July-August 2023

CONTENTS PAGE NO. TITLE 05 From the President’s DESK 06 From the DESK of Chief Editor Subspeciality 08 62 65 20 30 41 42 54 46 60 28 38 OSSN: Management update Femtosecond Laser: Applications in Modern Refractive Surgery Myopia and Pregnancy: Understanding the Relationship, Effects, and Care Allergic conjunctivitis - Pearls in Diagnosis and Management Sensory and Motor Evaluation of Strabismus Elschnig Pearls Beyond IOP: A Lucid Approach To Secondary Glaucoma Optic Disc Pit Maculopathy Advances in Trabeculectomy Capillary hemangioblastoma in Von-HippelLindau Syndrome Bilateral Nodular Scleritis with Sweet Syndrome Stereopsis: An Overview Ocular Oncology Refractive Surgery Systemic Diseases Ocular Oncology Squint Lens/Cataract Glaucoma Retina Low Vision Rehabilitation Expert Corner Surgical Techniqe 67 72 77 81 Head-Mounted Display (HMD) Assistive Technology for Low Vision and Vision Rehabilitation Malingering: A non-organic disorder in Ophthalmology 2 Millimetre Chord Manual Small Incision Cataract Surgery: New kid on the block Combined Manual Small Incision Cataract Surgery and Trabeculectomy by M Incision a Procedure

www.dosonline.org/dos-times DOS Times Volume 29, Number 4, July-August 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 4, July-August 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 4, July-August 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 4, July-August 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 4, July-August 2023 05 From the President's DESK Dr. Rajendra Prasad MBBS, MD DOS TIMES Dear friends greetings for the day! This issue of DOS Times comes to you as an amalgamation of, original scientific articles describing clinical investigations, clinical observations, clinically relevant diagnostic tools with medical and surgical management of various ocular disorder covering most of the subspecialty, not restricted to a specialized readers but encompasses to the entire members of our society while maintaining its highest standard of scientific work. I would like to express my gratitude to all the authors, the advisory and the editorial board, the office bearers and the publisher for their support in bringing out yet another issue of DOS Times. I also take the opportunity to acknowledge the contribution rendered by the editorial board in bringing out this issue of DOS Times in time and look forward to their unrelenting support in bringing out rest of the issues too in scheduled time with quality articles. This is only possible through continuous effort put forward by the editorial board and authors because without continual growth and progress, the words like improvement, achievement, and success have no meaning. Dr. Rajendra Prasad President DOS

DOS Times Volume 29, Number 4, July-August 2023 www.dosonline.org/dos-times 06 DOS TIMES From the DESK of Chief Editor Dr. Jatinder Singh Bhalla, MS, DNB, MNAMS Secretary Delhi Ophthalmological Society IT IS NOT ABOUT YOUR REFLECTION. IT IS WHAT YOU SEE BEYOND IT. It gives us immense satisfaction to present new issue of DOS TIMES. I & my Editorial Team feel honored and fortunate to be a part of this popular journal. The continued success of the journal is mainly due to the efforts of our predecessors and the Experts in our team from various Subspecialities, reviewers, contributors, readers, and supporting staff. Increasing popularity within the Ophthalmic Community all across the country & beyond has been extremely satisfying. India on the Moon. Indians over the Moon. India scripted history with the successful landing of Chandrayaan 3 on the Moon joining the elite & small space club of Nations that have Land rovers over the Moon. India became the first country in the World to land a space probe on the lunar South pole & only the fourth nation after the US, China & the erstwhile Soviet Union to land a Rover on the Moon’s Surface. The joy and pride generated by India’s successful lunar landing still washes over a billion people. Already, there is much talk of missions to planet Mars, the Sun and beyond. But the successful Moon mission has many lessons to offer us here on Earth. Here are key takeaways that apply to all ‘moon walks’ of life including Indian Ophthalmology. 1. Frugality: The relatively low cost of the Chandrayaan missions has been widely telegraphed. Modest budgets force creative thinking. A mindset of thrift aids innovation. India’s lunarlanding success suggests that a frugal mindset is not at odds with high ambition. We Indian Ophthalmologists are already providing Eye surgeries to masses with very modest budgets. Aravind eyecare ,Chitrakoot & Many others are prime examples. SICS is Indian way to give sight to masses with in a modest cost. 2. Learning from failure: The adage that “failure is a stepping stone to success” was in direct display here. The failure of Chandrayaan 2 made ISRO change the landing vehicle’s approach to the lunar surface. The inspiring story of inventor of B Hex ring is a motivating example. 3. Preparedness and planning: For Indians, it seemed like an epiphany that a self-propelled vehicle, subject to many uncertainties, would land almost a minute early. The foresight & planning by our greats that established Premier Ophthamic centres as prestigious Apex centres of learning & now successful business models showcase their brilliance, passion & compassion for masses aswell as classes. 4. Resourceful supply chain management: Examples abound of how Chandrayaan’s project managers used local sources to reduce costs and substitute difficult-to-come-by parts. Our “Jugaad” mentality has been instrumental in invention from local resources even in Ophthalmology. 5. While the Indian Space Research Organisation (Isro) was the main protagonist in this successful mission, it used several other government and private institutions for assistance. While we have centres of excellence in Ophthalmology in Govt sector like RP centre & PGI, we also have great institutions in Private sector – LVPEI, Sankara nethralaya, NN, Aravind, CFS, Agarwals & many others.

www.dosonline.org/dos-times DOS Times Volume 29, Number 4, July-August 2023 07 DOS TIMES 6. Our missions have benefitted from partnerships with America’s NASA, Japan’s JAXA, the European Space Agency and Russia’s Roscosmos at various times. Interdependence creates mutually beneficial opportunities. Today Indian Ophthalmology is at such a vantage position, where we teach as much as we learn from others. 7. Watching for potholes: One of the major successes of Chandrayaan-3 was the flexibility built into the lander to alter its final position of rest. Two descent pauses were planned and executed immediately before touchdown to let the lander self-select a landing spot with the least probability of error. 8. Marketing/positioning: India is the fourth country on the Moon, and yet with the clever idea of landing near its south pole, India scored a gold-medal finish at the podium by becoming the first country to land on south pole. We Ophthalmologists of Indian origin have also positioned ourselves so well & given many gifts to the world after the great Sushruta-Vascular diseases of eye & optic nerve, Excimer laser shaping of Cornea, SLET, Polymegathism concept, Dua’s layer, SFT Pupilloplasty, Inside out hydrodelineation, Flap motility sign, CAIRS, Glued IOL, Omniglow & many more!! We have compiled Excellent articles by esteemed Authors from all across the country advances in trabeculectomy, Secondary Glaucoma, Combined SICS and Trabeculectomy by M incision, OSSN, Elschnig Pearls, SICS by 2 Millimetre Chord Incision, on relationship between Myopia and Pregnancy, Head-Mounted Assistive Technology for Low Vision and Vision Rehabilitation, Evaluation of Strabisums and Malingering. I hope, you find all these articles useful. Happy Reading. A WORD AFTER A WORD AFTER A WORD IS POWER. - Margaret Atwood Dr. Jatinder Singh Bhalla, MS, DNB, MNAMS Chief Editor - DOS Times, Consultant & Academic Incharge (Ophthalmology) DDU Hospital, Hari Nagar

DOS Times Volume 29, Number 4, July-August 2023 www.dosonline.org/dos-times 08 OSSN: Management Update Namita Kumari, MS, Sima Das, MS Oculoplasty and Ocular Oncology Services, Dr Shroff’s Charity Eye Hospital, New Delhi, India. Ocular surface squamous neoplasia (OSSN) refers to a broad spectrum of malignant changes involving the squamous epithelium of the conjunctiva, cornea, and limbus ranging from mild dysplasia, intraepithelial neoplasia (carcinoma in situ) to squamous cell carcinoma (SCC).[1] CIN (Conjunctival intraepithelial dysplasia or carcinoma in situ) includes various degrees of dysplasia ranging from mild (confined to the lower third of conjunctival epithelium), moderate (lower and middle third) and severe (entire thickness of epithelium). OSSN generally presents in the bulbar conjunctiva arising from the limbal area in the interpalpebral region, or less commonly, the forniceal and tarsal surfaces. OSSN has different morphological types based on the appearance of Placoid variety (gelatinous, papillary, leukoplakic, velvety), Nodular to Nodular-ulcerative, and Diffuse variant.[2] Nodulo-ulcerative lesions are rare, aggressive variants that have more tendency to involve the intraocular structures. Nodular-ulcerative lesions are often misdiagnosed as necrotizing scleritis.[3] The various clinical presentation of OSSN is depicted in Figure-1. Figure 1: Typical and atypical presentation of ocular surface squamous neoplasia. Papillary ossn at limbus (fig1a), leukoplakic variant with overlying surface keratin (fig1b), corneal epithelial involvement by ossn, note the fimbriated edge of the involved epithelium (fig1c), gelatinous ossn involving nasal limbus and cornea mimicking peripheral ulcerative keratitis with peripheral corneal thinning (fig1d, fig1e). Nodular corneal ossn in a patient with xeroderma pigmentosum (fig1f).OSSN mimicking necrotizing scleritis with scleral melt in a middle aged lady . Note the papillary nodular thickening of the conjunctiva (yellow arrowhead) at the edge of the scleral thinning (fig1g, fig1h).OSSN presenting as a subconjunctival nodule with extension beyond the fornix into anterior orbit (fig 1i). Subspeciality - Ocular Oncology

www.dosonline.org/dos-times DOS Times Volume 29, Number 4, July-August 2023 09 Management Management of OSSN includes correct diagnosis and appropriate treatment. With advances in newer diagnostic modalities and the availability of newer chemotherapeutic and immunomodulator drugs, there is a paradigm change in the diagnosis and management of OSSN. Diagnostic Modalities OSSN is often diagnosed clinically with the presence of surface keratin, prominent feeder vessels, and papillary surface with rose bengal staining. Less invasive modalities like impression or exfoliative cytology are also used for the diagnosis of the disease. However, histopathological evaluation following an incisional or excisional biopsy remains the gold standard for the diagnosis of OSSN. Recently, with the use of non-invasive modalities like high-resolution or ultra-high-resolution anterior segment optical coherence tomography (AS-OCT), ultrasound biomicroscopy (UBM), and in-vivo confocal microscopy (IVCM), for the diagnosis and monitoring of OSSN lesion has completely changed the management protocol.[4],[5],[6] HROCT not only aids in the diagnosis, but it’s also helpful in differentiating from other ocular surface lesions that closely mimic OSSN. 1. Impression Cytology Impression cytology refers to the application of a cellulose acetate filter to the ocular surface to remove the superficial layers of the ocular surface epithelium. The cells thus removed are smeared on the slide and stained by Papanicolaou or Giemsa stain and then subjected to histological, immunohistological, or molecular analysis. Egbert et al first described this minimally invasive method of studying conjunctival goblet cells in 1977.[7] Impression cytology has been used widely as a noninvasive method for conjunctival biopsy for suspected ocular surface squamous neoplasia (OSSN). Using a biopore membrane for specimen collection an 80% correlation was found between impression cytology diagnosis and histopathology specimens obtained from incisional biopsy.[8],[9] Advantages • Non-invasive • Useful in differentiating benign and malignant lesions. • Can be used to detect the recurrence. Disadvantages • Cannot differentiate between CIS and invasive carcinoma. • False-negative results in cases of abundant surface keratin resulting in a paucity of cells. 2. High-Resolution AS-OCT In recent years, AS-OCT has emerged as a valuable non-invasive imaging modality for evaluating OSSN. Its non-invasive nature, ability to visualize lesion depth and margins, and utility in monitoring treatment response make it an indispensable adjunctive technique. Role of AS-OCT in OSSN Diagnostic Tool: AS-OCT plays a valuable role in the diagnosis of OSSN. It aids in determining the lesion size, depth, and proximity to critical ocular structures. AS-OCT provides highresolution, in-vivo, cross-sectional images of the cornea and conjunctiva lesions. Apart from the classical features of ASOCT, epithelial thickness of over 140 um can also be a helpful indicator of potential neoplasia.[10],[11] The diagnostic classical hallmarks of OSSN on AS-OCT include: • A hyperreflective epithelium • Thickening of epithelium • An abrupt transition between the diseased and normal epithelium Differential Diagnosis: AS-OCT findings, such as specific patterns of lesion growth and depth of involvement, can help differentiate OSSN from other ocular surface pathologies, including pterygium, pinguecula, or other types of conjunctival neoplasms. This assists clinicians in making accurate diagnoses and avoiding unnecessary treatments. Different studies have proven the role of AS-OCT in differentiating pterygium from OSSN with sensitivity from 94%-100% and specificity of 100%.[12],[13] Follow-Up and Surveillance: Regular AS-OCT imaging during follow-up visits enables the detection of recurrent or residual disease. Serial measurements of lesion characteristics aid in evaluating treatment efficacy, guiding decisions regarding additional interventions, and monitoring long-term disease control. Figure-2 shows the AS-OCT findings of a patient with OSSN pre and post treatment with topical chemotherapy. Figure 2: OSSN involving limbus and corneal epithelium and AS-OCT showing thickened hyper-reflective epithelium with abrupt transition between normal and abnormal epithelium (Fig 2a, Fig 2b). Clinical and AS-OCT picture following topical chemotherapy showing resolution of limbal lesion with residual corneal scarring and AS-OCT showing subepithelial scarring and resolution of epithelial thickening (fig 2c, fig2d). HR-OCT may assist the surgeon in surgical planning by identifying tumor margins and sub-clinical disease. In the future, AS-OCT integrated into a surgical microscope holds the potential for visualization of tumor margins during per-op and can work as “Optical Mohs” during surgical Subspeciality - Ocular Oncology

DOS Times Volume 29, Number 4, July-August 2023 www.dosonline.org/dos-times 10 Figure 3: OSSN with scleral invasion mimicking necrotizing scleritis in an elderly patient (fig 3a). Note the papillary thickening of the conjunctiva at the edges of the scleral thinning suggestive of conjunctival squamous cell carcinoma with scleral invasion (fig3b). UBM showing intraocular extension of tumor involving the ciliary body visible as ciliary body thickening (fig3c). dissection.[14],[15] It also has certain limitations like technician expertise in determining the region of scanning, optical shadowing which can obscure the depth of penetration, especially in thick tumors, and difficulty with evaluating invasion into the substantia propria.[16] 3. Confocal Microscopy Confocal microscopy is a non-invasive imaging technique that provides high-resolution, real-time, in vivo imaging of cellular structures of the ocular surface. It allows visualization of cellular morphology abnormalities at the cellular level including cytoplasmic ratio, pleomorphism, and hyperreflectivity. Confocal microscopes can produce in-focus images of thin slices (5-20 micrometers) within a maximum depth of 1000m, a process known as optical sectioning.[17],[5],[18] Advantages of Confocal Microscopy It can examine cellular and subcellular details of OSSN lesions, providing insights into cellular atypia, dysplasia, and invasion. It aids in differentiating between benign lesions and malignant changes, enabling early detection and intervention. It can provide valuable insights into the diagnosis, grading, treatment monitoring, and prognostication of OSSN. Disadvantages • Only a small section of tissue can be visualized. • Lack of cross-sectional visualization • Inability to effectively visualize through keratinized and necrotic neoplastic tissue. 4. Ultrasound Biomicroscopy (UBM) Ultrasound biomicroscopy (UBM) utilizes high-frequency ultrasound waves (25-50 MHz) to provide detailed, crosssectional images of ocular structures and helps detect intraocular extension and infiltration into adjacent structures due to its higher optical penetration and higher resolution. UBM enables the assessment of lesion depth and invasion into underlying tissues, including the cornea, conjunctiva, and sclera. Blunting of the anterior chamber angle shows angle invasion by tumor and uveal thickening correlates with deeper invasion on histopathology.[19],[6] UBM aids in determining the extent of neoplastic involvement, guiding treatment planning, and predicting the risk of local recurrence or metastasis. Figure-3 shows the scleral and intraocular invasion by an ossn as detected on UBM. Indications of UBM • Tumours that may be at high risk for intraocular invasion include thick, nodular lesions of greater than five mm. • Nodular or ulcerative lesions • Recurrent tumor with a history of prior surgical intervention 5. OCT-A (Optical Coherence Tomography Angiography) It is an innovative technology that provides visualization of the vasculature within Ocular Surface Squamous Neoplasia (OSSN) lesions. Liu and colleagues have shed light on the potential application of vessel area density (VAD) as a marker for identifying “feeder” vessels in subclinical OSSN lesions.[20] The introduction of OCT-A has revolutionized imaging capabilities by enabling non-invasive evaluation of the microvasculature without the need for contrast agents. This technology utilizes the principles of optical coherence tomography to obtain highresolution, three-dimensional images of blood vessels within OSSN lesions. Treatment Medical Treatment In the last two decades, there has been a growing interest among ophthalmologists in the medical treatment of Ocular Surface Squamous Neoplasia (OSSN) using topical immunoand chemotherapy. This approach has gained popularity as an alternative to surgical excision as a non-surgical option for primary treatment, serves as an effective neoadjuvant therapy to shrink diffuse lesions, and offers adjuvant benefits by reducing the likelihood of recurrences, especially in cases with positive surgical margins. This reduction in lesion size allows for a more Subspeciality - Ocular Oncology

www.dosonline.org/dos-times DOS Times Volume 29, Number 4, July-August 2023 11 favorable surgical outcome when the lesions are ultimately excised. The management algorithm for ossn is provided in Figure-4. Indications of Medical treatment • Small and localized OSSN lesions not adhered to the sclera or cornea. • As Neoadjuvant therapy for multifocal and diffuse OSSN (> 4 o clock hours). • Tumors involving the pupillary axis of the cornea. • As Adjuvant therapy for positive margins following surgical excision and subclinical lesions • For recurrence cases • Not suitable for surgery because of co-morbidities The most commonly used drugs are 5-Fluorouracil (5-FU), Mitomycin-C (MMC), Interferon alpha 2b (INF-a2b) Chemotherapy 5 – FLUOROURACIL: 5-FU is a structural analogue of thymine that inhibits thymidylate synthase, an enzyme that catalyses the formation of nucleotides essential for DNA synthesis. This results in a cascade of events that ultimately inhibits the rapid proliferation of cancerous cells that rely heavily on DNA synthesis for division and growth.[21] Different studies have reported 5-FU to be very effective as primary therapy for OSSN, with high-resolution rates of 82-100% and low recurrence rates of 6–14%. Patient age, gender, and ethnicity did not affect the efficacy of medication[22], Compared to topical IFNα−2b, rates of tumour resolution, recurrence, and time to response were similar with 5-FU. The most widely used protocol recommends 1% 5-FU drops four times daily for 1 week, followed by 3 weeks off as one cycle, for a total of 4 cycles. Adjuvant 1% topical 5-FU appears to be effective in the prevention of the recurrence of conjunctival or corneal CIN and SCC after excision biopsy.[23] Figure-5 shows the pre and the post treatment pictures of a limbal ossn treated with topical 1% 5 FU eye drops. Figure 4: Management algorithm of OSSN. Subspeciality - Ocular Oncology

DOS Times Volume 29, Number 4, July-August 2023 www.dosonline.org/dos-times 12 Figure 5: OSSN treated with topical 5 FU. Appearance at Presentation (fig 5a), after 2 cycles of 5–FU (Fig 5b) and complete resolution after 3cycles of 5-FU (Fig 5c). Figure 6: Corneal epithelial ossn with central epithelial defect diagnosed as corneal abrasion following applanation tonometry elsewhere. Note the linear deposits of keratin with fimbriated edges (Fig 6a). Scrapping from the epithelial lesion showing large atypical cells on Giemsa staining (Fig 6b). Complete resolution following topical interferon alpha 2 b treatment (Fig 6c). Preparation of 1% 5-FU Topical Drop Take 2ml (100mg) from 500mg/10ml 5-FU injection and add 8 ml of 0.7% of Hydroxy propyl methyl cellulose to get a solution of 100mg in 10ml (10mg/ml 5-FU: 1% Topical 5-FU). Benefits of 1% 5 -FU • Least expensive among other topical medications • Intermediate side effect profile Pain, watering, redness, eyelid edema, and keratopathy are the most common ocular side effects of this medication. To prevent punctal stenosis, manual punctal occlusion for 3-5 minutes is recommended. Application of petroleum jelly on the eyelids and copious lubrications are advised to relieve any ocular discomfort. Interferon Alpha-2B IFNα-2b is a naturally existing glycoprotein possessing anti-viral and anti-cancer properties. The anti-cancer effects of interferons encompass various mechanisms, such as the induction of programmed cell death (apoptosis), inhibition of the formation of new blood vessels (angiogenesis), and prolongation of the cell cycle duration in cancer cells.[24] Multiple studies have provided evidence supporting the effectiveness of IFNα-2b as the primary treatment for Ocular Surface Squamous Neoplasia (OSSN). These studies have reported varying rates of resolution, ranging from 81% to 100%, and recurrence frequencies ranging from 0% to 20%. IFNα-2b has also been employed as a neoadjuvant and adjuvant therapy for OSSN. With the use of postoperative topical IFNα-2b, a significant reduction in the frequency of recurrence was noted, approaching the levels observed in patients with negative surgical margins.[22],[25],[26],[27],[28]. IFN can be used topically or intralesional as neoadjuvant (immuno-reduction), adjuvant (immune prevention), or primary therapy (immunotherapy). The most common regimen for topical IFNα-2b eye drops is 1 million IU/ml, 4 times daily until complete clinical resolution usually takes 12 weeks. The post-clinical resolution is used for 1 or 2 months for any subclinical disease. Perilesional or subconjunctival injections of IFN are mostly given at a dose of 3 million IU in 0.5 ml, administered weekly or 10 million IU in 0.5ml monthly dose usually in the cases of diffuse OSSN mainly around the base of the lesion. The most common side effect of the injection is Flu-like symptoms usually happened after 48 hrs of injection. Figure-6 shows the pre and post treatment pictures of a patient with corneal ossn treated with topical interferon alpha 2b eye drops. Subspeciality - Ocular Oncology

www.dosonline.org/dos-times DOS Times Volume 29, Number 4, July-August 2023 13 Preparation of Interferon-alpha 2b: Add 2.5ml distilled water to 0.5ml solution of INFα2b containing 3MIU to get the concentration of 1MIU INFα2b. Store the drug at 2-8 degree Celsius. Benefits • Minimal side effects • Can be given topical or injection. • Used as Neoadjuvant, Primary, and Adjuvant therapy. Limitations • Most expensive, affordability issues • Needs Refrigeration for storage. • Nowadays, very limited availability of drug due to production issues Mitomycin-C MMC is a non-cell-cycle dependant alkylating agent derived from Streptomyces caespitosus and possesses both antineoplastic and anti-biotic properties. In aerobic condition after activation MMC transforms into an alkylating agent that generates free radicals. These free radicals are responsible for causing breaks in DNA strands, disrupting the process of DNA synthesis, and creating a cytotoxic environment. As a consequence, MMC induces apoptosis in both actively dividing and non-dividing cells by triggering a series of cellular events that lead to programmed cell death. Several studies have reported resolution frequencies ranging from 79 to 100% and recurrence frequencies ranging from 0% to 15.1% on MMC therapy.[29],[30],[31],[32],[33],[34] MMC eye drops are usually dispensed in concentrations of 0.02 to 0.04%. We follow the drug regimen of 0.04% MMC four times a day for four consecutive days in a week for 4 weeks, followed by a drug holiday for 2 weeks (Figure-7). The most common side effect of MMC is Pain, redness, watering, corneal erosion, hyperaemia, punctate staining of the cornea, limbal stem cell deficiency, punctal stenosis. Punctal plugs and manual occlusion of punctum is recommended to prevent punctal stenosis. Figure 7: OSSN with diffuse corneal involvement with a papillary conjunctival nodular component at inferior limbus (Fig7a). Appearance following 1 cycle of MMC 0.04% eye drops (Fig 7b) , following 2 cycle of MMC(Fig 7c) and complete resolution after 3 cycles showing minimal corneal epithelial scarring.(Fig 7d). Subspeciality - Ocular Oncology

DOS Times Volume 29, Number 4, July-August 2023 www.dosonline.org/dos-times 14 Preparation of MMC 0.04% Add 5ml Hydroxy propyl methyl cellulose/distilled water to 2mg powder to get the concentration of 0.04% MMC. Benefits • Cost-effective • Easily available • Used as Neoadjuvant, Primary, Adjuvant therapy, and also intraoperatively. Limitations • Most severe surface toxicity profile • Need compounding of the drug weekly Indications of topical medications as adjuvant therapy • Post-surgical excision positive conjunctival margin • Post-surgical excision in cases of negative margin with risk factors o Tarsal involvement o Higher grade lesions o Superior location o Papillomatous appearance o Recurrent disease Limitations of Topical Medications Primary treatment with only topical Medications has no role in these conditions, it can be used as neoadjuvant or adjuvant therapy along with surgery. • Tumor involving sclera or bowman’s layer. • Tumor with intraocular involvement • Diffuse lesion involving forniceal conjunctiva. • Orbital spread of disease • Positive base involvement Alternatives Topical Therapies For The Treatment of OSSN 1. Retinoic Acid Retinoic acid, a metabolite of vitamin A, has significant growthrestricting properties and anti-neoplastic effects on normal, premalignant, and malignant cells. Retinoic acid (0.01%) is commonly used in conjunction with IFNα-2b for the treatment of Ocular Surface Squamous Neoplasia (OSSN). Its efficacy as a standalone treatment for OSSN is not well established. In a study involving 89 eyes with confirmed OSSN, treatment with topical IFNα-2b and retinoic acid resulted in complete clinical resolution in 98% of cases after an average of 1.69 months. Partial response was observed in 2% of cases.[35] It is generally well tolerated, with mild side effects such as allergic papillary conjunctivitis, epithelial microcysts, marginal keratitis, and eyelid irritation reported. 2. Anti-Vascular Endothelial Growth Factor Anti-VEGF agents, including bevacizumab and ranibizumab, are monoclonal antibodies that block the activity of VEGF, a potent angiogenic factor upregulated by neoplastic cells to promote neovascularization and meet increased metabolic demands. Few studies have shown positive outcomes with primary treatment with anti-VEGF treatments, others have reported minimal or no response.[36],[37],[38],[39] It is usually given in the topical preparation form of bevacizumab (5mg/ml) or subconjunctival injection of ranibizumab (0.05mg of 10 mg/ml). No significant side effects associated with the use of topical anti-VEGF agents for ocular surface lesions have been reported in the literature. However, bevacizumab may exhibit inhibitory effects that can delay corneal healing in eyes with epithelial defects. Future Advances in Systemic Therapy Programmed cell death-1 inhibitors Programmed death-1 (PD-1) is an inhibitory receptor expressed on T cells that suppresses their anti-neoplastic activities upon engagement with the inhibitory ligand, PD-L1, expressed by cancer cells. Expression of PD-L1 in neoplastic cells correlates with the degree of invasion in Ocular Surface Squamous Neoplasia (OSSN) and is upregulated in cancer cells treated with chemotherapy. Anti-PD1 therapies, such as nivolumab and pembrolizumab, have shown potential for treating squamous cell carcinoma in various locations, including the head, neck, oesophagus, and anal canal. According to the FDA, a dose of nivolumab 240 mg should be administered through intravenous infusion every 2 weeks or 480 mg every 4 weeks. Checkpoint inhibitors, such as pembrolizumab and cemiplimab, have demonstrated efficacy in select cases of advanced conjunctival squamous cell carcinoma with orbital extension and recurrent cases unresponsive to other treatments.[40] However, because of the high cost and limited availability of these checkpoint inhibitor therapies in different parts of world, they are still not a part of mainstay treatment in advanced cases.[41] Surgical Management in OSSN Surgical excision with wide margin and no-touch technique has been a gold standard treatment for OSSN. Surgical management has the advantage of potentially faster resolution than medical treatment. Surgical excision has been associated with unfavourable sequelae such as conjunctival scarring, symblepharon formation, conjunctival hyperaemia, and limbal stem cell deficiency specially for large lesions. Surgical excision with a positive margin has a higher recurrence rate of 56%, however, more recent studies have found lower recurrence rates of 0%–21% following surgical excision.[42],[43],[44],[43] One recent study did not find any significant difference in the recurrence rate of OSSN was found between surgical versus IFNα2b therapy.[45] Surgical Indications in OSSN • Extensive OSSN post chemo reduction • Recurrence cases with multifocal involvement for Map biopsy • OSSN with partial scleral involvement • Localized Conjunctival or corneal non-invasive OSSN in patients with compliance issues Subspeciality - Ocular Oncology

www.dosonline.org/dos-times DOS Times Volume 29, Number 4, July-August 2023 15 Surgical Technique in OSSN The primary method of surgical excision for OSSN is the Shields ‘no-touch’ technique with wide margins.[46] Intraoperative cryotherapy is performed to reduce recurrences after surgical excision. Important surgical points: • Wide margins of 3-4 mm are marked around the visible edges of the tumor. • Corneal epitheliectomy is performed using absolute alcohol for 1 minute for tumors with limbal and corneal components with tumor-free 2mm margin. • The lesion is excised in one piece, with careful manipulation only at the marked margins and a dry surgical field to prevent potential seeding of tumor cells. • The excised lesion should be sent for histopathology on filter paper with proper marking and orientation. • For adherent tumors, a 20% sclerectomy is recommended. • Cryotherapy is performed using a double freeze-slow thaw method on conjunctival margins, as well as the limbus and cornea if the margins extend to those areas and the base of the lesion. • Closure of the wound can be done with amniotic membrane tissue and fibrin glue or with sutures. Indication for Extended Enucleation Advanced OSSN cases invade the sclera and cornea to have intraocular extension; more commonly seen with the mucoepidermoid and spindle cell variants of OSSN Such cases are managed by extended enucleation, in which the peritomy is extended to surround the tumour to create a 3-4 mm clear margin, followed by confirmation of surgical margin clearance by frozen section per-operatively. The remaining conjunctival margin undergoes double cryotherapy before the prosthesis is inserted and followed by amniotic membrane grafting. Indications for Orbital Exenteration In the advanced stage of the disease, OSSN can spread to the orbit and regional lymph nodes and rarely distant metastasis. Any OSSN patients with proptosis, restricted extraocular movements, extensive disease or caruncle involvement, and beyond forniceal involvement should undergo orbital CT/MRI imaging to rule out orbital disease. FNAC of most enlarged lymph nodes should be done and sent for histopathology to confirm the disease. After radiological or histopathological confirmation of orbital involvement, before planning surgery metastatic workup and PET-CT scan should be done. Confirmed Orbital cases require surgical management in the form of Orbital exenteration, a lidsparing exenteration can be performed if the anterior lamellae are spared. However, if the involvement extends to the posterior lamellae of the eyelid, an eyelid-removing exenteration is necessary.[47] Figure-8 shows an aggressive ossn with orbital extension treated with orbital exenteration. Figure 8: Advanced ossn with scleral involvement (Fig 8a) with UBM showing partial thickness involvement of the sclera by the tumor (Fig 8b). Excision biopsy was done for the main tumor followed by plaque brachytherapy with Ruthenium -106 for residual scleral involvement. (Fig 8c) Follow up pictures at 6 months showing complete tumor resolution with healthy ocular surface.(Fig 8d). Subspeciality - Ocular Oncology

DOS Times Volume 29, Number 4, July-August 2023 www.dosonline.org/dos-times 16 Radiotherapy The Radiotherapy can be divided into external beam radiotherapy (EBRT) and brachytherapy (BT). EBRT: Proton and electron EBRT are favoured in OSSN as they limit radiation exposure to the tumour and minimise negative effects on the normal surrounding tissue (cornea, lens, and retina).[48] Fractionated radiotherapy is commonly employed, with the total dose and fractionation schedule determined based on tumor characteristics and patient-specific factors. Adjuvant radiotherapy may play a significant role in the treatment of individuals diagnosed with advanced ocular surface squamous neoplasia (OSSN) associated with HIV infection.[49] Indications for EBRT • As alternative treatment in extensive or recurrent advance orbital disease • Adjuvant therapy post orbital exenteration • For advance orbital cases where surgical resection is not possible because of co-morbidity. Figure 9: Advanced ossn involving nasal bulbar conjunctiva and sclera with extension into the medial orbit (fig 9a). Note the soft tissue mass in the medial orbit involving medial rectus insertion and nasolacrimal canal.(fig 9b) Treatment involved orbital exenteration followed by EBRT to the orbit. (fig 9c) Follow up picture showing epithelium lined healthy exenterated socket.(fig 9d). • As palliative treatment in cases of locally advance disease with nodal metastasis Complications • Radiation-induced keratopathy • Dry eye syndrome • Conjunctival scarring • Cataract formation Plaque Brachytherapy Brachytherapy is used as adjuvant therapy after surgical excision with residual scleral disease. It provides local radiation with minimal effect on surrounding structures. Plaque radiotherapy can be an effective alternative to enucleation for residual scleralinvasive conjunctival SCC following resection.[50] Three main isotopes mainly used for management include strontium-90 (Sr-90), iodine-125 (I-125) and ruthenium-106 (R-106), having 0 -12% recurrence rate with follow-up of more than 24 months.[51] Figure-9 shows the clinical and post treatment pictures of a patient treated with plaque brachytherapy. Subspeciality - Ocular Oncology

www.dosonline.org/dos-times DOS Times Volume 29, Number 4, July-August 2023 17 Indication • Post-surgical excision residual scleral invasion without intraocular or orbital involvement. Complication • Dry eyes • Corneal ulceration • Peripheral corneal vascularisation No. Medication Mechanism of Action Recommended Regimen Adverse Events 1. Mitomycin-C Alkylating agent (Cell cycle independent effects) MMC 0.04%, QID Cycle: 4 days on and 3 days off followed by 3 weeks off. • Punctal stenosis • Conjunctivitis • Lid toxicity • Recurrent corneal erosion • Punctate staining of cornea • Limbal stem cell deficiency 2. 5-Fluorouracil Pyrimidine analogue (Cell cycle dependent effects) 5FU 1%, QID Cycle: one week on and three weeks off, OR One month on and one month off. Duration: continue for one cycle after resolution. • Punctate epithelial erosions • Corneal ulceration • Lid toxicity • Keratoconjunctivitis 3. Interferon-α2b Anti-viral, cytostatic, proapoptotic, anti- angiogenic, immunomodulatory IFN 1 million IU/ml QID for 1–3 months after resolution. IFN 3 million IU/0.5 ml, perilesional injection weekly until resolution. • Follicular conjunctivitis • Corneal erosion • Corneal ulcer • Epithelial microcysts • Flu-like symptoms (with perilesional injections) Table 1: Comparison of topical MMC, 5- FU and IFN -α2b. Conclusion The emergence of primary monotherapy utilizing topical chemotherapeutic drugs and immunomodulatory agents has significantly enhanced the treatment approach for ocular surface squamous neoplasia (OSSN), particularly in cases of recurrent or extensive disease, while also reducing the associated surgical complications. The utilization of high-resolution optical coherence tomography (HR-OCT) can serve as a valuable complement to both medical and surgical interventions in the management of ocular surface squamous neoplasia (OSSN). HR-OCT plays a crucial role from diagnosis, monitoring the response to the therapy to detecting the subclinical disease. In the future, the integration of HR-OCT with operating microscopes will be helpful for precisely delineating the tumor margins, thereby minimizing the risk of recurrence and improving overall treatment outcomes. The selection of the optimal treatment modality should be tailored to each patient, taking into consideration various factors such as disease characteristics, co-existing medical conditions, logistical considerations (e.g., refrigeration, compounding), accessibility, cost, and the active involvement of an informed and compliant patient. The algorithm table provides a comprehensive overview of available treatment modalities for different stages of the disease and will be helpful to guide ophthalmologists in selecting the most suitable treatment regimen. References 1. Lee GA, Hirst LW. Ocular surface squamous neoplasia. Surv Ophthalmol. 1995;39(6):429–50. 2. Kao AA, Galor A, Karp CL, Abdelaziz A, Feuer WJ, Dubovy SR. Clinicopathologic correlation of ocular surface squamous neoplasms at Bascom Palmer Eye Institute: 2001 to 2010. Ophthalmology. 2012 Sep;119(9):1773–6. 3. Kaliki S, Freitag SK, Chodosh J. Nodulo-Ulcerative Ocular Surface Squamous Neoplasia in 6 Patients: A Rare Presentation. Cornea. 2017 Mar;36(3):322–6. 4. Thomas BJ, Galor A, Nanji AA, El Sayyad F, Wang J, Dubovy SR, et al. Ultra high-resolution anterior segment optical coherence tomography in the diagnosis and management of ocular surface squamous neoplasia. Ocul Surf. 2014 Jan;12(1):46–58. 5. Xu Y, Zhou Z, Xu Y, Wang M, Liu F, Qu H, et al. The clinical value of in vivo confocal microscopy for diagnosis of ocular surface squamous neoplasia. Eye Lond Engl. 2012 Jun;26(6):781–7. Subspeciality - Ocular Oncology

DOS Times Volume 29, Number 4, July-August 2023 www.dosonline.org/dos-times 18 6. Meel R, Dhiman R, Sen S, Kashyap S, Tandon R, Vanathi M. Ocular Surface Squamous Neoplasia with Intraocular Extension: Clinical and Ultrasound Biomicroscopic Findings. Ocul Oncol Pathol. 2019 Feb;5(2):122–7. 7. Egbert PR, Lauber S, Maurice DM. A Simple Conjunctival Biopsy. Am J Ophthalmol. 1977 Dec;84(6):798–801. 8. Tole DM, McKelvie PA, Daniell M. Reliability of impression cytology for the diagnosis of ocular surface squamous neoplasia employing the Biopore membrane. Br J Ophthalmol. 2001 Feb;85(2):154–8. 9. Nolan GR, Hirst LW, Wright RG, Bancroft BJ. Application of impression cytology to the diagnosis of conjunctival neoplasms. Diagn Cytopathol. 1994;11(3):246–9. 10. Nanji AA, Sayyad FE, Galor A, Dubovy S, Karp CL. High-Resolution Optical Coherence Tomography as an Adjunctive Tool in the Diagnosis of Corneal and Conjunctival Pathology. Ocul Surf. 2015 Jul;13(3):226–35. 11. Atallah M, Joag M, Galor A, Amescua G, Nanji A, Wang J, et al. Role of high-resolution optical coherence tomography in diagnosing ocular surface squamous neoplasia with coexisting ocular surface diseases. Ocul Surf. 2017 Oct;15(4):688–95. 12. Kieval JZ, Karp CL, Abou Shousha M, Galor A, Hoffman RA, Dubovy SR, et al. Ultra-high resolution optical coherence tomography for differentiation of ocular surface squamous neoplasia and pterygia. Ophthalmology. 2012 Mar;119(3):481–6. 13. Lozano García I, Romero Caballero MD, Sellés Navarro I. High resolution anterior segment optical coherence tomography for differential diagnosis between corneo-conjunctival intraepithelial neoplasia and pterygium. Arch Soc Espanola Oftalmol. 2020 Mar;95(3):108–13. 14. Karp CL, Mercado C, Venkateswaran N, Ruggeri M, Galor A, Garcia A, et al. Use of High-Resolution Optical Coherence Tomography in the Surgical Management of Ocular Surface Squamous Neoplasia: A Pilot Study. Am J Ophthalmol. 2019 Oct; 206:17–31. 15. Tran AQ, Venkateswaran N, Galor A, Karp CL. Utility of highresolution anterior segment optical coherence tomography in the diagnosis and management of sub-clinical ocular surface squamous neoplasia. Eye Vis Lond Engl. 2019; 6:27. 16. Patel U, Karp CL, Dubovy SR. Update on the Management of Ocular Surface Squamous Neoplasia. Curr Ophthalmol Rep. 2021 Mar;9(1):7–15. 17. Böhnke M, Masters BR. Confocal microscopy of the cornea. Prog Retin Eye Res. 1999 Sep;18(5):553–628. 18. Parrozzani R, Lazzarini D, Dario A, Midena E. In vivo confocal microscopy of ocular surface squamous neoplasia. Eye Lond Engl. 2011 Apr;25(4):455–60. 19. Finger PT, Tran HV, Turbin RE, Perry HD, Abramson DH, Chin K, et al. High frequency ultrasonographic evaluation of conjunctival intraepithelial neoplasia and squamous cell carcinoma. Arch Ophthalmol Chic Ill 1960. 2003 Feb;121(2):168–72. 20. Liu Z, Karp CL, Galor A, Al Bayyat GJ, Jiang H, Wang J. Role of optical coherence tomography angiography in the characterization of vascular network patterns of ocular surface squamous neoplasia. Ocul Surf. 2020 Oct;18(4):926–35. 21. Diasio RB, Harris BE. Clinical pharmacology of 5-fluorouracil. Clin Pharmacokinet. 1989 Apr;16(4):215–37. 22. Venkateswaran N, Mercado C, Galor A, Karp CL. Comparison of Topical 5-Fluorouracil and Interferon Alfa-2b as Primary Treatment Modalities for Ocular Surface Squamous Neoplasia. Am J Ophthalmol. 2019 Mar; 199:216–22. 23. Amin S, AlJboor M, Toro MD, Rejdak R, Nowomiejska K, Nazzal R, et al. Management and Outcomes of Unilateral Group D Tumors in Retinoblastoma. Clin Ophthalmol. 2021 Jan; Volume 15:65–72. 24. Houglum JE. Interferon: mechanisms of action and clinical value. Clin Pharm. 1983;2(1):20–8. 25. Vann RR, Karp CL. Perilesional and topical interferon alfa-2b for conjunctival and corneal neoplasia. Ophthalmology. 1999 Jan;106(1):91–7. 26. Shah SU, Kaliki S, Kim HJ, Lally SE, Shields JA, Shields CL. Topical interferon alfa-2b for management of ocular surface squamous neoplasia in 23 cases: outcomes based on American Joint Committee on Cancer classification. Arch Ophthalmol Chic Ill 1960. 2012 Feb;130(2):159–64. 27. Kusumesh R, Ambastha A, Sinha B, Kumar R. Topical Interferon α-2b as a Single Therapy for Primary Ocular Surface Squamous Neoplasia. Asia-Pac J Ophthalmol Phila Pa. 2015;4(5):279–82. 28. Shields CL, Constantinescu AB, Paulose SA, Yaghy A, Dalvin LA, Shields JA, et al. Primary treatment of ocular surface squamous neoplasia with topical interferon alpha-2b: Comparative analysis of outcomes based on original tumor configuration. Indian J Ophthalmol. 2021 Mar;69(3):563–7. 29. Frucht-Pery J, Rozenman Y. Mitomycin C therapy for corneal intraepithelial neoplasia. Am J Ophthalmol. 1994 Feb 15;117(2):164– 8. 30. Frucht-Pery J, Sugar J, Baum J, Sutphin JE, Pe’er J, Savir H, et al. Mitomycin C treatment for conjunctival-corneal intraepithelial neoplasia: a multicenter experience. Ophthalmology. 1997 Dec;104(12):2085–93. 31. Wilson MW, Hungerford JL, George SM, Madreperla SA. Topical mitomycin C for the treatment of conjunctival and corneal epithelial dysplasia and neoplasia. Am J Ophthalmol. 1997 Sep;124(3):303–11. 32. Russell HC, Chadha V, Lockington D, Kemp EG. Topical mitomycin C chemotherapy in the management of ocular surface neoplasia: a 10-year review of treatment outcomes and complications. Br J Ophthalmol. 2010 Oct;94(10):1316–21. 33. Ballalai PL, Erwenne CM, Martins MC, Lowen MS, Barros JN. Longterm results of topical mitomycin C 0.02% for primary and recurrent conjunctival-corneal intraepithelial neoplasia. Ophthal Plast Reconstr Surg. 2009;25(4):296–9. 34. Khong JJ, Muecke J. Complications of mitomycin C therapy in 100 eyes with ocular surface neoplasia. Br J Ophthalmol. 2006 Jul;90(7):819– 22. 35. Krilis M, Tsang H, Coroneo M. Treatment of conjunctival and corneal epithelial neoplasia with retinoic acid and topical interferon alfa-2b: long-term follow-up. Ophthalmology. 2012 Oct;119(10):1969–73. 36. Asena L, Dursun Altınörs D. Topical Bevacizumab for the Treatment of Ocular Surface Squamous Neoplasia. J Ocul Pharmacol Ther Off J Assoc Ocul Pharmacol Ther. 2015 Oct;31(8):487–90. 37. Teng CC, Chin KJ, Finger PT. Subconjunctival ranibizumab for squamous cell carcinoma of the conjunctiva with corneal extension. Br J Ophthalmol. 2009 Jun;93(6):837–8. 38. Faramarzi A, Feizi S. Subconjunctival bevacizumab injection for ocular surface squamous neoplasia. Cornea. 2013 Jul;32(7):998– 1001. 39. Finger PT, Chin KJ. Refractory squamous cell carcinoma of the Subspeciality - Ocular Oncology

www.dosonline.org/dos-times DOS Times Volume 29, Number 4, July-August 2023 19 conjunctiva treated with subconjunctival ranibizumab (Lucentis): a two-year study. Ophthal Plast Reconstr Surg. 2012;28(2):85–9. 40. Demirci H, Elner VM, Demirci FY, Robinson DR, Chinnaiyan A, Schlachter D, et al. Immunotherapy for Conjunctival Squamous Cell Carcinoma with Orbital Extension. Ophthalmology. 2021 May;128(5):801–4. 41. Andrews A. Treating with Checkpoint Inhibitors-Figure $1 Million per patient. Am Health Drug Benefits. 2015 Aug;8(Spec Issue):9. 42. Tabin G, Levin S, Snibson G, Loughnan M, Taylor H. Late recurrences and the necessity for long-term follow-up in corneal and conjunctival intraepithelial neoplasia. Ophthalmology. 1997 Mar;104(3):485–92. 43. Bowen RC, Soto H, Raval V, Bellerive C, Yeaney G, Singh AD. Ocular surface squamous neoplasia: outcomes following primary excision with 2mm margin and cryotherapy. Eye Lond Engl. 2021 Nov;35(11):3102–9. 44. Chen C, Louis D, Dodd T, Muecke J. Mitomycin C as an adjunct in the treatment of localised ocular surface squamous neoplasia. Br J Ophthalmol. 2004 Jan;88(1):17–8. 45. Nanji AA, Moon CS, Galor A, Sein J, Oellers P, Karp CL. Surgical versus medical treatment of ocular surface squamous neoplasia: a comparison of recurrences and complications. Ophthalmology. 2014 May;121(5):994–1000. 46. Shields JA, Shields CL, De Potter P. Surgical management of conjunctival tumors. The 1994 Lynn B. McMahan Lecture. Arch Ophthalmol Chic Ill 1960. 1997 Jun;115(6):808–15. 47. Shields CL, Shields JA. Tumors of the conjunctiva and cornea. Surv Ophthalmol. 2004;49(1):3–24. 48. Murthy R, Gupta H, Krishnatry R, Laskar S. Electron beam radiotherapy for the management of recurrent extensive ocular surface squamous neoplasia with orbital extension. Indian J Ophthalmol. 2015 Aug;63(8):672–4. 49. Ndlovu N, Ndarukwa S, Kadzatsa W, Rusakaniko S. Evaluation of the radiotherapy management of ocular surface squamous neoplasia in a high HIV prevalence setting- a retrospective review. Infect Agent Cancer. 2016; 11:18. 50. Arepalli S, Kaliki S, Shields CL, Emrich J, Komarnicky L, Shields JA. Plaque radiotherapy in the management of scleral-invasive conjunctival squamous cell carcinoma: an analysis of 15 eyes. JAMA Ophthalmol. 2014 Jun;132(6):691–6. 51. Lecuona K, Stannard C, Hart G, Rice J, Cook C, Wetter J, et al. The treatment of carcinoma in situ and squamous cell carcinoma of the conjunctiva with fractionated strontium-90 radiation in a population with a high prevalence of HIV. Br J Ophthalmol. 2015 Sep;99(9):1158– 61. Dr. Sima Das, MS Dr Shroff’s Charity Eye Hospital 5027 Kedar Nath Road, Daryaganj, New Delhi. Corresponding Author: Subspeciality - Ocular Oncology

DOS Times Volume 29, Number 4, July-August 2023 www.dosonline.org/dos-times 20 Allergic Conjunctivitis - Pearls in Diagnosis and Management Mekhla Naik[1], MD, Jay Sheth[1], MD, Deeksha Thorat[2], DNB, Somasheila I Murthy[1,2], MD 1. Shantilal Shanghvi Eye Institute, Mumbai. 2. LV Prasad Eye Institute, Hyderabad. Overview Allergic conjunctivitis is a common eye disease that is often underdiagnosed and undertreated.[1] The increase in allergic eye disease and systemic allergies is attributed to factors like air pollution, environmental changes, and animal dander.[1] Symptoms can range from mild discomfort to severe visionthreatening conditions, impacting quality of life and productivity. Treatment often requires a combination of medications. This review aims to assess the epidemiology, immunopathogenesis, clinical features, and differential diagnosis of allergic conjunctivitis, with emphasis on treatment strategies. The prevalence of allergic conjunctivitis varies by country and region due to allergens, environmental factors, and ethnicities.[1,2] It has been reported to range from 15-20% up to 40% in North America.[1,2] The International Study of Asthma and Allergies in Childhood (ISAAC) found a mean prevalence of 14.6% in children aged 13-14, lower in Northern and Eastern Europe, Africa, and Latin America.[3] A study from India reported a 12.2% prevalence among children aged 5-15 years, with boys more affected (13.4%) than girls (10.7%).[4] Common co-morbidities include allergic rhinitis/hay fever (23.9%), dermatitis (9.7%), and asthma (0.5%).[4] Only 44% of affected children sought medical attention, and one-quarter completed their treatment course.[4] Figure-1 enlists the spectrum of ocular conditions within the taxonomy of allergic conjunctivitis.[1] Figure 1: Spectrum of Allergic Eye Disease. Figure 2: Common Associates of Allergic Conjuctivitis. Allergic conjunctivitis is a multifaceted disorder that involves numerous risk factors. such as environmental allergens, pollen, dust mites, and pet dander.[1,5] Individuals with a family history of allergies are pre-disposed due to a possible genetic overlay. Other potential risk factors include a weakened immune system, certain medications, and pre-existing medical conditions such as asthma or eczema.[1,5] Ultimately, the underlying cause of allergic conjunctivitis can vary greatly from person to person and may require careful evaluation by a healthcare professional. Figure-2 illustrates the common risk factors of allergic conjunctivitis stratified by its subtype.[1,5] All forms of allergic conjunctivitis have a similar immunopathogenesis, clinical characteristics, and complications, although they differ in their period of onset and severity.[5,6] These are enumerated in Table-1. Clinical image 1 depicts some signs seen in various forms of allergic conjunctivitis. Identifying and differentiating the kind of allergic conjunctivitis is vital in order to start the patient on the most appropriate therapy.[1,6] Following the clinical flowchart provided in Figure-3 can aid in making an accurate diagnosis and initiating appropriate therapy. Subspeciality - Ocular Surface

www.dosonline.org/dos-times DOS Times Volume 29, Number 4, July-August 2023 21 Table 1: Immunopathogenesis, clinical features, and complications of allergic eye diseases. Subspeciality - Ocular Surface

DOS Times Volume 29, Number 4, July-August 2023 www.dosonline.org/dos-times 22 Figure 3: Diagnosis of Allergic Conjuctivitis. All Apart from medical history and physical examinantion, a number of complementary laboratory tests are utilized in order to identify the specific allergen. This data is helpful for immunotherapy as well as for disease prognostication. These tests are divided into two categories: in-vivo and in-vitro.[7-10] Table-2 provides the details of all the investigative modalities employed for allergic conjunctivitis. The treatment of allergic conjunctivitis can be broadly categorized into 4 types: non-pharmacological treatment (NPT), general pharmacological treatment (GPT), steroids and immunomodulators treatment (SIT), and immunotherapy (IT).[1,6,11-15] Table-3 and Figure-4 provides the details and suitability of these modalities for all the types of allergic conjunctivitis. Additionally, Figure-4 demonstrated the therapeutic modalities for the various stages of vernal keratoconjunctivitis (VKC). The recent advances in the management of allergic conjunctivitis are provided in Figure-6.[12,14,15] In conclusion, this review article has provided a comprehensive overview of allergic conjunctivitis, a common ocular condition affecting a significant portion of the population. It causes a significant impact on quality of life, productivity, and vision. We have explored the etiology, pathophysiology, clinical manifestations, and diagnostic approaches associated with allergic conjunctivitis. Additionally, we have delved into the various treatment modalities available, including both pharmacological and non-pharmacological interventions. Moreover, emerging research has shed light on novel therapeutic approaches, such as biologics targeting specific immune pathways, which hold promise for patients with refractory or severe forms of allergic conjunctivitis. Future studies focusing on the identification of biomarkers, genetic predisposition, and personalized treatment algorithms will further enhance our understanding of this condition and refine therapeutic interventions. Overall, this review article emphasizes the significance of allergic conjunctivitis as a prevalent ocular disorder, emphasizing the importance of accurate diagnosis, appropriate management, and ongoing research efforts. By improving our understanding of the disease’s pathogenesis and advancing treatment options, we can provide better care and relief to individuals affected by allergic conjunctivitis, ultimately enhancing their overall eye health and quality of life. Subspeciality - Ocular Surface

www.dosonline.org/dos-times DOS Times Volume 29, Number 4, July-August 2023 23 Table 2: Diagnostic Tests for allergic conjuctivitis. Subspeciality - Ocular Surface

DOS Times Volume 29, Number 4, July-August 2023 www.dosonline.org/dos-times 24 Table 3: Management of the allergic conjunctivitis spectrum. Subspeciality - Ocular Surface

www.dosonline.org/dos-times DOS Times Volume 29, Number 4, July-August 2023 25 Figure 4: Treatment of allergic eye disease at a glance. Subspeciality - Ocular Surface

DOS Times Volume 29, Number 4, July-August 2023 www.dosonline.org/dos-times 26 Figure 5: Management of different stages of VKC. Subspeciality - Ocular Surface

www.dosonline.org/dos-times DOS Times Volume 29, Number 4, July-August 2023 27 References 1. La Rosa M, Lionetti E, Reibaldi M, Russo A, Longo A, Leonardi S, et al. Allergic conjunctivitis: a comprehensive review of the literature. Ital J Pediatr. 2013;39:18. 2. Singh K, Axelrod S, Bielory L. The epidemiology of ocular and nasal allergy in the United States, 1988-1994. J Allergy Clin Immunol. 2010;126(4):778-83.e6. 3. Aït-Khaled N, Pearce N, Anderson HR, Ellwood P, Montefort S, Shah J; ISAAC Phase Three Study Group. Global map of the prevalence of symptoms of rhinoconjunctivitis in children: The International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three. Allergy. 2009;64(1):123-48. 4. Kahol P, Thakur M, Gupta A, Saini SK. Prevalence, morbidity and treatment seeking behavior for allergic T conjunctivitis in children in a North Indian community. Clinical Epidemiology and Global Health. 2019; 7:239–45. 5. Chigbu DI. The pathophysiology of ocular allergy: a review. Cont Lens Anterior Eye. 2009;32(1):3-15; quiz 43-4. 6. Sacchetti M, Abicca I, Bruscolini A, Cavaliere C, Nebbioso M, Lambiase A. Allergic conjunctivitis: current concepts on pathogenesis and management. J Biol Regul Homeost Agents. 2018;32(1 Suppl. 1):49-60. 7. Bonini S, Sacchetti M, Mantelli F, Lambiase A. Clinical grading of vernal keratoconjunctivitis. Curr Opin Allergy Clin Immunol. 2007;7(5):436-41. 8. Leonardi A, Doan S, Fauquert JL, Bozkurt B, Allegri P, Marmouz F, et al. Diagnostic tools in ocular allergy. Allergy. 2017;72(10):1485-98. 9. Ansotegui IJ, Melioli G, Canonica GW, Caraballo L, Villa E, Ebisawa M, et al. IgE allergy diagnostics and other relevant tests in allergy, a World Allergy Organization position paper. World Allergy Organ J. 2020;13(2):100080. Erratum in: World Allergy Organ J. 2021;14(7):100557. 10. Agache I, Bilò M, Braunstahl GJ, Delgado L, Demoly P, Eigenmann P, et al. In vivo diagnosis of allergic diseases--allergen provocation tests. Allergy. 2015;70(4):355-65. 11. Leonardi A. In-vivo diagnostic measurements of ocular inflammation. Curr Opin Allergy Clin Immunol. 2005;5(5):464-72. 12. Bielory L, Schoenberg D. Emerging Therapeutics for Ocular Surface Disease. Curr Allergy Asthma Rep. 2019;19(3):16. 13. Singhal D, Sahay P, Maharana PK, Raj N, Sharma N, Titiyal JS. Vernal Keratoconjunctivitis. Surv Ophthalmol. 2019;64(3):289-311. 14. Bielory L, Schoenberg D. Ocular allergy: update on clinical trials. Curr Opin Allergy Clin Immunol. 2019 Oct;19(5):495-502. 15. Li Y, Liu X, Yu J, Li Z, Chen Y, Li H, Chen X, Su W, Liang D. Tofacitinib suppresses mast cell degranulation and attenuates experimental allergic conjunctivitis. Int Immunopharmacol. 2020 Sep;86:106737. Dr. Mekhla Naik, MD Shantilal Shanghvi Eye Institute, CS No: 3/207, 4/207, Mitha Ghar, RJ Gaikwad Road, Barkat Ali Dargah Rd, Wadala, Mumbai, Maharashtra. Corresponding Author: Subspeciality - Ocular Surface

DOS Times Volume 29, Number 4, July-August 2023 www.dosonline.org/dos-times 28 Introduction Sweet Syndrome, also known as Acute febrile neutrophilic dermatosis or Gomm Button disease is an inflammatory dermatosis characterized by non itchy, tender, erythematous plaques on arms, upper body, head and neck. It may occur at any age but most common in the age group of 30-60 years of age. Females are more commonly affected with female male ratio of 4:1. Histological findings include a dense dermal neutrophilic infiltrate with edema. Reported associations include leukemias, inflammatory bowel disease, sarcoidosis, rheumatoid arthritis and erythema nodosum.[1] Case Report A 26 years old female presented to our department with pain and redness in both her eyes for the last 2 weeks. (Figure-1). On taking detailed history, she also complained of red raised painful lesions over anterior aspect of both her lower legs which on examination were found to be tender nodular plaques measuring about 5cm by 3cm in size. Distributed bilaterally and symmetrically over anterior aspect of both her lower legs (Figure-2). Detailed slit lamp and fundus examination was done. She was diagnosed to have bilateral nodular scleritis which was confirmed by phenlyephrine test (Figure-3). Detailed investigations were then done after consultation with the dermatologist. Findings were suggestive of leucocytosis (13,500 cmm) with predominant neutrophilia (72%), elevated erythrocyte sedimentation rate (120 mm in first hour) and positive C reactive protein (Figure-4). Provisional diagnosis of Sweet syndrome was made. Punch skin biopsy was then done and sent for histopathological examination. Histopathological report showed findings consistent with Sweet syndrome i.e. dermal neutrophilic infiltrate. The patient was then started on Tab. Prednisolone 1mg/kg once a day along with topical steroids. The patient reported back after 2 weeks. She responded well to treatment with marked improvement in her signs and symptoms (Figure-5). Bilateral Nodular Scleritis with Sweet Syndrome Mukta Sharma[1], MS, Neeraj Sharma[2], MD 1. Department of Ophthalmology, Dr. RKGMC, Hamirpur, HP. 2. Department of Dermatology, Dr. RKGMC, Hamirpur, HP. Abstract: Sweet syndrome or Acute febrile neutrophilic dermatitis is a disease of unknown etiology characterized by abrupt eruption of painful, erythematous cutaneous plaques and nodules on face, neck and limbs accompanied by fever, leucocytosis and neutrophilia. Here we report a case of Sweet syndrome in a 26 years old female who presented with nodular scleritis in both her eyes. She demonstrated good response to oral steroids with complete resolution of scleritis. Ocular manifestations are uncommon in Sweet syndrome but it is important to diagnose and treat them at the earliest to prevent ocular morbidity and ensure good clinical outcome. Figure 1: Picture showing bilateral nodular scleritis. Figure 2: Magnified view of left eye showing nodular scleritis. Subspeciality - Ocular Surface

www.dosonline.org/dos-times DOS Times Volume 29, Number 4, July-August 2023 29 Figure 3: Picture showing erythematous nodular plaques in both lower legs. Figure 5: Picture showing improvement in ocular findings. Figure 4: ESR 120mm in 1st hour. Discussion Sweet syndrome is the end point of unrestricted neutrophil production with consequent infiltration of skin and sometimes other organs. A predisposition could be either genetic or acquired. Three main types have been described: Classical, malignancy associated or drug induced. Most patients have fever and history of infection. URTI commonly preceeds appearance of skin lesions by 1-3 weeks.[2] The specific involvement of other organs is extracutaneous sweet syndrome.[3] CNS involvement or ‘neuro sweets’ may present as encephalitis, aseptic meningitis and psychiatric symptoms.[4] Respiratory involvement in the form of aseptic pulmonary effusion is known.[5] Ocular involvement in the form of bilateral nodular scleritis has been reported earlier by few authors.[6,7] Early diagnosis and timely treatment is needed to ensure complete resolution of ocular and dermal lesions. References 1. Sweet RD. An acute febrile neutrophilic derrmatosis. Br J Dermatol.1964.Aug-Sept;76: 349-56. 2. Von den Driesch P.Sweet syndrome (acute febrile neutrophilic dermatosis). J Am Acad Dermatol.1994;31:535-6. 3. Matta M, Kurban AK :Sweet syndrome: systemic association. Cutis.1973;12:561-65. 4. Hisanaga K, Hosokawa M, Sato N etal. Neuro-sweet disease: benign recurrent encephalitis with neutrophilic dermatosis. Arch Neurol.1999;56:1010-13. 5. Takimoto CH,Warnock M, Golden JA.Sweet syndrome with lung involvement. Am Rev Respir Dis.1991 Jan;143(1):177-9. 6. Kato T, Kunikata N, Taira H etal.Acute febrile neutrophilic dermatosis with nodular episcleritis and polyneuropathy. Int J Dermatol.2002;41:107-9. 7. Chen TC, Goldstein DA, Tessler HH etal.Scleritis associated with acute febrile neutrophilic dermatosis. Br J Ophthalmol.1998;82:328-9. Dr. Mukta Sharma, MS Senior Resident, Department of Ophthalmology, Dr. RKGMC, Hamirpur (HP). Corresponding Author: Subspeciality - Ocular Surface

DOS Times Volume 29, Number 4, July-August 2023 www.dosonline.org/dos-times 30 Sensory and Motor Evaluation of Strabismus Jatinder Singh Bhalla, MBBS, MS, DNB, MNAMS, Tarun Patidar, MBBS, Ridhima Sakhuja, MBBS, MS, DNB, FPOS, Sadiqua Khatoon, MBBS, DO, Ashish Kumar Sain, MBBS, DO Department of Ophthalmology, DDU Hospital, Hari Nagar, New Delhi. Introduction Strabismus presents a complex challenge in achieving binocular vision and overall quality of life. It demands meticulous evaluation and intervention. This article offers a roadmap for clinicians navigating the intricate landscape of strabismus. By equipping them with the knowledge and tools to diagnose strabismus effectively, we aim to facilitate early intervention, ultimately improving the visual outcomes and quality of life for the patients. History Key questions for the clinician to ask when obtaining a strabismus or torticollis history include the following: • At what age did the deviation or AHP appear? (Reviewing old photo graphs may be helpful.) • Did onset coincide with trauma or illness? • Is the deviation or AHP constant or intermittent? • Is it present for distance or near vision or both? • Is it present only when the patient is inattentive or fatigued? • Is it associated with double vision or eyestrain? • If a deviation is noted, is it present in all positions of gaze? • If a deviation is noted, is it unilateral or alternating? • Does the patient close 1 eye? • Is there a history of other ocular disease or ocular surgery? It is important to review any previous treatment, such as amblyopia therapy, spectacle correction, and eye muscle surgery. The initial assessment also includes observation of the patient’s habitual head position, head movement, and attentiveness. In adults, reports of diplopia warrant taking additional history to determine whether the double vision has a monocular origin. Monocular diplopia can arise from corneal irregularities, cataract, uncorrected refractive error, and retinal distortion. Binocular and monocular diplopia can coexist. Key additional questions for the clinician to ask when taking a history from a person who may have monocular diplopia include: • Is double vision pre sent when viewing with only 1 eye? • Does 1 or both of the images appear to be distorted? • Does the double vision resolve briefly with blinking? Visual Acuity Visual acuity is evaluated for each eye separately and together for both distance and near vision, and with and without glasses techniques for younger children: observation, optokinetic nystagmus, visual evoked potential, forced choice preferential looking visual acuity assessment according to age • Age 0-12 months: VEP, OKN catford etc • 12 months - 2 yrs: stycar balls, Cardiff cards etc • 2 -3 yrs: kay pictures, lea symbols etc • 3 yrs and above: landolt C, snellens, LogMar etc Sensory Testing Titmus or Randot Introduction These tests are used the most often to quantify stereopsis, it can also be used to detect ARC (abnormal retinal correspondence). The level of dissociation is moderate. This test should be done on all patients who are bi-foveal and can be used as a quick screening to see if the patient is using two eyes together. Patients with deviations of 8Δ or less should also be tested as well as patients with constant tropias, as finding of stereopsis will indicated that the deviation is actually intermittent. The test can also uncover malingering in a patient claiming severe vision loss or blindness in one eye.[1][2] Procedure The patient is directed to put on polarized glasses. They are then shown a book with stereoscopic images (3-dimensional) and 2-dimensional images. The patient is asked to identify which pictures are stereoscopic. The book either has a titmus fly or a randot stereogram. The other side of the book has stereoscopic animals and circles. It is typical to ask the patient to identify the animals after the fly or shapes and the circles last. Interpretations The “titmus fly” is considered to be 3000 seconds of arc where as the “9th circle” is about 40 seconds of arc. Some could argue that the titmus fly gives off monocular clues that allow patients with reduced stereo to able to identify the image. One way to verify if the patient truly has stereopsis is to flip the book at a 90 degree Subspeciality - Squint

www.dosonline.org/dos-times DOS Times Volume 29, Number 4, July-August 2023 31 angle, the image should appear 2-dimensional. Falsely good stereopsis is very common when using the titmus fly because it is the most commonly used stereopscopic test.[1][2] Conditions such as strabismus and amblyopia can reduce stereopsis, however, some degree of stereopsis can be seen in patients with anisometropic amblyopia or small angle strabismus of 8 prism diopters or less (as noted in Park’s Monofixation Syndrome).[2] If a patient has reduced stereopsis, it would be beneficial to then test them with the Worth 4 Dot to confirm fusion status or if in fact they have a central suppression scotoma consistent with Monofixation Syndrome. 4Δ Base Out Test Introduction The four-prism diopter base-out prism test is of some value in determining whether a patient has bifoveal (sensory) fusion or a small suppression scotoma under binocular conditions or to assess the quality of binocular vision in postoperative orthotropes. This test was introduced by Irvine.[3] Procedure A four-prism diopter base-out prism is held before one eye while the patient fixates on a penlight and the observer notes the presence or absence of a biphasic movement of the fellow eye Interpretations A. When a prism is placed over the left eye, dextroversion occurs during refixation of that eye, indicating absence of foveal suppression in the left eye. If a suppression scotoma is present in the left eye, there will be no movement of either eye when placing the prism before the left eye. B. A subsequent slow fusional adduction movement of the right eye is observed, indicating absence of foveal suppression in the right eye. C. In a second patient the right eye stays abducted, and the absence of an adduction movement (B) indicates foveal suppression in the right eye or anomalous retinal correspondence. D. Another cause for absence of the adduction movement is weak fusion, and such patients will experience diplopia until refusion occurs spontaneously. Figure 1: Titmus test on right (polarized glasses above), Randot test on [4] left. Figure 2: 4 Prism base out test. Subspeciality - Squint

DOS Times Volume 29, Number 4, July-August 2023 www.dosonline.org/dos-times 32 The Worth Four-Dot Test Introduction The purpose of this test is used to detect peripheral sensory fusion and foveal suppression. The level of dissociation is high. This test can be used for any verbal child with any angle of strabismus especially with reduced stereopsis.[5] Procedure This can be done with the lights on or the lights off depending on what level of dissociation is preferred. With the lights off, the depth of suppression can be measured. Place the red-green glasses on the patient, with the red glass on the right eye. Ask the patient to report how many lights they see at the distance and at near (1/3 of a meter). Interpretation • Patient sees all four lights: peripheral fusion with orthophoria or esotropia with anomalous retinal correspondence. Depending on ocular dominance, the light in the 6-o’clock position is seen as white or pink. • Patient sees two vertically displaced red lights: suppression OS. • Patient sees three green lights: suppression OD. • Patient sees five lights. The red lights may appear to the right, (uncrossed diplopia with esotropia), or to the left of the green lights (crossed diplopia with exotropia).[5][6][7][8] Bagolini Glasses Introduction The striated glasses are plano glasses without refractive power that do not modify the state of accommodation. They have fine parallel linear striations that do not alter significantly the visual acuity and the perception of the visual space. Procedure The patient fixates a small light, at the reading distance or at the end of the examination lane, through the striated glasses placed before each eye in a trial frame. The glasses are usually placed at 45o and 135o . Optical correction should be worn during the test. Through each striated glass the fixation light is perceived as crossed by an elongated streak across one meridian. The light source is a fusible stimulus, equal for each eye. The striations are check marks and allow differentiation of a single perception of the light due to suppression (one streak) from binocular perception in normal or patients with ARC (two streaks crossed in the centre) or from diplopia (two streaks separate from each other or crossing in the peripheral part of the streaks). Interpretation A. Crossing of the luminous lines when a manifest ocular deviation (cover test) is present indicates ARC. B. Suppression of the right eye. C. Fixation point scotoma (with manifest deviation and ARC) or foveal scotoma (with orthophoria and normal retinal correspondence) of the right eye.[9][10] D. Double vision with esotropia. Figure 3: Worth four dot test. Figure 4: Interpretation of bagolini glasses. After Image Test Introduction Hering found convincing proof for the unity of the binocular field in the following simple experiment. A small, lasting Subspeciality - Squint

www.dosonline.org/dos-times DOS Times Volume 29, Number 4, July-August 2023 33 afterimage is produced in the left eye, and the eye is then closed. In the open right eye the afterimage appears in the field of vision and shifts with the movements of the eyes, just as if the left eye were open. After images produced successively on the foveae of the two eyes will appear in their common visual direction regardless of whether the eyes are open or closed and regardless of the position of the eyes relative to each other. Procedure and Interpretation In clinical practice the test is performed by using a batterypowered camera flash to produce a vertical afterimage in one eye and a horizontal afterimage in the other eye. The reflecting surface is covered with black paper to expose a narrow slit, the center of which is covered with tape and serves as a fixation mark, thus protecting the fovea from exposure. The resulting afterimage is that of a line with a break in its middle, which represents the fovea. The patient is required to fixate steadily the central mark, first with one eye while the slit is in a horizontal position and then with the other eye while the slit is in a vertical position. The nonexposed eye must be well covered. During the exposure, a strong stimulus reaches the principal horizontal and vertical meridians of the right and left eyes but in neither eye is the foveal area stimulated. In a darkened room or with the eyes closed, the patient now sees the two successively imprinted afterimages simultaneously as positive afterimages (bright lines). In a lighted room or with the eyes open, negative afterimages (dark lines) will be seen.[11] Motor Evaluation Observation of Head Position Patients with comitant heterotropias, especially those with comitant horizontal heterotropias, usually carry their head in a normal position, but there are exceptions. Patients who have a high amblyopia of one eye occasionally tend to turn their head in a direction away from the amblyopic eye, especially when reading or looking intently at an object. Patients with infantile esotropia, manifest-latent nystagmus, and strong fixation preference for one eye often have their face turn toward the side of the fixating eye. Abnormal head positions in connection with incomitant and paretic deviations are usually assumed in the interest of obtaining binocular cooperation or avoiding diplopia. Abnormal head positions take either the form of tipping the chin up or down, a head turn (i.e., a turn around a vertical axis), or a head tilt to one shoulder. For example, a patient with an A or V pattern of deviation may tend to carry the head with the chin depressed or elevated. On the other hand, a patient with a right lateral rectus paresis may turn the head to the right, causing levoversion to bring the eyes into a position in which the right lateral rectus muscle receives no impulses to contract. With these positions of head and eyes, patients avoid diplopia and gain binocularity. Bielschowsky wrote that ‘‘the patient chooses the least inconvenient position of the head by which the paretic muscle is sufficiently relieved so that binocular single vision can be obtained.’[12] Hirschberg (H) Test On infants or an individual with a poor seeing eye, it is useful to use the Hirschberg Test. The examiner is looking at the corneal light reflex.[1] Procedure A muscle light or penlight is used at 1/3 of a meter and patient is asked to fixate on the light. If the light reflex is centered in both eyes, the patient does not have a manifest misalignment. If the light reflex is displaced, it shows a manifest misalignment. The amount of decentration can be used to estimate the degree of the misalignment. 1mm of displacement is roughly 7 degrees or 15Δ. For example, the light reflex at the pupillary margin is about 2 mm from the center (with a normal 4 mm pupil). This corresponds with 15 degrees or about 30Δ. The mid-iris region is about 4mm from the center of the pupil, which is about 30 degrees or 60Δ. A reflex at the limbus is about 45 degrees or 90Δ. Interpretation If the light reflex is displaced nasally, the patient has an exotropia. If the light reflex is displaced temporally, the patient is esotropic. It is important to note the light reflex is always slightly nasal, even in an orthophoric patient. It is also important to note that angle kappa can affect light reflex measurements. A positive angle kappa simulates an exotropia, a negative angle kappa simulates an esotropia.[2] Krimsky (K) Test Corneal reflection is produced in the two eyes by an appropriately placed penlight, which is fixated by the patient’s better eye. The examiner places him- or herself on the side of the deviated eye to avoid parallax errors in observation. Prisms are then placed in front of the fixating eye to center the corneal reflection in the deviated eye. The amount of prism power necessary to achieve this is a measure of the deviation. This test, first described by Krimsky,69 who suggested the name ‘‘prism reflex test,’’ is a practical method of estimating the size of the angle of squint in patients with a blind or deeply amblyopic eye with or without eccentric fixation. It is important for the examiner to be seated Figure 5: Hirschberg test. Subspeciality - Squint

DOS Times Volume 29, Number 4, July-August 2023 www.dosonline.org/dos-times 34 Cover Test Introduction The simple cover and cover-uncover tests establish whether orthotropia or an ocular deviation is present, whether a deviation is latent or manifest, the direction of a deviation, the fixation behavior, and even whether visual acuity is significantly decreased in one eye. Procedure A cover is placed briefly before the eye that appears to fixate while the patient looks at a small object, a figure pasted on a tongue depressor, or a 6/9 visual acuity symbol. The test should always be done for distance and near fixation to establish any differences between the two conditions. As a cover, one may use the palm of the hand or some form of occluder or paddle. Covering one eye of a patient with normal binocular vision interrupts fusion. Interpretation If the patient has a heterotropia and the fixating eye is covered, the opposite eye, provided it is able to do so, will make a movement from the heterotropic position to take up fixation, and the covered eye will make a corresponding movement in directly in front of the deviating eye to avoid false readings caused by parallax. In another version of this test, prisms are placed in front of the deviating eye until the corneal reflection is centered.[13] accordance with Hering’s law. An exotropia is present when the eye taking up fixation moves toward the nose, an esotropia when it moves toward the temple, and so forth. If there is no movement of the fellow eye, that eye is then covered and the other eye is observed. Cover and Uncover Test Procedure When it has been established that no manifest strabismus is present (no movement of the fellow eye when either eye is covered), a cover-uncover test will determine whether the patient has a latent deviation. Again, one and then the other eye is covered while the patient maintains fixation. Interpretation The possible results of the cover and cover uncover tests may be summarized as follows: 1. On covering the seemingly fixating eye: a. No movement of the other eye: there was binocular fixation before applying the cover. b. Movement of redress of the other eye: a manifest deviation was present before applying the cover. 2. On uncovering the eye: a. Movement of redress of the uncovered eye (fusional movement); no movement of the other eye: heterophoria is present. b. No movement of either eye; uncovered eye deviated; opposite eye continues to fixate: an alternating heterotropia is present. c. Uncovered eye makes movement of redress and assumes fixation; opposite eye deviates; preference for fixation with one eye: a unilateral heterotropia is present. Madox Rod Test Introduction This device, consisting of small glass rods, causes an astigmatic elongation of the fixation light and may be placed to produce a vertical or horizontal streak to measure the horizontal and vertical deviation. If the streak does not go through the fixation light, prisms of increasing strength are placed in front of the eye until it does. The amount of prism power required to achieve this goal is a measure of the heterophoria. Interpretation A. Maddox rod in testing position for horizontal heterophoria. B. Patient sees the line going through the light: no horizontal phoria is present. C. The line is seen to the left of the light (crossed diplopia): exophoria. Add prisms, base-in, to OD until the line is centered on the light. The power of the prism is read and equals the amount of phoria. D. The line is seen to the right of the light[14] Figure 6: Krimsky test. Subspeciality - Squint

www.dosonline.org/dos-times DOS Times Volume 29, Number 4, July-August 2023 35 Double Maddox Rod Introduction This test is used to determine the presence of a cyclodeviation. This test is very dissociating. Clinically, it is useful to use this on patients who have a suspected 4th Nerve Palsy, or Thyroid Eye Disease.[6] It is also important to note that patients will usually tolerate excyclotorsion more than incyclotorsion.[4] Procedure Orient two Maddox rods (one white and one red) at 90 degrees, so the striations are vertical, in trial frames. When shown to the patient with a muscle light at 1/3 of a meter, the patient should see a red line and a white line. Instruct the patient to turn the knobs to rotate the lenses until both lines are horizontal. For a 4th Nerve Palsy, it could be helpful to put the red rod on the eye that is paretic.[4] It can be useful for the examiner to put the glasses on themselves to show the patient the trial frame and demonstrate use of the knobs. Interpretation If the lines are horizontal with the rods , there are 0 degrees of torsion. If the lines aren’t parallel, there is torsion present. The patient should be able use the knob to rotate the line until it is parallel line. If the rod has to be rotated inward, the patient has incyclotorsion. If the rod has to be rotated outward, the patient Diplopia Charting Introduction Diplopia chart is the record of separation of the diplopic or double images in the nine positions of gaze. It can be plotted charted in patients who cooperate and can appreciate double vision with incomitant or comitant deviation. Procedure The patient should be comfortable with head erect and preferably be still throughout the examination. The test is carried out in dark room. Red glass is placed in front of right eye. The examiner holds the torch (vertical source of light) at around half meter or 1 meter (it is important to mention distance on the chart). This source of light could be horizontal if the complaint is of vertical separation of images. The light is held directly in front of the patient at first. If the patient sees a single image, the examiner must establish whether it is fused image, if suppression is present or if one image is obscured, for example by the patients nose bridge. If there is no doble vision in the primary position, the position in which double vision appears and is maximal is to be noted if the patient noted double image the relative position of this images is noted. the light is now carried to all other positions of gaze. In each gaze position the patient asked whether the images are parallel or tilted; if the torsion is present colored pencils can be given to an observant patient to show the separation of torsion. Interpretation To interpret the diplopia chart the most important questions are • The position in which diplopia appears has excyclotorsion. The trial frame has an axis marked, so the examiner can determine the amount of torsion. Figure 7: Maddox rod test. Figure 8: Double Maddox rod test. Subspeciality - Squint

DOS Times Volume 29, Number 4, July-August 2023 www.dosonline.org/dos-times 36 • The position in which the separation of the image is greatest In the direction of the action of paralysed muscle, double vision or separation would be greatest because of the under-action of the muscle and over action of antagonist yolk muscle. Figure 9: Diplopia charts. Subspeciality - Squint

www.dosonline.org/dos-times DOS Times Volume 29, Number 4, July-August 2023 37 Hess Chart Introduction A Hess chart is plotted to aid in the diagnosis and monitoring of a patient with incomitant strabismus, such as an extraocular muscle palsy (e.g. third, fourth or sixth nerve paresis) or a mechanical or myopathic limitation (e.g. thyroid ophthalmopathy, blow-out fracture or myasthenia gravis). The chart is commonly prepared using either the Lees or Hess screen, which facilitate plotting of the dissociated ocular position as a measure of extraocular muscle action. Interpretation • The smaller chart indicates the eye with the paretic muscle (right eye). • The larger chart indicates the eye with the overacting yoke muscle (left eye). • The smaller chart will show its greatest restriction in the main direction of action of the paretic muscle (right lateral rectus). • The larger chart will show its greatest expansion in the main direction of action of the yoke muscle (left medial rectus). Conclusion The diagnostic assessment of strabismus demands a comprehensive understanding of its nature. Ultimately, the goal of this diagnostic process is to tailor treatment strategies effectively. Whether through optical correction, occlusion therapy, or surgical intervention, addressing strabismus in patients requires a multidimensional approach that considers the unique needs and characteristics of each individual. By delving into the complexities of these conditions and employing a comprehensive diagnostic toolkit, ophthalmologists can provide the best possible care, ultimately improving the visual outcomes and quality of life for their patients. References 1. Arnoldi, Kyle. Orthoptic Evaluation and Treatment. Pediatric Ophthalmology: Current Thought and Practical Guide. By M. Edward. Wilson, Richard A. Saunders, and Rupal H. Trivedi. Berlin: Springer-Verlag, 2009. P.113-40. 2. Wright, Kenneth W. Pediatric Ophthalmology and Strabismus. St. Louis, MO: Mosby, 1995. P.159-157. 3. Irvine SR: A simple test for binocular fixation: Clinical application useful in the appraisal of ocular dominance, amblyopia ex anopsia, minimal strabismus and malingering. Am J Ophthalmol 27:740, 1944. 4. From Noorden GK von: Present status of sensory testing in strabismus. In Symposium on Strabismus: Transactions of the New Orleans Academy of Ophthalmology. St Louis, Mosby–Year Book, 1978, p 51. 5. Campos EC: Binocularity in comitant strabismus: Binocular visual fields studies. Doc Ophthalmol 53:249, 1982. 6. Herzau V: Untersuchungen u¨ber das binokulare Gesichtsfeld Schielender. Doc Ophthalmol 49:221, 1980. 7. Olling G, Schuy K: Statische Perimetrie beim Mikrostrabismus convergens und bei Vernebelung durch Plusgla¨ser und Bangerter Folien. Fortschr Ophthalmol 83:507, 1986. 8. Kommerell G: Das Fixierpunktskotom des schielenden Auges: Ein Artefakt? Orthoptik Pleoptik 13:29, 1986. 9. Bagolini B: Tecnica per l’esame della visione binoculare senza introduzione di elementi dissocianti: ‘‘test del vetro striato.’’ Boll Ocul 37:195, 1958. 10. Bagolini B, Campos EC: Practical usefulness of anomalous binocular vision for the strabismic patient. Int Ophthalmol 6:19, 1983. 11. Hering E: Zur Lehre vom Ortssinn der Netzhaut. Beitra¨ge zur Physiologie, vol 3. Leipzig, Wilhelm Engelmann, 1861, p 182.en. 12. Bielschowsky A: Lectures on Motor Anomalies, Hanover,NH, Dartmouth College Publications, 1943/1956. 13. Krimsky E: The binocular examination of the young child. Am J Ophthalmol 26:624, 1943. 14. Lyle TK, Wybar KC: Lyle and Jackson’s practical orthoptics in the treatment of squint (and other anomalies of binocular vision), ed 5. Springfield, IL, Charles C Thomas, 1967. Dr. Tarun Patidar, MBBS Department of Ophthalmology, Deen Dayal Upadhyay Hospital, New Delhi. Corresponding Author: Figure 10: Hess chart. Subspeciality - Squint

DOS Times Volume 29, Number 4, July-August 2023 www.dosonline.org/dos-times 38 Stereopsis: An Overview Aarushi Saini[1], MS, FICO, Agam Bhandari[2], MD, FICO 1. Senior Resident, ESIC Medical College and Hospital, Faridabad. 2. Consultant, Bhandari Starlife Eye Hospital and LASIK Laser Centre, Ludhiana. Stereopsis is routinely known as the third grade of binocular vision. In simple terms, it is the ability to assess depth and 3D field of vision. In more scientific terms, our eyes have different vantage points which means that images falling on the retina are not identical. This difference in the locations of images is termed as binocular disparity. Our ability to assess depth arises from this disparity and is known a stereopsis.[1] Integration of two minutely dissimilar retinal images results in stereopsis and it needs some degree of retinal disparity. It starts developing between 3 and 5 months of age and attains adult level by 5-7 years.[2] Normal level of stereopsis in an Adult is 40 seconds of arc. In children, 70 seconds of arc is normal in 3-5 years age, 50 seconds of arc in 5-7 years of age and 40 seconds of arc above 8 years of age. Why is Stereopsis Important? Significance of stereopsis has been largely neglected. Having stereopsis is advantageous in understanding complex visual presentations and a good hand eye coordination.[2] A sign of good binocular function, it provides a better quality of life as well as offers more profession choices to a person. It has been seen that those with normal stereoacuity had a better motor performance than those will nil stereoacuity. Motor skill tasks are reduced under monocular conditions. It was also noted that some level of stereoacuity is better than nil stereoacuity in performing motor tasks.[3] Some studies have reported that tasks such as reading and writing in children are also affected to some extent by stereoacuity.[4,5] 3D tasks like movies, televisions and animation games have gained more importance today as compared to previous times and a child with no stereopsis is bound to miss out on these forms of entertainment.[6] Thus, stereopsis is important for many specific visuomotor tasks in day-to-day life though absence of stereopsis does not visually impair an individual. Early management of esotropia is advocated to increases chances of development of stereopsis. Wright et al have shown that very early management of esotropia not only results in ocular alignment but also a high grade of stereoacuity.[7] Presence of stereopsis after deviation correction has been seen to be associated with less risk of requiring re-surgery. In a study of infantile and accommodative esotropias, it was seen that patients who didn’t have stereopsis were more likely to require strabismus surgery for consecutive exotropia or recurrent esotropia. These patients had more risk of losing stereopsis if correction of strabismus was achieved at or more than 5 years of age. This risk was higher in accommodative esotropia as compared to infantile esotropia.[8] Therefore, surgical outcomes are more dependable if done at early age so that stereopsis can be achieved. A study from R.P. Centre, AIIMS, New Delhi, determined the amount of deviation compatible with attainment of stereopsis after correction of strabismus. A deviation of less than or equal to 8 Prism dioptres was found to have better outcomes in terms of gaining stereoacuity.[9] Not only esotropia, but exotropia management also has a role of stereopsis. In patients with exotropia having poor distance stereoacuity and near fusional amplitudes, an improvement in both parameters was seen after surgical alignment.[10] Superior sensory outcomes are seen with ocular alignment done at a timely interval and when the deviation is intermittent.[11,12] Hence, if a patient with intermittent exotropia has subnormal stereoacuity, then a timely management can restore it to normal values. A manifest exotropia is as detrimental as esotropia and should be corrected with urgency. Managing infantile esotropia at 6 months and intermittent exotropia at 6 years should be the norm.[6] Apart from the above advantage, a relationship between amblyopia and presence of stereopsis has also been noted. Severe amblyopia is less likely to be associated with patients having stereopsis.[13] In practice, we see that stereopsis can be very helpful in assessing the relevance and manifestations of strabismus in patients. Hence, the outcome and ultimate goal of strabismus and amblyopia management today is no longer just alignment but also gain of stereopsis.[6] Tests for Stereopsis[14] Qualitative Test 1. Lang two pencil test (Figure-1) Patient is asked to touch the tip of a pen to the tip of another pen held by the examiner. Conventionally, it is done with either eye in turn and then with both eyes together. This gives a crude assessment of stereopsis and doesn’t quantify it but nonetheless is a good method to check gross stereopsis. 2. Synaptophore (Figure-2) With the use of slides (Figure-3) meant to check stereopsis, one can assess the stereopsis with a synaptophore. It may give artefactual information, hence not very reliable. Subspeciality - Squint

www.dosonline.org/dos-times DOS Times Volume 29, Number 4, July-August 2023 39 Figure 1: Lang two pencil test. Figure 2: Synaptophore. Figure 3: Slides. Figure 4: TNO Test. Quantitative Test 3. TNO Stereo Test (Figure-4) Computer generated red/green random dots are viewed at 40cm using red-green glasses. It can measure stereoacuity between 480-15 seconds of arc. Advantage: No monocular cues 4. Titmus Stereo Test (Figure-5) It has a vectograph in which targets are polarised at 90 degrees. It is viewed through polaroid filter glasses giving an illusion of depth perception. It measures stereopsis from 3000-40 seconds of arc. Disadvantage: Monocular cues can overestimate stereoacuity 5. Randot Stereo Test (Figure-6) It uses random dot targets which are viewed through polarized glasses. It is better than titmus stereo test but not as good as the TNO test. 6. Frisby Stereo Test (Figure-7) It uses actual depth of a target to quantify stereopsis. Its measurement ranges between 600-15 seconds of arc. Advantage: No glasses are required Disadvantage: Monocular cues can overestimate stereopsis Subspeciality - Squint

DOS Times Volume 29, Number 4, July-August 2023 www.dosonline.org/dos-times 40 Figure 5: Titmus Stereo Test. Figure 6: Randot stereo Test. Figure 7: Frisby Stereo Test. References 1. Cumming BG, DeAngelis GC. The Physiology of Stereopsis. Annu Rev Neurosci. 2001 Mar;24(1):203–38. 2. Fielder AR, Moseley MJ. Does stereopsis matter in humans? Eye. 1996 Mar;10(2):233–8. 3. Beauchamp GR, Black BC, Coats DK, Enzenauer RW, Hutchinson AK, Saunders RA, et al. The management of strabismus in adults- -III. The effects on disability. J AAPOS Off Publ Am Assoc Pediatr Ophthalmol Strabismus. 2005 Oct;9(5):455–9. 4. Kulp MT, Schmidt PP. A pilot study. Depth perception and near stereoacuity: is it related to academic performance in young children? Binocul Vis Strabismus Q. 2002;17(2):129-34; discussion 133. PMID: 12067270. 5. Kulp MT, Schmidt PP. Visual predictors of reading performance in kindergarten and first grade children. Optom Vis Sci. 1996 Apr;73(4):255-62. doi: 10.1097/00006324-199604000-00007. PMID: 8728493. 6. Sharma P. The pursuit of stereopsis. J AAPOS. 2018 Feb;22(1):2.e1-2. e5. doi: 10.1016/j.jaapos.2017.10.009. Epub 2017 Dec 30. PMID: 29292047. 7. Wright KW, Edelman PM, McVey JH, Terry AP, Lin M. Highgrade stereo acuity after early surgery for congenital esotropia. Arch Ophthalmol Chic Ill 1960. 1994 Jul;112(7):913–9. 8. Birch EE, Stager DR, Berry P, Leffler J. Stereopsis and long-term stability of alignment in esotropia. J AAPOS Off Publ Am Assoc Pediatr Ophthalmol Strabismus. 2004 Apr;8(2):146–50. 9. Nongpiur ME, Singh A, Saxena R, Sharma A, Sharma P. To evaluate stereoacuity in patients with acquired esotropia and to determine factors associated with favourable outcomes. Indian J Ophthalmol. 2014 Jun;62(6):695–8. 10. Sharma P, Saxena R, Narvekar M, Gadia R, Menon V. Evaluation of distance and near stereoacuity and fusional vergence in intermittent exotropia. Indian J Ophthalmol. 2008;56(2):121–5. 11. Singh A, Sharma P, Singh D, Saxena R, Sharma A, Menon V. Evaluation of FD2 (Frisby Davis distance) stereotest in surgical management of intermittent exotropia. Br J Ophthalmol. 2013 Oct;97(10):1318–21. 12. Abroms AD, Mohney BG, Rush DP, Parks MM, Tong PY. Timely surgery in intermittent and constant exotropia for superior sensory outcome. Am J Ophthalmol. 2001 Jan;131(1):111–6. 13. O’Connor AR, Birch EE, Anderson S, Draper H, the FSOS Research Group. The Functional Significance of Stereopsis. Invest Ophthalmol Vis Sci. 2010 Apr 1;51(4):2019–23. 14. Lee J, McIntyre A. Clinical tests for binocular vision. Eye. 1996 Mar;10(2):282–5. Dr. Aarushi Saini, MS, FICO Senior Resident, Department of Ophthalmology, ESIC Medical College and Hospital, Faridabad. Corresponding Author: Subspeciality - Squint

www.dosonline.org/dos-times DOS Times Volume 29, Number 4, July-August 2023 41 Elschnig Pearls Anubhav Chauhan, MS, Deepak Kumar Sharma, MS Department of Ophthalmology, Shri Lal Bahadur Shastri Government Medical College and Hospital, Nerchowk, Distt. Mandi, Himachal Pradesh. Case/Rare Ophthalmic Images A 74-year-old female, reported to us with a history of gradual, painless diminition of vision in her right eye for the past three months. She had undergone cataract extraction with posterior chamber intraocular lens implantation in her right eye three years back. There was no other significant history. Her best corrected visual aquity was 6/36 in the right eye and 6/6 in the left eye. Slit lamp examination revealed posterior capsular opacification(PCO) in the form of elschnig pearls in the right eye (Figure-1). Fundus of the right eye could not be assessed because of the PCO. Rest of the ocular examination was within normal limits. She underwent Nd:YAG laser capsulotomy (Figure-2) in her right eye and the vision was restored. Elschnig pearls is a form of after-cataract or PCO, and is an important cause for diminition of vision after intraocular lens implantation. These are formed by residual equatorial lens epithelium cells which migrate and proliferate between the posterior capsule and the intraocular lens.[1] Nd: YAG laser capsulotomy is the treatment of choice for PCO.[2] References 1. Findl O, Neumayer T, Hirnschall N, Buehl W. Natural Course of Elschnig Pearl Formation and Disappearance. Investigative Ophthalmology & Visual Science 2010; 51(3):1547-1553. 2. Bhargava R, Kumar P, Prakash A, Chaudhary KP. Estimation of mean Nd:YAG Laser capsulotomy energy levels for membranous and fibrous posterior capsule opacification. Nepal J Ophthalmol 2012;4:108‐13. Dr. Anubhav Chauhan, MS Assistant Professor (Designated) Deptt. of Ophthalmology, Shri Lal Bahadur Shastri Government Medical College and Hospital, Nerchowk, Distt. Mandi, Himachal Pradesh, India. Corresponding Author: Figure 1: Elschnig Pearls. Figure 2: Post Yag Capsulotomy. Subspeciality - Lens/Cataract

DOS Times Volume 29, Number 4, July-August 2023 www.dosonline.org/dos-times 42 Beyond IOP: A Lucid Approach To Secondary Glaucoma Shweta Tripathi[1], DNB, MNAMS, FMRF, Jatinder Singh Bhalla[2], MS, DNB, MNAMS 1. Senior Consultant Glaucoma Services, Indira Gandhi Eye Hospital and Research Centre Lucknow. 2. Consultant and Incharge Academics DDU Hospital, Hari Nagar, New Delhi. Abstract: We report a case of Secondary glaucoma which led to the diagnosis of granulomatosis with polyangiitis (Wegener’s granulomatosis) with prevention of sequalae and improvement of prognosis. Keywords: Secondary Glaucoma, Granulomatosis polyangiitis A 50 year old female patient presented with the chief complaint of occasional heaviness. There was past history of irregular use of anti-glaucoma medications prescribed elsewhere. On examination both eye BCVA was 6/6 & N6. Anterior segment did not have any significant findings. On gonioscopy angles were open for both eyes. On fundus examination CDR was 0.7 with early notch in right eye, left eye had a CDR of 0.6 with healthy NRR with a central corneal thickness of 562µ in both eyes. She was started on lubricating eye drops in both eyes along with beta blocker in right eye. Patient was reassured at all visits due to her non-compliant nature. Again 8 months after the 1st presentation she presented with chief complaint of both eyes redness and by now she had stopped using AGM on her own. On Examination Diffuse conjunctival congestion was present with rest anterior segment within normal limits with applanation tonometry was 18 mmHg in both eyes. Patient was treated for conjunctivitis with topical antibiotics and lubricating eye drops. On regular follow up over a period of 1 month (follow up visit 1) conjunctival congestion showed a varied pattern of increase or decrease in nature with no involvement of any further anterior or posterior segment along with fluctuating IOP. The following table shows a varied pattern of conjunctival congestion with fluctuation of IOP. (Table-1) Day of Presentation Clinical Features IOP OD IOP OS Treatment Follow up visit 2 (8 months after first visit) Conjunctival congestion had reduced 16 26 In OS:ONH was healthy we decided to wait till Next Visit Follow up visit 3 (4 days after follow up visit 2) Conjunctival Congestion Increased, AC Quiet 16 26 OU Loteprednol & Gatifloxacin along with AGM (Combination of beta blocker & alpha agonist) along with oral Diamox for 1day. Follow up visit 4 (5 days after follow up visit 3) Pt symptomatically improved 16 29 OU continued same treatment Follow up visit 5 (5 days after follow up visit 4) Conjunctival Congestion had again increased with mild Pain AC Quiet (No E/O Sclerouveitis) 23 23 Oral Wysolone 60mg/day was started in a tapering mode for 1 week each Follow up visit 6 (2 days after follow up visit 5) Congestion had reduced. 28 29 OD (combination beta blocker & alpha agonist) was started with OS addition of Brinzolamide. Follow up visit 7 (3 days after follow up visit 6) No Congestion 16 18 OU continued same treatment Subspeciality - Glaucoma

www.dosonline.org/dos-times DOS Times Volume 29, Number 4, July-August 2023 43 Points to Consider Due to recurrent attacks of diffuse conjunctival congestion & anterior chamber being quiet all the while along with fluctuating IOP and no evidence of proptosis, lid edema, episcleritis, scleritis, iritis, vitritis or ophthalmoplegia, the history was taken again where this time the patient revealed that she had episodes of fever with no diurnal variation for which she had taken treatment for urinary tract infection. On seeing the urine lab reports it was noticed that she had a episode of haematuria for 10 days,with presence of protein & RBC in urine routine. There was no history of URTI, epistaxsis, cough, dyspnoea or hemoptysis. Immunologist opinion was seeked with following lab reports LAB Investigation: • ANCA Screen:AntiPR3>100,Anti MPO<3.0, • CRP:3.67mg/dl • CT Scan :Thorax/Nose-PNS WNL • Urine routine:protein ++++, RBC=25-30hpf, epithelial cells-4-5 hpf • Renal biopsy 8 out of 17 glomeruli show cellular crescents with neutrophillic infilteration. Glomeruli: segmental Necrosis Tubules: focal atrophy, mild acute tubular necrosis Interstitium – fibrosis/inflammation, no granulomas seen Keeping the above mentioned a diagnosis of granulomatosis with polyangitis, crescentric glomerulonephritis was made, So the treatment was started as: 1. Rituxivas regimen 2. Rituximab weekly 4 doses with cyclophosphamide 15mg/kg 3. Tab omnacortil 60 mg was in tapering dose before initiation of therapy and after each session as 60 mg OD. Patient was kept on regular follow up with maintenance rituximab therapy and low dose of steroids. BVAS score 3 improved from 15 (before initiation of therapy) to O (maintenance therapy as of 06.06.2020) The Pattern of IOP improvement with gradual withdrawal of AGMs is given in (Table-2) Day of Presentation IOP OD IOP OS Treatment Follow up visit 8 (3 days after follow up visit 7) 16 18 • OU combination of beta blocker and alpha agonist B.D with OS carbonic anhydrase inhibitor B.D. • Topical Steroids OD Follow up visit 9 (15 days after follow up visit 8) 12 12 OS Carbonic anhydrase inhibitor B.D. Follow up visit 10 (two days after follow up visit 9) 18 18 Continued with same treatment Topical Steroids Stopped. Follow up visit 11 (four weeks after follow up visit 10) 16 16 Continued with oral steroids and topical AGMS Follow up visit 12 (7 weeks after follow up visit 11) 13 14 Continued with same treatment Follow up visit 13 (14 weeks after follow up visit 12) 16 16 OS Carbonic anhydrase inhibitor stopped Follow up visit 14 (5 weeks after follow up visit 13) 12 12 OU combination AGM stopped & beta blocker started Follow up visit 15 (23 weeks after follow up visit 14) 14 14 Continued with single beta blocker As we can see from the above table IOP was raised due to the underlying inflammation because of the systemic condition. On further Follow ups IOP showed a improving trend as the patient is continued on cycles of rituximab therapy despite being on steroid treatment. Discussion The criteria for the diagnosis of granulomatosis polyangiitis (GPA) are i) Urinary sediment containing red blood cell casts or more than five red blood cells per high-power field, Subspeciality - Glaucoma

DOS Times Volume 29, Number 4, July-August 2023 www.dosonline.org/dos-times 44 ii) Abnormal findings on the chest radiograph, iii) Oral ulcers or nasal discharge iv) Granulomatous inflammation on biopsy.[1] The presence of two or more of these four criteria was associated with an 88% sensitivity and 92% specificity. Of all the ANCA associated with GPA, 80-95% of cases are associated with c-ANCA with autoantibodies directed against proteinase 3 antibodies (PR3) the remainder are p-ANCA directed against myeloperoxidase antibodies (MPO)[1-2] ESR correlates better with disease activity than does CRP . In a survey of 701 north american patients with GPA, 30% of patients were reported to have ocular involvement.[4] Other studies have reported similar findings, with ocular involvement in about 50% of the patients.[5,6] Ocular disease can be the presenting or even the only clinically apparent manifestation of GPA. Learning Milestones: Comprehensive History and systemic examination with the patten of fluctuating IOP lead to the diagnosis with appropriate management of the systemic condition preventing further morbidities. Figure 1: A and B: Slit lamp examination of both eyes with conjunctival congestion. Figure 2: A and B: Fundus images of both eyes. Subspeciality - Glaucoma

www.dosonline.org/dos-times DOS Times Volume 29, Number 4, July-August 2023 45 Figure 3: A and B: HUF images of both eyes. Figure 4: RNFL analysis of both eyes. References 1. Venning MC, Quinn A, Broomhead V, Bird AG. Antibodies directed against neutrophils (c-ANCA and p-ANCA) are of distinct diagnostic value in systemic vasculitis. Q J Med. 1990; 77:1287-1296. 59. 2. Savige JA, Gallicchio M, Georgiou T, Davies DJ. Diverse target antigens recognized by circulating antibodies in antineutrophil cytoplasm antibody-associated renal vasculitides. Clin Exp Immunol. 1990; 82:238-243. 3. Hoffman GS, Kerr GS, Leavitt RY, Hallahan CW, Lebovics RS, Travis WD, Rottem M, Fauci AS. Wegener’s granulomatosis: An analysis of 158 patients. Ann Intern Med. 1992; 116:488-498. 4. Abdou NI, Kullman GJ, Hoffman GS, Sharp GC, Specks U, McDonald T, Garrity J, Goeken JA, Allen NB Wegener’s granulomatosis: Survey of 701 patients in North America. Changes in outcome in the 1990s. TJ Rheumatol. 2002; 29:309-316. 5. Hoffman GS, Kerr GS, Leavitt RY, Hallahan CW, Lebovics RS, Travis WD, Rottem M, Fauci AS. Wegener’s granulomatosis: An analysis of 158 patients. Ann Intern Med. 1992; 116:488-498. 6. Specks U, DeRemee RA. Granulomatous vasculitis. Wegener’s granulomatosis and Churg-Strauss syndrome. Rheum Dis Clin North Am. 1990; 16:377-397. Dr. Shweta Tripathi, DNB, MNAMS, FMRF Senior Consultant Glaucoma Services, Indira Gandhi Eye Hospital and Research Centre, Lucknow. Corresponding Author: Subspeciality - Glaucoma

DOS Times Volume 29, Number 4, July-August 2023 www.dosonline.org/dos-times 46 Advances in Trabeculectomy Julie Pegu, MBBS, MS, Anugya Sharma, MBBS, DNB, Priyasha Goel, MBBS, DNB Department of Glaucoma, Shroff’s Charity Eye Hospital. Glaucoma, characterized by the progressive degeneration of the optic nerve, is a global pandemic and a leading cause of preventable blindness. Early diagnosis and treatment are crucial to prevent irreversible vision loss.[1,2] However, the medical treatment of glaucoma can be costly, particularly in developing countries, posing a significant barrier to healthcare delivery. Untreated glaucoma can result in irreversible blindness, leading to individual suffering and imposing an economic burden on society. Trabeculectomy, initially described by Cairns in 1968, continues to be the gold standard for controlling intraocular pressure (IOP) in the treatment of glaucoma.[3-5] Trabeculectomy has undergone significant advancements over the years. From the historical technique of iridencleisis, where a strip of iris was plugged into a full-thickness fistula between the anterior chamber and the sub-conjunctival space through an anterior sclerostomy, the procedure has evolved to include the creation of a guarded flap. These modifications have aimed to improve the success rate and safety of trabeculectomy procedures and were influenced by advancements in our understanding of wound healing, the introduction of antimetabolite regimens, and evolving surgical techniques. This article mainly focuses on the advances in the technique of Trabeculectomy. Anesthesia Trabeculectomy surgery is typically performed under a Peribulbar block, which provides optimal comfort for the patient. It is advisable to avoid using adrenaline in the anesthetic solution, as it may potentially impede blood flow to the optic nerve head, leading to adverse effects in advanced glaucoma cases. A commonly used mixture for the block consists of 5-7 ml of Xylocaine combined with hyaluronidase and bupivacaine, which is usually sufficient for effective anesthesia. After the injection, gentle intermittent digital massage is given to prevent any increase in intraocular pressure that could occur with the use of a pinky ball or orbital Honan balloons. Other options for anesthesia during trabeculectomy include subtenons anesthesia and topical anesthesia with supplemental intracameral unpreserved 1% lidocaine. However, topical anesthesia has the limitation of lacking akinesia. It is important to consider paralyzing the orbicularis oculi to prevent globe compression in patients with prominent eyelid squeezing. Technique Surgeons have refined various aspects of trabeculectomy, including modifications to the size and shape of scleral flaps, optimization of wound closure techniques, and improvements in aqueous humor drainage. These enhancements aim to create a well-functioning filtration bleb while minimizing complications such as hypotony and bleb leaks. Traction Suture A traction suture is utilized to maintain the eye in the desired position during surgery. It can be placed either through the superior rectus muscle or the clear cornea. When topical or subtenons anesthesia is used, a corneal traction suture is preferred, employing a 6-0 black silk suture placed 1mm anterior to the limbus. Alternatively, a 4-0 silk suture is used for a superior rectus traction suture. The muscle tendon is grasped, and the needle is passed posterior to it to prevent accidental buttonholing and subsequent leak (Figure-1). Complications can arise if not performed correctly, such as a corneal tear or accidental anterior chamber entry with corneal traction suture, limited surgical access, conjunctival tension, and hemorrhage or tissue damage with superior rectus suture.[6] Figure 1: The muscle tendon is grasped, and the needle is passed posterior to it with 4-0 silk. Subspeciality - Glaucoma

www.dosonline.org/dos-times DOS Times Volume 29, Number 4, July-August 2023 47 Surgical Site The optimal positioning of the bleb is where it is completely concealed beneath the upper eyelid.[6] This positioning offers several advantages, including enhanced protection against infection and exposure. Additionally, it can help maintain more consistent intraocular pressure. The upper eyelid acts as a cushion, exerting gentle pressure on the bleb and aiding in the regulation of aqueous humor outflow. The superior limbus is often considered the widest region of the limbus, allowing for easier access to the underlying sclera and facilitating the creation of a sclerostomy, which is a key step in trabeculectomy. The superior limbus is often less vascular compared to other regions of the limbus, which reduces the risk of bleeding during the creation of the sclerostomy, allowing for better visibility and accuracy. Limbus-Versus Fornix-Based Flaps Conjunctival dissection along with tenons is carried out to access the scleral site for scleral flap creation. Two types of conjunctival flap techniques have been described for trabeculectomy. The limbal-based flap technique involves a conjunctival incision placed as posteriorly as possible, with a minimum length of 10mm, providing adequate exposure for trabeculectomy. On the other hand, fornix-based flaps (FBF) use a 6-8mm limbal incision, followed by a wider sub-tenon’s dissection of approximately 10-15mm posteriorly.[5] (Figure-2). FBF offers advantages such as a better surgical view, time savings, and easier application of antifibrotic agents, resulting in more diffuse blebs. In contrast, limbal-based flaps may lead to thin, cystic blebs and peri-bleb scarring with the formation of a “ring of steel”.[5] FBF minimizes the risk of localized concentrations, promoting uniform wound healing. In a study conducted over a 2-year period, it was found that 90% of limbus-based flaps and only 29% of fornix-based flaps developed into cystic blebs. Additionally, limbus-based flaps had a higher incidence of blebitis and infection (20%) compared to none in the fornix-based group.[7] However, there have been concerns regarding early leakage and subsequent failure or infection in fornix-based surgery. Nevertheless, by carefully closing the fornix-based flaps, leakage can be minimized, especially with the use of a new method involving tight corneal conjunctival sutures. A meta-analysis[8] comparing fornix-based flaps (FBF) versus limbus-based flaps (LBF), based on six randomized controlled trials, found that there was no significant difference in the efficacy of pressure reduction between the two techniques.[9-13] Flap Size Flap dimensions play a crucial role in regulating aqueous outflow in surgical procedures. Currently, there is no definitive evidence indicating that flap shape has a significant impact on surgical outcomes, although dedicated trials have not been Figure 2: Fornix-based conjunctival flap with creation of deep pockets. Figure 3 conducted. However, clinical observations suggest that limbal aqueous drainage is associated with cystic blebs, while more posteriorly draining aqueous (with larger flaps) results in thicker and more diffuse blebs.[6,14] To maximize posterior flow, certain strategies can be employed. Leaving the sides of the flap intact 1mm posteriorly to the limbus encourages posterior flow as has been recommended in Moorfields safer surgery system.[5] The flap thickness should be sufficient, ideally half the thickness of the sclera, to prevent dehiscence and anterior drainage, as well as avoid suture cheese wiring.[5,6,15] Additionally, ensuring an adequate flap size is important. Research indicates that a large flap with a correspondingly large mitomycin C treatment area leads to a less cystic and well-tolerated diffuse bleb, presumably due to increased posterior and lateral flow. The dimensions of a scleral flap in trabeculectomy can vary depending on the surgeon’s preference and the specific requirements of the patient’s eye. A rectangular flap commonly has a width of 5mm and a length of 4mm to enhance posterior flow (Figure-3). A commonly recommended guideline for the triangular scleral flap is to have a base width of approximately 3 to 4mm and a height of 4 to 5mm. Subspeciality - Glaucoma

DOS Times Volume 29, Number 4, July-August 2023 www.dosonline.org/dos-times 48 Size of Sclerostomy In modern trabeculectomy procedures, the fistula is created more anteriorly to avoid damage to the ciliary body and incarceration. Two common methods for making the fistula are using a blade and scissors or Kelly’s punch. With the blade and scissors technique, a posterior incision is made at the junction of the scleral spur and trabecular meshwork, followed by dissecting and removing a square block of approximately 1.5x1.5mm (Figure-4). A Kelly Descemet punch is used to Releasable Sutures Sutures are crucial for regulating flow during the early postoperative period. Antimetabolite use delays healing, making sutures even more important. Cutting sutures and releasable sutures help control postoperative hypotony. These advancements in suturing techniques have contributed to improved outcomes in trabeculectomy surgeries. Techniques[16] 1. Wilson’s Techniquc: The scleral flap suture used is a mattress-type suture. It involves passing the suture through the clear cornea underneath the limbus to reach the intact sclera. From there, the suture is threaded through the periphery of the scleral flap to the adjacent intact sclera. It is then passed through the intact sclera, back under the limbus to the clear cornea, and tied to secure the flap in place (Figure-5). 2. Cohen’s Technique: The suture technique for the triangular excise the trabecular meshwork and scleral lamellae, creating an opening in the desired location on the sclera. The punch is applied in 3-5 bites to achieve a 1.0mm sized opening, allowing for improved aqueous outflow and filtration. Subsequently, a surgical peripheral iridectomy (PI) is performed by carefully trimming the iris tissue adjacent to the sclerostomy, creating a small triangular opening flush with the surrounding scleral surface. Figure 4: Outlining of the sclerostomy with a lance tip blade anterior to scleral spur followed by removing a block of trabecular meshwork. scleral flap involves passing the suture through the intact sclera to the apex of the flap. From there, it is threaded through the center of the base of the flap, reaching the clear cornea. A 4 throw knot is then performed at the apex. Lastly, a small length of suture is left loose over the cornea, which can be easily removed during a slit lamp examination (Figure-6). 3. Kolker’s Technique: This technique is a modification of Cohen’s technique. After passing the suture to the clear cornea, it is then passed laterally to the clear cornea. The suture is then cut flush with the cornea, preventing it from lying loose and reducing the risk of windshield wiper keratopathy (Figure-7). 4. Releasable Cum Adjustable Suture: Another technique involves passing the suture from the intact sclera to the cornea just 1mm anterior to the limbus. It is then passed from the cornea to the limbus at the base of the scleral flap. Finally, the suture is threaded from the scleral flap back to Subspeciality - Glaucoma