CONTENTS PAGE NO. TITLE 05 From the President’s DESK 07 From the DESK of Chief Editor Subspeciality 09 12 15 21 31 34 39 50 55 65 Need for A Robust System for ROP Screening in India Guidelines for the Diagnosis and Management of Polypoidal Choroidal Vasculopathy (PCV) in India Approach to Investigate and Localize an Intraocular Foreign Body Imaging the Pachychoroid Spectrum Central Retinal Vein Occlusion in JAK2 Positive Polycythemia Vera Artificial Intelligence in Screening of Retinal Diseases: Current Applications and Future Perspectives Overveiw of Fundal Coloboma and its Consequences Update on Retinopathy of Prematurity Overview of Intraocular Tamponading Agents Used in Vitreoretinal Surgeries Drug Master File: Importance and Benefits Retina
www.dosonline.org/dos-times DOS Times Volume 29, Number 6, November-December 2023 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 6, November-December 2023 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 6, November-December 2023 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 6, November-December 2023 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 6, November-December 2023 05 From the President's DESK Dr. Rajendra Prasad MBBS, MD DOS TIMES Dear friends, as I approach the last few weeks 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 you all who sincerely contributed towards the favorable outcome of all the issues of DOS Times and actively participating in teaching and learning programs in my successful tenure. This wouldn’t have been possible without the support of each and every one of you dear members. I am also grateful to our teachers, our seniors, our colleagues and dear friends for their contrition towards the progress of our society. These past two 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 contribute along with the passionate elected executive members to build upon the successes of the past and to fulfill the society’s mission to support, promote and protect our members interests. Each of them provided me with valuable local and contextual insight that has reshaped my understanding of working for Delhi ophthalmological society. I offer my humble salutations to all our Past Presidents, Secretaries, office bearers and executive members, for their great and incessant work over the past many years in the field of redefining the science, education and enormously contributing towards brightening the image of the DOS across the Globe, in an enviable manner. Our Statutes were carefully crafted by our predecessor, with a unified view of science as the lodestar. Although the Statutes have undergone a few changes, in large part to enable more effective functioning of the society; but the core remains firmly in place. And there is a good reason why, right up front, we declare not only the vision and mission of the DOS, but significantly, our values, and an explicit declaration of the principle of freedom and responsibility in the society. Our core values were the primary guide to everything we did: that is excellence and professionalism; inclusivity and diversity; transparency and integrity; and innovation and sustainability. It is as well that we return to these time and time again, as a constant reminder of what we are enjoined to uphold. As is characteristic of DOS, we have made a lot of progress in not only on the national but also on the international scene. Our vision was very clear “advancing science” and serving society with inclusive culture was our motto and work for the betterment of society and strengthen the welfare offered to the members and also to ensure that member’s voices are heard and create more opportunities for the members. We carriedout our programs of education, training and resources that strengthened our professionalism retained our commitment to solidarity, ensuring that our members get more opportunities and assistance. We had a strategic priority and plan to position action as essential for 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. 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 due to an amplification of the threats posed by misinformation and scientific nationalism,
DOS Times Volume 29, Number 6, November-December 2023 www.dosonline.org/dos-times 06 DOS TIMES which seek to undermine the core values of science. But due to the widespread prominence of society and scientific benchmark created by the predecessors we could push through all the plans we had promised to you with the strong support from my executive team and of course help from my seniors and colleagues. I tried my best to fulfill the responsibility given to me and worked for the betterment of the society and I am sure that during this year we have been able to meet the needs of our members in terms of educational and scientific programs. In the end I would also like to thank and extend note of appreciation to the team DOS times, its editorial board, production team and authors for their great contribution and making it one of the educational resource which is quite popular amongst the ophthalmic fraternity for publication of innovation, research work, original articles and case reports. This issue of DOS Times brings together original research articles on fundamental topics of general interest. I am sure this issue of DOS times is going to be a great reading and teaching to our readers. With this friends, I thank you profusely for being with me throughout the tenure and I wish you all a very happy prosperous and fruitful year ahead. May this year bring new happiness, new goals, new achievements, and a lot of new inspirations on your life. I look forward to a wonderful year of fun, fellowship and doing good to our community by the next executive team. Dr. Rajendra Prasad President DOS
www.dosonline.org/dos-times DOS Times Volume 29, Number 6, November-December 2023 07 DOS TIMES From the DESK of Chief Editor Dr. J S Bhalla, MS, DNB, MNAMS Secretary Delhi Ophthalmological Society As we approach the end of 2023, it is only fitting to refold on the journey of DOS Times throughout the year. We take a collective breath, glance backwards to look ahead. As the year concludes, I and my editorial team extend our heartfelt thanks to all the authors for sharing their excellent articles that adds to the academic value of DOS Times. Besides regular issues of DOS TIMES, We have had fruitful year inspite of numerous obstacles. There were Academic & other useful activities- Regular Monthly meetings, Evening Physical CMEs, Glaucoma awareness walk at GNEC & Shroff charity Eye Centre, Successful MID Term Conference, Eye donation walk at RP Centre(AIIMS ), World sight day walk at Iconic India gate, IDOS Conference at Phuket, DOS Teaching programme organised at RP Centre. During 1st year of my tenure, started many new activities with cooperation of Dynamic DOS Executive & guidance of Seniors & Teachers: Monthly DOS online quiz & DOS Online Video Teaching Programme, changed format of DOS TIMES & added new sections to make it more useful, Organised highly successful Mid term & Annual DOS Conference 2022. It was my conscious endeavor to Promote Young Ophthalmologists, Women Ophthalmologists & General Ophthalmologists. With collective efforts of all, now DOS is the world’s largest state Ophthalmological society with a current membership of 10,500 members. In 2024, as we are nearing end of our tumultuous tenure, we eagerly anticipate fulfilling our commitments & giving even more enriching academic events for all you valued DOS Members. Retinal diseases are one of the most frequently seen ailments in our daily Clinics. These ailments incorporate several infective, congenital, metabolic, auto immune, traumatic & surgical pathologies. DOS Times is an important knowledge dissemination podium for the researchers, students and medical practitioners. This issue dedicated to RETINA has excellent articles written by experts in this subspeciality for our academic society. We have articles on Intraocular Tamponading Agents Used In Vitreoretinal Surgeries, Update on ROP, Imaging the Pachychoroid Spectrum, AI in Screening of Retinal Diseases, Guidelines for Management of PCV and Intraocular FB – Investigation & Localization. Emerging practice patterns in this field needs a thorough confabulation to spread the knowledge so that the researchers, ophthalmologists and most importantly residents adopt them to pass on the benefits to the patients. As chief Editor of DOS TIMES, I consider a successful issue as the one which my dear DOS Members would like to open again & again & again. Reading & writing is essential for those who seek to rise above the ordinary. “I really wish that we all develop interest in writing . The essential key for writing is to write regularly — like it or not — great ideas come often by writing; releasing the subconscious — waiting for inspiration and ideas will not work, but it does help to have a notebook with you all the time for sudden brainstorms or inspiration.” – Prof. Robert Marc Friedman
08 DOS Times Volume 29, Number 6, November-December 2023 www.dosonline.org/dos-times 08 Always keep two books in your pocket, one to read, one to write in – Robert Louis Stevenson What I love most about reading: It gives you the ability to reach higher ground. “Today a reader, tomorrow a leader.” Happy Reading. Wishing you a nostalgic yet forward – looking December & a wonderful 2024 ahead. Dr. Jatinder Singh Bhalla, MS, DNB, MNAMS Chief Editor - DOS Times, Consultant & Academic Incharge (Ophthalmology) DDU Hospital, Hari Nagar DOS TIMES
www.dosonline.org/dos-times DOS Times Volume 29, Number 6, November-December 2023 09 Need for A Robust System for ROP Screening in India Komal Uppal[1], MBBS, DCH, DNB, Harijot Singh[2], MBBS, MD, Rajwinder Kaur[2], MBBS, MD, Balbir Khan[3], MBBS, MS, FVRS 1. Pediatrician, Genetic Lab, Lok Nayak Hospital, New Delhi. 2. Department of Pediatrics, Ophthalmology, Adesh Institute of Medical Sciences and Research, Bathinda, Punjab. 3. Professor, Department of Ophthalmology, Gian Sagar Medical College and Hospital, Banur. Retinopathy of prematurity (ROP), a disease of developing immature retinal blood vessels of the baby born prematurely caused mainly by oxygen toxicity, is a leading preventable cause of visual impairment in children.[1] Though, it is a disease of premature (less than 32 weeks of gestation) and low birth weight babies (weight less than 1500gm) but it can also occur in babies with gestation 32-36 weeks gestation and weight more than 1500gm especially in India due to sub-optimal neonatal intensive care, prolonged ventilation, and oxygen requirement and variable clinical condition of the babies.[2,3,4] Worldwide the reported number of preterm babies born is about 15 million, out of which about 53,000 suffered from vision-threatening ROP and require treatment, and 20,000 developed blindness or severe visual loss.[5] Out of 15 million preterm births, 3.5 million preterm births occur in India (the most preterm births in the world). 15% of all births (21 million newborns) have low birth weight (LBW). India has about 1.7 million weighing <2500g and about 0.4 million<1500g babies (the third highest incidence of LBW).[6] Not only does gestational age and birth weight of the baby affects the severity of ROP, but various other factors like the level of available neonatal intensive care and eye care services and the socioeconomic status of the region also affect it. The severity of ROP is relatively less in preterm babies born in high-income countries but ROP and its complications may contribute to about 40% of childhood blindness in babies born in middle-or low-income countries.[7,8,9] Unfortunately, little data is available on the exact incidence of ROP in India. Of 3.5 million premature births in India, approximately 600,000 children are of <32 weeks gestational age (GA), and about 40% of these get admitted to the neonatal intensive care unit (NICU), If 80% of these babies survive, then approximately 200,000 children are at risk of developing ROP every year, out of which at least 10% (20,000) will require treatment for ROP to prevent lifelong irreversible blindness.[10] In addition, children with GA 32-36 weeks may also be at risk of developing ROP. Literature estimated the incidence of ROP in India among screened neonates which varies from 20%- 52%, however, more recent studies have mentioned lower incidence (20%-30%).[2,4,11] It has been seen that the incidence of ROP has been on the rise in low to middle-income countries; depicted due to improved neonatal services (third wave of ROP epidemic) as well as due to poor neonatal services (first wave of ROP epidemic-like scenario). Besides prematurity and low birth weight, other risk factors for ROP like prolonged oxygen exposure, disease severity, severe sepsis, multiple blood transfusions, intraventricular hemorrhage, cardiac and respiratory defects, acidosis, and apnoea can also affect the production of vascular endothelial growth factor (VEGF) and lead to variable pathogenic effects on the retina of babies admitted in NICU. International Classification of Retinopathy of Prematurity (ICROP) has given ROP classification based on four elements, i.e. location, severity, plus disease, and extent. Based on location from the optic disc to the temporal retina, it has been divided into three zones (zone 1 – zone). Based on severity, five stages of ROP have been categorized [stage 1: clear demarcation line formation (mild) to stage 5: complete retinal detachment (severe)]. Plus disease is dilatation and tortuosity of retinal vessels at the posterior pole of the eye. Disease extent is circumferential involvement of the retina in 300 clock hours (a total of 12 clock hours of 300 each or 3600). Based on the above four elements, ROP can either manifest as a mild form (type 1 or type 2), which can regress spontaneously or with treatment with an excellent prognosis, or it can manifest as a severe form with long-term visual or neurological sequelae, such as aggressive posterior ROP disease. Aggressive ROP (A-ROP) replaces aggressive posterior ROP (AP-ROP), based on international input that this form doesn’t only occur posteriorly. Aggressive ROP involves lacy, flat, subtle neovascularization and skip stages 1 and 2. You may need extra magnification and will need to look closely for flat neovascularization because aggressive ROP progresses quickly and if you wait for classic stage 3 to develop, it’s likely too late for treatment to effectively prevent the severe form of ROP (Stage 5).[4] To prevent these short-term and long-term sequelae of ROP as late retinal detachments; macular anomalies, including smaller foveal avascular zone; retinal vascular changes such as persistent tortuosity; and glaucoma, there are various preventive, screening, diagnostic, and therapeutic modalities. Out of various preventive measures like prophylactic use of vitamin E therapy, reduction in exposure to light, early nutritional initiation, normalization of IGF-1, adequate postnatal weight gain, and administration of penicillamine, but only regulation of oxygen therapy has been shown to have a significant effect in the prevention of DOS TIMES
DOS Times Volume 29, Number 6, November-December 2023 www.dosonline.org/dos-times 10 ROP. Screening and diagnostic modalities include early, initial, and regular retinal examinations of high-risk infants. Depending upon the severity and progression of the disease and with the aim of early detection, all infants less than 2000g of birth weight (BW) and gestational age <34 weeks are to be screened for ROP at 4 weeks after birth (“Tees din Roshni ke”), all infants born before 28 weeks’ period of gestation and BW <1200g should be screened after 2-3 weeks after birth[18] and following it up regularly for its vigorous, time-bound progression via indirect ophthalmoscope or a wide-field digital camera (Ret-Cam). For preventing childhood blindness due to ROP sequelae, there is enough evidence supporting[12,13,14] the benefit of doing ROP screening and early treatment. Pandhi TR et al.[15] observed the annual progressive increase in the number of screened babies over the years, from 137 babies in 2010 to 2,413 in 2018 in the ROP screening program. They detected the prevalence of any stage of ROP, 38.45% (2,447 of 6,363 infants) during this period. In 80% of infants, ROP regressed spontaneously, and 20% required treatment. ETROP (Early Treatment of Retinopathy of Prematurity Study) landmark trial showed a reduction in unfavorable visual acuity outcomes with earlier treatment, from 19.8% to 14.3%, and unfavorable structural outcomes were reduced from 15.6% to 9.0% at 9 months.[13] ROP screening should be done according to the region-based (modified as practical workable conditions, available neonatal healthcare services, and the current literature) recommended guidelines.[16] Regarding the gestational age of babies for doing ROP, in India various efforts to customize ROP screening guidelines have been made, as in India ROP has been noted in heavier and term babies according to various studies.[17,18,19] To get the successful output of screening, the standard guidelines regarding gestational age (GA), prerequisites, procedure, and precautions should be followed.[11] To prove timely ROP screening and treatment to be an effective and extremely cost-effective medical intervention to save a significant number of babies per year from a lifetime of blindness and to reduce the overall burden of childhood blindness, enough literature has been published.[20,21] Rothschild M.I. et al, showed the high economic impact of ROP on Mexico’s society. The cost per neonate treated in Mexico is estimated to be USD 3,228; parental indirect cost due to estimated lost wages and productivity was USD 305,584; and a lifetime loss of productivity resulting from a blind individual was USD 142,172.[17] A study done by Nicoline E. Schalij-Delfos et al. showed improvement in the cost-benefit ratio of their ROP screening program by doing screening at the 5th postnatal week onwards for high-risk babies and screening once at the 7th postnatal week for low-risk babies. There was a reduction of 9.8% of ophthalmological examinations at the expense of missing 2.9% of non-vision-threatening ROP.[19] Because of being an effective and extremely cost-effective medical intervention, in India, Rashtriya Bal Swasthya Karyakram (RBSK) under National Health Mission Child Health ( NHM) and Indian Institute of Public Health along with Elizabeth Diamond Jubilee Trust has taken initiatives to formulate ROP screening guidelines specific to ROP in India.[20] But current literature shows that despite the initiation of the ROP screening program, at various places number of infants are at risk of developing ROP and its long-term sequelae due to lack of screening, inadequate screening, or delayed screening.[13,20,21] It can be due to various factors like nonimplementation of current programmes in a proper manner, inadequate time-bound and robust ROP screening protocols, lack of awareness of public and primary healthcare providers, non-acceptability, poor attitude of staff and parents regarding screening, lack of multidisciplinary team and support from NICU team, imaging staff, and ophthalmologist, lack of provision of screening and management services centres, poor assistance in referrals and transport of babies, shortage of funds, trained staff and technical equipment, inadequate training programmes for specialists (less than 500 registered ROP specialists in India at present to screen 2,00,000 at-risk neonates annually) and staff, delay in timing of first examination and following examinations, insufficient system to monitor compliance to oxygen use, to audit ROP screening regularly and to monitor patient outcomes, dearth of discharge policy and parental education, poor follow-up visits by parents, non-availability of integrated data management software, poor storage of medical record and contact details, and various other logistic, social, and ethical issues. Therefore, it is not sufficient only to start the ROP screening programs, but there is also an urgent need for AI-based imaging and screening modules on a similar pattern to the KIDROP (Karnataka Internet Assisted Diagnosis of Prematurity Model) protocol to be used throughout the country to handle the rising third wave of ROP epidemic in India and fill the gap between demand and supply or availability of trained manpower. There is also a need for a robust system for proper implementation, evaluation, and monitoring of an evidence-based universal eye screening program in India, which can focus on primary, secondary, and tertiary prevention of ROP childhood blindness in all high-risk babies on time.[22] To make it possible, everyone from health policymakers to healthcare workers should be aware of their roles and responsibilities at national, state, and health facility levels. If possible, a “hub and spoke” approach can be adopted, and the factors mentioned above, which are responsible for the failure of existing programs, should be considered. With the coordinating efforts of all healthcare personnel from public and private sectors and NGOs (Public Health Foundation of India (PHFI), Sight Savers, and Orbis), screening of all eligible babies before discharge, even if this is early, for in patients in the neonatal intensive care unit and for outpatients after discharge in the eye department can be planned. DOS TIMES
www.dosonline.org/dos-times DOS Times Volume 29, Number 6, November-December 2023 11 DOS TIMES To improve coordination for efficient service delivery, the national task force that is NHM (should run all three major national programs (NHM child health, RBSK, and National Programme for Control of Blindness NPCB) with good integration to achieve the aim of not missing any high-risk baby. Covering all the babies under screening will be an asset to the country, not a liability. ROP screening, a dramatic change in the healthcare system, can provide healthy youth to the country who can be the scriptwriters of the country’s destiny and can help in taking the country towards a brighter future!!. Source of Financial Support None Conflict of Interest None References 1. Gilbert, C., & Foster, A. Childhood blindness in the context of VISION 2020 – The Right to Sight. Bull World Health Organ 2001;79:227-32. 2. Gopal, L., Sharma, T., Ramachandran, S. Retinopathy of prematurity: A study. Indian J Ophthalmol 1995;43:59-61. 3. Jalali, S., Matalia, J., Hussain, A., & Anand, R. Modification of screening criteria for retinopathy of prematurity in India and other middle-income countries. Am J Ophthalmol 2006;141:966-8. 4. Chiang MF, Quinn GE, Fielder AR, et al. International Classification of Retinopathy of Prematurity, Third Edition. Ophthalmology. 2021;128(10):e51-e68. 5. Vinekar A, Dogra MR, Sangtam T, Narang A, Gupta A. Retinopathy of prematurity in Asian Indian babies weighing greater than 1250 grams at birth: ten-year data from a tertiary care center in a developing country. Indian J Ophthalmol. 2007;55:331-6. 6. Blencowe, H., Lawn, J. E., Vazquez, T., Fielder, A., & Gilbert, C. (2013). Preterm-associated visual impairment and estimates of retinopathy of prematurity at regional and global levels for 2010. Pediatric Research, 74 (Suppl.1), 35-49. 7. Honavar SG. Do we need India-specific retinopathy of prematurity screening guidelines? Indian J Ophthalmol. 2019 Jun;67(6):711-716. 8. Quinn GE. Retinopathy of prematurity blindness worldwide: Phenotypes in the third epidemic. Eye Brain 2016;8:31-6. 9. Gilbert C, Fielder A, Gordillo L, Quinn GE. Characteristics of infants with severe retinopathy of prematurity in countries with low, moderate, and high levels of development: Implications for screening programs. Pediatrics 2005; 115: e 518-25. 10. Sivanandan S, Chandra P, Deorari AK, Agarwal R. Retinopathy of Prematurity: AIIMS, New Delhi Experience. Indian Pediatr. 2016; 53 Suppl 2:S 123–8. 11. Bowe T, Nyamai L, Ademola-Popoola D, Amphornphruet A, Anzures R, Cernichiaro-Espinosa LA et al. Digit J Ophthalmol. 2019 Oct 12;25(4):49-58. 12. Sabherwal S, Gilbert C, Foster A, Kumar P. ROP screening and treatment in four district-level special newborn care units in India: a cross-sectional study of screening and treatment rates. BMJ Paediatr Open. 2021 Mar 10;5(1):e000930. 13. William V. Good M Detal, final results of the early treatment for retinopathy of prematurity (ETROP) randomized trial. Trans Am Ophthalmol Soc 2004; 102:233-250. 14. Vedantham V. Retinopathy of prematurity screening in the Indian population: It’s time to set our own guidelines! !.Indian J Ophthalmol 2007; 55:329-30. 15. Padhi TR, Das T, Kaur P, et al. Characteristics of ‘sawtooth shunt’ following anti-vascular endothelial growth factor for aggressive posterior retinopathy of prematurity. Int Ophthalmol. 2020;40(4):1007-1015. 16. Pejaver RK, vinekar A, bilagiA., National Neonatology Foundation’s Evidence-Based Clinical Practice Guidelines 2010. Retinopathy of Prematurity. 17. Rashtriya Bal Swasthya Karyakram, Ministry of Health & Family Welfare, Govt. of India- “Guidelines for Universal Eye Screening in Newborns Including Retinopathy of Prematurity, June 2017, of India.”. 18. Rothschild MI, Russ R, Brennan KA, et al. The Economic Model of Retinopathy of Prematurity (EcROP) screening and treatment: Mexico and the United States. 19. Nicoline Schalij-Delfos et al., Towards a universal approach for screening of Retinopathy of Prematurity (ROP). Documenta Ophthalmologica 92: 137-144, 1996. 20. Gudlavalleti VS, Shukla R, Batchu T, et al. Public health system integration of avoidable blindness screening and management, India. Bull World Health Organ 2018;96:705-15. 21. Vinekar A, Jayadev C, Mangalesh S, et al. Initiating retinopathy of prematurity screening before discharge from the neonatal care unit: effect on enrollment in rural India. Indian Pediatr 2016;53 (Suppl 2): S107-11. 22. Vinekar A, Gilbert C, Dogra M, Kurian M, Shainesh G, Shetty B, Bauer N. The KIDROP model of combining strategies for providing retinopathy of prematurity screening in underserved areas in India using wide-field imaging, telemedicine, non-physician graders and smartphone reporting. Indian J Ophthalmol. 2014 Jan;62(1):41-9. Dr. Rajwinder, MBBS, MD Professor, Department of Ophthalmology Adesh Institute of Medical Sciences and Research, Bathinda, Punjab. Corresponding Author:
DOS Times Volume 29, Number 6, November-December 2023 www.dosonline.org/dos-times 12 Guidelines for the Diagnosis and Management of Polypoidal Choroidal Vasculopathy (PCV) in India Sandhya Makhija, DO, DNB, MNAMS, FRF, FICO, Neelam Khatwani, DO, DNB Sant Parmanand Hospital, Civil Lines, Delhi. Polypoidal choroidal vasculopathy (PCV) is considered a variant of neovascular AMD and a significant cause of exudative maculopathy in Asians. Indian guidelines for the diagnosis and management of PCV were first published in 2018, with an updated literature search up to November 2015. The Vitreoretinal Society of India (VRSI) commissioned a comprehensive literature meta-analysis, up to September 2021, to develop current guidelines with the following inclusions: i) updated nomenclature of PCV; ii) discuss the newer diagnostic imaging features of PCV, especially in the absence of ICGA and iii) recommends the best possible therapeutic approach in the management of PCV, including the choice of anti-VEGF agents. Here is a summary of the main recommendations for managing polypoidal choroidal vasculopathy. 1. The terminology of “polyp” and “branching vascular network (BVN)” has been updated to “polypoidal lesion (PL)” and “branching neovascular network (BNN)” respectively. 2. For the clinical diagnosis of PCV, one of the following classical clinical features should be present: (i) Reddish-orange subretinal nodules, (ii) Serosanguineous maculopathy, (iii) A disproportionate amount of exudation as compared to the size of the lesion, (iv) Hemorrhagic PED. (Figure-1) 3. OCT findings may include any one of the following features: (i) Thumb-like polyp (TLP)/Sharp-peaked PED, (ii) Tomographic notch in PED: Signifies the polypoidal lesion at the margin of the PED. (iii) Sub- RPE ring-like lesion: Hyporeflective lumen surrounded by a hyperreflective ring attached to the undersurface of RPE. (iv) Double-layer sign (DLS): Presence of two hyperreflective lines on SD-OCT representing shallow irregular RPE elevation and Bruch’s membrane, signifying AVN. (Figure-2) 4. ICGA is now mandatory only for clinical trials and may not be essential in real-world management of PCV, as per the updated 2021 recommendations. In case of poor response to anti-VEGF, or in hemorrhagic PCV where extrafoveal polyps can be lasered, ICGA is recommended. (Figure-3) 5. FFA is not mandatory in the management of PCV in the updated 2021 recommendation. OCTA provides complementary information to ICGA regarding the morphology of the Polypoidal lesion and Branched neovascular network. (Figure-4) 6. Due to the non-availability of PDT, anti-VEGF monotherapy is the definite choice for the management of active subfoveal and juxtafoveal PCV. 7. Based on level 1 evidence, Aflibercept should be the preferred anti-VEGF agent for PCV. Brolucizumab for cases refractory to both aflibercept and ranibizumab, given the limited evidence and higher rates of intraocular inflammation. 8. Serial OCT is an important tool in following up the patients. Since PDT is not available, consider switching to Aflibercept if the patient has already received three-loading doses of Bevacizumab or ranibizumab with poor response. 9. Use of the T&E regimen with longer-acting agents such as aflibercept is recommended to reduce the treatment burden and follow-up visits of the patient. 10. Thermal laser with anti-VEGF monotherapy can be considered in cases with extrafoveal polyps located beyond 1000 μ and smaller lesions (≤1000 μ) within 500 μ to ≤1000 μ from fovea, and to the feeder vessel in cases where it is visible on ICG and it is>500 μ from the center of the fovea. Figure 1: Reddish-orange sub-retinal nodule with exudation & haemorrhagic PED. (Image source: Kanski’s Clinical Ophthalmology, 8th edition) DOS TIMES
www.dosonline.org/dos-times DOS Times Volume 29, Number 6, November-December 2023 13 DOS TIMES Figure 2: OCT features of PCV: Thumb-like pigment epithelial detachment (white asterisk); Tomographic notch in PED, Signifies the polypoidal lesion at the margin of the PED (red arrow); double layer sign (yellow arrow). Figure 3: ICGA image of Figure-1 showing hyperfluorescence due to polyps and leakage in polypoidal choroidal vasculopathy. Figure 4: (a) Fundus image showing nodular lesion and retinal hemorrhage. (b) The mid-phase ICGA- 3 polyps indicated by black arrows and BVN. (c), (d) Transverse & vertical OCT -Thumb like PED, (e) Automated OCTA en face image- BVN but no definite polyp. (f) OCTA en face image after manual adjustment of level of outer plexiform layer and bruch’s membrane, which clearly revealed 3 polyps (1~3) compatible with ICGA. (Image source: Kanski’s Clinical Ophthalmology, 8th edition) (Image source: Huang, CH., Yeh, PT., Hsieh, YT. et al. Characterizing Branching Vascular Network Morphology in Polypoidal Choroidal Vasculopathy by Optical Coherence Tomography Angiography. Sci Rep 9, 595 (2019). https://doi.org/10.1038/s41598-018-37384-y) (Image source: Sheth JU, Narayanan R, Anantharaman G, Bhende M, Agarwal A, Chawla S, et al. Updated guidelines for the management of polypoidal choroidal vasculopathy: Recommendations from the Indian Polypoidal Choroidal Vasculopathy Panel and the Vitreoretinal Society of India.Indian J Ophthalmol 2022;70:3102-11) References 1. Sheth JU, Narayanan R, Anantharaman G, Bhende M, Agarwal A, Chawla S, et al. Updated guidelines for the management of polypoidal choroidal vasculopathy: Recommendations from the Indian Polypoidal Choroidal Vasculopathy Panel and the Vitreoretinal Society of India.Indian J Ophthalmol 2022;70:3102-11. 2. Anantharaman G, Sheth J, Bhende M, Narayanan R, Natarajan S, Rajendran A, et al. Polypoidal choroidal vasculopathy: Pearls in diagnosis and management. Indian J Ophthalmol 2018;66:896 908. Further Reading 1. Kumawat, Devesh1; Bhayana, Amber2; Kumar, Vinod2,. Pachychoroid Spectrum Disorders: A Review of Clinical Features and Management. Delhi Journal of Ophthalmology 30(1):p 7-15, Jul–Sep 2019. | DOI: 10.7869/djo.471. 2. Shroff D, Sharma M, Chhablani J, Gupta P, Gupta C, Shroff C. PERIPHERAL EXUDATIVE HEMORRHAGIC CHORIORETINOPATHY-A NEW ADDITION TO THE
DOS Times Volume 29, Number 6, November-December 2023 www.dosonline.org/dos-times 14 SPECTRUM OF PACHYCHOROID DISEASE? Retina. 2021 Jul 1;41(7):1518-1525. doi: 10.1097/IAE.0000000000003063. PMID: 33315818. 3. Hua, R., Duan, J., & Zhang, M. (2021). Pachychoroid Spectrum Disease: Underlying Pathology, Classification, and Phenotypes. Current Eye Research, 46(10), 1437–1448. doi:10.1080/02713683.2 021.1942073 10.1080/02713683.2021.1942073. 4. Uppugunduri, Sushmitha & Rasheed, Abdul & Richhariya, Ashutosh & Jana, Soumya & Chhablani, Jay & Vupparaboina, Kiran. (2018). Automated quantification of Haller’s layer in choroid using sweptsource optical coherence tomography. PLOS ONE. 13. e0193324. 10.1371/journal.pone.0193324. Dr. Sandhya Makhija, DO, DNB, MNAMS, FRF, FICO Consultant, Vitreo-Retina, Sant Parmanand Hospital, Civil Lines, Delhi. Corresponding Author: DOS TIMES
www.dosonline.org/dos-times DOS Times Volume 29, Number 6, November-December 2023 15 Approach to Investigate and Localize an Intraocular Foreign Body Sanjeev Kumar Nainiwal , MD, DNB, MNAMS, Kavita Bajiya, MBBS, Siddharth Maanju, MS, Neha Kharwas, MBBS Vitreo Retinal Services, Department of Ophthalmology, Sawai Man Singh Medical College & Hospital, Jaipur Rajasthan, India. Ocular injuries are a major cause of blindness in India as well as the whole world.[1] The diagnosis of an intraocular/intraorbital foreign body is frequently a matter of considerable difficulty. If the foreign body is small then it’s presence may be completely overlooked as it may cause little to no inconvenience or cause (IOFB) only mild pain during its entry into the eye. Thus, it may go undetected for many months to years before the manifestation of ocular signs and symptoms such as siderosis or an implantation cyst. Therefore, in all cases in which an intraocular foreign body is suspected utmost care should be taken to exclude it’s presence for both the timely treatment of the patient and also to avert possible medicolegal implications. The localization of such a foreign body is equally important and may demand the use of techniques capable of greatest accuracy helping in its surgical removal. It is important to remember that an inaccuracy of even 1mm in localization could result in the misdiagnosis of an IOFB and may lead to a futile surgical procedure or involve the loss of the eye. A stepwise approach for the diagnosis and localization is therefore imperative in these cases. I. General Investigations A. History Taking In every case of injury, the first essential part of diagnosis is thoroughness with history. Questions which should be asked to the patient or his/her attendant (in children or unconscious patients) include the activity of the patient at the time of injury, the type of implement being used at the time of injury (such as hammer, chisel, emery wheel etc) and the history of visual acuity prior to the event. These questions are of utmost importance as they not only indicate the possibility of the presence of a foreign body but also provide a clue as to what the foreign body might be. B. Diffuse Torch Light and Slit-Lamp Examination A careful clinical examination should be made to search for a wound of entry. If this is in the cornea, the smallest perforation can be observed by the slit lamp, since a permanent scar is always left behind. However, in the sclera, the wound site may be rapidly obscured, and in the posterior segment of the globe it is, of course, invisible. Hence, the presence of such a wound is indicative of the possibility of entrance of a foreign body and it’s retention. It’s absence on clinical examination by no means rules out further methods of investigation. A hole in the iris is very suggestive of this type of accident and a localized track through the lens, though rare, is equally significant. A rapidly developing cataract after an injury should always incite suspicion of an IOFB. Furthermore, the position of a foreign body is often indicated by the line of direction of impact determined by the wound of entry and any localized injury to the iris or lens. The particle usually travels through the globe in a straight line and may reach the posterior wall of the globe or perforate it and travel further until it stops. On slit lamp examination, in chalcosis, the copper deposition will be seen near the limbus in the Descemet membrane, the Kayser-Fleischer ring similar to Wilson disease.[2-5] Sunflower cataracts may also present.[2] C. Direct and Indirect Ophthalmoscopy Ophthalmoscopic examination should be done if the FB is not seen/localized by diffuse torch light and slit-lamp examination, but if suspicion of the presence of a RIOFB is exists, slit lamp examination can reveal only the ocular structures up to the anterior one-third of the vitreous. If the FB is present in the vitreous cavity posterior to the limit of range of examination of the slit lamp or is lying over/in the retina, it cannot be seen by a slit lamp or torch-light examination. In these cases, a careful search of the retina with indirect ophthalmoscope must be made under full mydriasis. Particular attention should be given to the peripheral retina and this region can be explored up to the level of the ora serrata with the help of indirect ophthalmoscope using very bright illumination and by a depressor on the limbus of the anaesthetized eye (This should not be done in an acutely injured eye). This method of examination, of course, is not possible in many cases in which blood in any significant quantity is present in the anterior chamber or the vitreous, if the lens is cataractous or if sufficient time has elapsed to allow the vitreous to become cloudy or if encapsulation of the foreign body has occurred. D. Gonioscopy For a thorough search of the angle of the anterior chamber, goinoscopy is required. If corneal edema is present then this can be cleared by the instillation of drops of glycerol. Gonioscopy is not used as a routine investigation in all the suspected cases of RIOFB. However, this method of examination, indeed, is of inestimable value in the discovery of minute foreign bodies in this relatively inaccessible site, particularly if they are not radioopaque. E. Transillumination (Diaphanoscopy) Transillumination is a test which is not performed as a part of routine examination today. This test was previously performed DOS TIMES
DOS Times Volume 29, Number 6, November-December 2023 www.dosonline.org/dos-times 16 if the FB was not massive as it might have distorted the globe to such an extent that it’s localization was not possible by the above mentioned general investigations. Trans-scleral diaphanoscopy may reveal the foreign body if it is fairly large and opaque and situated in the anterior half of the eye. Indirect diaphanoscopy, may be of value if the particle is opaque and is situated in the posterior half of the globe. In this test, light is transmitted from the nasopharynx and the fundus is examined simultaneously with the ophthalmoscope. A transparent foreign body such as one of glass in the anterior segment is usually rendered evident with slit-lamp examination by indirect illumination or by oscillating the beam of light, but their presence is more certainly detected by the use of polarized light in the slit-lamp. Minute cotton fibers, pieces of lint and talc are also made visible with this method of illumination. II. Special Investigation After general investigations, if intraocular foreign body is visible in the eye by the means of clinical examination further investigations for it’s localization generally are not required. If at all, any investigation is required, is depends on the techniques of FB removal from the eye. If the plan of management is to remove the FB by the hand magnet, then it’s localization may be done by methods depending on electrical induction (e.g. Roper-Hall or Berman Locator). Methods Depending on Electrical Induction The principle of these methods depends on the fact that, if an alternating current is sent through a primary circuit, a current develops in a secondary coil by induction. If the voltages in the secondary coils are equalized, no current flows between them, but if in this state, the instrument approaches a metallic body, the balanced inductance is disturbed and a difference in potential is created in the secondary circuit, resulting in a flow of current, which after amplification, may be recorded by the deflection of the needle of an ammeter or detected by variations in the tone of a loudspeaker. The amount of this current varies with the magnetizability of the particle, it’s size and it’s distance from the instrument. A magnetic metal profoundly affects the magnetic field created around instrument, but nonmagnetic metals can also be detected. Since the alternating magnetic field around the instrument sets up small eddy currents within the mass of the metallic particles, these produce a local magnetic field around the foreign body which reacts with the field of the instrument and thereby causes detectable changes. The magnitude of difference between these changes allows differentiation to be made between a nonmagnetic and a magnetic particle. The classical examples of this method are the Berman locator and the Roper-Hall locator. Other examples are the ophthalmometalloscope of Hata, the Carnay locator, Beo locator etc. The Roper-Hall locator works on a higher frequency than the Berman locator which may be more suitable for nonmagnetic foreign bodies. The sensitivity of such an instrument to a ferromagnetic particle is very high indeed. Thus, in Berman Locator, the detection range for iron and steel is approximately 10 times the diameter of the foreign body (a particle of 1mm diameter is detectable at 10mm). In the case of nonmagnetic substance (copper, brass, aluminium, lead etc), however, it is much less, the effective range is only 1 or 2 times the diameter of the particle. Intraocular foreign bodies of this type can therefore be detected only if they are of relatively large size (greater than 3.0mm diameter). It must be admitted, however, that with all it’s elaborations, this method is not as accurate as radiography, either for the detection or more particularly, for the localization of a metallic foreign body. It is however of value when accurate radiography is not readily available (as may occur at times of war). Moreover, the locator has the advantage of being small, portable and readily usable by a person who need not be an expert in complicated radiographic technique. It is also a useful adjunct to X-ray, providing information as to the degree of magnetisability of a particle and therefore of the potentialities of it’s extraction by the magnet. Finally, since the active element is small and can be covered by a sterilizable cover shield, it can be used during an operation to confirm the position of a foreign body as determined by radiography both before and after the incision has been made. a) Radiological Localization If the FB is not localized because of significant media opacity (e.g. intraocular haemorrhage/cataract) or even in the eyes with clear media (e.g. peripheral FB), then the patient is investigated by means of the radiological (imaging) methods of FB localization. The primary radiological methods used in evaluating trauma are, plain film radiography, CT, MRI and ultrasonography. Each has a distinct utility, but none provides all the diagnostic information needed in all cases. A combination of complementary techniques, typically CT and ultrasonography, are used to evaluate the spectrum of soft tissue and bony changes seen in eye trauma and to identify and localize radio opaque and radiolucent foreign bodies. 1. Plain Film Radiography of Orbit Although plain film evaluation of the eye and orbit has been largely superseded by CT examination (because of the latter’s tomographic representation of the soft tissue), it still offers advantages in depicting the shape and number of metallic foreign bodies and localizing orbital wall fractures. In some cases, a negative plain film may make more expensive and invasive tests unnecessary. The first documented cases of successful use of plain film radiography for detecting and localizing metallic foreign bodies were published less than a year after Roentgen demonstrated the X-ray and their medical utility. Specific plain film series for orbital trauma visualization now include, use of the Caldwell projection. The Water’s projection and the lateral view are among others. The film series detect the presence of an intraocular, orbital or adnexal retained foreign body if it DOS TIMES
www.dosonline.org/dos-times DOS Times Volume 29, Number 6, November-December 2023 17 is sufficiently radiodense. In addition, most orbital wall and other skull fractures are well delineated by plain film series. The ability of the plain film to outline distinctly and compress the orbit into a single viewing plane allows easy identification of radiopaque foreign bodies. Limbal Ring Localization This method takes the most simple and direct approach to the problem. Two exposures are taken at right angles, one posteroanteriorly and the other laterally, and the position of the foreign body is located in relation to a radiopaque marker bearing a known relationship to the globe. In the postero-anterior view, Water’s position should be employed in order to exclude the shadow of the petrous bone from the orbit. The method is easy and in it’s simplest form, it is applicable in practically all circumstances. The variations of this method are numerous some of them depend on the use of different types of indicators affixed to the globe i.e. lead pellets (Holth, 1903-11; Velter, 1919), metallic rings (Spaeth, 1942) or contact lenses (Comberg, 1927-33), while in others an indicators is used at a distance (Ahlbom, 1931; Stenius, 1947) or the globe is oriented by an indicators which marks a fixed point in different positions of rotation (Kraus and Briggs, 1945). In all variations of this technique, the position of the foreign body is measured in both films in relation to the position of the marker employed and the results assessed in both frontal and sagittal planes with reference to a standard eye of 24mm diameter. A small correction is done amounting to a fraction of a millimeter, to allow for the error introduced by the conical projection of rays. The most commonly used indicator in clinical practice is the use of a metallic ring of known diameter (affixed to the globe at limbus by temporary sutures). After fixation of metallic ring at limbal area by 2 to 4 temporary sutures, two exposures are taken at right angles, one postero-anteriorly and other laterally. For the accurate localization of the FB, the 2nd exposure should be a true lateral (limbal ring in X-ray should be seen as a single vertical straight opaque white line). The magnification factor should be measured by measuring the size of indicator (metallic ring) in the x-ray plate divided by the actual size of the metallic ring. When radiographs of satisfactory quality are obtained, three measurements are made as follows. On the postero-anterior view: The centre of the circle formed by the limbal ring is marked and the distance of the foreign body on the nasal or temporal side from the vertical corneal axis is then measured. On the lateral view: The following measurements are obtained from the lateral film. a. The distance of the foreign body from the limbal ring and b. The distance of the foreign body, above or below to the horizontal corneal axis. All these measurements can then be repeated on repeated imaging the eye in different lateral gazes. If the measurements are not identical, the foreign body is either extraocular or mobile, in which case exact localization is not possible. Since the indicator (metallic ring) is fixed to the globe at the limbus, and then measurements are done on X-ray films, this whole method of FB localization is termed as “LIMBAL RING LOCALIZATION”. Since unfortunately eyes in all the patients are not of same size (24mm), this introduces an unavoidable error which occasionally may be considerable. To avoid this error, presently, instead of assuming the standard size (24mm) of the patient’s eyes, we can measure the real axial length with help of ultrasonography (A scan) and then measurements can be taken as described above. This method of FB localization is termed as “MODIFIED LIMBAL RING LOCALIZATION”. If the plain x-ray films of the orbit do not show any evidence of RIOFB, then further investigations of its localization are required on the basis of reliability of the history given by the patient or his/her attendant (children/comatose/mentally handicapped or uncooperative patients). If the history given itself is doubtful, then further investigations are not required. If, however, there is very reliable and strong suspicion of RIOFB (e.g. working with chisel and hammer at the time of injury) or there is/are clinical sign(s) suggestive of it’s presence in the eye (e.g. iris hole), then the patient must be investigated by means of more accurate and reliable imaging methods of intraocular foreign body localization, like computed tomography (CT scan). 2. Computed Tomography The CT scan is the standard diagnostic test for imaging the traumatized eye and orbit. Tomographic sections of the head in the axial, coronal and sagittal planes (directly or reconstructed) at the level of the eye and orbit provide an accurate anatomic view of soft tissue and bony changes resulting from trauma. Retained foreign bodies of sufficient size and radiodensity are easily located and the orbit allows detection of the exact extent of orbital wall fractures and possible incarceration of the orbital content. CT scan can accurately detect the number, size, shape, and location of a foreign body.[6] Current generation machines allow for a slice thickness of less than 1.5mm and a voxel size of less than 0.5mm3 . Current generation machines can detect metallic foreign bodies less than 1mm in size (as small as 0.7mm), except for aluminium and less radiodense objects which needs to be of a slightly larger size to permit detection. Sometimes small non-metallic fragments too close to sclera may be missed. The only drawback of CT in localization is seen when one or more foreign bodies have a sufficient attenuation coefficient and volume to cause streak and Hounsfield artifacts. These can obliterate the reproduction of individual objects and distort anatomic relationship. Artifact problems are usually seen with metallic foreign bodies but can also be present with less radiodense substances. DOS TIMES
DOS Times Volume 29, Number 6, November-December 2023 www.dosonline.org/dos-times 18 The other major type of injury for which the CT scan is particularly useful is orbital fractures. The location and extent of orbital floor, wall, roof and rim fracture as well as other skull fractures that may have an impact on the orbital repair, such as zygomatic arch and Le fort fractures are readily demonstrated. Soft tissue delineation is not as good as in MRI, but incarceration of orbital contents or scarring and adhesion of muscles to the orbital wall can be seen if proper slices and reconstructions are obtained. The lid speculum and waterbath technique does not put undue pressure on a possibly ruptured eye and enhance the sensitivity by allowing the focal zone to be placed in the areas of interest. The contact technique has the advantage of simplicity but does not permit optimal or sometimes any depiction of the lens or anterior chamber. This can be remedied by using a balloon stand-off of soft prophylactic latex partially filled with saline. When used with methylcellulose and a lid speculum; this can separate the “main bang” of the transducer from the eye and allow visualization of the anterior segment. A major advantage of the balloon stand-off is that it greatly reduces pressure on A CT examination of the orbits can often identify significant non ocular findings, such as occult local brain atrophy from a previous injury. Direct or reconstructed coronal views are important in evaluating blowout fractures. Saggital and oblique views may be informative in specific cases of ocular motility problems. Beyond this, consultation with the neuroradiologist and radiotechnologist on individual case is needed to ensure that the maximum amount of information for diagnosis and management is collected. Finally, the use of contrast media is not necessarily indicated in trauma evaluation, although it does enhance soft tissue delineation in orbit. 3. Ultrasonography Ultrasonography has proven to be a useful addition to the methods for the localization of an intraocular foreign body, both pre-operatively and during the surgical manipulations, particularly since it does not require optically clear media, and thus it may be of value when a suspected foreign body cannot be seen because of media haze (e.g. intraocular haemorrhage or cataract). The principle of ultrasonography depends on the propagation of a pulse of sound. When the sound wave strikes an interface such as the vitreous and retina or between the vitreous and a foreign body, a portion of the sound is reflected and received by the transmitting crystal. Distinct echo peaks correspond Figure 1: Large intraocular foreign body seen in right eye on Computed tomography. Figure 2: Large intraocular foreign body seen on ultrasonography. to the corneal surfaces, and the posterior wall of the eye are observed. No echo returns from the acoustically homogenous normal aqueous, lens substance or vitreous. The reflected sound waves are converted into sharp spikes of light on an oscilloscope, which can then be photographed, or recorded as a trace on a time-amplitude system. The distance of the echo-producing interface from the ultrasound probe are accurately projected, thus permitting measurement of the axial length of the eye and precise determination of the distance from the probe to any echo-producing surface within the eye. Ultrasonography may help to determine whether a foreign body is intra-ocular or extra-ocular. The radiological techniques of Comberg and Sweet depend upon the eye having standard axial length of 24mm, that introduces an unavoidable error in calculation, which occasionally may be considerable. In such cases, the accurate measurement of the axial length of the globe by ultrasonography will enable the appropriate correction to be made for radiological localization and, if the foreign body is extraocular, it will return an echo peak clearly beyond the sclera echo. Ocular ultrasound is generally used as a B-scan imaging technique for evaluating trauma, although the A-scan has a corroborative and correlative role. B-scans are performed with contact or immersion techniques. The immersion technique is not commonly used but has the advantage of showing the anterior chamber and lens. DOS TIMES
www.dosonline.org/dos-times DOS Times Volume 29, Number 6, November-December 2023 19 the eye during the contact B-scan examination. A membrane echo may produce an artifact but this can be easily identified by jiggling the transducer. Ocular ultrasound is generally performed at the frequencies of 8 to 10 MHz or higher. For orbital examination or in the presence of severe inflammation and haemorrhage, the use of lower frequencies, like 5MHz, may allow sufficient sensitivity for good visualization. Although ultrasound can demonstrate the orbital soft tissue changes quite well but it’s use is generally limited in visualizing the apex and bony structures and offers no advantages over CT scan of the orbit. However, it does have a considerable and unique advantage in demonstrating damage to the ocular structures. In the planning of vitreoretinal surgeries in traumatic cases, the four general indicators which have been suggested for USG use are; lens rupture, vitreous haemorrhage with or without retinal detachment, retained intraocular foreign body and vitreous incarceration to the wound. Each of these indications can be demonstrated with ultrasonography. The CT scan and x-ray generally excel at detecting foreign bodies, but ultrasound excels at localizing the foreign body relative to the ocular coats and demonstrating soft tissue changes. Glass and metallic foreign bodies are very reflective and appear as bright areas on the B-scan. Foreign bodies have such a high reflectance that they appear to absorb sound, and they often produce an anechoic zone behind them that resembles an echo-free “pointer” extending into the orbital fat, and sometimes resembling an optic nerve shadow. Shotgun pellets produce an unusual ring artifact that can extend into the anechoic zone like a comet tail. Contact ultrasound is also useful to have available in the operating room. When used with a sterile cover (e.g. a rubber balloon or glove with saline inside), it can be helpful in evaluating a repaired globe that could not be evaluated preoperatively because of the large size of the laceration. Pre-operative or intraoperative ultrasound can assist in determining the extent of repair to be performed during the primary procedure. This may be uniquely helpful when a foreign body is still in the eye because it can show the location of the foreign body relative to the retina and even it’s motility when it is rocked or jiggled by a magnetic field. DOS TIMES
DOS Times Volume 29, Number 6, November-December 2023 www.dosonline.org/dos-times 20 Magnetic Resonance Imaging (MRI) Magnetic resonance imaging technique is strongly contraindicated in all cases of suspected metallic foreign bodies, as it can dislodge it and cause further damage.[7] The potential for the tissue damage from movement of the ferromagnetic foreign body in an intense field of the magnet precludes the use of MRI as a screening technique because a magnetic foreign body, if present, could be dislodged and produce further damage to the eye. In some experimental series, MRI has been shown to detect a wide variety of vegetables, plastic and glass foreign bodies in the eye, orbit and adnexal tissue. With the use of surface coils, orbital imaging of concussive trauma with high resolution is also possible. The T1-weighted sequence provides the most contrast and detail for ocular and orbital imaging. Fat, with a short T1, has the highest signal intensity. The lens capsule outline, anterior uvea and iris plane are approximately isointense with the aqueous humor, with less signal intensity than fat. The vitreous, optic nerve and lens body are isointense at still lower signal intensity. The recti muscles and scleral and cortical bone are relatively hypointense in the image. In the normal T2-weighted image of the eye and orbit, the vitreous and aqueous have a long T2 and highest signal intensity if the image is sufficiently T2-weighted. The fat pad has an intermediate T2 and the next highest signal intensity. The optic nerve and muscles are isointense at lower signal intensity. The lens appears hypointense because of short T2 and the relative hyperintensity of the vitreous. The easiest way to distinguish between the two images, if the TR/TE numbers are not pointed on the scan, is to look for the hyperintense vitreous that denotes a T2-weighted image. Bone Free Methods The bone free method of FB localization were introduced by Vogt (1921-23) and allows some accuracy in localization in it’s simplest applications. If sufficiently soft rays are used and the lids are widely separated, the outline of the cornea is well seen, so that the relation of the foreign body to the corneal contour in the two exposures at right angles gives some idea of the position of the particle. The accuracy of localization can, however, be considerably increased by taking two radiographs in each projection with the eye rotated in different positions, so that the “rotational method” is adopted to this technique. Two procedures have been exploited for this purpose. a) Radiopaque marker is used to locate the foreign body directly (Vogt, Goldmann, Larsson, Lindblom). b) A technique similar to those described as “direct methods” is used with an indicator attached to the eye. The position of the foreign body being calculated indirectly by geometrical construction from the position of a radiopaque marker attached to the limbus (Bangerter and Goldmann). The corneal surface can be clearly outlined and exceedingly minute fragments of metal, pieces of glass and sometimes even wood may be detected in the anterior segment to an antero-posterior depth of 8 to 12mm. Hoffman (1947) demonstrated small splinters of iron of only 0.000052 gm in this way. Advantage It is the only method of FB localization available when the radio-density of the particle is such that this technique is required for it’s demonstration e.g. glass, wood. Bone free radiographs are particularly useful in the demonstration of foreign bodies in the anterior chamber. These are however not used routinely because of easily availability of CT scans which can easily pick up these foreign bodies. References 1. Iftikhar M, Latif A, Farid UZ, Usmani B, Canner JK, Shah SMA. Changes in the Incidence of Eye Trauma Hospitalizations in the United States From 2001 Through 2014. JAMA Ophthalmol. 2019 Jan 01;137(1):48-56. 2. Puranik C, Chaurasia S, Ramappa M, Sangwan V, Balasubramanian D. Corneal chalcosis following blast injury. Br J Ophthalmol. 2012 May;96(5):762. 3. McGahan MC, Bito LZ, Myers BM. The pathophysiology of the ocular microenvironment. II. Copper-induced ocular inflammation and hypotony. Exp Eye Res. 1986 Jun;42(6):595-605. 4. Tripathy K, Tomar AS, Sidhu T, Dada T. A 10-year-old boy with dystonia, expression-less facies, and tremors referred for ophthalmic examination. Oman J Ophthalmol. 2021 May-Aug;14(2):128-130. 5. Sridhar U, Tripathy K. Commentary: Kayser-Fleischer-like rings in patients with hepatic disease. Indian J Ophthalmol. 2021 May;69(5):1088. 6. Crowell EL, Koduri VA, Supsupin EP, Klinglesmith RE, Chuang AZ, Kim G, Baker LA, Feldman RM, Blieden LS. Accuracy of Computed Tomography Imaging Criteria in the Diagnosis of Adult Open Globe Injuries by Neuroradiology and Ophthalmology. Acad Emerg Med. 2017 Sep;24(9):1072-1079. 7. Cho WK, Ko AC, Eatamadi H, Al-Ali A, Abboud JP, Kikkawa DO, Korn BS. Orbital and Orbitocranial Trauma From Pencil Fragments: Role of Timely Diagnosis and Management. Am J Ophthalmol. 2017 Aug;180:46-54. Dr. Sanjeev Kumar Nainiwal, MD, DNB, MNAMS Senior Professor Ophthalmology, Sawai Man Singh Medical College & Hospital, Jaipur Rajasthan India. Corresponding Author: DOS TIMES
www.dosonline.org/dos-times DOS Times Volume 29, Number 6, November-December 2023 21 Imaging the Pachychoroid Spectrum Gagan Bhatia, DO, DNB, Daraius Shroff, MS, Sandeep Kumar, MS, Priyanka Gupta, DNB Shroff Eye Centre, New Delhi India. Abstract: Pachychoroid is a novel term which describes a phenotype characterized by thick choroid, pachyvessels and attenuation of choriocapillaries. It comprises different clinical entities which have common as well as individual features. Diagnostic investigation of pachychoroid spectrum disease is growing and emerging along with fast advancements in retinal imaging technology. OCT and OCT angiography have provided us with qualitative and quantitative assessment of choroidal and choriocapillaries changes in this spectrum of diseases. OCT angiography is particularly useful in looking for active and silent choroidal neovascular membranes. Ultra-wide field imaging has been particularly useful in peripheral choroidal pathologies of this spectrum. We summarize all modalities on reflecting the insights into novel findings related to all entities. Keywords: Pachychoroid, Haller’s layer, swept source optical coherence tomography, ICGA, Fundus fluorescein angiography, autofluorescence Introduction Pachychoroid is a relatively new term meaning thickened choroid. The term “pachychoroid was first introduced in 2013 by David Warrow, Quan Hoang and K. Bailey Freund.[1] Initially characterized by phenotype, other features have been added that form the pachychoroid spectrum to play an important pathogenic role in the development of the clinical manifestations. Pachyvessels (dilated Haller layer vessels), attenuated inner choroidal layers (the Sattler layer and choriocapillaris), choroidal hyperpermeability on ICGA, reduced fundus tessellation in the area of thickening, and club-shaped posterior terminal morphology of pachyvessels are all features of pachychoroid disease[2]; however, eyes do not need to have all of these features to be included in the pachychoroid disease spectrum. The presence of hypertrophy or congested vessels in the choroid (pachyvessels), rather than thickening choroid per se, under a region of decreased or nonexistent choriocapillaris in the posterior pole, appears to be the most distinguishing feature of pachychoroid. Central serous chorioretinopathy (CSCR), pachychoroid pigment epitheliopathy (PPE), pachychoroid neovasculopathy (PNV), polypoidal choroidal vasculopathy (PCV), focal choroidal excavation (FCE), and Peripapillary pachychoroid syndrome (PPS) were originally included in the Pachychoroid Spectrum Disease (PSD). Recently PEHCR has also been suggested to be a part of PSD.[3] In this era of imaging, studies on pachychoroid entities have grown as a result of the rapid progress of diagnostic technology. Detailed awareness of the most recent multimodal imaging features is required for efficient diagnosis and management of pachychoroid illnesses since the use of the developing modalities may change the approach to pachychoroid in the future. This review is based on current literature with an emphasis on the clinical and imaging features, the review is divided by covering the individual PSD according to the imaging modality and characterization of the findings in the various clinical entities. Common Characteristics of Pachychoroid Diseases: (Table-1) 1. Choroidal Thickening 2. Characteristic presence of Pachyvessels : Dilatation of large vessels in Haller layer 3. Attenuation of small calibre vessel in Sattler layer 4. Choroidal Hyper permeability 1. Focal or diffuse thickening of choroid: There’s a wide range of sub-foveal choroidal thickness, with a cutoff value for pachychoroid disorders of 200-390 m2 . Age, sex, axial length, lens status, diabetes, systemic hypertension, and time/diurnal variation of the day all affect the typical sub foveal choroid thickness. Setting a normal threshold for it is therefore challenging, and as a result, numerous investigations have generated a wide range of normative data.[4] The normal sub foveal choroidal thickness in the Indian population is reported to be 299.1±131.2µm.[5,6,7] 2. Pachyvessels: They are seen as large hypo reflective lumen located at the level of Haller’s layer. Increases in choroidal thickness occur due to dilatation of choroidal vessels in the Haller layer. Table 1: Key features of pachychoroid spectrum. DOS TIMES
DOS Times Volume 29, Number 6, November-December 2023 www.dosonline.org/dos-times 22 3. Attenuation of inner choroid Involves focal or diffuse attenuation of choriocapillaries and small calibre vessels in the Sattler layer overlying abnormal dilated Haller layer vessel.”[8] Clinical Entities and Imaging Features of Pachychoroid Spectrum: 1. Pachychoroid Pigment Epitheliopathy (PPE): The term PPE was first introduced by Warrow and colleagues.[9] They have been characterised as RPE changes occurring at the posterior pole over areas of choroidal thickening.[9] The age group of patients are typically young and are often seen in fellow eyes of CSCR or PNV and is not visually significant. These cases are sometimes misdiagnosed as RPE epithelitis or age-related macular degeneration.[9,10] Imaging Features: (Figure-1) The fundus appearance in these eyes is typical absence of soft drusen which is often seen in age-related macular degeneration and is characterised by RPE mottling with decreased fundus tessellations. OCT will show choroidal thickening with the presence of pachyvessels and focal RPE alterations. No Choroidal neovascular membrane or neurosensory detachment is seen. Interestingly, the outer nuclear layer was seen to be thinner in these eyes as compared to uncomplicated pachychoroid eyes which indicates that photoreceptors and/or RPE degeneration could occur independently in the absence of subretinal fluid.[11] ICG shows choroidal hyper permeability with pachyvessels and Autofluoroscence shows mixed granular patterns corresponding to other imaging modalities. 2. Central Serous Chorioretinopathy (CSCR): CSCR is characterised by serous PED with neurosensory detachment. Von Graefe first coined the term “central recurrent retinitis” and later on Gass gave the name “central serous choroidopathy” in 1967.[12,13] The choroidal changes in this entity are mainly focal, multiple and not diffuse. Imaging Features: (Figure-2) In CSCR the fundus appearance can be of two types depending Figure 1: Pachychoroid pigment epitheliopathy (PPE): multicolour image depicting RPE alterations at macula with corresponding autofluorooscence showing granular pattern. OCT shows focal RPE undulations with presence of pachyvessels and increased choroidal thickness. upon their duration of disease. Acute disease occurs <3 months and chronic which persists for more than 6 months. In Acute cases, there will be NSD associated with or without PED, which is typically seen as small defined elevated area orange colour present deep to NSD. These cases may sometimes be associated with sub-retinal fibrin. As compared to chronic cases will present as granular RPE mottling with shallow NSD. Autofluoroscence classical appearance of the presence of vertical DOS TIMES
www.dosonline.org/dos-times DOS Times Volume 29, Number 6, November-December 2023 23 3. Pachychoroid Neovasculopathy (PNV): Pang and Freund were the first to describe PNV in eyes developing type 1 CNV over background changes of PPE.[20] Pachychoroid Neovasculopathy is usually identified as an incidental finding in patients with a history of chronic CSCR, with or without associated sub-retinal fluid collections. Miyake et al[21] in their study proposed that PNV with polypoidal lesions should be distinguished from nAMD with polypoidal lesions. As compared to nAMD, PNV was illustrated by a lack gravitational tracts which can be hypo/hyper autofluoroscence & mixed. FFA shows a typical ink blot pattern or smoke stack pattern in acute cases. These leaks can be single or multiple also. On contrary in chronic cases, FFA will show stippled hyperfluoroscence with staining due to underline window defect. ICGA in acute cases will show diffuse choroidal hyperpermeability with visible large pachy vessels. In chronic cases, there may be diffuse hypercyanescence in areas of RPE mottling. OCT will show serous NSD with/without PED. Sometimes they have associated sub-retinal fibrin which is seen as heterogeneous reflectivity within the neurosensory elevation. Figure 2: Central serous chorioretinopathy (CSCR): Left eye Autofluoroscence (a) shows hyperfluoroscence at macula with FFA (b) shows smoke stack leakage inferior to the fovea. OCT (c) shows neurosensory detachment with adjacent PED with increased choroidal thickness and presence of pachyvessels. Right eye (fellow eye): Autofluoroscence and FFA (d,e) show no leakage and OCT (f) shows the presence of pachyvessels with increased choroidal thickness. of drusen, earlier onset, greater sub foveal CT, higher prevalence of RPE abnormality and choroidal vascular hyperpermeability. Imaging Features: (Figure-3) The fundus appearance shows a dirty grey membrane with minimal exudation and retinal haemorrhages. CNV is the chief feature of PNV, which may be foveal or extrafoveal in location. Autofluorescence reveals an abnormal FAF suggestive of RPE changes overlying areas of pachyvessels. Although Chronic Sometimes due to persistence of sub-retinal fluid there may be intraretinal lipid deposition with sub retinal yellowish dots and may lead to elongation of photoreceptor outer segments.[14] Research-based on EDI have shown thickened choroid in these eyes.[15,16] Imamura et al[15], yang et al[17] have found there is an increased thickness in both affected and asymptomatic fellow eyes of patients with CSC.[18] The enface SS-OCT shows presence of pachyvessels which are seen as focal or diffuse choroidal dilatation at both Hallers and sattlers layer.[19] OCT angiography is used to identify and differentiate noninvasively from other entities particularly the presence of choroidal neovascularization (CNV) secondary to chronic CSC. DOS TIMES
DOS Times Volume 29, Number 6, November-December 2023 www.dosonline.org/dos-times 24 CSCR exhibits comparable symptoms, the typical vertical gravitational tracts may not be present. This difference will be helpful in determining whether the SRF is due to the consequence of PNV or CSCR.[20] The presence of neovascularisation can be seen as early hyperfluoroscence with late leakage on FFA and a corresponding late plaque will be seen on ICGA. OCT will demonstrate the existence of type 1 neovascularization, which manifests as a “double layer sign” covering pachyvessels and appears as a shallow, uneven separation of the RPE from Bruch’s membrane known as FIPED. Localized choroidal thickening was also observed in these conditions in contrast to typical nAMD eyes which often have evidence of choroidal thinning.[22,23] OCTA helps in the diagnosis and confirmation of neovascularization in cases of suspected PNV. Neovascularization can be recognised noninvasively as a tangled network of flow signals between the RPE and Bruch’s membrane corresponding to the FIPED seen on structural OCT. In a series of 88 patients with chronic CSC, neovascularization was detected in 35.6% of eyes with shallow irregular PEDs using OCTA.[24] Using OCTA, Carnevali et al[25] described quiescent CNV in 10% of eyes which were diagnosed as PNV. Figure 3: Pachychoroid Neovasculopathy (PNV): Right eye Multicolour image (a) shows RPE alterations at macula with corresponding autofluoroscence (b) shows gravitational mixed autofluoroscence tract. OCTA (c) confirmed the presence of the vascular network. FFA & ICG (d,e) shows stippled fluorescence with no definite leakage or hot spot. OCT (f) shows NSD with hyper reflective ,fibro vascular PED with increased choroidal thickness and presence of pachyvessels. 4. Polypoidal Choroidal Vasculopathy: Yanuzzi et al. first identified polypoidal choroidal vasculopathy[17] (PCV), which was thought to be a subtype of nAMD. Polypoidal lesions, which are identified as dilations of branching vascular network (BVN) terminals, are the hallmark of PCV. Eyes with PCV have a greater mean sub foveal choroidal thickness (SFCT). Despite being the gold standard[26] for diagnosing PCV, ICGA is an invasive imaging procedure that should not be used on patients who have a history of iodine-based dye allergies. Therefore, using non-invasive imaging techniques to diagnose PCV may be helpful in clinical practice. Imaging Features (Figure-4) PCV is characterised by protruding orange-red nodular lesions[27] on colour photos. They are typically found at the posterior pole, in the macular or peripapillary region which according to the Japanese Study Group of Polypoidal Choroidal Vasculopathy was a significant diagnostic criterion.[27] Serous exudation and haemorrhage are frequently present with DOS TIMES
www.dosonline.org/dos-times DOS Times Volume 29, Number 6, November-December 2023 25 Figure 4: Polypoidal choroidal vasculopathy (PCV): Right eye Multicolour image (a) shows subretinal heme at the macula. FFA & ICG (b,c) shows leakage and presence of polyps at inferior to the fovea. OCTA (d) at choriocapillaries slab shows the presence of branching vascular network with corresponding OCT (e) shows NSD with double layer sign with presence of pachyvessels and increased choroidal thickness underneath. nodular lesions. Polyp lesions are mostly present at the margin and inside the serosanguinous PED, appearing as a “notch sign on OCT.[28] On AF the polyp either appears as a hyperfluorescent ring or even granular hypo fluorescence. As the BVN is located in Bruch’s membrane PCV appears as occult or minimal classic AMD on FFA.[28,29] The RPE in FA makes it difficult to see the BVN beneath it unless the RPE above it has atrophy or the fundus is less pigmented, that’s why it appears with classic hyperfluoroscence in cases of atrophy of overlying RPE or subretinal fibrin deposition or presence of type 2 CNV.[30] FFA has limitations in cases with serosanguinous deposits due to blocked fluorescence by heme or exudates. In such cases, ICGA has proved to be diagnostics in the visualisation of polyps. Within the first six minutes after the dye injection, PCV presents with one or more focal areas of hyperfluoroscence originating from the choroidal circulation, with or without an accompanying BVN. The PCV nodules and aneurysm are visualised as ICGA hyper fluorescence on the edge of BVN.[31] Active polyps have a hypo fluorescent halo that surrounds them, indicating that there is fluid around the polyp. Based on ICGA, PCV into two categories[32]: Type 1, there are many network vessels and both feeder and draining vessels are visible on the ICGA; in Type 2, there are few network vessels and neither feeder nor draining vessels are visualised. ON SD-OCT the PCV has the following signs.[33] 1) A sharp peak-like or thumb-like PED. 2) the double-layered sign. 3) Underneath the PEDs, a region of hypo reflectivity is surrounded by a moderately hyperreflective ring. 4) “V”-shaped depression between two PEDs or at the margin of a large PED. 5) Multiple PEDs. Based on EDI, PCV was subclassified into two subtypes[34]: Typical PCV with thick choroid which has a significant vascular choroid and PCV without thick choroid using choroidal vascular characteristics (polypoidal CNV). SS-OCTA has been a new armamentarium in diagnosing PCV, esp. in cases who ae allergic to ICGA dye. It has been observed that BVNs are better delineated on OCTA than on ICGA but do not show the polyps as clearly as ICGA. Various authors have described polyps on OCTA as either a hypo flow round structure at the level of the choriocapillaris or a hyper flow round structure surrounded by a hypo flow halo. Artefacts and auto-segmentation are the limitations of OCTA that cautions interpretation of the images. Recent studies have shown a wide range in the detection rate of polyps on OCTA compared to ICGA, from 45% to 92% detected.[35] DOS TIMES
DOS Times Volume 29, Number 6, November-December 2023 www.dosonline.org/dos-times 26 Figure 5: Peripheral exudative haemorrhagic chorioretinopathy (PEHCR): Right eye, Multicolour image shows temporal subretinal lesion with exudation. FFA & ICG shows peripheral polyp-like choroidal telangiectasia and abnormal choroidal vascular networks. OCTA shows high flow network correspondingly. OCT shows a temporal increase in choroidal thickness with the presence of pachyvessels underneath with PED. On FFA PEHCR haemorrhagic lesions show a significant masking effect, sometimes associated with the hyperfluoroscence of associated CNV. The most common FA findings are the blockage of choroidal fluorescence related to haemorrhage (subretinal/sub RPE) and window defect from peripheral atrophic RPE changes.[40] Other findings include diffuse peripheral hyper-or hypo fluorescence that correlates to RPE atrophy or hyperplasia. 20 of the 56 PEHCR eyes in Mantels 2009 series underwent ICG-A and 6 (30%) of them had pathologic choroidal vascular networks that resembled those observed in polypoidal choroidal vasculopathy (none of them had associated FA findings of neovascularization).[40] The dynamic ultrawide-field ICGA allowed us to identify delayed filling of the choriocapillaries in peripheral areas of pigmentary changes and atrophy in the periphery, denser choroidal veins, peripheral polyp-like choroidal telangiectasis and abnormal choroidal vascular networks. Recently, Widefield SS-OCTA has proved to be very helpful in avoiding misdiagnosis of PEHCR and formulating a treatment plan. The polyps are seen as a cluster of dilated vascular networks on the en face SS-OCTA and each of these networks showed a corresponding high flow signal on SS-OCTA. Charu et al[41] were also able to identify a BVN below the cluster of polyps on en face SS-OCTA. The PCV lesion complex on SS-OCTA correlated well with the ICGA. 5. Peripheral Exudative Haemorrhagic Chorioretinopathy (PEHCR): First reported in 1961, the spectrum of peripheral PEDs and haemorrhage was coined the name ‘PEHCR’ by Annesley in 1980.[36] Given the similarities between PEHCR and exudative age-related macular degeneration, several authors have proposed that PEHCR may result from a choroidal neovascular network.[37] While others have other authors have suggested that PEHCR could be more likely to share a common pathophysiological origin with polypoidal choroidal vasculopathy.[38] Recently Shroff et al[3] proposed to include PEHCR in the pachychoroid spectrum of disease entities, based on their findings that the mean temporal Choroidal Thickness (CT) is 60mm more than the mean SFCT in PEHCR and the area of maximum CT coincides with the site of the lesion. Imaging Features (Figure-5) Fundus Appearance Lesions are most frequently discovered in the temporal quadrant, (notably inferotemporal) and between the equator and the ora serrata, in more than 75% of cases.[39] Nasal lesions are frequently present alongside temporal lesions, either as an extension of a large temporal lesion or as separate lesions, and are frequently accompanied by bilateral involvement haemorrhagic PED, lipid exudation, subretinal fibrosis or haemorrhage, or even vitreous haemorrhage. DOS TIMES
www.dosonline.org/dos-times DOS Times Volume 29, Number 6, November-December 2023 27 6. Peripapillary Pachychoroid Syndrome (PPS): Peripapillary pachychoroid syndrome is a part of pachychoroid spectrum disorder which is first described by Phasukkijwatana et al.[42] It is characterised by pachychoroid features seen in the peripapillary area and nasal macula rather than the fovea. The most common differential diagnosis of this entity is uveal effusion syndrome since it is associated with hyperopia, crowded disc and serous retinal detachment at the posterior pole. The differentiating feature is no choroidal detachment is seen in this entity. Imaging Features (Figure-6) The clinical features include intraretinal and/or subretinal fluid Figure 6: Peripapillary Pachychoroid syndrome (PPS): Left eye. Multicolour shows RPE alterations nasal to the fovea with corresponding autofluoroscence showing same. OCT shows NSD with few intraretinal cystic spaces in the nasal quadrant with underline increased choroidal thickness and presence of pachyvessels. in the peripapillary area and optic nerve head oedema. Autofluoroscence shows mottled hypo fluorescence and gravitational tracks in the peripapillary area. FFA shows window defects in the corresponding areas without focal leakages. Mild late disc leakage may be seen in the majority of the cases. ICGA shows Choroidal vascular hyperpermeability and presence of pachyvessels. OCT shows intraretinal fluid and NSD in the Peripapillary area with thickened choroid and the presence of pachyvessels with choriocapillaries attenuation. The thickened choroid was especially noted in the nasal versus temporal macula when compared to other typical pachychoroid spectrum disorders.[43] 7. Focal Choroidal Excavation (FCE): Jampol et al in 2006[44] with time domain OCT mentioned FCE as an unusual concavity in the choroid occurring without posterior staphyloma or scleral ectasia. Margolis et al in 2011[45] coined the term “Focal Choroidal Excavation”. Chung and co-workers found increased choroidal thickness and presence of pachyvessels in OCT and choroidal hyperpermeability in ICGA in eyes with FCE. They suggested FCE as a distinct entity in PSD. The refractive error of many reported eyes with FCE was myopic; however, reports of FCE in emmetropic patients are not infrequent.[46] Imaging Features: (Figure-7) On clinical examination, there may be no visible funduscopic abnormalities that appear to correlate with the FCE detected on structural OCT. Colour fundus photographs of both eyes show subtle alteration of the RPE between enlarged choroidal vessels or show scattered pigmentary disturbances including the fovea. Sometimes the non-conforming variant appears as patchy areas of macular atrophy with a granular appearance or an accumulation of yellowish vitelliform-like material. Both hyper autofluorescence and hypo autofluorescence has been found in the fundus on autofluorescence, and they seem to correspond to RPE alterations that may happen with FCE. Based on the results of SD-OCT, FCE is categorized into two patterns[45]: Conforming FCE- Those lacking a gap between the photoreceptors and RPE. Nonconforming FCE- The photoreceptor tips in the affected area were separated from the underlying RPE. Based on the OCT appearance, Shinojima et al[46] defined three morphologic forms: cone-shaped, bowl-shaped, or mixed type. Atrophic changes were least noted in cone form. DOS TIMES
DOS Times Volume 29, Number 6, November-December 2023 www.dosonline.org/dos-times 28 There have been several accounts of FCE occurring in conjunction with other macular findings, such as central serous chorioretinopathy (CSC), choroidal neovascularization (CNV), nonneovascular age-related macular degeneration, and vitelliform macular disease.[47,48,49] Ischemia and RPE changes could precipitate CNV in some eyes with FCE as suggested by ICGA findings including choroidal filling defects, choroidal venous dilation, and focal or punctate hyperfluoroscence. Depending on the degree of the RPE changes, isolated lesions of FCE on FFA exhibit various degrees of hyperfluoroscence and hypo fluorescence. In the mid- or late- phase FA, hyperfluoroscence owing to transmission faults linked to RPE attenuation without leakage may be observed. EDI shows increased choroidal thickness with dilated choroidal vessels immediately surrounding or outside the area of FCE; SS-OCTA frequently detects the presence of pachyvessels, which are spatially correlated within the region of choroidal thickening linked to FCE.[50] In cases of FCE with type 1 or 2 or mixed ones, SS-OCTA may be helpful in the early detection of neovascular membranes or networks, that might be missed on SD-OCT. Figure 7: Focal choroidal excavation (FCE): OCT shows Cone shaped and bowl-shaped excavation with the surrounding presence of pachyvessels and increased choroidal thickness. ICGA shows the presence of hypercyanescence with pachyvessels seen. OCTA shows the presence of a vascular network. Conclusion Advancements in imaging technology has helped us in a proper understanding of pathological process implicated in pachychoroid diseases. MMI helps in enhanced disease diagnosis and therapy monitoring. MMI can help in tailoring and individualizing the treatment protocol according to the need and metabolic status of the patient. References 1. Warrow, David J.; Hoang, Quan V.; Freund, K. Bailey (September 2013). “Pachychoroid Pigment Epitheliopathy”. Retina. 33 (8): 1659– 1672. 2. Nickla DL, Wallman J. The multifunctional choroid. Prog Retin Eye Res. 2010 Mar;29(2):144-68. 3. Shroff D, Sharma M, Chhablani J, Gupta P, Gupta C, Shroff C. PERIPHERAL EXUDATIVE HEMORRHAGIC CHORIORETINOPATHY-A NEW ADDITION TO THE SPECTRUM OF PACHYCHOROID DISEASE? Retina. 2021 Jul 1;41(7):1518-1525. doi: 10.1097/IAE.0000000000003063. PMID: 33315818. 4. Chen G ,Tzekov R ,Li W ,et al.Subfoveal choroidal thickness in central serous chorioretinopathy: a meta-analysis. PloS one. 2017;12(1): 0169152 .14. 5. Bhayana AA, Kumar V, Tayade A, Chandra M, Chandra P, Kumar A. Choroidal thickness in normal Indian eyes using swept-source optical coherence tomography. Indian J Ophthalmol, 2019; 67(2):252–5. 6. Dansingani KK, Balaratnasingam C, Naysan J, Freund KB. EN Face Imaging of Pachychoroid Spectrum Disorders with Swept-Source Optical Coherence Tomography. Retina (Philadelphia, Pa), 2016; 36(3):499–516. 7. Cheung CMG,Lee WK,Koizumi H etal.Pachychoroid diseases .Eye (Lond)2019;33(1):14-33. 8. Balaratnasingam C, Lee WK, Koizumi H, Dansingani K, Inoue M, Freund KB. Polypoidal choroidal vasculopathy: a distinct disease or manifestation of many? Retina. 2016; 36:1–8. 9. Warrow DJ, Hoang QV, Freund KB. Pachychoroid pigment epitheliopathy. Retina. 2013; 33:1659–72. 10. Pang CE, Freund KB. Pachychoroid pigment epitheliopathy may masquerade as acute retinal pigment epitheliitis. Invest Ophthalmol Vis Sci, 2014; 55(8):5252. 11. Ersoz MG, Karacorlu M, Arf S, Hocaoglu M & Sayman Muslubas I (2018b): Outer nuclear layer thinning in pachychoroid pigment epitheliopathy. Retina 38: 957–961. 12. Von Graefe A. Ueber centrale recidivierende retinitis. Graefes Arch Clin Exp Ophthalmol. 1866; 10:211-5. 13. Gass JD. Pathogenesis of disciform detachment of the neuroepithelium. Am J Ophthalmol, 1967; 63(3): Suppl:1-139. 14. Spaide RF, Klancnik JM., Jr. Fundus autofluorescence and central serous chorioretinopathy. Ophthalmology. 2005; 112:825–33. DOS TIMES
www.dosonline.org/dos-times DOS Times Volume 29, Number 6, November-December 2023 29 15. Imamura Y, Fujiwara T, Margolis R, Spaide RF. Enhanced depth imaging optical coherence tomography of the choroid in central serous chorioretinopathy. Retina. 2009; 29:1469–73. 16. Maruko I, Iida T, Sugano Y, Ojima A, Ogasawara M, Spaide RF. Subfoveal choroidal thickness after treatment of central serous chorioretinopathy. Ophthalmology. 2010; 117:1792–9. 17. Yang L, Jonas JB & Wei W (2013): Optical coherence tomographyassisted enhanced depth imaging of central serous chorioretinopathy. Invest Ophthalmol Vis Sci 54: 4659–4665. 18. Yannuzzi LA, Freund KB, Goldbaum M et al. (2000): Polypoidal choroidal vasculopathy masquerading as central serous chorioretinopathy. Ophthalmology 107: 767– 777. 19. Ferrara D, Mohler KJ, waheed N,et al.Enface enhanced depth swept source optical coherence tomography features of chronic central serous chorioretinopathy. 20. Pang CE, Freund KB. Pachychoroid neovasculopathy. Retina (Philadelphia, Pa), 2015; 35(1):1. 21. Miyake M, Ooto S, Yamashiro K et al. (2015): Pachychoroid neovasculopathy and age-related macular degeneration. Sci Rep 5:16204. 22. Chung SE, Kang SW, Lee JH & Kim YT (2011): Choroidal Thickness in Polypoidal Choroidal Vasculopathy and Exudative Age-related Macular Degeneration. Ophthalmology118: 840–845. 23. Lee G-I. Kim AY, Kamg SW,et al. Risk factors and outcomes of choroidal neovascularisation secondary to central serous chorioretinopathy. Scientific reports.2019;9(1):1-10. 24. Bousquet E, Bonnin S, Mrejen S, Krivosic V, Tadayoni R, Gaudric A. Optical coherence tomography angiography of flat irregular pigment epithelium detachment in chronic central serous chorioretinopathy. Retina. 2018; 38:629–38. 25. Carnevali A,Capuano V,Sacconi R et al. OCT angiography of treatment naïve quiescent choroidal neovascularisation in pachychoroid neovasculoapathy. Ophthalmol Retina.2017;1(4):328-32. 26. Koh AH, Chen LJ, Chen SJ, Chen Y, Giridhar A, Iida T, Kim H, Yuk Yau Lai T, Lee WK, Li X, et al. Polypoidal choroidal vasculopathy: evidence-based guidelines for clinical diagnosis and treatment. Retina (Philadelphia, Pa). 2013;33(4):686–716. 27. Uyama M, Matsubara T, Fukushima I, Matsunaga H, Iwashita K, Nagai Y, et al. Idiopathic polypoidal choroidal vasculopathy in Japanese patients. Arch Ophthalmol 1999;117:1035-42. 28. Bessho H, Honda S, Imai H, Negi A. Natural course and funduscopic findings of polypoidal choroidal vasculopathy in a Japanese population over 1 year of follow-up. Retina 2011;31:1598-602. 29. Tsujikawa A, Sasahara M, Otani A, Gotoh N, Kameda T, Iwama D, et al. Pigment epithelial detachment in polypoidal choroidal vasculopathy. Am J Ophthalmol 2007;143:102-11. 30. Palkar AH, Khetan V. Polypoidal choroidal vasculopathy: An update on current management and review of literature. Taiwan J Ophthalmol. 2019 Apr-Jun;9(2):72-92. doi: 10.4103/tjo.tjo_35_18. PMID: 31198666; PMCID: PMC6557071. 31. Anantharaman G, Sheth J, Bhende M, Narayanan R, Natarajan S, Rajendran A, Manayath G, Sen P, Biswas R, Banker A, Gupta C. Polypoidal choroidal vasculopathy: Pearls in diagnosis and management. Indian J Ophthalmol. 2018 Jul;66(7):896-908. doi: 10.4103/ijo.IJO_1136_17. PMID: 29941728; PMCID: PMC6032720. 32. Kawamura A, Yuzawa M, Mori R, Haruyama M, Tanaka K. Indocyanine green angiographic and optical coherence tomographic findings support classification of polypoidal choroidal vasculopathy into two types. Acta Ophthalmol. 2013 Sep;91(6):e474-81. doi: 10.1111/aos.12110. Epub 2013 Jul 15. PMID: 23848133. 33. Iijima H, Iida T, Imai M, Gohdo T, Tsukahara S. Optical coherence tomography of orange-red subretinal lesions in eyes with idiopathic polypoidal choroidal vasculopathy. Am J Ophthalmol. 2000 Jan;129(1):21-6. doi: 10.1016/s0002-9394(99)00253-6. PMID: 10653408. 34. Ting DS, Cheung GC, Lim LS, Yeo IY. Comparison of swept source optical coherence tomography and spectral domain optical coherence tomography in polypoidal choroidal vasculopathy. Clin Exp Ophthalmol. 2015 Dec;43(9):815-9. doi: 10.1111/ceo.12580. Epub 2015 Aug 6. PMID: 26183457. 35. Inoue M, Balaratnasingam C, Freund KB. Optical coherence tomography angiography of polypoidal choroidal vasculopathy and polypoidal choroidal neovascularization. Retina. 2015; 35: 2265– 2274. 36. Annesley WH Jr. Peripheral exudative hemorrhagic chorioretinopathy. Trans Am Ophthalmol Soc. 1980;78:321-64. PMID: 7257064; PMCID: PMC1312148. 37. Cebeci Z, Dere Y, Bayraktar Ş, Tuncer S, Kır N. Clinical Features and Course of Patients with Peripheral Exudative Hemorrhagic Chorioretinopathy. Turk J Ophthalmol. 2016 Oct;46(5):215-220. doi: 10.4274/tjo.71354. Epub 2016 Oct 17. PMID: 28058163; PMCID: PMC5200833. 38. Yannuzzi LA, Nogueira FB, Spaide RF, Guyer DR, Orlock DA, Colombero D, Freund KB. Idiopathic polypoidal choroidal vasculopathy: a peripheral lesion. Arch Ophthalmol. 1998 Mar;116(3):382-3. PMID: 9514497. 39. Shields CL, Salazar PF, Mashayekhi A, Shields JA. Peripheral exudative hemorrhagic chorioretinopathy simulating choroidal melanoma in 173 eyes. Ophthalmology. 2009 Mar;116(3):529-35. doi: 10.1016/j.ophtha.2008.10.015. Epub 2009 Jan 20. PMID: 19157563. 40. Mantel I, Uffer S, Zografos L. Peripheral exudative hemorrhagic chorioretinopathy: a clinical, angiographic, and histologic study. Am J Ophthalmol. 2009 Dec;148(6):932-8.e1. doi: 10.1016/j. ajo.2009.06.032. Epub 2009 Oct 2. PMID: 19800613. 41. Wide-field swept source optical coherence tomography angiography for peripheral polyps in peripheral exudative hemorrhagic chorioretinopathy - A case report. Indian J Ophthalmol Case Rep 2022;2:454-7. 42. Phasukkijwatana N, Freund KB, Dolz-Marco R, Al-Sheikh M, Keane PA, Egan CA, et al. Peripapillary Pachychoroid Syndrome. Retina (Philadelphia, Pa), 2018; 38(9):1652-67. 43. Kumar, Vinod MS; Azad, Shorya V. MS; Verma, Saurabh MD; Surve, Abhidnya MD; Vohra, Rajpal MD; Venkatesh, Pradeep MD. PERIPAPILLARY PACHYCHOROID SYNDROME: New Insights. Retina: January 2022 - Volume 42 - Issue 1 - p 8 doi:10.1097/ IAE.0000000000003275. 44. Jampol LM, Shankle J, Schroeder R, Tornambe P, Spaide RF, Hee MR. Diagnostic and therapeutic challenges. Retina. 2006 NovDec;26(9):1072-6. doi: 10.1097/01.iae.0000248819.86737.a5. PMID: 17151497. 45. Margolis R, Mukkamala SK, Jampol LM, Spaide RF, Ober MD, Sorenson JA, Gentile RC, Miller JA, Sherman J, Freund KB. The expanded spectrum of focal choroidal excavation. Arch Ophthalmol. DOS TIMES
DOS Times Volume 29, Number 6, November-December 2023 www.dosonline.org/dos-times 30 2011 Oct;129(10):1320-5. doi: 10.1001/archophthalmol.2011.148. Epub 2011 Jun 13. PMID: 21670327. 46. Obata R, Takahashi H, Ueta T, Yuda K, Kure K, Yanagi Y. Tomographic and angiographic characteristics of eyes with macular focal choroidal excavation. Retina. 2013 Jun;33(6):1201-10. doi: 10.1097/IAE.0b013e31827b6452. PMID: 23514801. 47. Lim FP, Wong CW, Loh BK, Chan CM, Yeo I, Lee SY, Mathur R, Wong D, Wong TY, Cheung CM. Prevalence and clinical correlates of focal choroidal excavation in eyes with age-related macular degeneration, polypoidal choroidal vasculopathy and central serous chorioretinopathy. Br J Ophthalmol. 2016 Jul;100(7):918-923. doi: 10.1136/bjophthalmol-2015-307055. Epub 2015 Oct 26. PMID: 26504178. 48. Tang WY, Zhang T, Shu QM, Jiang CH, Chang Q, Zhuang H, Xu GZ. Focal choroidal excavation complicated with choroidal neovascularization in young and middle aged patients. Int J Ophthalmol. 2019 Jun 18;12(6):980-984. doi: 10.18240/ ijo.2019.06.16. PMID: 31236356; PMCID: PMC6580224. 49. Xu H, Zeng F, Shi D, Sun X, Chen X, Bai Y. Focal choroidal excavation complicated by choroidal neovascularization. Ophthalmology. 2014 Jan;121(1):246-250. doi: 10.1016/j.ophtha.2013.08.014. Epub 2013 Oct 4. PMID: 24095605. Dr. Gagan Bhatia, DO, DNB Consultant VR, Shroff Eye Centre, A-9, Kailash Colony, New Delhi, India. Corresponding Author: 50. Lim FP, Loh BK, Cheung CM, Lim LS, Chan CM, Wong DW. Evaluation of focal choroidal excavation in the macula using swept-source optical coherence tomography. Eye (Lond). 2014 Sep;28(9):1088-94. doi: 10.1038/eye.2014.78. Epub 2014 Jun 20. PMID: 24946847; PMCID: PMC4166641. DOS TIMES
www.dosonline.org/dos-times DOS Times Volume 29, Number 6, November-December 2023 31 DOS TIMES Central Retinal Vein Occlusion in JAK2 Positive Polycythemia Vera Daraius Shroff, MS, Sandeep Kumar, MS, Indranil Saha, MS, Charu Gupta, MS, Gagan Bhatia, DO, DNB, Cyrus Shroff, MS Shroff Eye Centre, New Delhi India. Abstract: Purpose: To report a case of Central Retinal Vein Occlusion in a patient of Polycythemia vera with JAK2 Exon 12 mutation. Method: The author describes a case of PV with JAK2 Exon 12 mutation presenting as CRVO. Multimodal imaging followed by anti VEGF therapy was performed. Patient: Single patient case report. Results: A 28-year-old male presented with sudden painless loss of vision due to CRVO. A detailed blood work up revealed PV. Genetic testing confirmed associated JAK2 Exon 12 mutation. Patient was treated & followed up with Anti-VEGF for Cystoid macular edema and phlebotomy for PV. Conclusion: To our knowledge, this is the first reported case of CRVO in a patient of Polycythemia vera with JAK2 Exon 12 mutation. Our case report extends the genetic spectrum of CRVO and its association with systemic diseases. It highlights the role of a comprehensive blood work up to unveil the underlying systemic etiology. Keywords: Central Retinal Vein Occlusion, Polycythemia Vera, JAK2 Exon 12 MUTATION. Summary: The patient presented with CRVO in PV with accompanying JAK2 Exon 12 mutation. This association has not been described previously to our knowledge. The case also presses on importance of detailed work up especially in young CRVO in establishing underlying diagnosis which in our case was Polycythemia. Introduction Central retinal vein occlusion (CRVO) has been known disease entity since 1878[1], and is the second most common visually disabling disorder that may cause significant ocular morbidity. Its pathogenesis is multifactorial and involves both local and systemic factors. Diabetes, hypertension and hypercholesterolemia have frequent association with CRVO in older patients.[2,3] Younger individuals may have an underlying hypercoagulable or inflammatory etiology.[4,5] Less well-established factors like chronic myeloproliferative disorders, Waldenstrom macroglobulinemia, thrombophilia incite increased blood viscosity and hypercoagubility further leading to development of occlusion of Central Retinal Vein.[6] Myeloproliferative neoplasms, Polycythemia Vera (PV) are commonly associated with JAK2V617F mutation.[7] PV patients with no JAK2V617F mutation have been reported with a variety of mutation targeting JAK2 Exon 12.[7] Study of this gene mutation is used to identify presence of underlying Myleoproliferative disorders as the cause of thrombosis. Till now JAK2 Exon 12 mutation has been reported and associated in Central Retinal Artery Occlusion patients[8], but no association has been linked to CRVO in PV patients. We report CRVO as the presenting complain in a patient of PV with JAK2 Exon12 mutation. Case Report A 28-year-old male presented with blurring of vision in the left eye (OS) for 1 week. Right eye (OD) had no functional vision following vitreo-retinal surgery for retinal detachment status post trauma, 10 years ago. On presentation OD was Negative to Perception of Light (PL-ve) and visual acuity (VA) in OS was 6/18, N18. Intraocular pressure was 8 & 18mm of Hg for OD and OS respectively. Slit lamp examination and anterior segment were within normal limits. Fundus examination of OS revealed significant disc edema of around two-disc diameter with collateral, scattered superficial retinal hemorrhages in all four quadrant, markedly tortuous and engorged veins and cystoid macular edema (CME). Significant amount of exudation was noted along the course of inferior branch of retinal vein. Clinical findings were highly suggestive of CRVO (Figure-1). A diagnosis of inflammatory CRVO was framed. Fundus fluorescein angiography revealed marked delay in arteriovenous transit time (24 sec), vessel wall staining, along with capillary non perfusion areas (CNP) in peripheral retina. Blocked fluorescence due to hemorrhages were noted. There was increasing intensity and area of fluorescence at the disc due to disc edema with no evidence of neovascularization at the disc or elsewhere (Figure-2). SD-OCT scan of OS revealed cystoid macular edema with increased macular thickness of 410 µm (Figure-3).
DOS Times Volume 29, Number 6, November-December 2023 www.dosonline.org/dos-times 32 Systemic work up ruled out diabetes mellitus, hypertension or hypercholesterolemia. Blood workup revealed patients hemoglobin level was raised to 19.5g/dl (12-14 g/dl), packed cell volume was 64% (39-50) and a raised serum homocysteine levels to 22.43umol/L (<15 ). A Carotid Doppler left side was within normal limits. Patient was referred to a hematologist and a diagnosis of Polycythemia Vera with JAK2 Exon 12 mutation was made after Polymerase Chain Reaction (PCR) testing. Patient was started on oral steroids (1mg/kg body weight) and was taken up for OS intravitreal Anti Vascular Endothelial Growth Factor (Anti VEGF) injection. Subsequently he underwent venesection for two units of blood for PV and was started on oral hydroxy urea (15mg/kg body weight), Ecospirin 75mg & Febuxostat 40mg once daily. For raised homocysteine levels patient was started on combination of Vit C, Vit B12, Vit Figure 1: Colour montage showing scattered superficial retinal haemorrhages in all four quadrants, markedly tortuous, engorged veins, cystoid macular oedema (CME) and exudation noted along the course of the inferior branch of the retinal vein (white). Figure 2: Fundus fluorescein angiography showing vessel wall staining, along with capillary non-perfusion areas (CNP) in the peripheral retina. Blocked fluorescence due to haemorrhages was noted. Figure 3: SD-OCT scan of OS revealed cystoid macular oedema (white arrow) with an increased macular thickness of 410 µm. Discussion Central Retinal Vein Occlusion (CRVO) is one of the leading causes of vision loss, the pathophysiology of which, is still not completely understood. It has been speculated that a hypercoagulable state and erythrocyte aggregation have a significant role in vein occlusion.[9] Diabetes mellitus, Polycythemia Vera (PV), sickle cell anemia create environment favorable for erythrocyte aggregation leading to CRVO. For same reason a systemic examination in CRVO patients has revealed underlying systemic diseases in many documented cases. Our patient presented with CRVO as the only sign of Polycythemia Vera. The patient had no systemic symptoms relatable to PV when he presented to us. Sicle Cell Disease, Diabetes Mellitus & Polycythemia Vera have B6 & Vit B9 (Cap Homocheck). Four weeks post Anti-VEGF, fundus showed reduced hemorrhages and macular edema. Vision at one month follow up was 6/5 N5 (OS), with a reduction in the retinal hemorrhages and resolved macular edema. Oral steroids were tapered over a period of six weeks and no recurrence of macular edema was noted till 6 months of follow up. DOS TIMES
www.dosonline.org/dos-times DOS Times Volume 29, Number 6, November-December 2023 33 DOS TIMES increased RBC adhesion, accounting for vascular complications in these diseases. The abnormal RBC interactions are determined by different endothelium cell receptors and associated mutations for example in diabetes mellitus RBC Band 3 protein that determine cell aggregation and adhesion, similarly in PV role of kinase JAK2 is of prime importance.[10] Wautier MP recently reported 27% of CRVO patients exhibit spontaneous in vitro growth of erythroid precursors in the absence of any detectable myeloproliferative disorder.[11] Red blood cells (RBCs) from these patients with polycythaemia vera have an abnormal CD239 phosphorylation, which is responsible for abnormal interactions with endothelial cells and is determined by JAk2 mutations. JAK2 V617F mutation is seen in the majority of patients with myeloproliferative disorders, the most common being Polycythaemia vera.[3-7] Scott et al identified a novel mutation in exon 12 of JAK2 in 10 out of 11 V617 un-mutated PV, and demonstrated in vivo stimulation of erythroid proliferation, in these patients.[2] JAK2 exon 12 mutations patients define a distinctive myeloproliferative syndrome that affects patients with a hematologic disorder consistent with the diagnosis of polycythemia vera or idiopathic erythrocytosis, polycythaemia vera. Patients with a JAK2 exon 12 mutations are characterized by erythrocytosis, with a raised hematocrit and haemoglobin level, reduced serum Erythropoietin (EPO) levels, and EPOhypersensitive erythroid progenitors, but often lack the proliferation of cells of the granulocytic or megakaryocytic lineages generally observed in patients with classic JAK2V617F positive PV. Patients with JAK2V617 NEGATIVE do have cytogenic abnormalities, dysplastic megakaryocytes and risk of transformation to myelofibrosis. Though the phenotypical association is not much different from classic PV cases it has been reported earlier not to be associated with CRVO. Dhrami-Gavazi E et al[8] described a young male with CRAO who was found to have polycythemia vera with JAK2 V617F mutation, but to date and to the best of our knowledge CRVO has not been associated with JAK2 exon 12 mutation. Our case underlines the importance of a comprehensive systemic workup in Retinal Vein occlusion patients, especially young patients. With the help of exhaustive screening and detailed blood investigations, we were able to diagnose the underlying condition, PV in our case and start relevant treatment for the same on time. PV if left untreated could lead to stroke, pulmonary embolisms or even myocardial infarction. CRVO in our patient was early and the only presentation of a hypercoagulable state created by PV. In the absence of an obvious local trigger, a thorough workup is warranted, especially in younger patients, as the ocular pathology often may herald severe systemic events. The early diagnosis of a treatable disorder avoided morbidity or even mortality in our case and lead to an improvement in his ocular condition. Though the phenotype does not have any distinguishing features now, a detailed follow up and research in future can open doors to better understanding of hypercoagulable state complications in Polycythemia Vera. References 1. Michel J. Ueber die anatomischen Ursachen von Veranderun- gen des Augenhintergrundes bei einigen Allgemeinerkrankun- gen. Deutsch Arch Klin Med 1878;22:339–345). 2. Hayreh SS, Zimmerman MB, Podhajsky P. Incidence of various types of retinal vein occlusion and their recurrence and demographic characteristics. Am J Ophthalmol 1994;117:429–41. 3. Mitchell P, Smith W, Chang A. Prevalence and associations of retinal vein occlusion in Australia. The Blue Mountains Eye Study. Arch Ophthalmol 1996;114:1243–7. 4. Gutman FA. Evaluation of a patient with central retinal vein occlusion. Ophthalmology 1983;90:481–3. 5. Fong AC, Schatz H. Central retinal vein occlusion in young adults. Surv Ophthalmol 1993 ;37:393–417. 6. Alexander P, Flanagan D, Rege K, Foss A, Hingorani M. Bilateral simultaneous central retinal vein occlusion secondary to hyperviscosity in Waldenstrom’s macroglobulinaemia. Eye (Lond). 2008 Aug;22(8):1089-92. doi: 10.1038/eye.2008.193. Epub 2008 Jul 4. PMID: 18600248. 7. McLornan D, Percy M, McMullin MF. JAK2 V617F: a single mutation in the myeloproliferative group of disorders. Ulster Med J. 2006 May;75(2):112-9. PMID: 16755940; PMCID: PMC1891745. 8. Dhami-Gavazi E, Lee W, Horowitz JD, Odel J, Mukkamala SK, Blumberg DM, Weiss M, Winn BJ. Jak2 mutation-positive polycythemia vera presenting as central retinal artery occlusion. Retin Cases Brief Rep. 2015 Spring;9(2):127-30. DOI: 10.1097/ ICB.0000000000000114. PMID: 25401994. 9. Rogers S, McIntosh RL, Cheung N, Lim L, Wang JJ, Mitchell P, Kowalski JW, Nguyen H, Wong TY., International Eye Disease Consortium. The prevalence of retinal vein occlusion: pooled data from population studies from the United States, Europe, Asia, and Australia. Ophthalmology. 2010 Feb;117(2):313-9.e1. 10. Wautier JL, Wautier MP (2018) Molecular Links between Erythrocyte Adhesion and Vascular Dysfunction in Diabetes Mellitus, Polycythemia Vera, Retinal Vascular Occlusion. J Hematol Thrombo Dis 6: 289. doi:10.4172/2329-8790.1000289. 11. Wautier MP, He´ron E, Picot J, Colin Y, Hermine O, Wautier JL. Red blood cell phosphatidylserine exposure is responsible for increased erythrocyte adhesion to endothelium in central retinal vein occlusion. J Thromb Haemost 2011; 9: 1049–55. Dr. Sandeep Kumar, MS Shroff Eye Centre, A-9, Kailash Colony, New Delhi, India. Corresponding Author:
DOS Times Volume 29, Number 6, November-December 2023 www.dosonline.org/dos-times 34 Artificial Intelligence in Screening of Retinal Diseases: Current Applications and Future Perspectives Sachit Mahajan, MBBS, MS, Alka Yadav, MBBS, MS, Manisha Singh, MBBS, MS, Rushil Kumar Saxena, MBBS, DNB, FICO, FLVPEI Dr Shroff’s Charity Eye Hospital, New Delhi. Abstract: To Artificial Intelligence (AI) has evolved rapidly and has benefited in research and medical field, since its introduction. With the introduction of technology in Ophthalmology for screening and diagnosis of various retinal diseases, AI is becoming established as new method for analysing ophthalmological data and providing insights into the pathogenic mechanisms of various retinal diseases. AI based algorithms are being used for diabetic retinopathy, age related macular degeneration, myopia, retinopathy of prematurity. In future, AI based algorithms can be expanded to various inherited retinal disorders, central serous choroioretinopathy, venous occlusion. There is optimism for integration of AI based algorithm in diagnosis, management and predicting response to treatment for various retinal disorders, which will help us in managing retinal diseases more effectively. Background of Artificial Intelligence Artificial Intelligence (AI) is a phenomenon in which software can mimic cognitive functions such as learning and problem solving by processing and recognizing patterns in large amounts of data.[1] Various diagnostic modalities are commonly employed in diagnosis of retinal diseases such as Fundus photograph, Optical Coherence Tomography (OCT) and Optical Coherence Tomography Angiography (OCTA), and with large amount of data generated, ophthalmology is one of the leading branches of medical filed in Artificial Intelligence (AI). The most common AI algorithms used in Ophthalmology include: Machine learning (ML), Deep learning (DL), Deep Neural Networks (DNN) and Convolutional Neural Networks (CNN). In ML, program is exposed to data and it tries to build algorithms and allocate it into different classes. For example, when presented with a fundus photograph of diabetic retinopathy, program will predict whether DR is present or not. ML can be supervised or unsupervised. [2] Deep learning (DL) is a sub-type of ML defined Figure 1: Different algorithms of AI. by the presence of multiple layers of artificial neural networks (ANN). It is able to extract and elaborate more complex patterns in data and is able to perform much more advanced analyses of data.[3-5] Deep Neural Networks (DNN) is a multilayered DL algorithm which is used for image classification.[6] Convolutional DOS TIMES
www.dosonline.org/dos-times DOS Times Volume 29, Number 6, November-December 2023 35 DOS TIMES Artificial Intelligence in Diabetic Retinopathy Diabetic retinopathy (DR) is one of the leading causes of visual impairment in developed and developing countries like India. Various complications are associated with diabetic retinopathy, therefore it is important to screen patients with diabetes at earliest stages of diabetic retinopathy and manage these patients more effectively. Various AI models have been developed with the aim of large scale DR screening. AI models for DR screening, use fundus photograph as an input, recognize various signs of DR such as hemorrhages, hard exudates, cottonwool spots; presence or absence of DR and grade DR. Several AI models have been developed. The IDx-DR system (Digital Diagnostics, Coralville, IA, USA) is first FDA approved AI algorithm for the detection of DR.[8] It can easily detect haemorrhages, exudate, cotton wool spot, neovascularization, and irregular lesion and grade DR. The IDx-DR system was tested in the Messidor-2 dataset (ADCIS, Saint-Contest, France) to facilitate the testing of computer-assisted diagnosis of DR. It had a sensitivity of 97% and a specificity of 59%.[9,10] The RetmarkerDR software (Critical Health SA, Coimbra, Portugal) is a Conformité Européene-marked class IIa medical device. This software is able to detect the rate of new microaneurysm formation and old microaneurysm disappearance known as “microaneurysm turn over”.[11,12] A study by Tufail et al showed that sensitivity for RetmarkerDR was 73% for any retinopathy, 85% for referable retinopathy and 97.9% for proliferative retinopathy.[13] EyeArt (Eyenuk Inc., Woodland Hills, CA, USA), is a similar AI model, which has a Figure 2: CNN representation. Neural Networks (CNN) is a type of DNN which is useful in image and video analysis. These algorithms divide the files into pixels, convert them into numbers or symbols, analyze them by multiple convolutional layers that filter, merge, mask, and/or multiply features, and feed the results to a dense neural network that will create an output layer.[7] sensitivity of 95% for any DR, 94% for referable DR and 99.6% for proliferative DR.[13] It is available as a smartphone-based DR screening, with a sensitivity of 96% for any DR, 99% for referable DR and 99% for sightthreatening DR.[14] Other AI based systems for DR screening include Google Inc. sponsored system (Mountain View, CA, USA), Bosch DR Algorithm (Robert Bosch, GmbH, Gerlingen, Germany), a system developed by the Singapore National Eye Centre, Singapore Eye Research Institute and National University of Singapore School of Computing, RetinaLyze (Retinalyze A/S, Hørsholm, Denmark)[23–25] and EyeWisdom® (Visionary Intelligence Ltd [Vistel], Beijing, China).[15-21] Artificial Intelligence in Age Related Macular Degeneartion Like DR, Age Related Macular Degeneartion (AMD) is also one of the leading causes of vision impairment in the elderly population in both developing and developed countries. Diagnosis of AMD relies on OCT, thereby several AI based- segmentation algorithms have been developed. These systems help in localizing and quantifying the fluid during treatment and follow-up of the patient. AI can also help in predicting the visual outcome in AMD by using the changes in intra-retinal and sub-retinal fluids after single injections as predictive factors.[22] AI can help in AMD by predicting the risk of AMD progression, highlighting the prognostic importance of intra-retinal cystoid fluid in neovascular AMD, developing automatic approaches for calculating fluid volumes to improve therapeutic management of neovascular AMD and by assessing the efficacy profiles of two different anti-vascular endothelial growth factor drugs.[23-26] AI
DOS Times Volume 29, Number 6, November-December 2023 www.dosonline.org/dos-times 36 based systems have also been employed for detecting the presence of geographical atrophy and for detecting the expansion of these lesions over time.[27] Notal Vision Home OCT (Notal Vision, Manassas, VA, USA), is a self monitoring system used for detecting and quantifying fluid. This system is fast and feasible and shows a good agreement with expert based garding of disease activity.[28] Artificial Intelligence in Retinopathy of Prematurity (ROP) ROP is a preventable cause of childhood blindness. Timely detection of ROP requires highly skilled personnel and equipment. AI based systems can help in detection of ROP by evaluating posterior pole images. Deep-ROP score and i-ROP DL system have been developed for evaluating ROP at posterior pole.[29,30] AI based systems have a important role in detection of Plus disease which is an aggressive form of ROP, requiring timely management.[31] Artificial Intelligence in Myopia Myopia is associated with several vision threatening complications like myopic maculopathy and retinal detachment. Therefore, AI based systems have been developed for detecting signs of pathological myopia.[32,33] AI based systems have also been used for detecting myopia progression and for detection of development of high or even pathological myopia.[34,35] New Frontiers for AI in Retinal Diseases AI based systems can be expanded to other retinal diseases like retinal vein occlusion, central serous chorioretinopathy, and vitreoretinal disorders.[36-43] AI based systems have also been used in various inherited retinal disorders like retinitis pigmentosa, Stargardt’s disease and choroidemia.[44-47] The goal of AI based systems in inherited retinal diseases is to study the genotype-phenotype of such patients. Limitations AI have a limited role in identifying co-existing significant ocular diseases such as glaucoma co-existing with DR. However, in future it may be possible to integrate screening for multiple retinal diseases. Also, quality of input data (images) may affect the output, called as ‘garbage in, garbage out phenomenon.’ There might be concerns regarding the patient privacy when collecting patient data, because there are no existing protocols worldwide. Nevertheless, teleophthalmology and AI has emerged as useful alternative in COVID-19 pandemic, in detection, prediction, and treatment of ocular pathologies. AI based telescreening for DR via teleophthalmology is a stand out model for other pathologies. AI can provide good results with holistic use of current technologies in detecting ocular pathologies. With emergence of 5G and 6G technology, it may be possible to use Extended Reality (XR) and high fidelity mobile holograms, which will have affect in remote health care. This will have positive impact for individuals who are innovative and willing to adopt new tools. References 1. Kapoor R, Walters SP, Al-Aswad LA. The current state of artificial intelligence in ophthalmology. Survey of Ophthalmology. 2019;64(2):233-240. 2. Daich Varela, M., Sen, S., De Guimaraes, T.A.C. et al. Artificial intelligence in retinal disease: clinical application, challenges, and future directions. Graefes Arch Clin Exp Ophthalmol 261, 3283–3297 (2023). https://doi.org/10.1007/s00417-023-06052-x. 3. Chauhan NK, Singh K. A review on conventional machine learning vs deep learning. 2018 International Conference on Computing, Power and Communication Technologies (GUCON); 2018, Greater Noida, Uttar Pradesh, India DOI: 10.1109/ GUCON.2018.8675097. 4. Choi RY, Coyner AS, Kalpathy-Cramer J, et al. Introduction to machine learning, neural networks, and deep learning. Transl Vis Sci Technol. 2020;9:14. DOI: 10.1167/tvst.9.2.14. 5. Kumar K, Kumar P, Deb D, et al. Artificial intelligence and machine learning based intervention in medical infrastructure: A review and future trends. Healthcare (Basel). 2023;11:207. DOI: 10.3390/ healthcare11020207. 6. Rashidi HH, Tran NK, Betts EV et al (2019) Artifcial intelligence and machine learning in pathology: the present landscape of supervised methods. Acad Pathol 6:2374289519873088. https://doi. org/10.1177/2374289519873088. 7. Sheng B, Chen X, Li T, Ma T, Yang Y,Bi L and Zhang X (2022) An overview ofartificial intelligence in diabetic retinopathy and other ocular diseases. Front. Public Health 10:971943.doi: 10.3389/ fpubh.2022.971943. 8. US Food and Drug Administration. FDA permits marketing of artificial intelligence-based device to detect certain diabetes-related eye problems. Available from:https://www.fda.gov/NewsEvents/ Newsroom/PressAnnouncements/ucm604357.htm. PublishedApril 11, 2018. 9. Abràmoff MD, Folk JC, Han DP, et al. Automated analysis of retinal images for detection of referable diabetic retinopathy. JAMA Ophthalmol. 2013;131:351–7. DOI: 10.1001/ jamaophthalmol.2013.1743. 10. ACDIS. Messidor. Available at: https://www.adcis.net/en/thirdparty/ messidor/ (Date last accessed: 9 June 2023). 11. Ribeiro L, Oliveira CM, Neves C, et al. Screening for diabetic retinopathy in the central region of Portugal. Added value of automated ‘disease/no disease’ grading. Ophthalmologica. 2015;233:96–103. DOI: 10.1159/000368426. 12. Ribeiro ML, Nunes SG, Cunha-Vaz JG. Microaneurysm turnover at the macula predicts risk of development of clinically significant macular edema in persons with mild nonproliferative diabetic retinopathy. Diabetes Care. 2013;36:1254–9. DOI: 10.2337/dc12- 149. 13. Tufail A, Kapetanakis VV, Salas-Vega S, et al. An observational study to assess if automated diabetic retinopathy image assessment software can replace one or more steps of manual imaging grading and to determine their costeffectiveness. Health Technol Assess. 2016;20:1– 72. DOI: 10.3310/hta20920. 14. Rajalakshmi R, Subashini R, Anjana RM, Mohan V. Automated diabetic retinopathy detection in smartphone-based fundus photography using artificial intelligence. Eye. 2018;32:1138–44. DOI: 10.1038/s41433-018-0064-9. 15. Gulshan V, Peng L, Coram M, et al. Development and validation of a DOS TIMES
www.dosonline.org/dos-times DOS Times Volume 29, Number 6, November-December 2023 37 DOS TIMES deep learning algorithm for detection of diabetic retinopathy in retinal fundus photographs. JAMA. 2016;316:2402–10. DOI: 10.1001/ jama.2016.17216. 16. Bawankar P, Shanbhag N, Smitha SK, et al. Sensitivity and specificity of automated analysis of single-field nonmydriatic fundus photographs by Bosch DR Algorithm— Comparison with mydriatic fundus photography (ETDRS) for screening in undiagnosed diabetic retinopathy. PLoS One. 2017;12:e0189854. DOI: 10.1371/journal. pone.0189854. 17. Ting DSW, Cheung CY-L, Lim G, et al. Development and validation of a deep learning system for diabetic retinopathy and related eye diseases using retinal images from multiethnic populations with diabetes. JAMA. 2017;318:2211–23. DOI: 10.1001/jama.2017.18152. 18. Larsen N, Godt J, Grunkin M, et al. Automated detection of diabetic retinopathy in a fundus photographic screening population. Invest Ophthalmol Vis Sci. 2003;44:767–71. DOI: 10.1167/iovs.02-0417. 19. Hansen AB, Hartvig NV, Jensen MS, et al. Diabetic retinopathy screening using digital non‐mydriatic fundus photography and automated image analysis. Acta Ophthalmol Scand. 2004;82:666–72. DOI: 10.1111/j.1600-0420.2004.00350.x. 20. Larsen M, Godt J, Larsen N, et al. Automated detection of fundus photographic red lesions in diabetic retinopathy. Invest Ophthalmol Vis Sci. 2003;44:761–6. DOI: 10.1167/iovs.02-0418. 21. Pei X, Yao X, Yang Y, et al. Efficacy of artificial intelligence-based screening for diabetic retinopathy in type 2 diabetes mellitus patients. Diabetes Res Clin Pract. 2022;184:109190. DOI: 10.1016/j. diabres.2022.109190. 22. Bogunović H, Mares V, Reiter GS, Schmidt-Erfurth U. Predicting treat-and-extend outcomes and treatment intervals in neovascular age-related macular degeneration from retinal optical coherence tomography using artificial intelligence. Front Med (Lausanne). 2022;9:958469. DOI: 10.3389/ fmed.2022.958469. 23. . Schmidt-Erfurth U, Waldstein SM, Klimscha S, et al. Prediction of individual disease conversion in early AMD using artificial intelligence. Invest Ophthalmol Vis Sci. 2018;59:3199–208. DOI: 10.1167/iovs.18-24106. 24. Schmidt-Erfurth U, Bogunovic H, Sadeghipour A, et al. Machine learning to analyze the prognostic value of current imaging biomarkers in neovascular age-related macular degeneration. Ophthalmol Retina. 2018;2:24–30. DOI: 10.1016/j. oret.2017.03.015. 25. Schmidt-Erfurth U, Vogl WD, Jampol LM, Bogunović H. Application of automated quantification of fluid volumes to anti-VEGF therapy of neovascular age-related macular degeneration. Ophthalmology. 2020;127:1211–9. DOI: 10.1016/j. ophtha.2020.03.010. 26. Schmidt-Erfurth U, Mulyukov Z, Gerendas BS, et al. Therapeutic response in the HAWK and HARRIER trials using deep learning in retinal fluid volume and compartment analysis. Eye (Lond). 2023;37:1160–9. DOI: 10.1038/s41433- 022-02077-4. 27. Vogl W-D, Riedl S, Mai J, et al. Predicting topographic disease progression and treatment response of pegcetacoplan in geographic atrophy quantified by deep learning. Ophthalmology Retina. 2023;7:4–13. DOI: 10.1016/j. oret.2022.08.003. 28. Liu Y, Holekamp NM, Heier JS. Longitudinal study: Daily selfimaging with home OCT for neovascular age-related macular degeneration. Ophthalmol Retina. 2022;6:575–85. DOI: 10.1016/j. oret.2022.02.011. 29. Li J, Huang K, Ju R et al (2022) Evaluation of artifcial intelligencebased quantitative analysis to identify clinically signifcant severe retinopathy of prematurity. Retina 42:195–203. https://doi. org/10.1097/IAE.0000000000003284. 30. Redd TK, Campbell JP, Brown JM et al (2018) Evaluation of a deep learning image assessment system for detecting severe retinopathy of prematurity. Br J Ophthalmol. https://doi.org/10. 1136/ bjophthalmol-2018-313156. 31. Brown JM, Campbell JP, Beers A et al (2018) Automated diagnosis of plus disease in retinopathy of prematurity using deep convolutional neural networks. JAMA Ophthalmol 136:803–810. https://doi. org/10.1001/jamaophthalmol.2018.1934. 32. Tan NM, Liu J, Wong DK, et al. Automatic detection of pathological myopia using variational level set. Annu Int Conf IEEE Eng Med Biol Soc. 2009;2009:3609–12. DOI: 10.1109/ IEMBS.2009.5333517. 33. Zhang Z, Xu Y, Liu J, et al. Automatic diagnosis of pathological myopia from heterogeneous biomedical data. PLoS ONE. 2013;8:e65736. DOI: 10.1371/journal.pone.0065736. 34. Foo LL, Ang M, Wong CW, et al. Is artificial intelligence a solution to the myopia pandemic? Br J Ophthalmol. 2021;105:741–4. DOI: 10.1136/bjophthalmol-2021-319129. 35. Lin H, Long E, Ding X, et al. Prediction of myopia development among Chinese school-aged children using refraction data from electronic medical records: A retrospective, multicentre machine learning study. PLoS Med. 2018;15:e1002674. DOI: 10.1371/journal.pmed.1002674. 36. Chen Q, Yu W-H, Lin S, et al. Artificial intelligence can assist with diagnosing retinal vein occlusion. Int J Ophthalmol. 2021;14:1895– 902. DOI: 10.18240/ijo.2021.12.13. 37. Ren X, Feng W, Ran R, et al. Artificial intelligence to distinguish retinal vein occlusion patients using color fundus photographs. Eye (Lond). 2022. DOI: 10.1038/s41433-022-02239-4. 38. Arrigo A, Calamuneri A, Aragona E, et al. Structural OCT parameters associated with treatment response and macular neovascularization onset in central serous chorioretinopathy. Ophthalmol Ther. 2021;10:289–98. DOI: 10.1007/s40123-021- 00336-3. 39. Pfau M, van Dijk EHC, van Rijssen TJ, et al. Estimation of current and post-treatment retinal function in chronic central serous chorioretinopathy using artificial intelligence. Sci Rep. 2021;11:20446. DOI: 10.1038/s41598-021-99977-4. 40. Xu F, Wan C, Zhao L, et al. Predicting post-therapeutic visual acuity and OCT images in patients with central serous chorioretinopathy by artificial intelligence. Front Bioeng Biotechnol. 2021;9:649221. DOI: 10.3389/fbioe.2021.649221. 41. Ko J, Han J, Yoon J, et al. Assessing central serous chorioretinopathy with deep learning and multiple optical coherence tomography images. Sci Rep. 2022;12:1831. DOI: 10.1038/s41598-022-05051-y. 42. Arrigo A, Calamuneri A, Bordato A, et al. Vitreomacular traction quantitative cutoffs for the assessment of resolution after ocriplasmin intravitreal treatment. Sci Rep. 2020;10:17583. DOI: 10.1038/s41598- 020-74472-4. 43. Shao E, Liu C, Wang L, et al. Artificial intelligence-based detection of epimacular membrane from color fundus photographs. Sci Rep. 2021;11:19291. DOI: 10.1038/s41598-021- 98510- 44. Camino A, Wang Z, Wang J, et al. Deep learning for the segmentation of preserved photoreceptors on en Face optical coherence tomography in two inherited retinal diseases. Biomed Opt Express. 2018;9:3092– 105. DOI: 10.1364/ BOE.9.003092. 45. Fujinami-Yokokawa Y, Pontikos N, Yang L, et al. Prediction of
DOS Times Volume 29, Number 6, November-December 2023 www.dosonline.org/dos-times 38 causative genes in inherited retinal disorders from spectral-domain optical coherence tomography utilizing deep learning techniques. J Ophthalmol. 2019;2019:1691064. DOI: 10.1155/2019/1691064. 46. Chen T-C, Lim WS, Wang VY, et al. Artificial intelligence-assisted early detection of retinitis pigmentosa the most common inherited retinal degeneration. J Digit Imaging. 2021;34:948–58. DOI: 10.1007/ s10278-021-00479-6. 47. Wang Z, Camino A, Hagag AM, et al. Automated detection of preserved photoreceptor on optical coherence tomography in choroideremia based on machine learning. J Biophotonics. 2018;11:e201700313. DOI: 10.1002/jbio.201700313. Dr. Sachit Mahajan, MBBS, MS Department of VitreoRetina and Uvea Dr Shroff’s Charity Eye Hospital, New Delhi. Corresponding Author: DOS TIMES
www.dosonline.org/dos-times DOS Times Volume 29, Number 6, November-December 2023 39 DOS TIMES Overveiw of Fundal Coloboma and its Consequences Sanjeev Kumar Nainiwal, MD, DNB, MNAMS, Kavita Bajiya, MBBS, Prithvi Raj, MS, Neha Kharwas, MBBS Vitreo Retinal Services, Department of Ophthalmology, Sawai Man Singh Medical College & Hospital, Jaipur Rajasthan, India. Typical ocular colobomas are due to defective closure of the embryonic cleft. The coloboma can be sporadic, hereditary or associated with chromosomal abnormalities. Ocular colobomata when associated with chromosomal abnormalities commonly present with systemic anomalies. It can present with a wide spectrum of ocular manifestations ranging from minimalistic involvement that hardly affects the structure and function of the eye to an eye that is hardly recognizable and nonfunctional- having been compressed by an orbital cyst. The size of the coloboma (anteroposterior and transverse extent) and the involvement of the optic disc and fovea also shows variability. Presence of retinal detachment, choroidal neovascular membrane, cataract, amblyopia due to uncorrected refractive errors or involvement of optic disc and fovea adversely affects the visual acuity. While the complications mentioned above can be corrected to a great extent, the chromosomal abnormalities cannot be altered. Coloboma-related retinal detachments that have been surgically treated have shown good results. The intraoperative complications in cataract surgeries in these eyes could be higher due to the presence of microphthalmos and relatively hard lenses. Prophylactic laser retinopexydone at the border of choroidal coloboma reduces the risk of coloboma-related retinal detachment. Since in most of these eyes the optic disc lies within the choroidal coloboma, hence safe administration of complete treatment becomes difficult. Introduction The Greek word for coloboma implies mutilated or with defect.[1] Coloboma of fundus is caused by defective closure of embryonic fissure. It is characterized by the absence of part of the retinal pigment epithelium and choroid, with the presence of abnormally thin neural retina. The etiology of the condition involves genetic, infectious, teratogenic and environmental factors.[2] Typical coloboma is the term used to describe the defects seen in the inferonasal part of the fundus that can be clearly attributed to a defect in closure of the embryonic fissure which normally develops gradually between sixth and seventh weeks of fetal life. It can affect one eye (unilateral) or both eyes (bilateral). Similar defects that are observed other than the inferonasal quadrant has been termed as atypical coloboma. Complete coloboma describes defects involving the optic disc, choroid/retina, ciliary body, zonules, lens (notching) and iris. In extreme cases, cysts can develop from the margin of the coloboma and extend into the orbit, making the eye functionless, while subtle involvement such as mild hypoplasia of iris, a notch in the pupillary border, etc. have no effect on the function of the eye. Fundus coloboma poses threat to vision by way of involvement of the macula and optic disc in the coloboma as well as the increased risk of retinal detachment (RD) during the lifetime of the individual. Since it is an embryological pathology chorio-retinal coloboma may also be associated with other ocular pathologies such as cataract, microphthalmia, anophthalmia.[3−6] Thus, the adequate diagnosis of a coloboma is imperative so as to provide adequate prophylactic treatment to prevent the development of the complications or to treat the complications timely so as to provide the patient with the best possible visual outcome and to prevent visual morbidity. This is what has been elaborated in the article below to the fullest extent possible. Embryology The primitive eye formation commences at the 3rd week of gestation. Anterior most part of neural plate gives rise to brain and eyes. The optic vesicles arise from an out pouching of the forebrain. Future neural retina develops from distal part of optic vesicle while the future retinal pigment epithelium (RPE) from the proximal part. The optic vesicle invaginates to form a double-layered optic cup, where the inner layer of the optic cup is formed by the distal part of the vesicle and develops into neural retina, while the outer layer derived from the proximal part of the optic vesicle forms the RPE. A ventral invagination along the optic cup and optic stalk known as the choroidal fissure normally closes by 5–7 weeks of gestation. PAX6, SIX3, LHX2, and RAX are some of the eye field transcription factors needed at each stage of optic development.[7] Transcription factors intrinsic to cells interact with and modulate extrinsic signals. The retinal stem cells present in optic vesicle can transform to neurosensory retinal cells, RPE, or optic stalk depending on the appropriate combination of signals. Genetics and Coloboma Coloboma cases that are inherited and associated with chromosomal defects can be associated with systemic anomalies in addition to the ocular coloboma. Choroidal coloboma or retinal coloboma are termed as chorio-retinal coloboma. The coloboma can be an isolated iris coloboma, isolated optic disc coloboma or chorio-retinal coloboma. The associations were also grouped based on inheritance pattern. The most common syndrome associated with coloboma is CHARGE syndrome (coloboma of eye, heart defect, choanal atresia in nose, growth
DOS Times Volume 29, Number 6, November-December 2023 www.dosonline.org/dos-times 40 retardation, genital and/or urinary abnormalities, and ear abnormalities with deafness). Genes like SHH gene, PAX2, PAX6, VAX genes, etc., are involved in optic fissure formation and closure. Figure 1: Optic cup and stalk seen from below to show the choroidal fissure. Table 1: Systemic associations with Coloboma. Sporadic Coloboma Factors causing sporadic occurrence of colobomaa) Intra-uterine insult due to environmental factors. b) Sporadic coloboma could be genetic in origin, but with a low expressivity or penetrance. c) An environmental factor may act as a precipitating factor if there is a genetic predisposition for sporadic coloboma. Environmental factors that are proposed to play role on the development of sporadic coloboma include- Vitamin A deficiency, maternal diabetes and hypothyroidism, maternal consumption of drugs such as thalidomide, carbamazepine, hydantoin, maternal alcoholism, etc. Familial Coloboma Other presentation of fundul coloboma may be autosomal dominant, autosomal recessive, X-linked dominant and X-linked recessive. Systemic Disorders and Coloboma CHARGE syndrome can be found in 15-30% of colobomas. The presence of systemic abnormalities was found more with bilateral cases of AMC (Anophthalmia, microphthalmos, coloboma), as shown by Shah et al. in a study in United Kingdom.[8] S.No. System with Abnormality Described Association 1. Peri Ocular Ptosis, hypertelorism, blepharophimosis, eversion of lateral third of lower eyelid, eyelid coloboma, epicanthal folds, epibulbar dermoids, arched eyebrows, prominent eyelashes 2. Facial Midface hypoplasia, frontal bone hypoplasia,, micrognathia, dental abnormalities, triangular facies, mandible and zygoma hypoplasia, webbed neck, low hairline, macrostomia, cleft lip and palate 3. Cephalic Macrocephaly, microcephaly, encephalocele, macro dolichocephaly, hydrocephaly, facial dysostosis (e.g. Treacher Collins syndrome), craniostenosis, trigonocephaly, cebocephaly 4. Central Nervous System Holoprosencephaly, agenesis of corpus callosum, lipoma of corpus callosum, cerebellar hypoplasia, cerebellar vermis abnormality (Dandy Walker malformations of brain), lissencephaly, pachygyria, asymmetry of hemispheres, seizures, ataxia 5. Ear, Nose and Throat Low set ears, microtia, anotia, deformed nostrils, choanal atresia, sensory neural deafness 6. Spinal Kyphoscoliosis, Chiari type 1 malformation 7. Limbs Dislocated hips, joint contractures, polydactyly—preaxial or post axial, telephalangy, arachnodactyly, syndactyly, campodactyly, hyperphalangy, bow legs 8. Cardio Vascular System Congenital heart defects, coarctation of aorta 9. Respiratory System Tracheal stenosis 10. Renal Cystic kidney, hydronephrosis, renal ectopia 11. Genito Urinary Vesiculo-ureteral reflux, hypogonadism 12. Gastro Intestinal Hirschprung disease, megacolon, imperforate anus 13. Cutaneous Eczema, migratory ichthyosiform dermatosis, linear dermal atrophy, skin pigmentation 14. General Growth retardation, mental retardation, obesity, large size of baby DOS TIMES
www.dosonline.org/dos-times DOS Times Volume 29, Number 6, November-December 2023 41 DOS TIMES Presenting Symptoms 1. Anomaly noticed by parents/pediatrician: The majority of cases are identified because of an anomalous looking eye. This visible anomaly could be due to obviously small eyeball, gross nystagmus, strabismus or an obvious iris coloboma. 2. Chronically poor vision: Coloboma even without superadded RD can cause chronically poor vision due to uncorrected refractive error, amblyopia, involvement of fovea, etc. These defects surface at time of initiation of schooling if they have not been already detected. 3. Acute reduction in vision with or without prior chronic poor vision: Acute onset RD is the commonest cause of acute loss of vision in an eye with coloboma. Other causes of acute reduction in vision can be sub foveal choroidal neovascular membrane. In children, often the visual disability is picked up when both eyes are affected with one eye having long-standing RD and the other having relatively recent RD. It is also difficult for the parents to note reduction in vision on top of an already existing poor vision. 4. Asymptomatic: Patients with small colobomata that do not involve disc and fovea can remain asymptomatic unless complicated by RD. 5. Leukocoria: Large coloboma can produce a yellow/white pupillary reflex. A complicated cataract can also draw the attention of the parent to an issue in a child’s eye. Clinical Features The involvement can be unilateral (33–47.5% of cases) or bilateral and when bilateral can be symmetric or asymmetric.[9] Nystagmus If central fixation is affected in both eyes due to macular involvement, nystagmus can be the presenting symptom. Often these eyes are also significantly microphthalmic. Anterior vs Posterior Segment Involvement The study by Nakamura has shown isolated anterior segment involvement (iris and ciliary body) in 36%; isolated posterior segment involvement (chorio retinal and optic nerve) in 39% and involvement of both in 24% of cases.[10] Microphthalmos and Microcornea It is important to understand that corneal diameter cannot always serve as surrogate marker of size of the eye. While eyes with microphthalmos have correspondingly small corneas, microcornea can exist with normal sized eyeballs.[11-12] Accurate assessment of eye-ball size is possible with ultrasonography, CT scan or MRI. By definition, an eye is labelled microphthalmic, when the axial diameter (adjusted for age) is <95th percentile.[13] In adults (and children >13 years age), axial diameter <18.5mm is considered microphthalmic. Note: Considering the often coexisting ectasia of the colobomatous area, the measurement on ultrasonography can be falsely normal/more than normal, if measurements are taken within the ectatic area. This is important in eyes with extensive coloboma involving significant part of the posterior pole. Microphthalmos with Orbital Cyst While the initial development is in process, neuroectodermal hyperplasia leads to eversion of the inner layer at the edge of the embryonal fissure, which leads to defective closure of embyonal fissure. Ectatic coloboma with intercalary membrane can occur if the fissure closes while the neuroectoderm has not differentiated into retina, however, if retinal differentiation has occurred, fusion of the fissure does not take place, leading to formation of true orbital cyst. The orbital cyst can sometimes be mistaken for orbital tumor, because of its variable size that can reach to large proportions. The cyst in very extreme cases pushes the eyeball aside or posteriorly to such an extent that it might lead to the development of severe microphthalmia, or the eyeball sometimes is hardly recognizable. The size of communication between the cyst and the vitreous cavity is variable. In majority of these cases, the retina is dysplastic which renders the eye as non-functional, and the management for these patients is mainly for cosmetic purposes. Iris Coloboma Fundus coloboma commonly, but not always, involves the iris and this association does not determine the severity of fundal coloboma. Partial iris coloboma can manifest as heterochromia, a notch in the sphincter, or defect in pigment epithelium, while complete iris coloboma is seen as a defect infero nasally that merges with pupil (key hole iris). Margins of iris coloboma are smooth, this can be used in order to differentiate it from traumatic iris defects. Choroidal Coloboma Fundus coloboma is the visually significant part of the colobomatous defect. The relationship of the coloboma with optic disc and macula are used in classifying it according to its severity and description. The area of coloboma lacks RPE and choroid. Ectasia of the coloboma can occur if the sclera present at the floor of coloboma is thinned out to variable degrees. The internal surface has bare sclera with occasional splash of pigment near the border and can be smooth or have scalloped surface. The coloboma can reach and break out into the periphery antero posteriorly, or it can remain restricted to an island along a line joining disc with inferior/infero-nasal periphery. The transverse extent of the coloboma varies directly with the anteroposterior extent in most cases. The entire inferior fundus can be occupied by the larger colobomas transveresly. Such colobomata can have a much severe involvement of the disc. Two islands of coloboma with normal retina in between are termed as bridge coloboma. The Optic Disc and the Choroidal Coloboma Choroidal coloboma classifications mostly revolve around the optic disc involvement- in terms of physical location within or outside the choroidal coloboma as well as whether the colobomatous process is involving the optic disc or not.
DOS Times Volume 29, Number 6, November-December 2023 www.dosonline.org/dos-times 42 Ida Mann’s classification[14] The disease severity is generally depicted from the most severe (type 1) to the least severe (types 6 and 7). Type 1 anomaly is expected to have the worst vision, while normal vision is expected in type 7 anomaly. The type 4 anomaly addresses Type 1: Chorodial Coloboma isolated disc coloboma while type 5 anomaly represents a small coloboma in mid fundus where the anterior and posterior retina is normal. Fundus Photograph of Choroidal Coloboma DOS TIMES
www.dosonline.org/dos-times DOS Times Volume 29, Number 6, November-December 2023 43 DOS TIMES Type 2: Chorodial Coloboma Type 5: Chorodial Coloboma Type 6: Chorodial Coloboma Type 3: Chorodial Coloboma Type 4: Chorodial Coloboma Transition Zone Between Coloboma and Normal Fundus The transition zone has significant features that influence the occurrence of retinal detachment in cases of coloboma. The terminated retinal pigment epithelium is adherent to the outer layers of retina near the level of coloboma margin. The retinal layers transition into the non-descript fibrotic tissue called inter-calary membrane (ICM) beyond this point. The zone of adhesion mentioned here is the point of least resistance termed ‘Locus minoris resistantiae’. A double layer of photoreceptors have been seen in this zone sometimes, this occurs when the photoreceptor layers turn back and merges with the terminated retinal pigment epithelium. There can be an abrupt or a gradual transition from the retina to the ICM. In sharply ectatic colobomas, the edge protrudes like an overhanging margin and this can be seen to turn inwards. A shallow retinal
DOS Times Volume 29, Number 6, November-December 2023 www.dosonline.org/dos-times 44 detachment can occur beyond coloboma if the ICM is taut and is exerting traction on the retina in the transition zone. This is best appreciated on optical coherence tomography (OCT). Variable levels of pigmentation and chorio retinal atrophy can be seen in the area just beyond the visible coloboma border. ICM detachment of variable degrees can be found in the areas of retinal detachment caused by coloboma. If even a rim of ICD detachment is identified, it is indicative of the cause of retinal detachment being coloboma. Dehiscence in the zone of least resistance, which is seen as communications between sub-retinal space and sub-ICM space, detected on OCT, can be seen in the case of ICM detachment. Optical Coherence Tomography (OCT) Images of Transition Zone Blood Vessels in the Coloboma 3 patterns of emergence of blood vessels from the disc have been described by Casper. (1) Blood vessels emerging from the lower part of the colobomatous optic disc (most common arrangement). The superior vessels progress directly across the excavated portion of A. OCT demonstrating gradual transition of retina to ICM (white arrow). The detachment of ICM with extension into normal retina beyond coloboma margin and the detached macula located just beyond the coloboma margin are also seen. B. OCT demonstrating an abrupt transition from retina to ICM (white arrow). Sudden thinning and subsequent absence of choroid at the margin of coloboma is also observed (orange arrows). C. OCT demonstrating the sharp upturn of the coloboma margin (white arrows). Macula close to the coloboma margin to be noted. D. OCT demonstrating the location of Locus minoris resistantiae (white arrow). Outer retinal layers turning back to merge with RPE (white arrow) can be appreciated. E. OCT demonstrating RD (orange curved arrow) extending into ICM detachment (white curved arrow). The sub-ICM space (white arrow) continues into sub-retinal space (orange arrow) due to break in Locus minoris resistantiae (thick white arrow). Inset shows location of the OCT scan. F. OCT demonstrating ICM detachment with shallow retinal detachment near coloboma margin and break in Locus minoris resistantiae (orange double arrow). Macular detachment just beyond the coloboma margin can be seen (color figure online). the optic disc while the vessels going towards the inferior fundus make a sharp bend, kinking over the edge before proceeding inferiorly. (2) an arrangement of blood vessels emerging from approximately the centre of the colobomatous disc, resembling the normal arrangment (3) the blood vessels seem to resemble the cilio-retinal vessels, because they emanate from the edge of the colobomatous disc. DOS TIMES
www.dosonline.org/dos-times DOS Times Volume 29, Number 6, November-December 2023 45 DOS TIMES 4 varieties of blood vessels in the coloboma have been described by the studies that correlated angiography with fundus photos. (1) Retinal blood vessels that is continuous with vessels emanating from the optic disc. (2) Retinal blood vessels emanating from bed of coloboma, and the continuity of these vessels with the central retinal artery or its branches can be established, although it’s not seen as obvious. (3) Retinal blood vessels emanating from bed of coloboma that could possibly be cilio-retinal vessels. (4) Broad deep vessels that are seen deep in the sclera, these vessels are presumed to be extra ocular vessels that are visible through the thinned out sclera. Inter-Calary Membrane Breaks In cases of ICM detachment, breaks can be made out within the ICM sometimes, despite the lack of contrast due to absence of RPE and choroid. Three types of ICM breaks have been described. 1) Presence of crescentic break along the border of coloboma Figure 4: Fundus photograph and ICG angiogram demonstrating the blood vessels in the coloboma. A total absence of chorio-capillaris in the area of coloboma and the adjoining chorio retinal atrophic patches has been shown by ICG angiography. The blood vessels supplying the extra colobomatous normal retina could traverse in the normal retina or cross the coloboma before reaching the normal retina. When seen within the coloboma, the entire blood vessel may be visible in the ICM or could be partially hidden by the ectatic sclera. The retinal blood vessels when present in the ICM, give out only a few branches and after they have crossed the coloboma, they show normal branching pattern again. where lifting up is seen only in the ICM peripheral to the break (figure-A). 2) Breaks in the macular area in the cases where the coloboma involves the macula (figure-B). 3) One or more oval in shape breaks that have all the edges lifted up (figure-C).
DOS Times Volume 29, Number 6, November-December 2023 www.dosonline.org/dos-times 46 RD and Choroidal Coloboma Retinal detachment is the most important complication of coloboma. Here, the term ‘RD’ is characterized by the separation of normal neuro-sensory retina (outside the coloboma) from the retinal pigment epithelium. Whereas, ‘ICM detachment’ Isolated Breaks in ICM These breaks can cause detachments of the ICM not extending beyond the coloboma border. Such detachments generally remain asymptomatic, and are commonly seen in the fellow eye when patients present with symptoms in one eye. These could be an important indication for prophylactic laser retinopexy as the risk of them becoming clinically significant retinal detachments is significant. Isolated Breaks in Peripheral Retina In a non-colobomatous eye, the retinal detachment stops at border of the coloboma and ICM detachment is not found. In such cases, the absence of even a rim of ICM detachment should be ascertained. indicates an elevation of the ICM from the floor of the coloboma. The below mentioned dehiscences in isolation or in combination need to be considered: (a) peripheral retinal breaks, (b) breaks in ICM and (c) dehiscence in the Locus minoris resistantiae. Mechanism of RD in Eyes with Coloboma A. Peripheral break present, no ICM breaks and no dehiscence at Locus minoris resistantiae: only peripheral break contributes to the RD and RD does not extend into coloboma. B. Peripheral break present, dehiscence is present at Locus minoris resistantiae, no ICM break: only peripheral break contributes to RD but RD extends into the coloboma. C. ICM break present, dehiscence at Locus Minoris resistantiae present, no peripheral retinal break: fluid spreads through ICM break to cause ICM detachment before spreading beyond coloboma to cause RD. D. ICM break present, dehiscence at Locus minoris resistantiae present, peripheral retinal break present: fluid enters sub-retinal space from peripheral retinal break and through break in ICM both. Breaks in Peripheral Retina and Locus Minoris Resistantiae Retinal detachment here will be associated with variable extent of ICM detachment and only a peripheral retinal break is appreciated. Breaks in ICM and Locus Minoris Resistantiae This is possibly the most common situation seen in colobomarelated RDs. Clinical retinal detachments can occur when there is a communication between sub-ICM space and the sub-retinal space by way of breaks in the Locus minoris resistantiae. Variable extent of ICM detachments are always found with them RD Unrelated to Coloboma The contribution of coloboma in the causation of retinal detachment in an eye with choroidal coloboma needs to DOS TIMES
www.dosonline.org/dos-times DOS Times Volume 29, Number 6, November-December 2023 47 DOS TIMES be identified in order to plan an appropriate management strategy. Retinal detachments that do not cross the border of the coloboma are likely caused by a peripheral lesion in the retina. This judgment could be clinically difficult in some cases because - (a) shallow ICM detachment is confined to the periphery of coloboma. (b) nystagmus present in the eye. (c) critical assessment of the fundus becomes difficult in cases with severe microphthalmia. In cases where doubt arises, it’s better to assume that the retinal detachment has coloboma as a causative factor. Acute vs Chronic vs Acute on Chronic RD Retinal detacments can be acute, chronic or acute on chronic. The evidence of long-standing RD in the form of thin retina, RPE alterations, etc., can often be found in the area immediately beyond the coloboma, whereas the detached retina beyond appears like a fresh RD. Thinning of the retina, subretinal gliosis, and variable degrees of PVR are seen in chronic retinal detachments. Sub-Clinical RD A shallow RD just beyond the border can be caused by a taut ICM that applies traction on retina at the border of the coloboma. OCT can be employed in its detection as it is not obvious clinically. Management Strategy of RD in Eyes with Coloboma of Choroid With the development of vitreo retinal surgical techniques, the management strategies have evolved. Vitrectomy is preferred in most cases, although sclera buckling was tried initially. In select cases, pneumatic retinopexy has also shown successful outcomes. Pneumatic Retinopexy Usage of this technique to reattach the retina followed by laser photocoagulation along the coloboma margin has been reported in isolated cases. This technique requires a high patient compliance and works in very select cases. Pars Plana Approach Critical evaluation and identification of even a small strip of ICM detachment and breaks in ICM is aided by the magnification provided by the operating microscope. Vitrectomy facilitates the controlled treatment of the coloboma border with laser retinopexy and offers long-term internal tamponade which helps in development of a firm adhesion along the border of coloboma. Gonvers was the first to report successful use of vitrectomy and silicone oil tamponade in coloboma RD in which scleral buckling for a more obvious peripheral break failed. Complications Choroidal Neovascularization (CNV) In coloboma of choroid, when the macula is close to the coloboma margin, sub foveal CNV was reported as a complication. The CNV may be pigmented and is usually classic. Treatment approaches include laser photocoagulation, anti VEGF injections, surgical removal of the CNV, and photodynamic therapy with Verteporfin. Sclaral Fistula A sclera fistula can result if the thin ectatic sclera gives way spontaneously or after minor trauma. Various techniques have been employed in its repair, including fibrin glue, buckle, scleral patch graft, etc. The presentation of these eyes is hypotonous maculopathy and a low IOP. Cataract People with uveal coloboma, may develop cataracts early in life and have a significant nuclear cataract. Cataract surgery can be more challenging and risky for these eyes. A study by Khokhar and colleagues showed that 21 eyes with this condition were successfully treated with phacoemulsification and IOL implantation done with the help of capsular and iris hook. They noticed that the lens material was very hard and leathery. They suggested placing the IOL in a way that its heptics are perpendicular to the coloboma in the eye to achieve better centration. Pars plana approach is suggested even for hard lenses, for extremely microphthalmic eyes, due to small cornea and hard to perform surgery through limbus. Repair of Iris Coloboma Along with Cataract Surgery Some people have had cataract surgery along with iris coloboma repair. The purpose of this extra step is to lessen the glare after the surgery. It is important to remember that these patients have had iris coloboma since birth, so they are used to the glare (if any) from the beginning of their life. Therefore, repairing the iris coloboma may be more for appearance than function. Prophylaxis Against RD in Eyes with Coloboma of Choroid Patients with coloboma of the choroid, have a high chance of developing retinal detachment (RD) in their lifetime. Therefore, it is important to try to prevent RD from happening. However, there are some challenges with using prophylactic laser. Some of these challenges are: 1. Completeness of treatment: To make the treatment efficacious, the whole edge of the coloboma must be covered by at least 2–3 rows of laser spots. This is to separate the coloboma from the rest of the retina and prevent any tears in the weak zone and ICM from causing RD. This can only be done safely in eyes that do not have the coloboma affecting the disc and macula and that have enough space between the coloboma edge and the disc and macula. However, most eyes with coloboma have the optic disc inside the coloboma. 2. Safety of laser treatment around the functional disc border: When the coloboma affects the optic disc, the laser treatment must be done around the functional border of the optic disc. If the laser spots are large in this area, they can damage the nerve fibre layer. It is harder to control the intensity of the laser spots with indirect ophthalmoscopy than with slit-lamp delivery. Unfortunately, indirect
DOS Times Volume 29, Number 6, November-December 2023 www.dosonline.org/dos-times 48 ophthalmoscopy is the only option for children under anaesthesia. A complete treatment around the coloboma, Choroid coloboma before prophylactic laser treatment. Choroid coloboma after prophylactic laser treatment. Conclusions Ocular coloboma can have different forms of presentation. Inherited cases and those with chromosomal abnormalities are well known, but sporadic cases are more common and may be related to environmental and maternal factors. Visual acuity can be affected by the coloboma itself if it involves the disc and fovea or by complications such as RD, choroidal neovascularisation, etc. It is essential to identify ICM detachment to understand how much the coloboma contributes to RD. Pars plana vitrectomy with silicone oil tamponade and endolaser along the coloboma edge is associated with good surgical outcomes. In eyes with coloboma, cataract surgery has a higher than normal risk of complications. However, future research should be done which can address: (a) better ways of finding out the causes of non-syndromic coloboma. (b) Better imaging using swept source OCT with longer scans that can give a panoramic view of the anatomy. (c) Randomized controlled trials to test the effectiveness of laser photocoagulation in preventing RD. (d) Randomized controlled trials to test the role of ideal internal tamponade in managing coloboma-related RDs. References 1. Duke-Elder S. Anomalous closure of embryonal cleft—typical colobomata. In: System of ophthalmology. St Louis: CV Mosby Company; 1963. p. 456–88. 2. Modrzejewska M, Krukar A. Wady wrodzone narządu wzroku. Pediatr Dypl 2016; 20: 62-68. 3. Gan NY, Lam WC. Retinal detachments in the pediatric population. Taiwan J Ophthalmol. 2018;8(4):222–236. 4. Uhumwangho OM, Jalali S. Chorioretinal coloboma in a paediatric population. Eye. 2014;28(6):728–733. 5. Berk AT, Yaman A, Saatci AO. Ocular and systemic findings associated with optic disc colobomas. J PediatrOphthalmol Strabismus. 2003; 40(5):272–278. 6. Chang L, Blain D, Bertuzzi S, et al. Uveal coloboma: clinical and basic science update. CurrOpinOphthalmol. 2006;17:447–470. 7. Zuber ME, Gestri G, Viczian AS, Barsacchi G, Harris WA. Specification of the vertebrate eye by a network of eye field transcription factors. Development. 2003;130:5155–67. 8. Shah SP, Taylor AE, Sowden JC, Ragge N, Russell-Eggitt I, Rahi JS, et al. Anophthalmos, microphthalmos, and Coloboma in the United kingdom: clinical features, results of investigations, and early management. Ophthalmology. 2012; 119:362–8. 9. Vogt G, Puhó E, Czeizel AE. A population-based case-control study of isolated ocular coloboma. Ophthalmic Epidemiol. 2005;12:191–7. 10. Nakamura KM, Diehl NN, Mohney BG. Incidence, ocular findings, and systemic associations of ocular coloboma: a populationbased study. Arch Ophthalmol. 2011;129:69–74. 11. Weiss AH, Kousseff BG, Ross EA, Longbottom J. Complex microphthalmos. Arch Ophthalmol. 1989;107:1619–24. 12. Bateman JB, Maumenee IH. Colobomatous macrophthalmia with where possible, should lower the risk of RD significantly. DOS TIMES