis involves systemic and locally injected antibiotics, and vitrectomy, a surgical removal of infected vitreous from the eye.[1,2] Although early treatment of endophthalmitis may improve visual outcomes, the prognosis of endophthalmitis remains poor.[2] Therefore, prevention of endophthalmitis after cataract surgery is essential to reduce the risk of poor visual outcomes. Prevention options include use of povidone iodine as a topical antiseptic, saline irrigation, and topical, oral, or injected antibiotics. Although povidone iodine is routinely used and widely accepted as a surgical antiseptic, risk of endophthalmitis remains and additional preventive measures are needed.[5,6] Topical antibiotic eye drops, commonly along with topical steroid drops, are often prescribed to prevent endophthalmitis after cataract surgery.[5,6] The efficacy of topical drops depends upon patient adherence and correct administration technique, and tracking of patient adherence and administration is difficult.[7] Barriers to proper administration and compliance with topical eye drops include age, physical disability, complex drug regimens that may require administration of more than 1 type of eye drop (ie, topical antibiotics and topic steroids), and inexperience using eye drops.[8,9] Topical eye drop compliance may be a particular challenge among older adults due to older age[10] and higher rates of comorbidity and disability compared to the general population.[11] In contrast to topical drops, intracameral antibiotics are administered only once (at the end of the surgical procedure after intraocular lens insertion).[4] Intracameral antibiotics are widely used after cataract surgery to prevent endophthalmitis.[4] Common antibiotics for intracameral delivery include cefuroxime, moxifloxacin, and vancomycin.[12] In 2007, the European Association of Cataract and Refraction Surgeons (ESCRS) published a randomized controlled trial (RCT) showing effectiveness of intracameral injection of cefuroxime compared to topical antibiotics.[13] However, concerns around antibiotic resistance and adverse effects, including toxic anterior segment syndrome (TASS), a severe acute intraocular inflammation, have led to reduced use of cefuroxime.[12,14] Similarly, vancomycin is used infrequently due to cases of vancomycin-associated hemorrhagic occlusive retinal vasculitis.[14-16] Moxifloxacin has more recently been explored to overcome the issues of antibiotic resistance and potential adverse effects, and studies have found that moxifloxacin may be beneficial for preventing endophthalmitis when delivered intracamerally after cataract surgery (compared to topical or no use of antibiotics).[14,16,17] Potential toxic effects of intracameral moxifloxacin, including endothelial cell damage and TASS, have been reported at higher doses (above 0.5 mg/mL),with the use of specific inactive ingredients (xanthan gum), and with the use of compounded moxifloxacin formulations.[18] However, intracameral moxifloxacin doses of up to 0.5 mg/0.1 mL without preservatives have been reported to be safe with no adverse effects.[15] At our hospital, we have large number of patients undergoing cataract surgery and we hereby would like to share our current protocol of using Moxifloxacin as intracameral route. All the patients undergoing cataract surgery are treated with Subspeciality - Lens/Cataract

DOS Times Volume 29, Number 7, January-February 2024 www.dosonline.org/dos-times 22 Moxifloxacin 0.5% (3 days prior to surgery) and Nepafenac 0.1% eye drops 3 times in day. We also prescribe ocular lubricants pre-operatively if patient has existing dry eye disease. All the patients received injection of 0.05 mL of Moxifloxacin 0.5% (Mahaflox, Mankind Pharma) immediately after intraocular lens (IOL) implant. Earlier we were using Moxifloxacin prefilled syringes; however now current brand of moxifloxacin is available with international quality, hence we switched from pre-filled syringe to Mahaflox (Mankind Pharma) as this provides similar efficacy and cost-effectiveness. Post cataract surgery, all the patients continued on Moxifloxacin 0.5% for 10 days, Nepafenac 0.1% for 20 days and prednisolone or dcexamethsome for 30-35 days on tapering use. All the patients had the follow up at 1st day, 7th day and 21st day postsurgery and checked for visual acuity, intraocular pressure (IOP) and slit lamp examination. None of our patients has shown any significant findings such a Toxic Anterior Segment Syndrome (TASS), endophthalmitis and any other ocular issues. Patients who are having IOP >20 mmhg were prescribed IOP lowering medications. Overall, our experience with Intracameral use of Moxifloxacin 0.5% (Mahaflox, Mankind Pharma) has been very satisfactory and none of the patient has shown any significant post-surgical complications. References 1. Durand ML. Endophthalmitis. Clinical Microbiology and Infection. 2013;19(3):227–234. 2. Sheu S-J. Endophthalmitis. Korean Journal of Ophthalmology. 2017;31(4):283–289. 3. Coleman A. How Big Data Informs Us About Cataract Surgery: The LXXII Edward Jackson Memorial Lecture. American Journal of Ophthalmology. 2015;160(6). 4. Javitt JC. Intracameral antibiotics reduce the risk of endophthalmitis after cataract surgery: does the preponderance of the evidence mandate a global change in practice? Ophthalmology. 2016;123(2):226–231. 5. Peck TJ, Patel SN, Ho AC. Endophthalmitis after cataract surgery: an update on recent advances. Current Opinion in Ophthalmology. 2021;32(1):62–68. 6. Haripriya A, Chang DF. Intracameral antibiotics during cataract surgery: evidence and barriers. Current Opinion in Ophthalmology. 2018;29(1):33–39. 7. Novack GD, Caspar JJ. Peri-Operative Intracameral Antibiotics: The Perfect Storm? Journal of Ocular Pharmacology & Therapeutics. 2020;36(9):668–671. 8. An JA, Kasner O, Samek DA, Lévesque V. Evaluation of eyedrop administration by inexperienced patients after cataract surgery. Journal of Cataract & Refractive Surgery. 2014;40(11). 9. Matossian C. Noncompliance with prescribed eyedrop regimens among patients undergoing cataract surgery—prevalence, consequences, and solutions. 2020. 10. VA Utilization Profile FY 2017. National Center for Veterans Analysis and Statistics. https://www.va.gov/vetdata/docs/Quickfacts/VA_ Utilization_Profile_2017.pdf. Updated May 2020. Accessed April 19, 2022. 11. Holder KA. The disability of veterans. Washington, DC: US Census Bureau Social, Economic, and Housing Statistics Division. 2016. 12. Intracameral Medications Following Cataract Surgery. 2021;2022(March 29). 13. Group EES. Prophylaxis of postoperative endophthalmitis following cataract surgery: Results of the ESCRS multicenter study and identification of risk factors. Journal of Cataract & Refractive Surgery. 2007;33(6):978–988. 14. Bowen RC, Zhou AX, Bondalapati S, et al. Comparative analysis of the safety and efficacy of intracameral cefuroxime, moxifloxacin and vancomycin at the end of cataract surgery: a meta-analysis. British Journal of Ophthalmology. 2018;102(9):1268–1276. [PMC free article] 15. American Academy of Ophthalmology, Hwang FS, Kim B, Pyun J. Intracameral Medications Following Cataract Surgery. https:// eyewiki.aao.org/Intracameral_Medications_Following_Cataract_ Surgery. Published 2021. Accessed March, 2022. 16. Huang J, Wang X, Chen X, Song Q, Liu W, Lu L. Perioperative Antibiotics to Prevent Acute Endophthalmitis after Ophthalmic Surgery: A Systematic Review and Meta-Analysis. PLoS ONE [Electronic Resource]. 2016;11(11):e0166141. 17. Wang XL, Huang XY, Wang Z, Sun W. The Anterior Chamber Injection of Moxifloxacin Injection to Prevent Endophthalmitis after Cataract Surgery: A Meta-analysis. Journal of ophthalmology. 2020;2020:7242969. 18. US Food and Drug Administration. FDA alerts health care professionals of risks associated with intraocular use of compounded moxifloxacin. https://www.fda.gov/drugs/drug-safety-and-availability/fdaalerts-health-care-professionals-risks-associated-intraocular-usecompounded-moxifloxacin. Published 2020. Accessed March, 2022. Dr. Anurag Narula, MS Senior Consultant Department of Ophthalmology, Safdarjung Hospital and Vardhman Mahavir Medical College, Delhi. Corresponding Author: Subspeciality - Lens/Cataract

www.dosonline.org/dos-times DOS Times Volume 29, Number 7, January-February 2024 23 Overview of Amblyopia- Clinical Features and Treatment Prasad Walimbe[1-3], MS, DNB, Ananya Mondal[1], MBBS, DNB, Parikshit Gogate[4-6] MS, DNB, FRCS, MSc, FAICO, ex-IPS 1. Department of Ophthalmology, Deenanath Mangeshkar Hospital, Pune, India 2. Dr. Walimbe Eye Clinic, Pune, India 3. Department of Ophthalmology, Jehangir Hospital & Research Centre, Pune, India 4. Community Eye Care Foundation, Dr. Gogate’s Eye Clinic, Pune, India 5. Department of Ophthalmology, D.Y. Patil Medical College, Pimpri, Pune, India 6. School of Health Sciences, Queens University, Belfast, UK Clinical Features Amblyopia is usually thought of as not having any clinical features. But quite a few do exist and are important to identify particularly in preverbal children and children unable to identify any optotypes. 1. Fixation Preference- Resistance to occlusion of fixating eye, and nystagmoid movements of the other eye, when fixating eye is occluded.[4] 2. Effect of Neutral Density Filter- Von Noorden and Burien in their study found that use of a neutral density filter in Test Finding Unilateral BCVA Interocular difference of 2 or more lines Response to monocular occlusion Asymmetric objection Fixation preference Strong preference for fixation in one eye Preferential looking Interocular difference of 2 or more octaves Bilateral BCVA Age 3 to <4 years VA worse than 6/12P in both eyes Age 4 to <5 VA worse than (6/12) in both eyes Age >= 5 VA worse than (6/9) in both eyes healthy eyes reduced the visual acuity, while in eyes with strabismic amblyopia, vision stayed the same, or actually improved.[6] 3. Reduced Foveal Acuity[7] 4. Reduced Stereoacuity[8] 5. Crowding phenomenon or separation difficulties[4] 6. Colour vision can be reduced or normal[4] 7. Reduced contrast sensitivity[4] 8. Reduced Accommodation[9] visual immaturity, for which no cause can be detected during the physical examination of the eye(s) and which in appropriate cases is reversible by therapeutic measures.[4] Von Graefe described it as, “the condition in which the observer sees nothing and the patient very little”. Diagnostic Criteria A diagnosis of amblyopia needs the detection of a deficit in visual acuity. The following table (Table-1) illustrates diagnostic criteria for amblyopia.[5] Amblyopia is an abnormal binocular interaction and foveal pattern vision deprivation or a combination of both factors. It can be unilateral or bilateral and is the most common cause of vision loss and monocular blindness in children.[1] The prevalence of amblyopia in the world is 1.44%.[2] Apart from decreased visual acuity amblyopia also results in reduced contrast sensitivity, abnormal spatial distortions and unsteady and inaccurate monocular fixation.[3] Amblyopia is defined as a decrease of visual acuity in one eye when caused by abnormal binocular interaction or occurring in one or both eyes as a result of pattern vision deprivation during Subspeciality - Squint

DOS Times Volume 29, Number 7, January-February 2024 www.dosonline.org/dos-times 24 9. Fixation pattern Bangerter’s classification of fixation patterns in amblyopia is as follows: • Central fixation • Eccentric fixation (non-foveolar) • No fixation[4] 10. Mesopic vision is better in amblyopes[4] Type of Amblyopia Initial Best Corrected Visual Acuity Mild 6/18 or better Moderate <6/18 to 6/30 Severe 6/30 to 3/60 Refractive Correction Occlusion Penalization Drugs Near Vision Therapy Optical Therapy (overplussed lenses) Bangerter Filter Binocular (digital) Dichoptic Therapy Surgical Correction of Visual Axis Refractive Surgery Pleoptics Cambridge Stimulator Treatment[13] According to Severity[11] According to Aetiology[4] 1. Strabismic 2. Refractive: Anisometropic/Ametropic/Isometropic 3. Stimulus Deprivation 4. Idiopathic 5. Organic Treatment Options Early diagnosis is imperative for starting treatment. Considering the above discussion, amblyopia not only affects the visual acuity but also the quality of vision. Therefore starting treatment at the right time can help to prevent permanent visual handicap. Good vision is crucial in the formative years of a child for 11. Relative Afferent Pupillary defect may or may not be present 12. Pursuit and Saccades are reduced 13. Latent Nystagmus can be present 14. Fine Motor skills are affected in amblyopes[10] Classification of Amblyopia acquiring skills and for motor development. It has an impact on the psychosocial development of the child. A retrospective study found that vision loss in the fellow eye was more likely to occur in children with amblyopia compared with those without amblyopia.[12] Thus the rationale behind early treatment. The Pediatric Eye Disease Investigator Group (PEDIG), formed in 1997, has been dedicated to clinical research of eye diseases affecting children. The PEDIG has studied the efficacy of amblyopia treatment regimes, and has followed the long-term outcomes of these regimes. These studies are known as the Amblyopia Treatment Studies (ATS). The current treatment options are listed in table-3 1. Refractive Correction Refractive correction plays a central role in amblyopia therapy. Amblyopes can have either central or eccentric fixation and refractive correction is necessary to bring the image onto the fovea and for foveal stimulation. Particularly in patients with anisometropic amblyopia refractive correction can improve the visual acuity- a phenomenon known as refractive adaptation.[14] ATS-5 concluded that Refractive correction alone improves VA in many cases (77%) of anisometropic amblyopia & results in resolution in 27% cases.[15] Subspeciality - Squint

www.dosonline.org/dos-times DOS Times Volume 29, Number 7, January-February 2024 25 Refractive correction is done with full cycloplegia. In younger children atropine 1% is used and in older children (>8yrs) cyclopentolate 1% is used. In anisometropic amblyopia, an age appropriate refractive correction is given. In bilateral ametropic amblyopia, refraction is the first line of treatment.[16] Strabismic amblyopia can improve with spectacle correction alone.[17] Refractive correction can be given for 4-6 weeks before proceeding to other treatment modalities or can be given simultaneously with patching or pharmacological therapy. According to ATS 7 treatment of bilateral refractive amblyopia with spectacle correction improves binocular visual acuity in children 3-10 years; old- most improving to 20/25 or better in 1 year.[16] 2. Occlusion Occlusion therapy is patching the better eye during waking hours preferably when doing some near activity. Occlusion can be full time occlusion (FTO) or part time occlusion (PTO). The ATS 2A was a randomized control trial to compare 6 hours Vs FTO for severe amblyopia. It showed that 6 hours patching and FTO are equally effective in severe amblyopia in 3-7 years old.[18] The ATS 2B compared 2 hours Vs 6 hrs. patching in moderate amblyopia. It showed that when combined with 1 hr of near visual activity, 2 hrs. daily patching is equivalent to 6 hrs. patching in treating moderate amblyopia in 3-7 years old.[18] ATS 2C was to evaluate the risk of amblyopia recurrence after successful treatment and it was observed that approximately 25% experience around 2 lines dip in 1st year. Therefore, patching regimen should be tapered instead of abrupt stopping.[19] The risk of occlusion amblyopia, or the development of amblyopia in the previously preferred/patched eye, is higher in patients undergoing FTO. Therefore, more frequent follow-up is needed. Visual acuity needs to be assessed in each visit. An important problem with occlusion therapy is compliance. Children need the active involvement of parents for compliance and strict adherence. Another issue is psychosocial where children feel lack of self confidence and also face stigma from their peers due to patched eye Many kinds of patches exist, such as adhesive or cloth types. A problem with the adhesive ones is skin irritation. Occluders which can be worn over glasses have the disadvantage that children can “peek” around them. Occlusion can be stopped if the VA in both eyes becomes equal, or the fixation becomes fully alternating, or when there is no further improvement despite 3-6 months of patching. The patching regimen is considered a failure if there is no visual improvement after 3-6 months of compliant patching.[11] Some children with severe amblyopia will respond to as little as 2 hours of patching.[20] The ATS also found an association between the number of hours of occlusion advised and amblyopic eye baseline VA, however no association was found with the final VA.[21] 3. Penalisation Penalisation may improve visual acuity in older age group. It is a cholinergic antagonist causing pupillary dilation and reduction in accommodation forcing amblyopic eye to be used for near task. Atropine penalisation consists of instillation of 1% atropine drop BD into sound eye thus blurring vision. In ATS 3 children age 7-12 years were treated with either atropine or patching in the non amblyopic eye. Treatment with patching or atropine produced similar degrees of improvement in visual acuity of the amblyopic eye, with about 40% of subjects having a 2 or more line improvement in visual acuity.[22] Potential side effects with atropine therapy are tachycardia, fever, dry mouth, rash and decreased urination. Parents should be warned of these side effects before starting therapy. In terms of compliance, penalisation has better compliance than occlusion. The quality of life assessment made with the Amblyopia Treatment Index favoured atropine with respect to compliance and social stigma.[22] According to the ATS 1 atropine and patching produce improvement of similar magnitude, and both are appropriate modalities for the initial treatment of moderate amblyopia in children aged 3 to less than 7 years. There was a similar improvement in visual acuity of both treatment modalities. Initially the improvement in visual acuity is more with patching, but eventually catches up in penalisation therapy.[23] The treatment effect of atropine can be enhanced by under correcting hypermetropic refractive error in the atropine-treated sound eye. A combination of atropine therapy and optical penalization may result in severe treatment-related amblyopia developing in the sound eye if parental noncompliance occurs. In a study two groups were compared, one with atropine therapy and the other with atropine plus plano lens. The latter group had sound eyes blurred full time and therefore increased blur with near viewing relative to the atropine-only group. However, the magnitude of visual acuity improvement in the amblyopic eye in the atropine plus plano lens group at the 18 week outcome visit was only marginally better (approximately 0.3 lines), a difference that was not statistically significant.[24] 4. Pharmacotherapy Sometimes incomplete resolution is achieved with conventional amblyopia therapy and some residual decrease in visual acuity is left behind. Pharmacotherapy is achieved with Levodopa-carbidopa, fluoxetine, GABA antagonist, and citicholine. Levodopa-Carbidopa It has been in use since 1993. Dopamine plays a role in the development of visual pathway and also in visual processing. Dopamine cannot cross the blood brain barrier. Levodopa is a Subspeciality - Squint

DOS Times Volume 29, Number 7, January-February 2024 www.dosonline.org/dos-times 26 prodrug and easily crosses the blood brain barrier. Carbidopa is a peripheral decarboxylase inhibitor which prevents conversion of levodopa to dopamine. Kasamatsu and Pettigrew in an animal study showed that even older amblyopic animals could recover some function if their brain is flooded with a dopaminergic drug. Their study suggested that dopaminergic drugs may influence visual cortical plasticity and hence visual recovery in the amblyopes.[25] Levodopa has been shown to improve visual acuity according to the PEDIG study. The results suggested that levodopa/carbidopa therapy for residual amblyopia in older children and teenagers is well tolerated and may improve visual acuity. There was a suggestion of partial regression of the improvement in VA after treatment was discontinued.[26] Greater improvement in visual acuity was seen in patients with dense amblyopia. Levodopa was seen to be beneficial for residual amblyopia following pathing and for management of amblyopia in older age groups. However it was found that there could be partial regression after stopping medication.[27] Levodopa may be associated with systemic adverse effects such as headache (most common), nausea and vomiting. Fluoxetine Fluoxetine is a selective serotonin reuptake inhibitor. It is an antidepressant. Guest et al in their study showed an increase in the percentage of synapses with split postsynaptic densities, a phenomenon that is characteristic of activity-dependent synaptic rearrangement. These findings suggest that there is increased synaptic remodelling.[28] Fluoxetine may be associated with various side effects like anxiety, insomnia, nervousness, tremors, anorexia, irritability, aggressiveness, impulsivity and psychomotor restlessness. A study was done to assess the efficacy of oral fluoxetine therapy in improving the visual function of amblyopic patients and an improvement in visual acuity was seen till 3 months after therapy even after the critical period. It also had a beneficial effect in contrast sensitivities in all spatial frequencies.[29] Citicholine Citicholine increases the synthesis of structural phospholipids in the neuronal cell membranes, which results in increased levels of neurotransmitters, and thus, has neuroprotective effect. It increases levels of norepinephrine and dopamine in the brain. A study was done to see if the addition of citicoline can help in amblyopia therapy. The study suggested that addition of citicholine, even after maximum improvement with conventional patching was achieved, can further improve the visual acuity.[30] Prabha and Lahre found improvement in VA and refractive status in patients of myopic amblyopia of age group 5-30 years before and after administration of oral citicoline (500mg daily for 12 weeks).[31] Donepezil Visual stimulus affects the development of the visual pathways during a time termed the “critical period.” Key effectors of critical period closure include transition from excitation to inhibition and establishment of structural barriers to plasticity. Therefore, strategies to lift the brakes on critical period closure can make for successful amblyopia treatment later in life. Lynx1 is an endogenous brake that decreases nicotiniccholinergic signalling. Several studies have also shown that cholinergic enhancement in healthy human adults augments neural plasticity.[32] Donepezil is an acetylcholine esterase inhibitor that has been successfully used in the treatment of Alzheimer’s disease, A recent study showed that Donepezil (±patching) treatment improved amblyopic eye visual acuity by 1.2 lines, and 25% of subjects improved by≥2 lines after only 12 weeks of treatment. Most notably, gains in visual acuity were sustained 10 weeks after cessation of treatment.[33] 5. Binocular Stimulation and Games Binocular vision therapy is based on simultaneous binocular visual stimulation and improves overall fusion and stereo acuity. Such therapies often involve playing computer games and watching movies on digital displays, which are more appealing and improve compliance. Binocular vision therapy includes perceptual learning and dichoptic training. Perceptual Learning Perceptual learning has been around for decades and was defined by Elanor Gibson in 1963. Adults are capable of improving performance on sensory tasks through repeated practice or perceptual learning, and this learning is considered to be a form of neural plasticity. These stimuli may be in the form of Vernier acuity, Gabor detection, positional discrimination, letter identification in noise, position discrimination in noise, and contrast detection. The first such device was the Cambridge Visual Stimulator (CAM), in which patients view high-contrast rotating sine-wave gratings with the amblyopic eye.[34] Dichoptic Training Dichoptic training is a visual training process involving the presentation of independent stimuli to each eye simultaneously and the integration of the two stimuli under binocular viewing conditions. Gradually, the contrast difference between the two eyes is reduced, potentially to a point where no difference is seen. VA gains follow improvements in binocularity and contrast sensitivity. Binocular I Pad Based Therapy Children have been seen to prefer playing games on I-Pad to conventional patching therapy. The amblyopic eye receives a display at a higher contrast, whereas the normal fixing eye, at a lower contrast. Simultaneous viewing with both eyes is required to play the game. The degree of progressive reduction in the interocular contrast helps to quantify improvements in suppression. In 2015, PEDIG conducted the first large-scale, multicentre randomized controlled trial comparing the effectiveness of Subspeciality - Squint

www.dosonline.org/dos-times DOS Times Volume 29, Number 7, January-February 2024 27 Subspeciality - Squint 1 hour/day, 7 day/week binocular game play to 2 hours/day patching in children <13 years. The same regimen was examined in children aged 13 to <17 years. Results in the younger cohort showed similar improvements in both types of treatment at 16 weeks.[35] Binocular treatment of amblyopia using video games (BRAVO) has been performed to compare the effectiveness of a binocular video game with a placebo video game for improving visual function. This study was a randomized controlled trial with 115 participants aged 7 to 55 years of age. The result indicated that binocular video games did not improve visual outcomes more than placebo video games in older children and adults, mainly because of poor compliance with games.[36] References 1. Gunton KB. Advances in amblyopia: what have we learned from PEDIG trials? Pediatrics. 2013; 131:540–7. 2. Fu Z, Hong H, Su Z, et al Global prevalence of amblyopia and disease burden projections through 2040: a systematic review and metaanalysis British Journal of Ophthalmology 2020;104:1164-1170. 3. Hess RF, Howell ER. The threshold contrast sensitivity function in strabismic amblyopia: evidence for a two type classification. Vision Res 1977; 17:1049-55. 4. Von Noorden GK, Campos E. Binocular Vision and Ocular Motility, 6th ed. St Louis, MO: Mosby, 2002. 5. Amblyopia: Preferred practice pattern 2022. 6. Von Noorden GK, Burian HM. Visual acuity in normal and amblyopic patients under reduced illumination. I. Behaviour of visual acuity with and without neutral density filter. AMA Archives of Ophthalmology. 1959;61(4):533-5. 7. Flom MC. Eccentric fixation in amblyopia: is reduced foveal acuity the cause? Am J Optom Physiol Opt. 1978 Mar;55(3):139-43. 8. Levi DM, Knill DC, Bavelier D. Stereopsis and amblyopia: A minireview. Vision Res. 2015 Sep; 114:17-30. 9. Hatsukawa Y, Otori T: A study of accommodation of amblyopic eye by simultaneous measurement of refraction of both eyes. In Campos E, ed: Proceedings of the Fifth International Strabismological Association Congress, Rome, ETA, 1986 p 131. 10. Webber AL, Wood JM, Gole GA, Brown B. The effect of amblyopia on fine motor skills in children. Invest Ophthalmol Vis Sci. 2008 Feb;49(2):594-603. 11. Kaur S, Sharda S, Aggarwal H, Dadeya S. Comprehensive review of amblyopia: Types and management. Indian J Ophthalmol 2023;71:2677-86. 12. Tommila V, Tarkkanen A. Incidence of loss of vision in the healthy eye in amblyopia. Br J Ophthalmol. 1981;65:575-577. 13. Terrell A. Cambridge stimulator treatment for amblyopia. An evaluation of 80 consecutive cases treated by this method. Aus J Ophthalmol. 1981 May;9(2):121-7. 14. Moseley MJ, Neufeld M, McCarry B, et al. Remediation of refractive amblyopia by optical correction alone. Ophthal Physiol Opt 2002;23:1–4. 15. Cotter SA, Edwards AR, Wallace DK, Beck RW, Arnold RW, Astle WF, et al. Pediatric eye disease investigator group. Treatment of anisometropic amblyopia in children with refractive correction. Ophthalmology 2006;113:895 903. 16. Wallace DK, Chandler DL, Beck RW, Arnold RW, Bacal DA, Birch EE, et al. Treatment of bilateral refractive amblyopia in children three to less than 10 years of age. Am J Ophthalmol 2007;144:487 96. 17. Cotter SA, Edwards AR, Arnold RW, Astle WF, Barnhardt CN, Beck RW, et al. Pediatric eye disease investigator group. Treatment of strabismic amblyopia with refractive correction. Am J Ophthalmol 2007;143:1060 3. 18. Holmes JM, Kraker RT, Beck RW, Birch EE, Cotter SA, Everett DF, et al. A randomized trial of patching regimens for treatment of severe amblyopia in children. Ophthalmology 2003;110:2075 87. 19. Holmes JM, Beck RW, Kraker RT, Astle WF, Birch EE, Cole SR, Cotter SA, Donahue S, Everett DF, Hertle RW, Keech RV, Paysse E, Quinn GF, Repka MX, Scheiman MM; Pediatric Eye Disease Investigator Group. Risk of amblyopia recurrence after cessation of treatment. J AAPOS. 2004 Oct;8(5):420-8. 20. Chen AM, Cotter SA. The Amblyopia Treatment Studies: Implications for Clinical Practice. Adv Ophthalmol Optom. 2016 Aug;1(1):287- 305. 21. Pediatric Eye Disease Investigator Group. A comparison of atropine and patching treatments for moderate amblyopia by patient age, cause of amblyopia, depth of amblyopia, and other factors. Ophthalmology. 2003;110:1632–7. 22. Scheiman MM, Hertle RW, Kraker RT, et al. Patching vs atropine to treat amblyopia in children aged 7 to 12 years: a randomized trial. Arch Ophthalmol. 2008;126(12):1634-1642. doi:10.1001/ archophthalmol.2008.107. 23. Pediatric Eye Disease Investigator Group. A randomized trial of atropine vs. patching for treatment of moderate amblyopia in children. Arch Ophthalmol. 2002 Mar;120(3):268-78. 24. Pediatric Eye Disease Investigator Group. Pharmacological plus optical penalization treatment for amblyopia: results of a randomized trial. Arch Ophthalmol. 2009;127(1):22-30. 25. Kasamatsu T, Pettigrew JD. Preservation of binocularity after monocular deprivation in the striate cortex of kittens treated with 6-hydroxydopamine. J Comp Neurol. 1979;185:139–61 26. Pediatric Eye Disease Investigator Group; Repka MX, Kraker RT, Dean TW, Beck RW, Siatkowski RM, Holmes JM, Beauchamp CL, Golden RP, Miller AM, Verderber LC, Wallace DK. A randomized trial of levodopa as treatment for residual amblyopia in older children. Ophthalmology. 2015 May;122(5):874-81. 27. Basmak H, Yildirim N, Erdinç O, Yurdakul S, Ozdemir G. Effect of levodopa therapy on visual evoked potentials and visual acuity in amblyopia. Ophthalmologica. 1999;213:110–3. 28. Guest PC, Knowles MR, Molon-Noblot S, Salim K, Smith D, Murray F, Laroque P, Hunt SP, De Felipe C, Rupniak NM, McAllister G. Mechanisms of action of the antidepressants fluoxetine and the substance P antagonist L-000760735 is associated with altered neurofilaments and synaptic remodelling. Brain Res. 2004 Mar 26;1002(1-2):1-10. 29. Sharif MH, Talebnejad MR, Rastegar K, Khalili MR, Nowroozzadeh MH. Oral fluoxetine in the management of amblyopic patients aged between 10 and 40 years old: a randomized clinical trial. Eye (Lond). 2019 Jul;33(7):1060-1067. 30. Pawar PV, Mumbare SS, Patil MS, Ramakrishnan S. Effectiveness of the addition of citicoline to patching in the treatment of amblyopia around visual maturity: a randomized controlled trial. Indian J Ophthalmol. 2014;62(2):124-129.

DOS Times Volume 29, Number 7, January-February 2024 www.dosonline.org/dos-times 28 31. Prabha D, Lahre Y. Role of citicoline for the management of myopic amblyopia patients in tertiary care hospital of India. IJCMR 2019;6:1. 32. Levi DM, Li RW, Silver MA, Chung STL. Sequential perceptual learning of letter identification and "uncrowding" in normal peripheral vision: Effects of task, training order, and cholinergic enhancement. J. Vis. 2020; 20:24. 33. Wu C, Gaier ED, Nihalani BR, Whitecross S, Hensch TK, Hunter DG. Durable recovery from amblyopia with donepezil. Sci Rep. 2023;13(1):10161. 34. Chaturvedi, Isha; Jamil, Rana; Sharma, Pradeep1,. Binocular vision therapy for the treatment of Amblyopia—A review. Indian Journal of Ophthalmology 71(5):p 1797-1803, May 2023. | DOI: 10.4103/IJO. IJO_3098_22. 35. Holmes JM, Manh VM, Lazar EL, Beck RW, Birch EE, Kraker RT, et al. Effect of a binocular iPad game vs part-time patching in children aged 5 to 12 years with amblyopia: A randomized clinical trial. JAMA Ophthalmol 2016;134:1391–400. 36. Guo CX, Babu RJ, Black JM, Bobier WR, Lam CS, Dai S, et al. Binocular treatment of amblyopia using videogames (BRAVO): Study protocol for a randomised controlled trial. Trials 2016;17:504. Dr. Parikshit Gogate, MS, DNB, FRCS, MSc, FAICO, ex-IPS Community Eye Care Foundation, Dr. Gogate’s Eye Clinic, Pune, India. Corresponding Author: Subspeciality - Squint

www.dosonline.org/dos-times DOS Times Volume 29, Number 7, January-February 2024 29 Cross Linking in Thin Cornea - A Mini Review Pradeep Dubey, MBBS, DNB, Bithi Chowdhury, MS, FRCS Department of Ophthalmology, Hindu Rao Hospital & NDMC Medical College, Delhi. Introduction Photosensitized oxidation of biological tissue has been demonstrated as early as 1968. Cross-linking of collagen has been used to stiffen cardiac valve prosthesis and for tissue fixation.[1,2] Sporletal demonstrated cross-linking in corneal tissue of porcine eyes in 1998.[3] Wollensak et al first reported the use of Riboflavin UVA in human eyes in 2003.[4] FDA approval was given in 2016 for its use in keratoconus and post-LASIK ectasia following a one-year clinical trial.[5] The structure of collagen is strengthened by intermolecular cross-links between collagen monomers. Cross-linking occurs in 3 ways in human tissue namely enzymatic, glycation, and oxidation. Normal maturation of collagen involves the use of the enzyme lysine oxidase in the human body.[6] The process of glycation involves sugar bonding with amino group of protein forming pentosidin which forms covalent bonds between arginine and lysine residues.[6] Glycation occurs in diabetes patients and to a small extent in the elderly and is responsible for the stiffening of the cornea in diabetes and elderly patients. In the oxidative process, cross-linking between collagen fibrils occurs in the presence of oxygen and reactive oxygen species. This method is used to halt the progression of corneal ectatic disease. The presence of oxygen is important for the crosslinking process as during the process oxygen levels get depleted rapidly and lower levels of oxygen reduce the effect of CXL.[7] Indications of CXL 1. Corneal ectatic disorders • Keratoconus • Pellucid marginal degeneration • Terrien marginal degeneration • Post-refractive surgery (such as LASIK, PRK, or radial keratotomy) 2. Sterile corneal melts 3. Microbial keratitis 4. Refractive surgery The most widely used procedure is the conventional CXR using the Dresden Protocol. (Figure-1) The Dresden protocol[4] requires epithelium debridement to allow riboflavin to penetrate the stroma, UV fluence delivery duration of 30 minutes and a 400µm minimum corneal thickness is required for corneal endothelial protection. Limitations of this method are the long duration, presence of postoperative pain, potential risk of microbial infection and requirement of corneal thickness of at least 400µm. A significant proportion of keratoconus patients especially moderate to severe cases have pachymetry of less than 400 microns at initial presentation. Also during the CXL procedure, there is a significant reduction in corneal thickness due to desiccation and dehydration of corneal tissue during the prolonged UVA exposure which makes the procedure unfit for thin corneas (<400nm). All these factors make the conventional method unsuitable for treatment of many of the ectatic corneas. Figure 1: Flowchart showing Dresden protocol. Modification in Surgical Technique for Thin Cornea (<400 μm) Since 2009, modifications to the conventional corneal crosslinking (CXL) procedure have been explored to address the issue of thin corneas and to overcome the 400µm limit. Some of these modifications include (Figure-2 & Table-1) 1. Increasing thickness of cornea • Hypoosmolar riboflavin • Contact lens-assisted CXL • SMILE-lenticule assisted CXL 2. Epithelium on CXL • Transepithelial CXL, • Epithelial island technique (leaving epithelium on the pachymetry thinnest point area) 3. Alteration of fluence • Accelerated CXL • Sub400 protocol • M Protocol Subspeciality - Cornea

DOS Times Volume 29, Number 7, January-February 2024 www.dosonline.org/dos-times 30 Hypo Osmolar Technique In this method hypo-osmolar riboflavin without dextran (310mosm/L) is used to induce corneal swelling.[8] The rest of the procedure is similar to conventional CXL. While no endothelial toxicity was reported by this method the efficacy was found to be less by some authors. This has been attributed to less number of collagen fibers available for crosslinking in the edematous cornea due to the formation of “collagen-free lakes” in the stroma. Also, the diffusion factor of oxygen through the hydrated corneal stroma is lower than normal corneal tissue. Taking into consideration that at least 250 microns of crosslinked stroma is required to prevent ectasia a preoperative thickness of 330 micron have been advised for safe and effective CXL.[9] Contact Lens Technique In this technique, the bandage contact lens soaked in 0.1% isoosmolar riboflavin is used for 30 minutes over the cornea.[10] It is performed in corneas with pachymetry of 350-400µm after epithelial removal. The procedure was found to be effective however the riboflavin-soaked contact lens reduces the oxygen availability to the deeper tissues and it also absorbs the UVA radiation which in turn reduces the surface irradiance level by 40–50%. Smile Lenticular Assisted Technique In this technique, Sachdeva et al used the stromal lenticule extracted from patients undergoing small incision lenticule extraction (SMILE) for myopic correction and used them in patients with thin corneas undergoing CXL After epithelial debridement, the stromal lenticule of appropriate thickness was placed over the patient’s cornea centered over the apex of the cone.[11] This was followed by conventional CXL. The advantage of the technique is that the lenticule used is biologically similar to the treated cornea and the thickness of the lenticule can be customized as per the need based on pachymetry. Transepithelial CXL In this method the cornea is treated without epithelial debridement. For enhancing the penetration of riboflavin through the intact epithelium substances like benzalkonium chloride (BAC), ethylenediaminetetraacetic acid (EDTA), gentamicin, and trometamol are combined with riboflavin.[12,13] The effect of CXL is attenuated due to the decreased penetration of oxygen through intact epithelium and absorption of UVA by the riboflavin soaked epithelium.[14,15] It is estimated that the biomechanical rigidity increases by approximately 64% after transepithelial CXL as compared to 320% after standard CXL. Iontophoresis is another method to enhance penetration of riboflavin into the corneal stroma through an intact epithelium. In this method, one electrode is placed on cervical vertebrae or on the patient’s forehead and the other electrode is applied to the cornea using a suction ring.[16] The annular ring of the iontophoresis device is irrigated with 0.1% riboflavin in distilled water till the grid is submerged. Following this, a current of 1 mA is given for 5 min. The advantage of this procedure is that the soakage time for riboflavin is decreased to 5 min as compared to 30 minutes in conventional CXL and improvement in contrast sensitivity has been reported post operatively.[17,18,19] The procedure was found to be effective in halting the progression in early keratoconus patients. Epithelial island technique involves keeping an intact epithelium over the thinnest part of cone, and debridement of the paracentral area of the cone. This allows for proper penetration of riboflavin into the stroma and the intact epithelium provides endothelial protection at the thinnest part. Lesser CXL effect has been observed under the intact epithelium while some authors have reported endothelial loss after the procedure.[20,21] Accelerate CXL In recent decades, variations in riboflavin preparation or irradiation dosage with shorter duration of treatment without compromising the outcome have been tried. These alternatives are called “AcceleratedCXL”. According to the photochemical law of reciprocity (Bunsen-Roscoe law)[22], the same photochemical effect can be achieved with reduced illumination time and correspondingly increased irradiation intensity, meaning that 3-minute irradiation at 30mW/cm2 , 5-minute irradiation at 18.0 mW/cm2 , and 10-minute irradiation at 9.0 mW/ cm2 should provide the same effect obtained with a 30-minute irradiation at 3.0mW/cm2 , all delivering a total fluence of 5.4 J/cm2 . Accelerating the fluence delivery is associated with oxygen depletion at an increasingly faster rate than it can be replenished by diffusion from the surrounding atmosphere.[23] A setting of a 9mW/cm2 /10-minute epithelium-off protocol was found to be an acceptable trade-off between shortening the duration while retaining acceptable biomechanical strengthening effects.[24] Several strategies have been employed to deal with oxygen availability. One is pulsed fractionation of UV-A energy delivery to let oxygen diffuse into the stroma during the UV ‘off ’ periods.[25,26] Another strategy is combining pulsed UV-A irradiation with supplemental oxygen applied to the corneal surface.[27,28] Sub 400 Protocol The sub400 protocol was formulated based on a retrospective study conducted on 39 patients of progressive keratoconus with thin corneas (average thickness 343 µm). In the study, the stromal thickness at the thinnest point was measured after epithelial debridement in each patient using a hand-held ultrasound pachymeter. This was followed by a customized UV irradiation time, which was selected using a look-up table, at an intensity of 3mW/cm².[29] The sub400 protocol was successful in preventing one-year progression in 90% of the keratoconus patients with ultra-thin corneas (214-398mm) with no incidence of endothelial decompensation.[29] M Protocol Mazzotta et al.[30] proposed a protocol that integrated all available evidence on the demarcation line depths achieved by different cross-linking protocols and then suggested the appropriate protocol for any given corneal depth. It has been Subspeciality - Cornea

www.dosonline.org/dos-times DOS Times Volume 29, Number 7, January-February 2024 31 seen that protocols that accelerate UV irradiation had resulted in a lower depth of cross-linking due to lower oxygen availability. Similarly the trans epithelial protocols are also associated with less oxygen penetration into the stroma resulting in shallower cross linking effects. Furthermore, each CXL approach results in a different cross-linking depth. The “M nomogram” offered the advantage of a uniform CXL method for the treatment of normal and thin corneas having progressive ectatic disorders, sparing endothelium, ensuring a sufficient CXL penetration, presetting the depth of CXL photo-oxidative effect penetration. Thus the nomogram provide a standardized management protocol of thin corneas ≤ 400 µm that are often encountered in the ophthalmological clinical practice. However, this M protocol would require access to multiple sophisticated equipments which is its major limitation. Modification Author, Year Outcome 1. Hypoosmolar Riboflavin Solution (Riboflavin used on the De-epithelized thin cornea) Hafezi et al.[8] 2009 - Topographic changes were stable at 6 months of follow up - Failure of CXL in a cornea that was 268μm thick Raiskup et al.[31] 2011 - Topographic changes were stable at 1 year of follow up - No stromal scar Stojanovic et al.[32] 2014 - Topographic changes were stable at 1 year of follow up - Effect was lower than that seen with CXL in normal cornea 2. Transepithelial Cross-Linking (Riboflavin used on intact epithelium of thin cornea with permeability enhancers like EDTA, BAC, trometamol) Caporossi et al.[33] 2013 - Improvement in UDVA & BDVA in first 3-6 months then returned to preoperative levels gradually - Topographic changes are stable upto 12 months then worsening noted at 24 months follow up Gatzioufas et al.[34] 2016 - No change in UDVA & BDVA or corneal pachymetry at 6-12 months - Topographically progression seen in 46% cases at 1 year of follow up Filippello et al.[35] 2012 - Significant improvement in UDVA, BDVA, Kmax & higher order aberrations as well - Topographic changes were stable after 18 months follow up Leccisotti et al.[36] 2010 - Effect was less than conventional CXL - Topographic changes were stable after 1 year follow up 3. Iontophoresis-Assisted Crosslinking (I-CXL) (Riboflavin used on intact epithelium of thin cornea with small electric current to facilitate penetration) Bikbova et al.[16] 2014 - UDVA and BDVA remained stable with no significant corneal haze - Topographic changes were stable upto 1 year follow up Vinciguerra et al.[37] 2014 - Significant improvement in BDVA & a non-significant improvement in Kmax & aberrometry - Topographic changes were stable upto 1 year follow up Jouve et al.[38] 2017 - After 2 years of follow up I-CXL halted progression less efficiently than conventional CXL - Failure rate was 20% in I-CXL Vs 7.5% in conventional CXL Subspeciality - Cornea

DOS Times Volume 29, Number 7, January-February 2024 www.dosonline.org/dos-times 32 Modification Author, Year Outcome 4. Customised Epithelial Debridement (Riboflavin used after epithelial debridement of thin cornea but sparing epithelium over thinnest location) Kymionis et al.[39] 2009 - Stabilization of the ectasia upto 9 months of follow up - No intraoperative or postoperative complications Mazzotta et al.[20] 2014 - Topographic changes were stable upto 1 year of follow up - But lower CXL effect seen under stomal area of intact epithelium Cagil et al.[21] 2017 - Topographic changes were stable upto 1 year of follow up - But significant endothelial cell loss were seen 5. Lenticule-Assisted Crosslinking (Stromal lenticule of appropriate thickness was placed over ultrathin cornea for stromal expansion before CXL procedure) Sachdev et al.[11] 2019 - This technique was safe in their few cases - Thickness of the lenticule can be customized based on the pachymetry of the keratoconic cornea 6. Contact Lens-Assisted Crosslinking (CACXL) (Bandage contact lens having thickness of approx. 0.9mm used on ultrathin cornea for increasing corneal thickness before CXL procedure) Jacob et al.[10] 2014 - Found that this technique was effective in their study of 14 eyes - Studies with larger sample size & longer follow-ups are needed 7. Individualized Corneal Crosslinking (Lower UV dose used after riboflavin application for ultrathin cornea by shortening the irradiation time while maintaining standard UV Irradiance) Hafezi et al.[27] 2021 - Successful in preventing one-year progression in 90% of the keratoconus patients with ultra-thin corneas (214-398mm) - No incidence of endothelial decompensation. Mazzotta et al.[28] 2018 - Can manage all-thickness progressive ectatic corneas, sparing endothelium. - Require access to multiple sophisticated equipments to implement this technique. UDVA- uncorrected distance visual acuity; BDVA-best measured distance visual acuity. Table 1: Some of the important studies related to CXL in thin cornea. Figure 2: Methods of performing CXL in thin corneas. Subspeciality - Cornea

www.dosonline.org/dos-times DOS Times Volume 29, Number 7, January-February 2024 33 Subspeciality - Cornea Conclusion Ongoing research and advancements in the field continue to shape the best practices for CXL in thin corneas. Long term studies are required not only to determine the efficacy of the different methods of CXL but also to assess the safety of the procedures. Additionally it’s important to note that the specific details of the CXL procedure may vary based on the patient’s condition and the preferences of the treating ophthalmologist. References 1. Balguid A, Rubbens MP, Mol A, Bank RA, Bogers AJ, van Kats JP, et al. The role of collagen cross-links in biomechanical behavior of human aortic heart valve leaflets-relevance for tissue engineering. Tissue Eng. 2007;13(7):1501-11. 2. Sompuram SR, Vani K, Messana E, Bogen SA. A molecular mechanism of formalin fixation and antigen retrieval. Am J Clin Pathol. 2004;121(2):190-9. 3. Spoerl E, Huhle M, Seiler T. Induction of cross-links in corneal tissue. Exp Eye Res. 1998;66(1):97-103. 4. Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003;135(5):620-7. 5. Lowes R. FDA Approves Photrexa for Corneal Crosslinking in Keratoconus.2016. 6. Ashwin PT, McDonnell PJ. Collagen cross-linkage: a comprehensive review and directions for future research. Br J Ophthalmol. 2010;94(8):965-70. 7. Krueger RR, SpoerlE, Herekar S. Rapid vs standard collagen CXL with equivalent energy dosing: Paper Presented at: Proceedings of the 3rd International Congress of Corneal Collagen Cross-linking.2007 Dec. 8. Hafezi F, Mrochen M, Iseli HP, Seiler T. Collagen crosslinking with ultraviolet-A and hypoosmolar riboflavin solution in thin corneas. J Cataract Refract Surg. 2009;35(4):621-4. 9. Hafezi F. Limitation of collagen cross-linking with hypoosmolar riboflavin solution: failure in an extremely thin cornea. Cornea. 2011;30(8):917-9. 10. Jacob S, Kumar DA, Agarwal A, Basu S, Sinha P, Agarwal A. Contact lens-assisted collagen cross-linking (CACXL): a new technique for cross-linking thin corneas. Journal of Refractive Surgery. 2014;30(6):366-72. 11. Sachdev MS, Gupta D, Sachdev G, Sachdev R. Tailored stromal expansion with a refractive lenticule for crosslinking the ultrathin cornea. J Cataract Refract Surg. 2015;41(5):918-23. 12. Chang SW, Chi RF, Wu CC, Su MJ. Benzalkonium chloride and gentamicin cause a leak in corneal epithelial cell membrane. Exp Eye Res. 2000;71(1):3-10. 13. Majumdar S, Hippalgaonkar K, Repka MA. Effect of chitosan, benzalkonium chloride and ethylenediaminetetraacetic acid on permeation of acyclovir across isolated rabbit cornea. Int J Pharm. 2008;348(1-2):175-8. 14. Hersh PS, Lai MJ, Gelles JD, Lesniak SP. Transepithelial corneal crosslinking for keratoconus. J Cataract Refract Surg. 2018;44(3):313- 22. 15. Wollensak G, Aurich H, Wirbelauer C, Sel S. Significance of the riboflavin film in corneal collagen crosslinking. J Cataract Refract Surg. 2010;36(1):114-20. 16. Bikbova G, Bikbov M. Transepithelial corneal collagen cross-linking by iontophoresis of riboflavin. Acta Ophthalmol. 2014;92(1):e30-4. 17. Lombardo M, Serrao S, Raffa P, Rosati M, Lombardo G. Novel Technique of Transepithelial Corneal Cross-Linking Using Iontophoresis in Progressive Keratoconus. J Ophthalmol. 2016;2016:7472542. 18. Lombardo M, Giannini D, Lombardo G, Serrao S. Randomized Controlled Trial Comparing Transepithelial Corneal Cross-linking Using Iontophoresis with the Dresden Protocol in Progressive Keratoconus. Ophthalmology. 2017;124(6):804-12. 19. Jia HZ, Peng XJ. Efficacy of iontophoresis-assisted epitheliumon corneal cross-linking for keratoconus. Int J Ophthalmol. 2018;11(4):687-94. 20. Mazzotta C, Ramovecchi V. Customized epithelial debridement for thin ectatic corneas undergoing corneal cross-linking: epithelial island cross-linking technique. Clin Ophthalmol. 2014;8:1337-43. 21. Cagil N, Sarac O, Can GD, Akcay E, Can ME. Outcomes of corneal collagen crosslinking using a customized epithelial debridement technique in keratoconic eyes with thin corneas. Int Ophthalmol. 2017;37(1):103-9. 22. Bunsen RW, Roscoe HE. Photochemical researches. – PartV. On the measurement of the chemical action of direct and diffuse sunlight. ProcR SocLond1862;12:306–312. 23. Koç M, Uzel MM, Koban Y, Tekin K, Taşlpnar AG, Ylmazbaş P. Accelerated corneal cross-linking with a hypoosmolar riboflavin solution in keratoconic thin corneas: Short-term results. Cornea2016;35:350-4. 24. Mazzotta C, Raiskup F, Hafezi F, Torres-Netto EA, ArmiaBalamoun A, Giannaccare G, et al. Long term results of accelerated 9mW corneal crosslinking for early progressive keratoconus: the Siena EyeCross Study 2. Eye Vis (Lond). 2021;8(1):16. 25. Moramarco A, Iovieno A, Sartori A, Fontana L. Corneal stromal demarcation line after accelerated crosslinking using continuous and pulsed light. J Cataract Refract Surg. 2015;41(11):2546-51. 26. Peyman A, Nouralishahi A, Hafezi F, Kling S, Peyman M. Stromal Demarcation Line in Pulsed Versus Continuous Light Accelerated Corneal Cross-linking for Keratoconus. J Refract Surg. 2016;32(3):206- 8. 27. Seiler TG, Komninou MA, Nambiar MH, Schuerch K, Frueh BE, Büchler P. Oxygen Kinetics During Corneal Cross-linking With and Without Supplementary Oxygen. Am J Ophthalmol. 2021;223:368- 76. 28. Hill J, Liu C, Deardorff P, Tavakol B, Eddington W, Thompson V, et al. Optimization of oxygen dynamics, UV-A delivery, and drug formulation for accelerated epi-on corneal crosslinking. Current eye research. 2020;45(4):450-8. 29. Hafezi F, Kling S, Gilardoni F, Hafezi N, Hillen M, Abrishamchi R, et al. Individualized Corneal Cross-linking With Riboflavin and UV-A in Ultrathin Corneas: The Sub400 Protocol. Am J Ophthalmol. 2021;224:133-42. 30. Mazzotta C, Romani A, Burroni A. Pachymetry-based accelerated crosslinking: the “M Nomogram” for standardized treatment of all-thickness progressive ectatic corneas. Int J Keratoconus Ectatic Corneal Dis. 2018;7:137–44. 31. Raiskup F, Spoerl E. Corneal cross-linking with hypo-osmolar riboflavin solution in thin keratoconic corneas. Am J Ophthalmol. 2011;152(1):28-32.e1.

DOS Times Volume 29, Number 7, January-February 2024 www.dosonline.org/dos-times 34 32. Stojanovic A, Zhou W, Utheim TP. Corneal collagen cross-linking with and without epithelial removal: a contralateral study with 0.5% hypotonic riboflavin solution. Biomed Res Int. 2014;2014:619398. 33. Caporossi A, Mazzotta C, Paradiso AL, Baiocchi S, Marigliani D, Caporossi T. Transepithelial corneal collagen crosslinking for progressive keratoconus: 24-month clinical results. J Cataract Refract Surg. 2013;39(8):1157-63. 34. Gatzioufas Z, Raiskup F, O’Brart D, Spoerl E, Panos GD, Hafezi F. Transepithelial Corneal Cross-linking Using an Enhanced Riboflavin Solution. J Refract Surg. 2016;32(6):372-7. 35. Filippello M, Stagni E, O’Brart D. Transepithelial corneal collagen crosslinking: bilateral study. J Cataract Refract Surg. 2012;38(2):283- 91. 36. Leccisotti A, Islam T. Transepithelial corneal collagen cross-linking in keratoconus. J Refract Surg. 2010;26(12):942-8. 37. Vinciguerra P, Randleman JB, Romano V, Legrottaglie EF, Rosetta P, Camesasca FI, et al. Transepithelial iontophoresis corneal collagen cross-linking for progressive keratoconus: initial clinical outcomes. J Refract Surg. 2014;30(11):746-53. 38. Jouve L, Borderie V, Sandali O, Temstet C, Basli E, Laroche L, et al. Conventional and Iontophoresis Corneal Cross-Linking for Keratoconus: Efficacy and Assessment by Optical Coherence Tomography and Confocal Microscopy. Cornea. 2017;36(2):153-62. 39. Kymionis GD, Diakonis VF, Coskunseven E, Jankov M, Yoo SH, Pallikaris IG. Customized pachymetric guided epithelial debridement for corneal collagen cross linking. BMC Ophthalmol. 2009;9:10. Dr. Bithi Chowdhury, MS, FRCS Senior Specialist & Head Department of Ophthalmology, Hindu Rao Hospital & NDMC Medical College, Delhi. Corresponding Author: Subspeciality - Cornea

www.dosonline.org/dos-times DOS Times Volume 29, Number 7, January-February 2024 35 Newer Treatment Modalities in the Management of Keratoconus Bhupesh Singh, MBBS, DO, FLVPEI, FCE NN Department of Ophthalmology, Bharti Eye Foundation & Hospitals, New Delhi. Keratoconus management has seen a paradigm shift. The newer treatment modalities from corneal collagen cross-linking, intrastromal corneal ring segment, corneal addition procedures to Bowman’s membrane transplant has revolutionized the management of keratoconus. Advances in the management of keratoconus have provided the clinicians many options to visually rehabilitate the keratoconus patients based on the severity of the disease. In this current article different and newer treatment modalities for keratoconus will be discussed. 1. Corneal Collagen Cross-Linking This procedure is done to prevent the progression of Keratoconus. This procedure consist of two components; Photosensitizer that is Riboflavin and UV-A Light. The total fluence required was found to be 5.4J/cm2 . As the absorption peak of riboflavin was noted to be 370 nm, UV-A light was found to be ideal for CXL. Different protocols have been designed to achieve this fluence level by modifying UV-A intensity and riboflavin drop exposure time. Studies have shown that an irradiation dose of 10mW/cm2 for 9 minutes has a better therapeutic and safety profile than higher irradiation doses for shorter periods. It has been seen that CXL is not effective once the energy intensity exceeds 45mW/cm2 . Epithelium-off Method The epithelium-off method is the standard and most effective method for CXL. In this procedure epithelium is manually debrided before the instillation of riboflavin 0.1% and dextran 20% to allow its better penetration in the corneal stroma. B) Contact Lens Assisted Collagen Cross-Linking: This technique can be used in keratoconus eyes with thickness between 350 and 400 microns. After epithelium removal recipient’s cornea is soaked with iso-osmolar riboflavin 0.1%. An ultraviolet barrier-free soft contact lens was also soaked in iso-osmolar riboflavin 0.1% for 30 minutes. Then this contact lens was placed on the cornea and ultraviolet-A- irradiance was given. Contact lens was discarded after the procedure and BCL was placed on the cornea. Epithelium-on Method In this method corneal epithelium is not removed and riboflavin drops are instilled on top of that. Hypo-osmolar 0.1% riboflavin, dextran 15% is used for epi on cross-linking. Epi on crosslinking is done in cases of thinner corneas, which are not fit for epi-off cross inking. CXL in Thin Corneas The main limitation of conventional CXL is that it cannot be performed in corneas thinner then 400 micron. Many of keratoconus eyes have thinner corneas and not fit for epi-off cross-linking. Where as epi on cross-linking have not shown as effective results as epi-on cross-linking. To overcome this limitation many innovative methods and techniques have been devised. Some of the common methods are as follows: A) Corneal Tissue Assisted Collagen Cross-Linking: In this techniques donor corneal tissue is used to increase the thickness of recipient’s cornea intraoperative. First of all recipients corneal epithelium is removed. Donor corneal tissue of 100 to 120 micron is prepared with microkeratome or with femtosecond laser. This prepared tissue, which was soaked in riboflavin solution, is placed on top of recipient’s cornea and then CXL is done. After the procedure this donor tissue is discarded and bandage contact lens is placed on recipients cornea. Figure 1: Showing collagen cross-linking in progress and UV light exposure. Figure 2: Showing placement of donor corneal tissue after removal of epithelium. Subspeciality - Cornea

DOS Times Volume 29, Number 7, January-February 2024 www.dosonline.org/dos-times 36 Figure 3: Showing riboflavin soaked contact lenses and method depicting contact lens assisted CXL. Figure 4: a) Showing smile lenticular insertion in stromal pocket, b) Showing removal of epithelium, c) Showing donor lenticule in situ. C) Lenticule Addition Combined with Collagen Cross Linking: In this innovative technique of managing advanced cases ofkeratoconus donor SMILE (small incision lenticule extraction) lenticule is used. These lenticules were soaked in riboflavin during the procedure and in eyes with corneal thickness between 300 to 400 microns donor lenticule of known thickness was placed in the intra stromal pocket created by femtosecond laser. This addition of tissue will increase the corneal thickness making it biomechanically stronger as well as make the thinner cornea suitable for epi off cross linking. 2. Bowman’s Membrane Transplant Bowman`s layer is the strongest biomechanical layer of the human cornea and its shows fragmentation in advanced cases of keratoconus. The main treatment objective of the surgery is to halt the progression and reduce corneal steepness. Bowman stromal inlay is prepared with the help of femtosecond laser after removing the corneal epithelium from donor cornea. Stromal pocket is created in the keratoconus eyes in anterior stroma and this inlay is placed in the stromal pocket. BCL is placed. This technique has shown keratoconus stabilization. Long term results and larger studies are still needed to support the efficacy of this procedure. 3. Intracorneal Ring Segments Keratoconus causes reduction in visual acuity because of corneal steepening. Cross-linking halts the progression of keratoconus but does not alter the corneal steepening significantly. To achieve corneal flattening these ring segments works very well. ICRS flatten and regularize the central cornea in keratoconus. Planning of ICRS is most important step in achieving good results. ICRS are placed in the mid-corneal peripheral stroma (6–7mm zone) at approximately two-thirds of depth to reshape the anterior corneal surface while maintaining the prolate profile of the cornea. These rings can be used as a single ring or can be used in pairs depending upon the cone location in keratoconus. 4. Corneal Allogenic Intrastromal Ring Segments (CAIRS) This is as new innovative technique in which instead of using plastic ring segments, donor corneal tissue strips are inserted in mid peripheral zone of keratoconus cornea to cause its flattening. These segments are more biocompatible and less Subspeciality - Cornea

www.dosonline.org/dos-times DOS Times Volume 29, Number 7, January-February 2024 37 rigid in comparison to plastic ring segments. As these segments integrate well with recipient’s cornea so reversibility could be an issue in long term. 5. Topography Guided PRK with Simultaneous Corneal Collagen Cross-Linking This procedure is performed in mild to moderate keratoconus cases with thinnest pachymetry above 450 microns at least. The aim of this treatment is regularize the cornea to achieve better best-corrected visual acuity. 50 micron is maximum ablation depth that is corrected in most of the cases. CXL augments the laser flattening. Outcomes of these procedures are encouraging although standardized guidelines are needed to perform TPRK+CXL. 6. Toric ICL Toric ICL works well in cases of stable keratoconus for the correction of refractive error. Eyes who already underwent collagen cross-linking and got no change in refraction for atleast 1 year are the best candidates for these lenses. Eyes with clear central cornea and anterior chamber depth of 2.8mm or more and best-corrected visual acuity of 6/18 with glasses are the essential requisite for TICL in keratoconus. 7. Keratoplasty Techniques DALK (deep anterior lamellar Keratoplasty) and PKP (penetrating Keratoplasty) are time tested treatments reserved as last resort for very advanced stage cases of keratoconus. Dr. Bhupesh Singh, MBBS, DO, FLVPEI, FCE NN Department of Ophthalmology Bharti Eye Foundation & Hospitals, New Delhi. Corresponding Author: This is the brief summary of current treatment modalities for cases of keratoconus. Choice of treatment always depends on the severity of disease and age of the patient. Many newer treatment modalities mentioned above still require long-term results to prove its efficacy and safety in the management of keratoconus. Subspeciality - Cornea

DOS Times Volume 29, Number 7, January-February 2024 www.dosonline.org/dos-times 38 Corneal Collagen Crosslinking: Then and Now Isha Gupta, MS, Parul Jain, MS, FICO, FAICO, FRCS, MRCSEd, Avani Hariani, MS, Gahan Reddy, MBBS Cornea and Refractive Surgery Services, Guru Nanak Eye Centre, Maulana Azad Medical College, New Delhi. Keratoconus is a chronic, bilateral, often asymmetric, noninflammatory progressive ophthalmic disease that leads to bulging and thinning of the cornea, resulting in increasing irregular astigmatism and, ultimately, poor vision. The management of keratoconus was revolutionized when corneal collagen cross-linking (CXL) was introduced to halt the progression of ectasia.[1,2] It is a minimally invasive procedure. This technique was developed in Europe by researchers at the University of Dresden in the late 1990s. UV light was used to induce collagen cross-linking in riboflavin soaked porcine and rabbit corneas and the results were promising. Human studies of UV-induced corneal cross-linking began in 2003 in Dresden and since then it has been used as a therapeutic approach to strengthen the cornea and halt various ectatic corneal disorders. The main components of CXL are a photosensitizer, a UV light source, and the resulting photochemical reaction. In CXL, Riboflavin is used as the photosensitizer. It is safe systemically and can be adequately absorbed by the corneal stroma topically. It has an absorption peak at 370nm.[3] Once exposed to UV-A light, the riboflavin generates reactive oxygen species, which induce the formation of intra and interfibrillar covalent bonds between collagen molecules and between collagen molecules and proteoglycans.[4] At the same time, the riboflavin acts to shield the corneal endothelium from ultraviolet-induced damage and cell death. The best candidate for this therapy is an individual with a progressive ectatic disease of the cornea such as keratoconus. Conventional CXL The conventional treatment protocol, called the Dresden protocol, was formulated by Wollensak et al. for corneas with minimal thickness of 400µm after removal of epithelium.[2] As the corneal epithelium offers a barrier to the diffusion of riboflavin to the stroma, the epithelium is manually debrided to enable better penetration. Following removal of central 8-9 mm of epithelium, the cornea is saturated with iso-osmolar riboflavin solution (riboflavin-5-phosphate 0.5% with dextran T500 20%) every 3 minutes for 30 minutes followed by irradiation with UV-A for 30 mins at 3mW/cm2 (total energy density 5.4J/cm2 ). It can be safely performed only when the corneal thickness after de-epithelialization is more than 400µm. This is the standard method and remains the most effective.[5] However, it can cause severe pain and discomfort, temporary decreased visual acuity, stromal blurring, and risk of infections as a consequence of epithelium debridement.[6-7] Modifications of Standard Protocol Accelerated CXL - Variations in UV Exposure Time The conventional procedure is time-consuming, lasting approximately 1 hour and can result in patient discomfort. So accelerated CXL protocols that use a higher UVA irradiance intensity with a shorter exposure time while providing the same cumulative irradiation dose (5.4 J/cm2 ) are being widely used.[8] The rationale for the high-intensity approach is based on the Bunsen-Roscoe reciprocity law, which states that the time and intensity of irradiation can be varied without changing the total radiation energy of 5.4 J/cm2 of the standard protocol of Dresden. By setting the UV-A power at 9 mW/cm2 for 10 minutes, 30 mW/cm2 for 3 minutes, 18 mW/cm2 for 5 minutes, or 45 mW/cm2 for 2 minutes and maintaining a constant energy of 5.4 J/cm2 delivered to the corneal tissue, the same effect as the standard Dresden protocol at 3 mW/cm2 for 30 minutes is achieved.[9-10] The advantage for shorter duration is increased efficiency, improved patient comfort, reduced corneal dehydration and a shortened keratocyte exposure time resulting in potentially less fibrocyte damage. Pulsed Accelerated CXL The effect of CXL in providing biomechanical strength has been shown to be oxygen dependent. Therefore, pulsed accelerated CXL(P-ACXL) protocol has evolved which has on & off periods of illumination of UV-A light (1 second on and 1 second off) giving intermittent time to replenish oxygen in corneal stroma. It has been shown to be safe, effective to halt the disease in adults. Mazzotta et al showed that P-ACXL cohort shows a statistically significant improvement of mean keratometry values & reduction of apical curvature in adults.[11] Transepithelial CXL - Variations in Riboflavin Delivery To overcome the problems associated with conventional CXL, transepithelial CXL which does not require removal of epithelium has been described. Riboflavin is able to diffuse into the cornea easily after epithelium debridement; however, its hydrophilic and macromolecule properties limit the passage through intact epithelium. Therefore, in transepithelial CXL, substances impairing epithelial tight connections such as Subspeciality - Cornea

www.dosonline.org/dos-times DOS Times Volume 29, Number 7, January-February 2024 39 benzalkonium chloride (BAK), ethylenediaminetetraacetic acid (EDTA), and trometamol (TRIS) are added to riboflavin solution.[12] However, its efficacy remains controversial as the epithelial barrier limits the depth and amount of cross-linking, evidenced as shallow and uneven distribution of the keratocytes apoptosis on confocal microscopy and ectatic progression in many clinical trials as compared to epithelium off CXL.[13-14] In 2016, riboflavin solution with D-alpha-tocopheryl polyethylene-glycol 1000 succinate (vitamin E-TPGS) as a permeation enhancer was described with encouraging results.[15] Thin Corneas The application of corneal collagen cross linking in thin corneas poses a challenge. Wollensak et al. demonstrated that when ultraviolet light was used with riboflavin in corneas thinner than 400µm after epithelial debridement, the cytotoxicity threshold of 0.35mW/cm2 for the endothelium can be reached leading to its damage.[16] Various methods have been proposed to circumvent this limitation: Hypoosmolar CXL - Variations in Riboflavin Osmolarity It is a modified technique of CXL described first by Hafezi et al using hypoosmolar riboflavin solution to induce stromal swelling and increase the stromal thickness before CXL in cases with preoperatively thin corneas.[17] Hypoosmolar riboflavin 0.1% solution is generated by diluting vitamin B2-riboflavin5-phosphate 0.5% with physiological salt solution (sodium chloride 0.9% solution). It does not contain dextran T500 unlike isoosmolar riboflavin. After debridement of the corneal epithelium, isoosmolar riboflavin 0.1% solution with dextran T500 is applied to the cornea every 3 minutes for 30 minutes. After 30 minutes, ultrasound pachymetry is performed on the deepithelialized cornea at approximately the thinnest point. Hypoosmolar riboflavin is then applied every 20 seconds for 5 more minutes, and the corneal thickness is checked again. Hypoosmolar riboflavin solution is administered until the minimal corneal thickness reaches 400 µm. This is followed by UV exposure. The safety and efficacy of hypoosmolar riboflavin CXL was validated by Shaofeng et al.[18] This method of preoperative swelling of the cornea safely broadens the spectrum of CXL indications to corneas that would otherwise not be eligible for treatment due to low minimum stromal thickness. However, the iatrogenic swelling effect might not be durable throughout the CXL procedure increasing the risk of postoperative complications. Contact Lens Assisted CXL (CLCXL) It was introduced by Jacob et al in 2012 for treating thin keratoconic corneas using riboflavin-soaked soft contact lens to artificially increase the functional corneal thickness.[19] It is advantageous over the above thin corneal cross-linking technique as it works independent of swelling properties of the cornea. The contact lens provides the functional pachymetry necessary to overcome the two major potential complications that are associated with cross-linking thin corneas- ultravioletrelated endothelial cell damage and permanent stromal haze. A UV barrier-free contact lens must be used for the treatment to be effective. The contact lens is soaked in 0.1% riboflavin for the same half an hour that the de-epithelialized cornea is soaked. The rest of the procedure is the same as the conventional protocol. It has been established by various studies that the safety and visual outcomes of CLCXL were comparable to conventional CXL.[20] Smile Lenticule Assisted CXL Sachdev et al. described a technique for CXL of thin corneas, where they used a stromal lenticule removed from patients undergoing small incision lenticule extraction (SMILE) for myopic correction, customized according to corneal thickness.[21] Using a lenticule presoaked in riboflavin solution allows us to increase corneal thickness by adding tissue with the same biological and absorptive properties. Though similar in principle to CLCXL, this technique has disadvantages of limited access to donor SMILE lenticule; need for a lenticule of sufficient thickness (generally 7-8 dioptres of refractive correction would be needed to get a lenticule of sufficient thickness to provide shielding effect for CXL); unpredictability and variability of donor tissue pachymetry depending on cylindrical correction performed in donor, days post-harvest of lenticule and storage medium used; erroneous shifts in pachymetry in case of edema or dehydration of the lenticule; variable riboflavin absorption based on hydration status of the donor lenticule; dependency on human donor tissue, need for serology of donor lenticule and need for storage and eye banking facilities. Epithelial Island CXL Another CXL technique for thin corneas is based on customised pachymetry guided epithelial debridement. It was first reported by Kymionis et al and involves epithelial debridement of the keratoconic cornea sparing the epithelium over the apex of the cone as determined on topography.[22] The molecular mechanism of UV attenuation by the riboflavin soaked epithelium serves as selective apical zonal shield preserving endothelium and allowing the possibility to extend CXL treatment to thin corneas. Removing the epithelium where the cornea is thicker allows a better penetration in the paracentral area and periphery ensuring a stronger biomechanical effect. The epithelial island left in situ protects the thin apical cornea from the UV radiation and its borders provide a refraction of UV-A rays deviating their impact in an intermediate stromal level allowing a better biomechanical and biochemical impact of the treatment. Although this technique has some advantages - preventing local stromal dehydration, blocking excess UV-A in the most sensitive region, but it fails to strengthen the thinnest regions Subspeciality - Cornea

DOS Times Volume 29, Number 7, January-February 2024 www.dosonline.org/dos-times 40 that most require cross-linking, and an anterior segment optical coherence tomography (AS-OCT) and confocal microscopy study has demonstrated stromal haze and the demarcation line (optical reflection line correlating with treatment penetration in areas corresponding to de-epithelialized stroma and not in areas with an intact epithelium. SUB400 CXL The various modifications of the epithelium-off Dresden protocol to overcome the 400µm limit have been promising but each of these techniques has limitations and were not standardized. For these reasons, an algorithm was developed that adapted the overall fluence in the collagen crosslinking procedure based on the patient’s individual stromal thickness to cross-link the stroma, still protecting the corneal endothelium from damaging amounts of UV-A irradiation.[23] Hafezi et al.[24] introduced this ‘sub-400 protocol’ in 2020, where the fluence is individualised according to a published algorithm based on the minimal corneal thickness at the end of riboflavin application. It is based on estimating diffusion of riboflavin and oxygen by Fick’s law of diffusion and UV energy by the Lambert-Beer law of light absorption. This allowed for corneas as thin as 214um to be cross linked, halting keratoconus progression with a success rate of 90% at 12 months. Figure 1: Table showing individual fluence in increments of 10 µm. Subspeciality - Cornea

www.dosonline.org/dos-times DOS Times Volume 29, Number 7, January-February 2024 41 S.No. CXL Protocol Description 1. IontophoresisAssisted Transepithelial CXL Iontophoresis is a noninvasive technique for delivering a charged substance into the corneal stroma by repulsive electromotive force. Iontophoresis-assisted transepithelial CXL (I-CXL) is one of the epithelium-on approaches, which increases the imbibition of riboflavin into the corneal stroma with a non-invasive delivery system via a small electric current.[25] The iontophoresis device consists of a power supply, two electrodes and a connection cable. The negative electrode (8-mm-diameter stainless steel grid) is inserted into a rubber ring which is then applied to the cornea using a suction ring, while the positive electrode is connected to the patient's forehead using a patch. The ring is irrigated with 0.1% riboflavin in distilled water, ensuring the grid is completely immersed. The power generator is then turned on and a constant current of 1.0 mA given. Iontophoresis is done for 5 min. After saturation of the corneal stroma is confirmed using slit-lamp microscopy, UV irradiation is done. Studies have found it to be non-inferior to epi off CXL for stopping the progression of keratoconus in its early stages.[26] 2. High Fluence CXL Studies suggest that the irradiation damage threshold for the corneal endothelium is far higher than previously assumed and that increased irradiation intensity, meaning 5-minute irradiation at 18mW/cm2 can be delivered safely to the cornea. Studies have found high-fluence accelerated protocol to be safe and effective.[27] 3. TopographyGuided CXL In this technique, topography- guided UV-A irradiation is performed in three concentric circular areas centered on thinnest point, with treatment energies ranging between 10J/cm2 and 5.4J/cm2 and fluence of 10 mW/cm2 . Maximum irradiation exposure is in innermost circle. It leads to stable inferior corneal Kmax flattening and superior steepening with significant improvement of vision.[28] 4. M Protocol Mazotta et al combined the in vivo the corneal cellular modifications, endothelial safety and demarcation line boundary between cross-linked and non-cross-linked stroma of various corneas to generate a customized “pachymetry based” CXL nomogram, called “M nomogram.[29] This allows safe and efficacious CXL parameters setting based on preoperative minimum corneal thickness also including a more standardized treatment of thin ectatic corneas between 250 µm and 400 µm. 5. Bharat Protocol It is a topography-guided excimer laser ablation in conjunction with accelerated, high-fluence crosslinking in corneal ecstatic disease using the NIDEK CXIII equipped with CATz algorithm from the FinalFit software. Described by Jain et al in first of its kind study, it has been proved as safe and efficacious alternative to arrest keratectasia progression and improve corneal regularity.[30] It is similar to the Athens protocol described using the “T-CAT” algorithm of the WaveLight Allegretto Wave Excimer Laser System (WaveLight Laser Technologie AG).[31] References 1. Raiskup F, Theuring A, Pillunat LE, Spoerl E. Corneal collagen crosslinking with riboflavin and ultraviolet-A light in progressive keratoconus: ten-year results. Journal of Cataract & Refractive Surgery. 2015 Jan 1;41(1):41-6. 2. Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-A–induced collagen crosslinking for the treatment of keratoconus. American journal of ophthalmology. 2003 May 1;135(5):620-7. 3. Sorkin N, Varssano D. Corneal collagen crosslinking: a systematic review. Ophthalmologica. 2014;232(1):10-27. 4. Subasinghe SK, Ogbuehi KC, Dias GJ. Current perspectives on corneal collagen crosslinking (CXL). Graefes Arch Clin Exp Ophthalmol. 2018 Aug;256(8):1363-84. 5. Randleman JB, Khandelwal SS, Hafezi F. Corneal cross-linking. Surv Ophthalmol. 2015 Nov-Dec;60(6):509-23. 6. Mazzotta C, Balestrazzi A, Baiocchi S, Traversi C, Caporossi A. Stromal haze after combined riboflavin-UVA corneal collagen crosslinking in keratoconus: in vivo confocal microscopic evaluation. Clin Exp Ophthalmol. 2007 Aug;35(6):580-2. 7. Zamora KV, Males JJ. Polymicrobial keratitis after a collagen crosslinking procedure with postoperative use of a contact lens: a case report. Cornea. 2009 May;28(4):474-6. 8. Medeiros CS, Giacomin NT, Bueno RL, Ghanem RC, Moraes HV Jr, Santhiago MR. Accelerated corneal collagen crosslinking: Technique, efficacy, safety, and applications. J Cataract Refract Surg. 2016 Dec;42(12):1826-35. 9. Shetty R, Pahuja NK, Nuijts RM, Ajani A, Jayadev C, Sharma C, Nagaraja H. Current protocols of corneal collagen cross-linking: visual, refractive, and tomographic outcomes. Am J Ophthalmol. 2015 Aug 1;160(2):243-9. 10. Agca A, Tülü B, Yasa D, Yildiz BK, Sucu ME, Genç S, Fazil K, Yildirim Y. Accelerated corneal crosslinking in children with keratoconus: 5-year results and comparison of 2 protocols. J Cataract Refract Surg. 2020 Apr 1;46(4):517-23. 11. Mazzotta C, Traversi C, Caragiuli S, Rechichi M. Pulsed vs continuous Table 1: Few other CXL protocols. Subspeciality - Cornea

DOS Times Volume 29, Number 7, January-February 2024 www.dosonline.org/dos-times 42 light accelerated corneal collagen crosslinking: in vivo qualitative investigation by confocal microscopy and corneal OCT. Eye (Lond). 2014 Oct;28(10):1179-83. 12. Boxer Wachler BS, Pinelli R, Ertan A, Chan CC. Safety and efficacy of transepithelial crosslinking (C3-R/CXL). J Cataract Refract Surg. 2010 Jan;36(1):186-8. 13. Caporossi A, Mazzotta C, Baiocchi S, Caporossi T, Paradiso AL. Transepithelial corneal collagen crosslinking for keratoconus: qualitative investigation by in vivo HRT II confocal analysis. Eur J Ophthalmol. 2012;22:81-8. 14. Çerman E, Toker E, Ozarslan Ozcan D. Transepithelial versus epithelium-off crosslinking in adults with progressive keratoconus. J Cataract Refract Surg. 2015 Jul;41(7):1416-25. 15. Caruso C, Ostacolo C, Epstein RL, Barbaro G, Troisi S, Capobianco D. Transepithelial Corneal Cross-Linking With Vitamin E-Enhanced Riboflavin Solution and Abbreviated, Low-Dose UV-A: 24-Month Clinical Outcomes. Cornea. 2016 Feb;35(2):145-50. 16. Wollensak G, Spörl E, Reber F, Pillunat L, Funk R. Corneal endothelial cytotoxicity of riboflavin/UVA treatment in vitro. Ophthalmic Res. 2003 Nov-Dec;35(6):324-8. 17. Hafezi F, Mrochen M, Iseli HP, Seiler T. Collagen crosslinking with ultraviolet-A and hypoosmolar riboflavin solution in thin corneas. J Cataract Refract Surg. 2009 Apr;35(4):621-4. 18. Gu S, Fan Z, Wang L, Tao X, Zhang Y, Mu G. Corneal collagen crosslinking with hypoosmolar riboflavin solution in keratoconic corneas. Biomed Res Int. 2014;546-67. 19. Jacob S, Kumar DA, Agarwal A, Basu S, Sinha P, Agarwal A. Contact lens-assisted collagen cross-linking (CACXL): A new technique for cross-linking thin corneas. J Refract Surg. 2014 Jun;30(6):366-72. 20. Srivatsa S, Jacob S, Agarwal A. Contact lens assisted corneal cross linking in thin ectatic corneas - A review. Indian J Ophthalmol. 2020 Dec;68(12):2773-8. 21. Sachdev MS, Gupta D, Sachdev G, Sachdev R. Tailored stromal expansion with a refractive lenticule for crosslinking the ultrathin cornea. J Cataract Refract Surg. 2015 May;41(5):918-23. 22. Kymionis GD, Diakonis VF, Coskunseven E, Jankov M, Yoo SH, Pallikaris IG. Customized pachymetric guided epithelial debridement for corneal collagen cross linking. BMC Ophthalmol. 2009 Aug 28(9):10. 23. Kling S, Hafezi F. An Algorithm to Predict the Biomechanical Stiffening Effect in Corneal Cross-linking. J Refract Surg. 2017 Feb 1;33(2):128-36. 24. Hafezi F, Kling S, Gilardoni F, Hafezi N, Hillen M, Abrishamchi R, Gomes JAP, Mazzotta C, Randleman JB, Torres-Netto EA. Individualized Corneal Cross-linking With Riboflavin and UV-A in Ultrathin Corneas: The Sub400 Protocol. Am J Ophthalmol. 2021; 224: 133–142. 25. Bikbova G, Bikbov M. Transepithelial corneal collagen cross-linking by iontophoresis of riboflavin. Acta Ophthalmol. 2014;92(1):e30–e34. 26. Cantemir A, Alexa AI, Galan BG, Anton N, Ciuntu RE, Danielescu C, Chiselita D, Costin D. Iontophoretic collagen cross-linking versus epithelium-off collagen cross-linking for early stage of progressive keratoconus - 3 years follow-up study. Acta Ophthalmol. 2017 Nov;95(7):e649-e655. 27. Gatzioufas Z, Richoz O, Brugnoli E, Hafezi F. Safety profile of highfluence corneal collagen cross-linking for progressive keratoconus: preliminary results from a prospective cohort study. J Refract Surg. 2013 Dec;29(12):846-8. 28. Costa C. Topography-guided corneal crosslinking for keratoconus - Is it enough to treat the cone? Presented at: European Society of Cataract and Refractive Surgeons winter meeting; March 10-12, 2023; Vilamoura, Portugal. 29. Mazzotta C, Romani A, Burroni A. Pachymetry-based accelerated cross-linking: the “M Nomogram” for standardized treatment of all-thickness progressive ectatic corneas. Int J Keratoconus Ectatic Corneal Dis. 2018;7:137–144. 30. Jain R, Shuaib Y, Mohan N, Mittal V. Outcomes of topography-guided PRK/CXL in keratoconus using the NIDEK CXIII system-"Bharat Protocol" (Pilot study). Indian J Ophthalmol. 2023 Sep;71(9):3203-9. 31. Kanellopoulos AJ. Comparison of sequential vs same-day simultaneous collagen cross-linking and topography-guided PRK for treatment of keratoconus. J Refract Surg. 2009;25:S812–8. Dr. Isha Gupta, MS Cornea and Refractive Surgery Services Guru Nanak Eye Centre, Maulana Azad Medical College, New Delhi. Corresponding Author: Subspeciality - Cornea

www.dosonline.org/dos-times DOS Times Volume 29, Number 7, January-February 2024 43 Subspeciality - Cornea Pediatric Keratoplasty Avani Hariani, MS, Parul Jain, MS, FICO, FAICO, FRCS, MRCSEd, Isha Gupta, MS, Gahan Reddy, MBBS Cornea and Refractive Surgery Services, Guru Nanak Eye Centre, Maulana Azad Medical College, New Delhi. Introduction Keratoplasty in children is a very commonly debated topic. Once considered contraindicated in children under 16 years of age[1] it has now become the standard of care children with corneal opacities that preclude the development or maintenance of normal visual function.[2-4] Caring for children with corneal disease requires a high level of commitment and a dedicated team including the pediatrician, cornea specialist, pediatric ophthalmologist, glaucoma and retina specialist. However, the child’s caregivers are the most important members of this team, and they need to be counselled regarding the expectations about the outcomes, challenges, and long-term care that will be Congenital Peters’ anomaly Glaucoma with corneal edema Posterior polymorphous dystrophy Multiple anterior segment anomalies Sclerocornea Other corneal dystrophy (CHED, CHSD) Mucopolysaccharidosis Birth trauma to cornea Corneal dermoid Acquired, Nontraumatic Herpes simplex keratitis Bacterial keratitis Stevens–Johnson syndrome Keratoconus Neurotrophic keratitis Interstitial keratitis Fungal keratitis Exposure keratopathy Acquired, Traumatic Corneal or corneoscleral laceration Blood stain Nonpenetrating injury with scar required. Careful case selection, preoperative, intraoperative, and postoperative protocols are essential in reducing the risk of complications and achieving a desirable functional outcome. Indications Indications for pediatric corneal transplantation vary widely. For the sake of uniformity, the indications of corneal opacities are classified into three groups.[4,5] (Table-1) a. Congenital b. Acquired non-traumatic c. Acquired traumatic Case selection is of utmost importance for prognostication. Cowden[6] reported a series of pediatric keratoplasties in which Table 1: Indications for pediatric keratoplasty. he concluded that the prognosis for PK in children was related to the indication for surgery. Many authors have studied the

DOS Times Volume 29, Number 7, January-February 2024 www.dosonline.org/dos-times 44 Graft Survival A corneal graft is generally considered to have failed when it becomes cloudy or opaque. Overall, success rates with penetrating keratoplasty are lower in children than in adults. Dana et al. in a series of 164 grafts, reported clear grafts in 80% of pediatric patients at 1 year and 67% at 2 years, and compared this to reported success rates for adult keratoplasty of 91% at 1 year and 72% at 5 years.[2] The most common reason for graft failure reported by many groups is Allograft rejection (42.3%) followed by infectious keratitis and secondary glaucoma[11] (Table-3). In India[10] graft infection was reported as the most common cause of graft failure. As opposed to common belief no relation was observed between the age of surgery and graft failure in many studies[2-4,15], however a difficult surgery and rate of intraoperative and post operative complications were more in infants under 13 months.[16] Study Congenital Acquired Non-Traumatic Acquired Traumatic Stulting[4] (1984) 60% 73% 70% Dana[2] (1995) 80% 76% 84% Schaumberg[7] (1999) 71% at 2 years (All CHED) N/A N/A Yang[9] (1999) 35% at 10 years (All Peter’s) N/A N/A Aasuri[11] (2000) 64% 71% 55% Patel[12] (2005) at 1 year 78% 85% 100% Al-Ghamdi[3] (2007) 33% (excluding CHED); 28% CHED 86% 41% Sharma[10] (2007) 77% ‘similar’ ‘similar’ Low[13] (2014) 78.1% 92.9% 85.2 % Santos[14] (2020) 62% 85.7% 85.7% Table 2: Graft survival in pediatric penetrating keratoplasty. Table 3: Reasons for Graft Failure. probability of graft survival using the Kaplan- Meier method popularized by Stulting et al[4] which has facilitated comparisons among series. (Table-2) summarizes the graft survival rates based on the indications for which PK was performed. It is of importance to note that the indications of PK in children are different based on the economic status of the country. CHED[7], Keratoconus[8], Peters anomaly[9], post traumatic scars[8] were the more common indications in the developed countries whereas in India Sharma et al[10] reported infective keratitis as the most common indication for PK in children overall. Graft survival largely depends upon the indication for surgery (Table-2) with the higher survival rate associated with acquired opacities.[3,11,12] Amongst the congenital corneal opacities CHED is associated with the best survival probability[7,15] followed by mild variant of Peters anomaly type 1.[17] Concomitant procedures performed[3,16], repeat grafts[7], and associated anterior segment anomalies[7] are all associated with increased rate of graft failures. The survival curve of a pediatric graft suggests that a primary graft is most likely to fail in the first 2 post operative years[3,7] and more than half of the failures occur in the first 3 months.[7] Yang et al[9] reported at 10 years, 35% of primary grafts remained clear, but the probability of a second or subsequent graft remaining clear for 3 years was <10%. Additional surgical procedures for glaucoma, cataract, or vitreoretinal problems increased the rate of failure (38.5% survival vs 51.3%, p < 0.02).[3] Visual Outcome In a pediatric keratoplasty, there is disparity between the graft survival and visual outcome unlike adults. Although anatomic results may be good, visual recovery is often less impressive. Indication for which PK has been done single handedly contributed to the visual outcome. Studies have shown that children with CHED[3,7] (Figure-1A, Figure-1B), keratoconus[12], and type I Peters’ anomaly (with no lenticular abnormalities)[17] may do better as compared to other cases. However, PKs performed for congenital opacities have worse outcomes than those performed for acquired opacities. Aasuri et al[11] noted a better visual outcome after PK in acquired Allograft rejection Primary graft failure Graft decompensation Infection Corneal ulcer Glaucoma Trauma Phthisis bulbi Subspeciality - Cornea

www.dosonline.org/dos-times DOS Times Volume 29, Number 7, January-February 2024 45 Subspeciality - Cornea conditions with visual acuity of ≥20/400 in 33% of eyes with congenital opacities, 58.3% with acquired nontraumatic opacities, and 67% of posttraumatic opacities. The reasons for poor vision after successful surgery are multifactorial. Factors associated with poor visual outcome by univariate analysis include preoperative corneal edema, preoperative glaucoma, preoperative anterior synechiae, preoperative and postoperative aphakia, vitrectomy, no optical correction, no amblyopia therapy, bilateral corneal disease, and postoperative complication.[2] Amblyopia treatment is the only independently significant prognosticator for visual improvement after surgery. Other reasons cited for poor vision after pediatric keratoplasty are frequent graft failures, optical distortion caused by the graft, and associated ocular pathology.[5,18] Despite the hurdles associated with visual gain in a pediatric PK, McClellan[19] noted that visual acuity following PK was better than or equal to pre-graft visual acuity in all cases. Furthermore, corneal transplantation may be the only opportunity for some children to obtain functional vision. Figure 1A: Case of Bilateral severe CHED. Figure 1B: A 9 year old photophobic child with Bilateral CHED with OD operated PK. Surgical Management After knowing the nuances associated with a Pediatric PK, a good preoperative evaluation, meticulous case selection, counselling of the caregivers, setting realistic expectations, intra-operative skills and the commitment to manage the patient post operatively may be the only ray of hope for many kids. A. Preoperative considerations A thorough preoperative history and physical examination is essential. A detailed prenatal, antenatal and post-natal history (Table-4)[5] must be elicited in order to evaluate surgical candidacy, formulate a surgical plan, and predict the visual prognosis. An examination under anesthesia should be performed in any patient who is unable to cooperate fully with a clinical examination. An ultrasonic biomicroscopy is a must to locate the pupil when it is not clinically visible, and to delineate potential associated structural abnormalities of the eye, including keratolenticular and iridocorneal adhesions, ectopia lentis, aniridia, and congenital aphakia.[20] Prenatal History Maternal health Presence of infections-TORCH Gestational diabetes, toxemia, medication use Birth History Gestational age Birth weight Delivery method? History of forceps delivery or birth trauma Growth and Developmental Milestones Age 0-6 mo Able to fix and follow, raises head and chest when lying on stomach, begins to imitate sound Age 7-12 mo Visually interested in pictures; can sit unsupported; begins to crawl, cruise, and walk (10-12 mo); responds to simple verbal requests; 1-word sentences

DOS Times Volume 29, Number 7, January-February 2024 www.dosonline.org/dos-times 46 Pediatric PK is more complicated and technically difficult than adult PK owing to decreased scleral rigidity, increased scleral and corneal elasticity, positive vitreous pressure, anterior movement of the lens-iris diaphragm. Difficulty can be encountered with corneal suturing, damage to the donor endothelium, iris incarceration into the wound, and even dramatic lens expulsion and suprachoroidal hemorrhage. Under GA all attempts should be made and discussed with the anaesthetist to reduce the posterior pressure preoperatively. A nondepolarizing muscle relaxant should be used for paralysis, because depolarizing agents such as succinylcholine can cause contraction of extraocular muscles, leading to compression of the globe and an increase in intraocular pressure.[21] The anesthesiologist can also hyperventilate the patient.[22] The decrease in the IOP is caused any of 3 factors: A. A decrease in the volume of aqueous humor either due to decreased production/increased drainage. B. Due to vascular constriction due to CO2 washout, intraocularly or extraocularly. C. A decrease in the tone of the extra ocular muscles. Changes in the opposite direction due to hypercapnea would cause a rise in the IOP.[22] Ocular massage or a Honan balloon can be used to reduce intraocular pressure and vitreous volume. Intravenous mannitol 20% at a dose of 0.5-1.5 g/kg may be given, but the side effects of electrolyte disturbance, renal failure, and congestive heart failure must be considered. Placement of the patient in minimal reverse Trendelenburg with the feet below the head can reduce venous return and posterior pressure.[23] Preoperative retrobulbar anesthesia injections should be avoided because of the small orbital volume. B. Intraoperative Considerations Scleral support in the form of a Flieringa ring is necessary in a pediatric PK due to reduced scleral rigidity. Scleral support helps prevent globe collapse, helps maintains the anterior chamber during surgery, aids in trephination and suturing of the cornea.[16] Because of the increased elasticity of the infant cornea and sclera, it is recommended that the diameter of the donor tissue be 0.5-1.0 mm larger than the recipient opening. Donor diameters of 5.5-7.0 mm are recommended for infants. The use of oversized donor buttons is particularly important when the recipient tissue is thin, because compression of recipient tissue and cheese-wiring can compromise wound closure.[24] The choice of wound closure using running or interrupted 10-0 nylon sutures depends on the surgeon preference. However, it is postulated that a running suture provides rapid wound closure Growth and Developmental Milestones Age 1-2 y Holds objects close for inspection, identifies pictures in books, uses both hands, Age 2-5 y Uses eyes and hands together with increasing skill, copies simple forms and letters. Table 4: Preoperative History. minimizing the time of contact between the lens, iris, and the grafted corneal endothelium. This reduces the likelihood that iris will adhere to the peripheral cornea or surgical wound because of exuberant fibrin formation.[24] Theoretically, selective suture removal of interrupted sutures can minimize astigmatism, but this is not practical in children as the sutures loosed quickly and are typically removed in a few months. The benefits of using interrupted sutures include selective removal in cases of exposed knots, vascularisation and suture infiltrates. Intraoperative procedures such as vitrectomy, lensectomy, and secondary intraocular procedures are known to be associated with poor graft survival and poor visualoutcome.[4,16] A dense cataract must be removed during the open sky procedure. However, if the lens has only mild to moderate opacity and its effect on vision is questionable, it is preferable to leave the lens in place and remove it at a later time if necessary.[18] In a pediatric PK it is important to perform a posterior capsulotomy approximately 7 mm in diameter with a vitrector, a thorough anterior vitrectomy and a peripheral iridectomy to prevent pupillary block.[18] The decision to implant a PCIOL in a pediatric PK is still under debate. Although aphakic eyes are more likely than pseudophakic eyes to develop graft failure in adults, PCIOL implantation in children for isolated cataracts can be associated with increased postoperative inflammation, corneal edema, dislocated lenses, and additional surgical operations.[6,25] There have not been many reports on the outcome of PCIOL implantation in pediatric PK[11,26] therefore the surgeon must look at the risk to benefit ratio, case selection, patient profile, compliance of the parents and take a decision. C. Postoperative Considerations An intense regimen of antibiotics, steroids and cycloplegics is given. A fourth-generation fluoroquinolone is used four times a day until all sutures are removed. The postoperative steroid regimen consists of prednisolone acetate 1% every hour for the first 2 days, with a reduction in the dosage to five times daily on postoperative day 3. The steroid dosage is then tapered over the next few months. By 6 months, steroid therapy is usually discontinued in phakic eyes and reduced to one drop daily in aphakic eyes. A long-acting cycloplegic such as atropine is used postoperatively for the first 2 weeks until substantial inflammation subsides.[18] Strict instruction to the parents to be watchful for eye rubbing, which may traumatize the eye. A protective shield that does not hinder vision should be used for the first 3 weeks after surgery, Subspeciality - Cornea

www.dosonline.org/dos-times DOS Times Volume 29, Number 7, January-February 2024 47 Subspeciality - Cornea and a metal shield should be used for protection during sleep for the first 3 months. They should be made aware of the signs of infection, broken sutures, and graft rejection which should be observed carefully while instilling eye drops with a penlight. Early post operative complications like wound leak, persistent epithelial defects and graft infection need to be addressed promptly. Suture removal in children is done much earlier than in adults typically at 4-6 weeks in infants, 6-8 weeks for patients aged 1-2 years, 8-12 weeks for patients aged 2-3 years, 3-4 months for children aged 4-6 years and for 7-9 years sutures are removed at 4-6 months post operatively[18] (Table-5). Optical correction after cycloplegic refraction should begin as soon as 2 weeks after surgery. The refraction should be repeated every month till all the sutures are removed. Parents should be informed about the multiple changes of prescription post Age Suture Removal < 12 months 4-6 weeks 1-2 years 6-8 weeks 2-3 years 8-12 weeks 4-6 years 3-4 months 7-9 years 4-6 months Table 5: Guidelines for removal of all sutures after PK. operatively. Optical correction can be obtained with spectacles, dailywear soft or hard contact lenses, or extended-wear soft contact lenses. However, the use of contact lenses comes with inherent risks and they should not be prescribed until all sutures are removed, because of the increased risk of infection from unrecognized loose, broken, or exposed sutures. A pediatric ophthalmologist should be closely involved in the post operative care of the patient. Amblyopia therapy should be started as soon as 2 weeks postoperatively after the prescription of spectacles. Advances in Pediatric Keratoplasties With the advent of lamellar surgeries, the focus now has shifted to pediatric deep anterior lamellar keratoplasties (DALK)[27] (Figure-2A, 2B, 2C, 2D) and Descemet stripping endothelial keratoplasties (DSEK)[28] (Figure-3A, Figure 3B). The advantages of lamellar keratoplasties over PK include a reduced risk of rejection, a smaller wound, less postoperative astigmatism, more rapid visual rehabilitation, and fewer restrictions on activities postoperatively. Another option besides PK for children with poor prognosis for graft survival includes the use of keratoprosthesis. The advantages include elimination of allograft rejection, rapid visual rehabilitation without postoperative astigmatism, and earlier initiation of ambylopia therapy.[29] Advances in imaging techniques like the use of MicroscopeIntraoperative Optical Coherence Tomography (Mi-OCT) in paediatric keratoplasty helps in improving surgical planning and optimising the postoperative outcome.[30] Figure 2A: Preop clinical photo of advanced keratoconus with scarring. B. Postop Day 2 after a DALK with a clear cornea. C: Preop ASOCT showing a steep cornea with anterior stromal scaring. D: Postop ASOCT showing a well opposed Donor and Host Descemet membrane with a decrease in corneal curvature.

DOS Times Volume 29, Number 7, January-February 2024 www.dosonline.org/dos-times 48 Figure 3A: Pre op ASOCT of a 6 year old child with CHED. B: Post op ASOCT showing well attached lenticule with decreased corneal thickness. Conclusion Pediatric keratoplasty is challenging in many ways. There is a lot of debate around it regarding the indication for which it should be performed, the optimal time of keratoplasty, parental consent and stress and the risk to benefit ratio. Studies have shown that there is often a noticeable postoperative improvement in the behavior of, communication with, and ambulation of children with bilateral corneal opacities, despite the fact that they have cloudy grafts or a measured visual acuity of 20/200 or less. Even a cloudy graft may provide better vision than a dense opaque cornea. However, the care required by the patient post keratoplasty is multifaceted and concerted efforts from the cornea specialist, pediatric ophthalmologist, glaucoma, retina specialists and family members are required. With the advances in technology and a tonne of case-based evidence supporting this procedure in children we can say that keratoplasty might be the only hope for visual rehabilitation of an otherwise blind eye, and the ability to affect such change is remarkable and extremely gratifying. References 1. Leigh AG. Corneal grafting. Br J Clin Pract. 1958;12:329–332. 2. Dana MR, Moyes AL, Gomes JA, Rosheim KM, Schaumberg DA, Laibson PR, Holland EJ, Sugar A, Sugar J. The indications for and outcome in pediatric keratoplasty: a multicenter study. Ophthalmology. 1995 Aug 1;102(8):1129-38. 3. Al-Ghamdi A, Al-Rajhi A, Wagoner MD. Primary pediatric keratoplasty: indications, graft survival, and visual outcome. Journal of American Association for Pediatric Ophthalmology and Strabismus. 2007 Feb 1;11(1):41-7. 4. Stulting RD, Sumers KD, Cavanagh HD, Waring III GO, Gammon JA. Penetrating keratoplasty in children. Ophthalmology. 1984 Oct 1;91(10):1222-30. 5. Chan AS, Colby K. Update on pediatric keratoplasty. Int Ophthalmol Clin. 2008;48(2):25–33. 6. Cowden JW. Penetrating keratoplasty in infants and children. Ophthalmology. 1990 Mar 1;97(3):324-9. 7. Schaumberg DA, Moyes AL, Gomes JA, Dana MR. Corneal transplantation in young children with congenital hereditary endothelial dystrophy. American journal of ophthalmology. 1999 Apr 1;127(4):373-8. 8. Gulias-Cañizo R, Gonzalez-Salinas R, Hernandez-Zimbron LF, Hernandez-Quintela E, Sanchez-Huerta V. Indications and outcomes of pediatric keratoplasty in a tertiary eye care center: A retrospective review. Medicine. 2017 Nov;96(45). 9. Yang LL, Lambert SR, Lynn MJ, Stulting RD. Long-term results of corneal graft survival in infants and children with peters anomaly. Ophthalmology. 1999 Apr 1;106(4):833-48. 10. Sharma N, Prakash G, Titiyal JS, Tandon R, Vajpayee RB. Pediatric keratoplasty in India: indications and outcomes. Cornea. 2007 Aug 1;26(7):810-3. 11. Aasuri MK, Garg P, Gokhle N, Gupta S. Penetrating keratoplasty in children. Cornea. 2000 Mar 1;19(2):140-4. 12. Patel HY, Ormonde S, Brookes NH, Moffatt LS, McGhee CN. The indications and outcome of paediatric corneal transplantation in New Zealand: 1991–2003. The British Journal of Ophthalmology. 2005 Apr;89(4):404. 13. Low JR, Anshu A, Tan AC, Htoon HM, Tan DT. The outcomes of primary pediatric keratoplasty in Singapore. American Journal of Ophthalmology. 2014 Sep 1;158(3):496-502. 14. DOS Santos Araújo ME, Santos NC, de Souza LB, Sato EH, de Freitas D. Primary pediatric keratoplasty: etiology, graft survival, and visual outcome. American Journal of Ophthalmology. 2020 Apr 1;212:162- 8. 15. Javadi MA, Baradaran-Rafii AR, Zamani M, Karimian F, Zare M, Einollahi B, Jafarinasab MR, Yazdani S. Penetrating keratoplasty in young children with congenital hereditary endothelial dystrophy. Cornea. 2003 Jul 1;22(5):420-3. 16. Comer RM, Daya SM, O’Keefe M. Penetrating keratoplasty in infants. Journal of American Association for Pediatric Ophthalmology and Strabismus. 2001 Oct 1;5(5):285-90. 17. Zaidman GW, Flanagan JK, Furey CC. Long-term visual prognosis in children after corneal transplant surgery for Peters anomaly type I. American journal of ophthalmology. 2007 Jul 1;144(1):104-8. 18. Gloor P. Pediatric penetrating keratoplasty. In: Krachmer JH, Mannis MJ, Holland EJ, eds. Cornea. Philadelphia: Elsevier; 2005:1591–1618. 19. McClellan K, Lai T, Grigg J, Billson F. Penetrating keratoplasty in children: visual and graft outcome. The British Journal of Ophthalmology. 2003 Oct;87(10):1212. 20. Rezende RA, Uchoa UB, Uchoa R, Rapuano CJ, Laibson PR, Cohen EJ. Congenital corneal opacities in a cornea referral practice. Cornea. 2004 Aug 1;23(6):565-70. 21. Stead SW, Miller KM. Anesthesia for ophthalmic surgery. In: Spaeth GL, ed. Ophthalmic surgery. Philadelphia: Saunders; 2003:22. 22. Duncalf D, Weitzner SW. Ventilation and hypercapnea on intraocular pressure during anesthesia. Anesthesia and Analgesia. 1963;42:232– 237. 23. Ozcan MS, Praetel C, Bhatti MT, Gravenstein N, Mahla ME, Seubert CN. The effect of body inclination during prone positioning on intraocular pressure in awake volunteers: a comparison of two operating tables. Anesthesia & Analgesia. 2004 Oct 1;99(4):1152-8. 24. Stulting RD. Penetrating keratoplasty in children. In: Brightbill F, ed. Corneal surgery: theory, technique, and tissue. St. Louis: Mosby; 1993. 25. Lambert SR, Lynn M, Drews-Botsch C, Loupe D, Plager DA, Medow NB, Wilson ME, Buckley EG, Drack AV, Fawcett SL. A comparison of grating visual acuity, strabismus, and reoperation outcomes among children with aphakia and pseudophakia after unilateral cataract surgery during the first six months of life. Journal of American Subspeciality - Cornea