DJO_Oct_Dec_2023_ Theme: i Examination for e-book

Delhi Journal of Ophthalmology Editorial Board Editor-in-Chief Kirti Singh Official Journal of Delhi Ophthalmological Society Volume 33 Number 4 October-December, 2023 DJO Associate Editors Annu Joon Devesh Kumawat Divya Jain Mainak Bhattacharyya Arshi Singh Khushboo Chawla Priya Saraf Shweta Viswanath Assistant Editors Akanksha Ankita Bhardwaj Anjali Mehta Bhupesh Charu Khurana Deepanjali Arya Himshika Aggarwal Gunjan Budhiraja Jatinder Bali Jatinder Bhalla Jigyasa Sahu Manisha Agarwal Neha Chawla Neha Rathi Nisha Choudhary Palak Gupta Pooja Bansal Priyadarshi Gupta Priyanka Golhait Prachi Dave Rahul Mayor Rajat Jain Ritu Aurora Shipra Sharda Shruti Bhattacharya Siddharth Baindur Suma Ganesh Sumit Grover Siddharth Madan Tanvi Gaonkar V.Krishna Vaibhav Khanna Vaibhav Nagpal Vineet Sehgal Section Editors Arun Nrayanswami Bhavna Chawla George L. Spaeth Milind Pandeya Sonal Dangda Satish Kotta M. Vanathi Rajesh Sinha Ruchi Goel Vinod Kumar International & Emeritus Editor A. K. Grover Atul Kumar Bithi Chowdhary Deepak Verma Jolly Rohtagi J.S.Titiyal N.P. Singh Mahipal S. Sachdev M.D. Singh M. Vanathi Namrata Sharma Pawan Goyal Pradeep Sharma Praveen Vashisht Rakesh Bhardwaj Ramanjeet Sihota Ritu Arora Rajender Khanna Sarita Beri Suneeta Dubey S.C. Dadeya Advisory Board Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023 i

Contents Editorial Learning Ophthalmology using Kaizen and Kintsugi Principles........................................................... 277 Kirti Singh Guest Editorial Preparing and Performing in Postgraduate Exams..............................................................................278 Jeewan Singh Titiyal Review Articles Evolving Trends in Corneal Surgery ..................................................................................................... 280 Supriya Dhar, Sanjay Kumar Mishra, Amrita Joshi, Alok Sati, Pradeep Kumar, Deepesh Unni Clinical Trials in Myopia Control: A Review...........................................................................................290 Deepti Joshi, Nilima Khochikar, R. Krishnaprasad Original Articles Correlate Ocular Surface Disease Index with Convergence Insufficiency Symptom Score Among Optometry Students.......................................................................................................296 Niravkumar Mehta, Rupam Desai, Jainisha Ajudiya Parental Eye Care Seeking Behavior and Knowledge of Common Eye Diseases................................. 301 Veenu Maan, Pradeep Agarwal, Lokesh Chauhan Effect of Short-Term Oral Vitamin A on Ocular Tear Film in Dry Eye .................................................. 309 Jagruti Navalsinhji Jadeja, Vaibhavi Gulabbhai Patel, Tejal Rameshbhai Garasiya Association of Disability Quotient with Ocular and Systemic Manifestations in Children with Developmental Delay ..................................................................................................... 314 Meenakshi Wadhwani, Sehzadi Malhotra, Dhulika Dhingra, Manika Manika, Shubhangi Kursange, Rahul Singh, Sneha Kumari, Amit Kumar Case Reports Bilateral Epidermal Inclusion Cysts with Unusual Symmetrical Presentation and Review................. 319 Rajwinder Kaur, Priyanka Dahiya, Panku Baghla, Arnav Kr Roychoudhary A Case Report of Intracorneal Detergent Particles Deposits ............................................................... 322 Shivani Sharma, Vaishali Tomar, Rinky Agarwal, Subhash Dadeya Idiopathic Hypertrophic Pachymeningitis Presenting with Unilateral Diminution of Vision and Papilloedema ...................................................................................................................... 325 Namrata, Rahul Sidheshwar Ranjan, Ruchika Agarwal, Anil Kumar Singh, Kumar Varun Viral Retinitis with Co-Infection Cytomegalovirus and Varicella Zoster .............................................328 Dhaivat Shah, Ravin Punamia, Bennet Chacko Mathew, Rahul Singh, Milind Rokade Photo Essay Intra-Lenticular Choppy Wave in Hypermature Cataract..................................................................... 331 Siddharth Sheth, Gaurav Kamble, Smitesh Shah, Sonal Shah, Sushilkumar D. Zende, Onkar H. Pirdankar ii Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023

Mercedes-Benz Logo Cataract...............................................................................................................333 Navneet Sidhu, Neiwete Lomi, Radhika Tandon Retinal imaging in Angiomatous Retinae .............................................................................................334 Deeksha Singh, Anamika Nath, Divya Swamyraj Letter to Editor Incidence and Risk Factors of Retinopathy of Prematurity Have Post COVID Period .........................336 Mahendra Singh, Suraj Kumar Chaurasiya, Jayant Jha, Radhika Pushkar Omnibus Humans Art of Ophthalmology - Glimpses From a Journey of 51 years .............................................................338 K. P. S. Malik Theme Sections Pediatric Eye Examination: An Overview .............................................................................................340 Siddharth Baindur, Siddharth Madan, Aparna Soman, Umesh Sharma, Meghna Sethi, Kashish Garg, Chitra Ogio, Anju Rastogi Demystifying Corneal Examination: A Guide for Post Graduates........................................................349 Avani Hariani, Isha Gupta, Parul Jain Examination and Presentation of a Glaucoma Case.............................................................................356 Arshi Singh, Kirti Singh, Divya Jain History Taking and Examination in a Retina Case ............................................................................... 360 Apoorva Ayachit, Akshay Mishra, Rajashree Satish Salvi, Shrinivas Joshi, Guruprasad Ayachit Oculoplasty Evaluation for Postgraduates...........................................................................................365 Rwituja Thomas, Aman Vaishya Neuro-Ophthalmology – An Approach to Common Cases in the Outpatient Department .................369 Shalin Shah, Paromita Dutta Cover Image Pictorial depictions of eye examination: Disc damage DDLS, Corneal colour coding, Amsler Dubois chart colour coding, Ptosis and proptosis measurement Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023 iii

DOS Executive Members 2022-2023 Dr. Subhash C. Dadeya DOS Office Bearers Executive Members DOS Representative to AIOS Ex-Officio Members Dr. Pawan Goyal Dr. Rohit Saxena Vice President Dr. Rajendra Prasad President Dr. Jitender Singh Bhalla Secretary Dr. Sandhya Makhija Joint Secretary Dr.Alkesh Chaudhary Treasurer Dr. Kirti Singh Editor Dr. Jitender Bali Library Officer Dr. J.S. Titiyal Dr. M. Vanathi Dr. Namrata Sharma Dr. O. P. Anand Dr. Gagan Bhatia Dr. Vivek Gupta Dr. Vivek Kumar Jain Dr. Prafulla Maharanaa Dr. Amar Pujari Dr. Bhupesh Singh Dr. Pankaj Varshney iv Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023

Editorial Ophthalmology training involves imparting requisite skills in clinical, surgical, and doctor–patient relationship and assessment tools are focused on achieving these outcomes. Ophthalmology as a surgical specialty differs from other surgical branches in that the surgical outcome are immediately visible. Delivering such outcomes requires surgical finesse, which comes with inherent baggage of stress. Continuing explosion of knowledge, evolving science and spiraling surgical enhancements all to be accomplished within mere three years of postgraduate training, makes the trainee doctor feel that he is riding on a roller coaster ride. Learning material ranging from textbooks, journals, EyeWiki, YouTube emerge as an ever expanding hydra-headed monster. The student’s mind, however, has a finite capacity of absorbing and, more important, regurgitating that knowledge. The Kaizen principle of constant improvement coupled with weeding out waste helps to balance out these diverging requirements. Value stream mapping, eliminating unnecessary clogging of brain requires smart learning. Some wellknown tips for smart learning include preparing a blueprint of study schedule, prioritizing workplace learning like ward rounds, working up outpatient cases, assisting surgeries, with filtering out noise of information is utilizing the principle of Kaizen. Patient learning at any time beats any textbook learning. Ophthalmology training requires the acquisition of various psychomotor and surgical skills. Our constant goal of imparting vision and tasting multiple failures often leads to frustration and sadly burnout. Failures have to be accepted as part of growth and as occupational hazards of our profession. Acknowledging and leavening from these failures, flaws (surgical or otherwise) and sealing them with the gold of resolve, utilizes the principle of Kintsugi. This would create a unique surgical personality, with flaws embedded as learnt behavior. Teaching your hands to feel, to stumble on despite the initial and often mid-path hiccups, is the best way to learn resilience and not absorb the pain of failure. There is no perfect surgery, and there is no perfect surgeon. It is rightly said that a surgeon who has no complications has just not operated enough. The eye, the finest optical instrument of nature has inherent aberrations. As a student of this science do not expect the novice student learner to have none. The third aspect of training and assessment of communication skills is often relegated to shadows. This is unfortunate, as it often is a critical skill in our profession. Recollecting my national board examination, I had a retinal detachment case, who was scheduled for surgery, the next day. Despite all efforts, I could not find the elusive retinal break. The patient also got anxious. I calmed her and squeezed her hand. At the time of my viva, this lady looked at my examiner and said in her language, “Please pass this girl, she is good.” That hand squeeze outweighed the discomfort she had experienced during my inexpert indirect ophthalmoscopy. Despite all hard work, examination time is a testing time for all students. Incorporating Kaizen and Kintsugi during the runoff helps in performing well during those critical hours. To help our postgraduate students, this issue of the Delhi Journal of Ophthalmology comes with the theme of “i exams.” What all to present and how to present in the subjects of cornea, glaucoma, retina, pediatric ophthalmology, neuro-ophthalmology, and oculoplasty are detailed in this issue. Drawing diagrams with colored pencils on your paper always has more weightage than a detailed write-up. The theme articles carry the necessary diagrams and must do tests at the examination. Carrying your own essential instruments like biomicroscopy lens, gonioscope, and indirect ophthalmoscope would eliminate the energy and time wasted in asking or using unfamiliar ones at the examination site – Kaizen. Awrong answer or intimidating examiner should not make you blank out on future right answers – Kintsugi. For an ophthalmologist, exams never stop, their frequency and pattern only changes. In our quest to restore vision for all, learn to treat challenges as milestones in our never-ending journey to achieve surgical and clinical perfection. Kirti Singh Guru Nanak Eye Centre, Maulana Azad Medical College and Associated Hospital, New Delhi, India. E‑mail: [email protected] Learning Ophthalmology using Kaizen and Kintsugi Principles This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non‑commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. How to cite this article: Singh K. Learning ophthalmology using Kaizen and Kintsugi principles. Delhi J Ophthalmol 2023;33:277. Access this article online Quick Response Code: Website: https://journals.lww.com/djo DOI: 10.4103/DLJO.DLJO_202_23 © 2024 Delhi Journal of Ophthalmology | Published by Wolters Kluwer - Medknow 277

Guest Editorial Preparing for postgraduate ophthalmology examinations can be very stressful and overwhelming for a trainee resident due to the sheer volume of syllabus and the range of clinical skills that they are expected to be adept at. In my view the process of postgraduate exam preparation for a resident starts from the 1st day of their residency. Each day of residency is test of their skills and grooms them for the final examination. No work should be looked upon as futile as even the most mundane tasks, if performed with proper application of mind can eventually add up to their value as an ophthalmologist. The final exam usually comprises theory papers that assess the candidate’s in-depth knowledge in various ophthalmic sub-specialties, as well as evaluation of practical skills such as clinical examination, interpretation of investigations and formulation of management plan. In India, guidelines for competency-based postgraduate training program for MS ophthalmology have been published by the National Medical Council. While these guidelines do provide the broad heads under which the resident needs to be evaluated for, they have not detailed the assessment methodology as such. However, the subject‑specific competencies provided in this directive can act as a guide for the examiner and examinee in terms of skills that a postgraduate in ophthalmology is expected to acquire during their training. During the 3 years of residency, the skill of writing answers for theory papers is rarely emphasized, and students may not be adequately prepared to effectively answer the long theory questions during examination. The level of answers should match the postgraduate skill level, with illustrations, tables, highlighting and a conclusion or summary to reiterate the important points. Some universities appoint a panel of examiners, and different examiners may be involved in checking the theory paper and conducting the practical examination. It is all the more imperative to do well in theory individually and translate the knowledge gained during the residency onto the paper as well. The practical examination and viva voce is often more feared by the candidates owing to the unpredictability of the cases they may encounter, the need for presenting the case to the examiner and answering the questions in a confident manner. Over the years we have witnessed a change in the practical exam pattern with the introduction of Objective Structured Clinical Examination, spotters, recorded surgical videos, etc., There has also been a shift in the pattern of questioning due to the availability of advanced image-based diagnostic modalities such as optical coherence tomographys (OCTs), topography and clinical photographs which the students are expected to be well versed with. Meanwhile, the emphasis on traditional topics such as optics and refraction has somewhat lessened. While working up a case for practical examination, the student should re-read the answer sheet before going in for viva and ensure that all the salient points in history and examination have been covered. The students should always think of multiple differential diagnoses based on their findings, and come up with the likely diagnosis with subsequent management plan. The students should be well-versed in optics, refraction, and basics of investigative modalities. Bedside teaching constitutes an important part of residency training. In Dr. R. P. Centre for Ophthalmic Sciences, we have ward rounds twice a week during which a faculty interacts with residents regarding the patient management. Apart from teaching and learning, the ward round has multiple other roles including patient care, communication of patient care plans, reviewing of diagnostic test results and completion of documentation. Regular participation in ward rounds during their residency can prepare the students for their final MD exam by helping them hone their clinical examination and communication skills. In my experience students who perform well in the routine ward rounds are the ones who eventually shine in their final exams as well, possibly because the ward rounds so closely imitate the actual examination set-up. I believe senior residents or senior colleagues after often the best teachers for trainee residents and knowledge gained by interacting with them in specialty clinics and outpatient departments is invaluable. Group discussion sessions on salient topics with fellow examinees can be a very effective and efficient mode of learning as it helps them imbibe significant volume of information in a short period of time. Such discussions allow active learning with critical review of the topic, instills a sense of confidence as well as improves rapport among residents. Another important aspect that the students need to focus upon is their soft skills. Acquiring soft skills is very important for a medical student due to the nature of their profession, which involves interpersonal contact with patients and families. Traditional medical education does not formally include soft skills such as ethics, professionalism, or communication. However, it is crucial that the students educate themselves regarding this as it not only improves the overall quality of care and patient satisfaction but also helps in the personal and professional development of the trainee resident. Positive attitudes to such soft skills are often acquired through direct teaching, or via clinical experience and appropriate role modeling. Being confident is crucial while presenting a case during the practical exams and is reflected in the candidate’s way Preparing and Performing in Postgraduate Exams 278 © 2024 Delhi Journal of Ophthalmology | Published by Wolters Kluwer - Medknow

Titiyal: Postgraduate exam preparation of speaking, body language and attitude. Having mock viva’s with seniors or colleagues can be a good way to develop an effective and confident communication strategy. Good communication skills during viva-voce encompass comprehending the question, trying to figure what the examiner is expecting by way of an answer, and formulating the answer mentally before speaking. Surgical skills constitute an important aspect of postgraduate teaching in ophthalmology. These skills are continually acquired throughout residency as the students learn from each surgery they perform. Furthermore, the introduction of wet labs that allow training on animal eyes and simulators have helped provide a safe and standardized method for training before operating upon actual patients. However, there is no clearly defined structural format for assessment of ophthalmic surgical skills prescribed in India at present. At are our center, we assess the residents’ surgical skills by evaluating their surgical video while conducting a viva voce alongside it. This contrasts with the traditional assessment approach where the students were evaluated while they performed the surgery live before the examiner. In future we may witness the adoption various objective tools such as objective assessment of skills in intraocular surgery or the International Council of Ophthalmology – Ophthalmology Surgical Competency Assessment Rubric for this purpose. Surgical log books should be presented for evaluation as well. Research aptitude is another important domain that is evaluated in postgraduate exams and is largely based on students’ thesis work and presentation. Students should be thorough with their thesis work including the methodology, results, and its interpretation. A brief presentation is usually a good way to judge the student’s thesis work. It is advisable to be well-versed in basic biostatistics and research methodology. In addition to the core subspecialties in ophthalmology, the allied specialties such as ocular-microbiology, ocular-pathology, ocular-radiology, and community ophthalmology form an important part of the postgraduate curriculum and should be given due attention during the preparation. Being updated on the recent advances on the subject is paramount both for theory and practical exams. Going through the recently published landmark articles can help the students in this respect. For grand viva, community ophthalmology is an important part and the students should read about various National Programs, survey methods, organizations working toward elimination of blindness. Medicolegal aspects of ophthalmology including aspects of informed consent should be studied. As far as black box and instruments viva is concerned, the students should be able to identify the instrument or investigation and give its applied indications. Clinical pictures, fluorescein angiography, OCT images, and topography images are also asked in viva and the student should be well-versed in it. In this era of internet and electronic learning devices where the students have access to limitless information at the click of a button, the use of good old textbooks by residents has become an unusual sight. While such devices can be excellent sources of knowledge, they cannot replace the conventional textbooks which often provide a more comprehensive yet concise coverage of the topic and aid in better retention too. The practice of making notes while reading the textbooks can help the students not only structure their answers in theory papers but can also serve as a convenient source material for revision during their final weeks of preparation. Competency-based medical education has been introduced by the National Medical Council in undergraduate medical education in India since 2019 and assesses each student in an objective, quantifiable standard, independent of the performance of other students. Such an approach wherein assessment is done in a criterion-referenced manner in an actual or near identical clinical setting may be adopted for postgraduate exams as well as in future. A systematic and thorough preparation for MD exams lays a strong foundation for a budding ophthalmologist. While the methods of assessment may vary the course objectives essentially remain the same. Rather than viewing the entire process as a 2-or 3-days ordeal that students need to tide over, these exams should be regarded as an opportunity to imbibe and assimilate the vast ocean of knowledge that comprises ophthalmic sciences. The stress during postgraduate exams can be overwhelming for some students to the extent that it takes a toll on their mental health. Under such circumstances, residents should not hesitate to seek support and solace from their peers and seniors or even get professional help if required. Last but not the least, it is important to take good rest, approach the exam with a clear mind, be professionally dressed and confident, and do not begin the viva with preconceived notions of diagnosis. Be attentive to what the examiner is asking, answer confidently, and it is always better to accept mistakes gracefully rather than argue with the examiner. The postgraduate examination, although an important milestone, would not be the last exam in the life of an ophthalmologist. Trials and tribulations will continue to arise at each stage of life, and I have seen my students evolve and adapt wonderfully to their circumstances over the years, both professionally and personally, after passing out of R. P Centre. Jeewan Singh Titiyal1,2 1 Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India, 2 Department of Cornea and Refractive Surgery (Unit‑III), All India Institute of Medical Sciences, New Delhi, India. E‑mail: [email protected] This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non‑commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. How to cite this article: Titiyal JS. Preparing and performing in postgraduate examinations. Delhi J Ophthalmol 2023;33:278-9. Access this article online Quick Response Code: Website: https://journals.lww.com/djo DOI: 10.4103/DLJO.DLJO_200_23 Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023 279

Abstract Review Article Introduction Corneal surgery has seen significant advancements in recent years, revolutionizing the way we treat various corneal conditions. These advancements have improved patient outcomes, reduced recovery time, and expanded the scope of treatable conditions. It involves a wide gamut of procedures ranging from managing infective keratitis with tissue adhesives to performing partial or full-thickness transplants on one side and procedures like corneal cross-linking to tissue regeneration techniques on the other hand. Types of Corneal Surgeries Corneal transplantation (keratoplasty) This is the most performed corneal surgery. From Eduard Konrad Zirm’s successful corneal transplant in 1906 to modern femtosecond laser-assisted keratoplasty, the evolution of corneal surgery is remarkable. The term keratoplasty was coined by Frans Reizinger in 1824.[1] Although Von Hippel,[2] Durr and Fox[3] tried lamellar grafts much earlier than Zirm the actual human corneal tissue transplantation with the usage of graft protection techniques was first performed by Zirm in 1906. The modern-day transplant came only 50 years later in the picture along with the contribution of the development Corneal surgery has seen significant advancements in recent years, revolutionizing the way we treat various corneal conditions. These advancements have improved patient outcomes, reduced recovery time, and expanded the scope of treatable conditions. It involves a wide gamut of procedures ranging from managing infective keratitis with tissue adhesives to performing partial or full-thickness transplants on one side and procedures such as corneal cross-linking to tissue regeneration techniques on the other hand. Corneal transplant procedures include full-thickness procedures such as penetrating keratoplasty and lamellar transplant procedures which can be performed manually and using a femtosecond laser. Corneal transplant procedures include full-thickness procedures such as penetrating keratoplasty and lamellar transplant procedures which can be performed manually or using a femtosecond laser like Bowman layer transplant, anterior and posterior lamellar keratoplasty, Descemet’s Stripping endothelial keratoplasty, Descemet’s membrane endothelial keratoplasty, Descemet’s stripping only, and use of Rho kinase inhibitors for endothelial disorders. Keratoprosthesis can be utilized in cases where conventional keratoplasty is contraindicated or is fraught with high chances of failure such as chemical burns and Ocular Cicatricial Pemphigoid (OCP). Corneal Collagen cross‑linking is the only modality to treat progressive keratoconus and includes various protocols such as conventional and accelerated. Tissue adhesives significantly treat corneal disorders such as corneal perforations and other procedures such as post-pterygium surgery, simple limbal epithelial transplantation, and post-laser-assisted in situ keratomileusis(LASIK) epithelial ingrowth removal. Amniotic membrane transplant assisted with fibrin glue use has also been described in managing larger corneal perforations/melts. Customized treatments in the form of wavefront-optimized and wavefront-guided LASIK and femtosecond-enabled procedures are available for precise treatments with better visual outcomes. Regenerative therapy, including cell therapy, regenerative medicine, bioengineered corneal grafts, and gene therapy, represents the future of keratoplasty. Keywords: Bioengineered cornea, bowman layer transplant, corneal cross-linking, corneal surgery, customized assisted in situ keratomileusis, Descemet’s membrane endothelial keratoplasty, Descemet’s stripping automated endothelial keratoplasty, descemet stripping only, femtosecond laser enabled surgery, keratoprostheses, lamellar keratoplasty, penetrating keratoplasty, regenerative therapy Address for correspondence: Dr. Supriya Dhar, Department of Ophthalmology, Army Hospital Research and Referral, New Delhi, India. E‑mail: [email protected] This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non‑commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. For reprints contact: [email protected] How to cite this article: Dhar S, Mishra SK, Joshi A, Sati A, Kumar P, Unni D. Evolving trends in corneal surgery. Delhi J Ophthalmol 2023;33:280-9. Evolving Trends in Corneal Surgery Supriya Dhar, Sanjay Kumar Mishra, Amrita Joshi, Alok Sati, Pradeep Kumar, Deepesh Unni Department of Ophthalmology, Army Hospital Research and Referral, New Delhi, India Access this article online Quick Response Code: Website: https://journals.lww.com/djo DOI: 10.4103/DLJO.DLJO_163_23 Submitted: 06-Oct-2023 Revised: 21-Nov-2023 Accepted: 28-Nov-2023 Published: 15-Jan-2024 280 © 2024 Delhi Journal of Ophthalmology | Published by Wolters Kluwer - Medknow

Dhar, et al.: Evolving trends in corneal surgery of eye banks and the availability of monofilament nylon microsuture materials.[4] Penetrating keratoplasty It involves the transplant procedure in which full-thickness, host corneal tissue is replaced with donor corneal tissue. The various objectives include: 1. To establish a clear central cornea/visual axis (OPTICAL) [Figure 1] 2. To reduce refractive error in severely distorted corneas (OPTICAL) 3. To provide structural integrity (TECTONIC) [Figure 2] 4. To eliminate infection/relieve pain (THERAPEUTIC) [Figure 3]. The success rates are defined by graft clarity at 1 year, approaching or exceeding 90% in numerous series.[5,6] The present definition of a successful penetrating keratoplasty has changed. The need is not only to maintain a clear cornea but also to achieve a successful refractive result. Component keratoplasty The replacement of a specific layer of cornea is the only requirement in certain cases instead of a total thickness corneal transplant procedure. This disease‑specific replacement has conceptualized customized component corneal surgery. Shimmura gave the idea of the corneal component surgery in 2004[7] Subsequently, Vajpayee et al. documented the use of one donor cornea for three recipients.[7] These surgeries have a lesser risk of graft rejection and avoid risks associated with open-sky procedures. These techniques are especially useful in developing countries with a scarcity of donor tissue; hence, one tissue can be utilized for multiple patients. The level of dissection, layer involved, and indications is summarized in Table 1. Figure 4: (a) Neurotrophic keratitis with central persistent epithelial defect, (b) Bilayered amniotic membrane transplantation a b Bowman’s layer transplant The dissection is done anterior to midstroma in cases of advanced keratoconus. The stabilization occurs due to the splinting action of Bowman’s layer and the wound healing effect between the host stroma and Bowman layer graft.[8] Lamellar keratoplasty It is indicated in cases of stromal diseases sparing the corneal endothelium. It involves anterior and posterior lamellar keratoplasty. Anterior lamellar keratoplasty Superficial anterior lamellar keratoplasty It involves microkeratome-assisted or femtosecond laser-assisted lamellar dissection up to 130–150 µm depth of both the host and donor cornea. Sharma et al. [9] have also described a modified technique of femto-assisted SALK called Tuck in femtosecond laser-assisted anterior lamellar keratoplasty for the management of superficial anterior corneal scars where graft margins are tucked inside the host bed 360°. Posterior/deep anterior lamellar keratoplasty There are multiple techniques to achieve the dissection. Layer‑by‑layer manual dissection 50%–70% depth is achieved with vacuum/guarded trephine followed by multiple lamellar dissections to reach near Descemet’s plane.[10] Air‑assisted deep anterior lamellar keratoplasty This technique was described by Archilla. Near DM depth of dissection is achieved by injecting sterile air into the stroma followed by lamellar dissection, which may have to be repeated several times.[7] Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023 281 Figure 1: (a) Healed maculo‑leucomatous corneal opacity, (b) Immediate post optical penetrating keratoplasty a b Figure 2: (a) Perforated leucomatous corneal scar, (b) Immediate Post Tectonic penetrating keratoplasty a b Figure 3: (a) Recalcitrant fungal keratitis with near total corneal involvement, (b) Therapeutic penetrating keratoplasty (intra‑operative) a b

Dhar, et al.: Evolving trends in corneal surgery Big bubble deep anterior lamellar keratoplasty It was described by Anwar and Teichmann[11] where the air is injected up to 60%–80% depth of stroma after partial trephination in the recipient. Dua etal. [12] have reported two types of Big Bubble; Type 1 Bubble is a central, well-circumscribed, dome-shaped elevation of 8.5 mm diameter due to separation anterior to the pre‑Descemet layer. Type 2 bubble is a large 10 mm) bubble which extends till the periphery is due to the separation between the Descemet’s and pre Descemet’s/Dua’s layer. Double bubble technique Jhanjhi et al. [13] described the technique where an air bubble is first injected in the anterior chamber, then into the stroma, and shifting these bubbles to the periphery identifies the plane of DM separation. Miscellaneous modifications 1. Viscoelastic assisted deep anterior lamellar keratoplasty (DALK):[14] A stromal pocket is created and dissection is carried out with viscoelastics help. It utilizes the “air to endothelium” interface as a guide for the depth of stromal dissection 2. Hydrodelamination: Sugita and Kondo[15] described saline injection to increase the identification and removal of deep stromal fibers. 3. Femtosecond laser-assisted: It provides an accurate, precise, and desired depth of dissection. 4. Diamond knife-assisted DALK: It is utilized in cases of healed corneal hydrops, advanced ectasias, and severe corneal thinning. Vajpayee et al. described the use of a diamond knife at a depth of 30 µm less than the pachymetry reading and created an initial 2.0 mm cut which is extended circumferentially and centripetally to remove anterior stroma.[16] Complications Intraoperative 1. DM perforation: It is the most important and most common intraoperative complication.[17] 04%–20% of cases; especially in cases of healed hydrops, advanced ectasia, and corneal thickness <250 µm 2. Pseudo anterior chamber: In <1% of cases there can be double anterior chamber or interface fluid, due to retention of fluid because of DM perforation or viscoelastic retention. Postoperative 1. Urrets-Zavalia syndrome: Fixed dilated pupil with or without associated iris atrophy 2. Interface wrinkling: Due to mismatched donor and recipient bed size leading to DM folds 3. Epithelial/stromal rejection: 03%–15%;[7] usually visually insignificant Table 1: Types of Corneal Surgeries based on Component layer involved[7] Name of the layer Level Name of surgery Indications Bowman’s layer Anterior to midstroma Isolated bowman layer transplantation Advanced keratoconus Stroma (lamellar) Superficial 130–150 µ SALK Anterior stromal corneal opacities Anterior stromal scarring following pterygium excision and trachomatous keratopathy Anterior corneal dystrophies and degenerations Superficial 250 or 350 µ ALTK Corneal ectasias (keratoconus, PMD, and Terrien’s marginal degeneration) Corneal dystrophies and degenerations such as lattice dystrophy, salzmann nodular degeneration, and spheroidal degeneration Postoperative complications of refractive surgery such as scars or ectasia Ocular surface diseases such as SJS, OCP, and chemical or thermal burns Corneal trauma and infections Superficial 90% of stroma manual dissection pd-DALK Anterior corneal opacities or scars Keratoconus corneal dystrophies such as avellino, granular, and lattice Ocular surface diseases, for example, SJS, OCP, chemical or thermal Burns, and vernal keratoconjunctivitis with stromal opacity Infectious keratitis (therapeutic DALK) or descemetocele Mucopolysaccharidosis sparing endothelium Complete baring of DM MD-DALK/d-DALK As above EndotheliumDM complex Lenticule of posterior stroma with endothelium DSEK/DSAEK Endothelial diseases, for example, FECD, PBK, and corneal graft failure DM and endothelium DMEK As above Predescemet’s layer along with DM and endothelium pDEK As above DM: Descemet’s membrane, SALK: Superficial anterior lamellar keratoplasty, ALTK: Automated lamellar therapeutic keratoplasty, DALK: Deep anterior lamellar keratoplasty, pd-DALK: Predescemetic DALK, DMEK: Descemet membrane endothelial keratoplasty, pDEK: Predescemetic endothelial keratoplasty, MD-DALK: Maximum depthDALK, d-DALK: Descemetic DALK, SJS: Steven’s Johnson syndrome, DSEK/DSAEK: Descemet stripping endothelial/automated endothelial keratoplasty, FECD: Fuchs endothelial corneal dystrophy, PBK: Pseudophakic bullous keratopathy, OCP: Ocular cicatricial pemphigoid, PMD: Pellucid marginal degeneration 282 Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023

Dhar, et al.: Evolving trends in corneal surgery 4. Interface keratitis: Sight-threatening complication. Candida Is the most identified organism. Endothelium‑Descemet’s Membrane Complex It is the present procedure of choice for patients with diseases involving DM-Endothelium complex such as pseudophakic bullous keratopathy, Fuchs endothelial dystrophy, and congenital hereditary endothelial dystrophy. Currently, the two main procedures commonly employed routinely are DSEK/DSAEK and Descemet’s membrane endothelial keratoplasty (DMEK). Descemet’s stripping endothelial/automated endothelial keratoplasty It includes donor preparation using manual, single and double-pass microkeratome and femtosecond laser methods. The standard single-pass technique utilizes microkeratome head size 350 µm leading to an average graft thickness of 150–200 µm. An ultrathin lenticule described by Busin et al. [18] (CT <100 µm.) can be made using a double pass or using a 400 µm head and decreased speed of pass. Host bed is prepared considering white to white and DM stripping is optional and avoided unless DM is wrinkled or scarred. The various donor insertion methods utilized are pull through (Endo Glide and Busin Glide) and push in (injectors such as endoserter, endoshield, and neusidil). Descemet’s membrane endothelial keratoplasty Only DM is transplanted into the host after stripping diseased endothelium through a 3 mm clear corneal incision. 1. Graft preparation techniques.[19] Manual dissection 1. No touch technique: It was described by Groeneveld-van et al. [20] Trabecular meshwork bordering DM was loosened 360°  by scraping, using a hockey‑stick knife positioned outside the trabecular meshwork. This way, the DM was detached from the adjacent trabecular meshwork and completely stripped from the posterior stroma, during stripping, and trabecular meshwork was kept intact and pulled together with the DM simultaneously. Then, on a 13 mm–6.0 D contact lens, DM was trephined with a 9.5-mm trephine 2. Scuba technique: Submerged cornea using the backgrounds away technique: Giebel and Price in 2008[21] described manual harvesting of DM with the rim submerged in Optisol or BSS on a Teflon block. Pneumatic dissection Reverse big bubble technique Zarei-Ghanavati et al.; 2010.[22] a. Trypan blue stained corneoscleral button placed on the Barron punch base b. A 27‑gauge needle was attached to an air‑filled syringe with the entry point outside the Schwalbe’s line c. Small bubbles form after gentle air injection d. Coalesced small bubbles form into a big bubble, detaching DM from the posterior stoma e. The needle is reinserted into the big bubble from the scleral part of the corneoscleral rim to collapse the bubble f. Punched and rolled donor DM ready to transplant. Descemet’s membrane endothelial keratoplasty with stromal rim[23] Air bubble injected into the pre-DM plane removing 80% stroma and a circle of 6 mm diameter demarcated with S written on the stromal rim. The bubble was then entered with scissors, remaining central stroma was eliminated. Agraft with a stromal rim is obtained. Pre‑Descemet’s endothelial keratoplasty Agarwal et al. [24] described this technique. To prepare for transplantation, an air bubble was created between the pre-DM and stroma or pre-DM and DM. Once the bubble was successfully formed, it was marked with a trephine, and trypan blue was injected to enhance the visibility of the graft. To ensure proper detachment along the full circumference of the trephination, corneal scissors were utilized. Hydrodissection techniques Muraine et al. described a technique in which superficial trephination of DM was performed over 330° rather than over 360°. A spatula or Troutman forceps was used to detach the endothelium on either side of the uncut 30° to create a liftable flap and enter the pre‑DM plane with a needle. Aculture medium or BSS was injected to obtain DM detachment. Standardized submerged hydroseparation technique (SubHyS technique) Salvalaio et al. in 2014[25] described graft preparation of tissue submerged in organ culture medium and injection of medium to separate DM from the rest of the stroma. Liquid bubble dissection[26] The surgical procedure involved making a precise cut below the base of the iris to access the Schlemm’s canal. Using a blunt spatula, the area of high attachment was loosened through tangential dissection. To detach DM, a vital dye was injected into the pre-DM plane while simultaneously blocking reflux with a surgical pad. Next, a corneal trephination was performed, and the donor tissue was lifted from the stromal side using an olive spatula with a smooth, rounded tip to facilitate harvesting. Miscellaneous techniques 1. i-OCT-assisted intraoperative OCT-assisted microscope can be utilized for DM peeling as well for surgery. 2. “Ghost” DMEK Technique:[27] Livny et al. described trypan blue-assisted staining of Descemet’s membrane for DMEK graft preparation. 3. “Yogurt “Technique:[28] The new punch tool has a circular blade with a missing section, creating an uncut hinge on the donor cornea. Two straight cuts are also made by the punch tool, perpendicular to the edge of the cornea, toward the trabecular meshwork in the hinge area. Once the donor corneoscleral rim Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023 283

Dhar, et al.: Evolving trends in corneal surgery is in place with the endothelial side facing upward, a partial-thickness trephination is performed without rotating the cornea. The Descemet’s membrane is then lifted from Schwalbe’s line in the hinge area, and the DMEK graft is peeled off after marking without additional preparation. 4. Viscoelastic Method:[29] The Healon 5 is positioned on the endothelial side, followed by folding the Descemet’s membrane in half with the stromal side facing up over the ophthalmic viscoelastic device. The F mark is drawn on the stromal side of the folded Descemet’s membrane. Graft insertion techniques Bimanual technique[30] This method involves injecting Endothelium-DM complex after reducing the irrigation fluid pressure. The infusion cannula must be withdrawn just before the injector is retracted from the main incision to avoid the EDM roll from sweeping through the incision. To position the graft, a Gills cannula connected to an automated irrigation aspiration system is used. Contact lensassisted pullthrough technique[31] In this technique, the donor lenticule is harvested to an 8.25 mm diameter and tri-folded with the endothelium inside. Using a sterile soft contact lens as a scaffold; the tissue is loaded into a disposable cartridge and inserted into the anterior chamber under continuous irrigation using a bimanual pull-through technique. Endoillumination‑assisted Descemet’s membrane endothelial keratoplasty[32] Oblique light from the Endo illuminator improves visualization in DMEK, especially with corneal edema. Descemet without endothelial keratoplasty (DWEK) or Descemet’s stripping only[33] In cases of Central Fuchs Endothelial Dystrophy or PBK, removal of central Descemet’s alone leads to corneal clearing as a result of migration of peripheral healthy endothelial cells toward the center. Role of rho kinase inhibitors[34] These inhibitors increase cell proliferation and cell adhesion and decrease cell apoptosis thus helping in the promotion of healing. Two topical preparations are commercially available in the form of ripasudil 0.4% BD and netarsudil 0.02% OD. The most common side effect is conjunctival hyperemia seen with both preparations. The honeycomb reticular corneal edema is a peculiar side effect of netarsudil which reverses on stopping the treatment. Artificial endothelium[35] In 2021, Auffarth and his team introduced a device called Endoart. It is a flexible and thin artificial endothelial layer, measuring 50-μm, that mimics the curvature of the cornea’s posterior. This device acts as a fluid barrier at the posterior stroma and replaces the damaged endothelium. Like the DMEK method, it is implanted into the anterior chamber and positioned on the posterior stroma with precision. It is then secured using an air-gas mixture. Keratoprostheses The research into artificial corneas or keratoprostheses has advanced significantly. These devices aim to restore vision in individuals who are not suitable candidates for traditional corneal transplantation. Recent developments have shown promise in improving the biocompatibility and longevity of artificial corneas. Graft survival remains a challenge in eyes with underlying conditions such as Stevens–Johnson syndrome, ocular mucous membrane pemphigoid, Sjogren’s syndrome, chemical and thermal ocular burns, despite advances in lamellar or penetrating keratoplasty and limbal stem cell transplantation, and with the widespread use of systemic immunosuppression. In such situations, a keratoprosthesis (KPro) may be the only option. The KPro is a synthetic device that replaces the central diseased cornea in settings where a routine keratoplasty has a higher risk of failure. It has a relatively early visual recovery and no requirement for any systemic immunosuppression.[36] The Type I (prototype Boston KPro type 1) is meant to help those with corneal blindness and a moist surface, particularly in cases of blindness caused by non-autoimmune diseases. Meanwhile, the Type II Kpro is better suited for those with end-stage dry eye disease, keratinized surfaces, and/or abnormal ocular surface and eyelid anatomy. Eg of Type 2 Kpro are osteoodonto KPro (OOKP), the Boston KPro type II (BKproII), the Moscow eye microsurgery complex in Russia Kpro (MICOF), the tibial osteoKpro (OKP), the LVP Kpro (LV Prasad) (LVP) Kpro, the Lux Kpro, and the Pintucci Kpro.[36] Corneal Cross‑linking[37,38] It is a technique of corneal tissue strengthening using Riboflavin as photosensitizer and UVA to increase the formation of intra‑ and interfibrillar covalent bonds leading to halting/ regression of corneal ectatic process causing polymerization using photosensitized oxidation, corneal collagen, VA, and riboflavin thus producing Type 1 and type 2 reactions which lead to biomechanical and biochemical stability. Indications[39] i. Progressive keratoconus ii. Post-refractive surgery ectasia iii. Pellucid marginal degeneration iv. Infective keratitis v. Pseudophakic bullous keratopathy. Techniques CORNEAL THICKNESS >400 µm after epithelial debridement: Conventional/Epi Off/Dresden protocol. The 284 Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023

Dhar, et al.: Evolving trends in corneal surgery complete epithelium is scraped off manually by a blunt spatula in central 8–10 mm. Riboflavin dye 0.1% in 20% dextran T 500,1 drop every 3 min for 30 min is applied. UV–A irradiation from 5 cm @3 mw/sq cm for 30 min (5.4 j/sq cm) during which riboflavin is reapplied at 5‑min interval. Modifications Accelerated corneal cross‑linking Principal: Bunson Roscoe law: It’s valid only for transillumination intensity up to 45 mw/cm2 and irradiance time for 02 min. It was described by Kanellopoulos. It shortens the time of procedure, decreases patient discomfort, and avoids excessive stromal thinning and endothelial damage. Pulsed corneal cross‑linking It is described by Peyman et al.[40] There is pulsed delivery of UV-A irradiation with predetermined on and off patterns 0.1% riboflavin with HPMC presoak for 10 min, followed by 8 min (1 s on/1 s off) of 30 mW/cm2 UVA light. It is an ideal protocol. Topography‑guided corneal cross‑linking protocols The use of corneal cross‑linking (CXL) with PRK offers improvements in both visual acuity and topographic irregularity. The primary aim is the regularization of the corneal surface. Simultaneous cross-linking leads to an increase in the biomechanical strength of the cornea as measured by corneal hysteresis and corneal resistance factor.[41] The biomechanical strength of the cornea usually decreases in the acute phase after treatment but improves on a long-term follow-up. Patients who are intolerant to contact lenses showing progression of the disease will need to be considered for TPRK with adjunctive CXL rather than CXL alone. There are various protocols mentioned for the same. Athens protocol[42] Partial-refraction topography-guided PRK treatment followed by 50-μm phototherapeutic keratectomy (PTK) to account for epithelial removal followed by high‑fluence CXL with ultraviolet-A of 6 mW/cm2 fluence (applied for 15 min with 0.1% riboflavin solution stromal soaking) sequentially to the excimer laser treatments the same day. Cretan protocol[43] i. Combined transepithelial PTK and corneal collagen crosslinking for keratoconus ii. Cretan protocol plus:[44] Combined transepithelial PTK and conventional PRK followed simultaneously by CXL iii. Bharat protocol:[45] Jain et al. described combined. Same-day topography-guided photo-refractive keratectomy (PRK) using the Nidek CXIII excimer laser equipped with the customized aspheric treatment zone (CATz) algorithm followed by accelerated CXL (Avedro Inc., Waltham, USA) in patients with keratoconus. The above‑mentioned protocols (a‑c) were performed using the “T-CAT” algorithm of the WaveLight Allegretto Wave Excimer Laser System (WaveLight Laser Technologie AG). M‑nomogram for corneal cross‑linking[46] It is a new customized epithelium off accelerated crosslinking (ACXL) nomogram based on preoperative corneal optical thinnest point for progressive keratoconus and iatrogenic corneal ectasia. It allows the possibility to preoperatively estimate the depth of the treatment according to baseline optical thinnest point pachymetry data, thus maintaining endothelial safety (a safety endothelial margin of +50 μm is used in the M nomogram offset) and including ectatic thin corneas under 400 μm (range 250–400 μm) with epithelium. Corneal thickness <400 µm after epithelial debridement a. Use of hypo‑osmolar Riboflavin b. Contact Lens‑assisted CXL:[47] Use of riboflavin‑soaked soft hydrophilic lens Hilafilcon B after epithelial debridement during the treatment phase. c. Transepithelial CXL):[48] To disr upt epithelial integrity, enhancers are used. A solution of enhanced riboflavin (containing riboflavin 0.1% dextran T 500, Trometrol, and EDTA) is applied to intact epithelium every 5 min for a total of 30 min. Following this, UV-A irradiation is applied for the next 30 min at standard fluence, with enhanced riboflavin being applied every 5 min for the same duration. d) Iontophoresis‑assisted CXL:[49] It is based on the principle that transepithelial riboflavin penetration occurs after applying mild current. A generator-assisted constant current of 1 mA is given locally to the cornea for 5–10 min. Irradiation is then administered as in the standard or accelerated protocol. e) High fluence transepithelial CXL: Mazzotta et al. [50] have significantly improved the I‑CXL method. They achieved improved results by increasing the fluence to 7 J/cm2 , pulsing the light illumination, and washing the riboflavin biofilm away from the corneal surface before starting the UV-A light. This approach eliminates the riboflavin shielding effect beyond the epithelium, improving treatment efficacy and a deeper demarcation line. The enhanced fluence pulsed light iontophoresis, or the new iontophoresis protocol is the name given to this novel approach. f) Sub 400 individualized fluence CXL Protocol: Guhan et al. [51] have developed an algorithm that adjusts the overall fluence during the CXL procedure, taking into account the individual stromal thickness of the patient, which is known as the sub400 protocol. This algorithm helps to cross-link the stroma while protecting the corneal endothelium from harmful levels of UV-A radiation. The algorithm is based on a published formula that considers stromal riboflavin, oxygen, and UV availability during the cross-linking procedure. It is based on estimating the diffusion of riboflavin and oxygen by Fick’s law of diffusion and UV energy by Lambert–Beer’s law of light absorption. The speed and amount of the induced photochemical reactions (type I and II) are determined by the presence Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023 285

Dhar, et al.: Evolving trends in corneal surgery of these three factors. It is assumed the amount of singlet oxygen (Soxy) produced during the treatment interacts with the available extracellular matrix (EM) and thereby forms the relevant cross-link. Surgical Adhesives in Corneal Perforations[52] Tissue adhesives have the potential to enhance the results of existing ophthalmic surgical procedures by reducing surgical time and minimizing complications such as postoperative leaks, inflammation, and infections. An ideal adhesive should possess superior tensile strength, and be non-toxic, anti‑inflammatory, efficient, and cost‑effective. Adhesives are classified into two main categories: synthetic glues (such as cyanoacrylate and polyethylene glycol [PEG] derivatives) and biological glues (such as fibrin). The higher molecular weight cyanoacrylates, such as n-butyl, iso-butyl, and octyl-cyanoacrylates, are stronger and less toxic than their lower molecular weight counterpart, methyl‑cyanoacrylate. In addition, fibrin glue is another type of adhesive that consists of two components that, when combined, form an insoluble glue. The first component of fibrin products such as Tisseel and Tissucol includes fibrinogen, human factor XIII, and aprotinin while the second component contains thrombin and calcium. Once combined, thrombin breaks down the fibrinogen into fibrin monomers, which then polymerize into a linear structure and crosslink through calcium-activated human factor XIII. Indications in corneal surgery[53] a. Central/mid-peripheral Corneal perforations up to 3 mm size b. As an adjunct to partial or full-thickness corneal transplants c. Pterygium surgery d. Simple limbal epithelial transplantation e. Post-LASIK epithelial ingrowth treatment f. Management of flap tears and dislocation. Corneal Patch Grafts and Tenon Patch Graft Patch grafts can be utilized for the management of corneal perforations that are not amenable to repair with the use of tissue adhesives, i.e., more than 03 mm in size and also those peripheral in location.[54] Tenon’s patch graft is a surgical technique used to manage large corneal perforations, which are too big for tissue adhesive to be effective. The technique involves using the Tenon’s capsule, which is a layer of connective tissue surrounding the eyeball, to create an autologous transplant. This allows for the production of fibroblasts and connective tissue, which can be incorporated into the host’s corneal tissue. As it is an autologous transplant, no immune response is evoked, and there is no tissue rejection. Unlike corneal grafting or AMT, which rely on donor tissue and eye banks, the Tenon’s capsule transplant does not require these resources, making the supply more readily available. In addition, as there is no heterologous antigenic sensitization, the likelihood of success for corneal grafting is higher if performed at a later stage.[55] Amniotic Membrane Transplants Recently, increased attention has been given to the regenerative properties of amniotic membranes. These membranes often support corneal healing and reduce inflammation associated with ocular surface disorders. There are various methods of amniotic membrane preservation:[56] a. Cryopreservation: This involves adding Dulbecco’s Modified Eagle Medium containing cryoprotectants such as glycerol to the tissue and freezing it at -80°C to limit degradation from unregulated enzymatic reactions. b. Freeze–Drying/Lyophilization: After cooling the amnion to -80°C, a process of sublimation removes water from the tissue, followed by sterilization using gamma irradiation. c. Dehydration and low-temperature vacuum evaporation: The moisture in tissue can be removed and the tissue can be dehydrated using either air or heat. Unlike lyophilized or cryopreserved amnion, this process does not involve freezing the tissue, so it does not face any issues related to freezing. To sterilize the tissue, gamma irradiation is used. Indications in corneal and ocular surface disorders[56] A. Corneal ulceration and persistent epithelial defects: They can be used as Inlay (amnion side up)/Onlay (amnion side down) or Combinatorial (combination of two) [Figure 4] technique. In a specific case, Grau and Duran utilized a double-layered amniotic membrane and a single-layered amniotic membrane to sandwich a 3 mm corneal perforation. They then used TachoSil to glue the membranes together at the perforation site. This treatment showed promising results.[52] B. Limbal stem cell deficiency: i. Simple limbal epithelial transplantation ii. Amnion-assisted conjunctival epithelial redirection: It uses an amnion patch to redirect conjunctival cells, allowing corneal epithelial cells to regenerate with less dilution from the conjunctival epithelium. iii. Cultivated stem cell transplantation iv. Pterygium surgery especially in recurrent and bi-headed pterygia. v. Chemical/Thermal Injury: Amnion, due to its various biological properties, is considered a suitable treatment for chemical burns. Its epitheliotropic, anti-inflammatory, and anti-neovascular effects make it an attractive option. It also offers better oxygen permeation and reduces mechanical epithelial trauma from eyelid friction, increasing patient comfort and reducing pain. However, the success of amnion transplantation in chemical burns depends on the burn’s severity, particularly the epithelialization rate. Nonetheless, studies suggest that amnion transplantation can improve other outcome measures such as pain and inflammation 286 Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023

Dhar, et al.: Evolving trends in corneal surgery reduction, provided it is applied within the 1st week of the injury. vi. Dry eye disease vii. Cicatrizing Conjunctivitis – Stevens–Johnson Syndrome (SJS), Toxic Epidermal Necrolysis(TEN), Graft versus Host Disease and Pemphigoid viii. Recurrent Corneal Erosion (RCE). Corneal Inlays They are becoming popular for the treatment of presbyopia. Developing new materials and designs have expanded options for patients seeking presbyopia correction. A recent retrospective review by Darian-Smith et al. [53] of 35 patients with KAMRA inlay showed significant improvement in uncorrected near visual acuity (P = 0.00009), uncorrected intermediate visual acuity (P = 0.00006), and uncorrected distance visual acuity (P = 0.02), but levels of patient dissatisfaction were 43%. Femtosecond Laser Technology It enables precise incisions, creating flapless procedures in techniques such as LASIK and SMILE. It has also facilitated corneal graft preparation in both full-thickness and lamellar transplantation thus enhancing surgical accuracy. Customized Treatments Advancements in imaging and diagnostic technologies have enabled customized corneal treatments. Wavefront-guided and topography-guided procedures offer personalized treatment plans, improving visual outcomes and reducing side effects such as glare and halos. Regenerative Therapies Research into regenerative therapies, such as stem cell transplantation and growth factor treatments, holds promise for corneal regeneration. These therapies aim to repair and replace damaged corneal tissue, potentially reducing the need for transplantation in the future. There are four distinct categories that newer corneal therapeutics fall under, namely cell therapy, regenerative medicine, bioengineered corneal grafts, and gene therapy.[57] Cell therapy It encompasses the cultivation of cells, such as corneal endothelial cells (CECs) and keratocytes to replenish the depleted native cell population. In 2018, Kinoshita et al. [58] published a landmark study demonstrating the clinical efficacy of this approach for the treatment of bullous keratopathy in humans, with the primary cause being Fuchs endothelial corneal dystrophy (FECD) in many cases. For stromal diseases, animal studies have shown that intrastromal injections of cultivated keratocytes promote proteoglycan deposition and connective tissue remodeling, which can potentially ameliorate stromal scarring. Regenerative medicine It is mainly applicable to the corneal endothelium, and is dependent on the ability of native, healthy CECs to restore the corneal endothelium following trauma or descemetorhexis; this approach may be effective for the treatment of Peter’s anomaly and FECD.[57] Bioengineered corneal grafts There are artificial materials that are made with the purpose of replacing corneal grafts taken from deceased donors. These materials can be biological, such as amniotic membranes, or synthetic, such as collagen-based bio-ink, polyvinyl acetate and collagen composites, gelatin and polycaprolactone composites, and methacrylated gelatin hydrogels. The ideal material for this purpose should have sufficient mechanical strength, optical transparency, and biocompatible properties that support the growth and metabolism of keratocytes. Mehrdad Rafat and colleagues have recently reported using bioengineered corneal tissue to restore vision in patients with advanced keratoconus using minimally invasive techniques.[59] Gene therapy[57] Antisense oligonucleotides and CRISPR endonucleases, including deactivated Cas9, can potentially treat corneal dystrophies related to FECD and TGFBI. Conclusion Recent trends in corneal surgery reflect a shift toward more precise, minimally invasive, and personalized approaches. These advancements not only improve visual outcomes but also offer hope to patients with previously untreatable corneal conditions. As technology continues to evolve, we can anticipate even more exciting developments in the field of corneal surgery, benefiting patients worldwide. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. References 1. Reisinger F. Keratoplasty: An Attempt to Expand the art of ophthalmology. Bayer Ann 1824;1:207-15. 2. von Hippel A. A new method of corneal transplantation. Arch Ophthalmol 1888;34:105-30. 3. Mannis MJ, Mannis AA. Corneal Transplantation: A History in Profiles. Belgium: JP. Wayenborgh; 1999. 4. Nijm LM, Mannis MJ, Damani MR, Holland EJ. The evoluation of contemporary keratoplasty. In: Krachmer Textbook of Cornea. 5th ed., Ch. 108. Elsevier: USA; 2021. 5. Thompson RW Jr., Price MO, Bowers PJ, Price FW Jr. Long-term graft survival after penetrating keratoplasty. Ophthalmology 2003;110:1396-402. 6. Cornea Donor Study Investigator Group, Gal RL, Dontchev M, Beck RW, Mannis MJ, Holland EJ, et al. The effect of donor age on corneal transplantation outcome results of the cornea donor study. Ophthalmology 2008;115:620-6.e6. 7. Maharana PK, Sahay P, Singhal D, Garg I, Titiyal JS, Sharma N. Component corneal surgery: An update. Indian J Ophthalmol Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023 287

Dhar, et al.: Evolving trends in corneal surgery 2017;65:658-72. 8. van DijkK, LiarakosVS, ParkerJ, HamL, LieJT, Groeneveld-van BeekEA, et al. Bowman layer transplantation to reduce and stabilize progressive, advanced keratoconus. Ophthalmology 2015;122:909-17. 9. Sharma VK, Sati A, Kaushik J, Kumar S, Agarwal M. Tuck in femtosecond laser assisted anterior lamellar keratoplasty (T‑FALK) for the management of superficial anterior corneal scars‑a modified technique. Cornea 2021;40:125-30. 10. Shimmura S, Tsubota K. Deep anterior lamellar keratoplasty. Curr Opin Ophthalmol 2006;17:349-55. 11. Anwar M, Teichmann KD. Deep lamellar keratoplasty: Surgical techniques for anterior lamellar keratoplasty with and without Baring of Descemet’s membrane. Cornea 2002;21:374-83. 12. Dua HS, Faraj LA, Said DG, Gray T, Lowe J. Human corneal natomy redefined: A novel preDescemet’s layer (Dua’s layer). Ophthalmology 2013;120:177885. 13. Jhanji V, Beltz J, Sharma N, Graue E, Vajpayee RB. “Double bubble” deep anterior lamellar keratoplasty for management of corneal stromal pathologies. Int Ophthalmol 2011;31:257-62. 14. Melles GR, Remeijer L, Geerards AJ, Beekhuis WH. A quick surgical technique for deep, anterior lamellar keratoplasty using visco-dissection. Cornea 2000;19:427-32. 15. Sugita J, Kondo J. Deep lamellar keratoplasty with complete removal of pathological stroma for vision improvement. Br J Ophthalmol 1997;81:184-8. 16. Vajpayee RB, Maharana PK, Sharma N, Agarwal T, Jhanji V. Diamond knife-assisted deep anterior lamellar keratoplasty to manage keratoconus. J Cataract Refract Surg 2014;40:276-82. 17. Maharana PK, Agarwal K, Jhanji V, Vajpayee RB. Deep anterior lamellar keratoplasty for keratoconus: A review. Eye Contact Lens 2014;40:382-9. 18. Busin M, Madi S, Santorum P, Scorcia V, Beltz J. Ultrathin descemet’s stripping automated endothelial keratoplasty with the microkeratome double-pass technique: Two-year outcomes. Ophthalmology 2013;120:1186-94. 19. Birbal RS, Sikder S, Lie JT, Groeneveld-van Beek EA, Oellerich S, Melles GR. Donor tissue preparation for descemet membrane endothelial keratoplasty: An updated review. Cornea 2018;37:128-35. 20. Groeneveld-van Beek EA, Lie JT, van der Wees J, Bruinsma M, Melles GR. Standardized ‘no-touch’ donor tissue preparation for DALK and DMEK: Harvesting undamaged anterior and posterior transplants from the same donor cornea. Acta Ophthalmol 2013;91:145-50. 21. Giebel AW, Price FW. Descemet’s membrane endothelial keratoplasty (DMEK): The bare minimum. In: Price FW, Price MO, editors. DSEK: All You Need to Know About Endothelial Keratoplasty. Thorofare, NJ: Slack, Inc; 2008. p. 119-46. 22. Zarei-Ghanavati S, Khakshoor H, Zarei-Ghanavati M. Reverse big bubble: A new technique for preparing donor tissue of Descemet membrane endothelial keratoplasty. Br J Ophthalmol 2010;94:1110-1. 23. Studeny P, Farkas A, Vokrojova M, Liskova P, Jirsova K. Descemet membrane endothelial keratoplasty with a stromal rim (DMEK‑S). Br J Ophthalmol 2010;94:909-14. 24. Agarwal A, Dua HS, Narang P, Kumar DA, Agarwal A, Jacob S, et al. Pre‑Descemet’s endothelial keratoplasty (PDEK). Br J Ophthalmol 2014;98:1181-5. 25. Salvalaio G, Parekh M, Ruzza A, Ferrari S, Camposampiero D, Ponzin D. DMEK lenticule preparation from donor corneas using a novel ‘SubHyS’ technique followed by anterior corneal dissection. Br J Ophthalmol 2014;98:1120-5. 26. Szurman P, Januschowski K, Rickmann A, Damm LJ, Boden KT, Opitz N. Novel liquid bubble dissection technique for DMEK lenticule preparation. Graefes Arch Clin Exp Ophthalmol 2016;254:1819-23. 27. Livny E, Bahar I, Nahum Y. “Ghost DMEK” technique: Circular peripheral staining of descemet’s membrane endothelial keratoplasty grafts. Cornea 2019;38:252-5. 28. Tzamalis A, Vinciguerra R, Romano V, Arbabi E, Borroni D, Wojcik G, et al. The “Yogurt” technique for descemet membrane endothelial keratoplasty graft preparation: A novel quick and safe method for both inexperienced and senior surgeons. Cornea 2020;39:1190-5. 29. Or L, Krakauer Y, Sorkin N, Knyazer B, Ashkenazy Z, Gushansky K, et al. A novel marking technique for descemet membrane endothelial graft using an ophthalmic viscoelastic device. Cornea 2021;40:529-32. 30. Güell JL, Morral M, Gris O, Elies D, Manero F. Bimanual technique for insertion and positioning of endothelium-descemet membrane graft in descemet membrane endothelial keratoplasty. Cornea 2013;32:1521-6. 31. Busin M, Leon P, Scorcia V, Ponzin D. Contact lens-assisted pull‑through technique for delivery of tri‑folded (endothelium in) DMEK grafts minimizes surgical time and cell loss. Ophthalmology 2016;123:476-83. 32. Jacob S, Agarwal A, Agarwal A, Narasimhan S, Kumar DA, Sivagnanam S. Endoilluminator-assisted transcorneal illumination for Descemet membrane endothelial keratoplasty: Enhanced intraoperative visualization of the graft in corneal decompensation secondary to pseudophakic bullous keratopathy. J Cataract Refract Surg 2014;40:1332-6. 33. Garcerant D, Hirnschall N, Toalster N, Zhu M, Wen L, Moloney G. Descemet’s stripping without endothelial keratoplasty. Curr Opin Ophthalmol 2019;30:275-85. 34. Moshirfar M, Parker L, Birdsong OC, Ronquillo YC, Hofstedt D, Shah TJ, et al. Use of rho kinase inhibitors in ophthalmology: A review of the literature. Med Hypothesis Discov Innov Ophthalmol 2018;7:101-11. 35. Auffarth GU, Son HS, Koch M, Weindler J, Merz P, Daphna O, et al. Implantation of an artificial endothelial layer for treatment of chronic corneal edema. Cornea 2021;40:1633-8. 36. Sharma S, Donthineni PR, Iyer G, Chodosh J, de la Paz MF, Maskati Q, et al. Keratoprosthesis in dry eye disease. Indian J Ophthalmol 2023;71:1154-66. 37. Koller T, Mrochen M, Seiler T. Complication and failure rates after corneal crosslinking. J Cataract Refract Surg 2009;35:1358-62. 38. Mastropasqua L. Collagen cross-linking: When and how? A review of the state of the art of the technique and new perspectives. Eye Vis (Lond) 2015;2:19. 39. Frucht-Pery J, Wajnsztajn D. (2017). Clinical Application and Decisionmaking. In: Sinjab M, Cummings A. (eds) Corneal Collagen Cross Linking. Springer, Cham. https://doi.org/10.1007/978-3-319-39775-7_5. 40. Peyman A, Nouralishahi A, Hafezi F, Kling S and Peyman M: Stromal demarcation line in pulsed versus continuous light accelerated corneal cross-linking for keratoconus. J Refract Surg 2016:32;206-8. 41. Shetty R, Kaweri L, Pahuja N, Nagaraja H, Wadia K, Jayadev C, et al. Current review and a simplified “five‑point management algorithm” for keratoconus. Indian J Ophthalmol 2015;63:46-53. 42. Kanellopoulos AJ, Asimellis G. Keratoconus management: Long-term stability of topography-guided normalization combined with high‑fluence CXL stabilization (the Athens protocol). J Refract Surg 2014;30:88-93. 43. Kymionis GD, Grentzelos MA, Kankariya VP, Liakopoulos DA, Karavitaki AE, Portaliou DM, et al. Long-term results of combined transepithelial phototherapeutic keratectomy and corneal collagen crosslinking for keratoconus: Cretan protocol. J Cataract Refract Surg 2014;40:1439-45. 44. Grentzelos MA, Kounis GA, Diakonis VF, Siganos CS, Tsilimbaris MK, Pallikaris IG, et al. Combined transepithelial phototherapeutic keratectomy and conventional photorefractive keratectomy followed simultaneously by corneal crosslinking for keratoconus: Cretan protocol plus. J Cataract Refract Surg 2017;43:1257-62. 45. Jain R, Shuaib Y, Mohan N, Mittal V. Outcomes of topography-guided PRK/CXL in keratoconus using the NIDEK CXIII system‑“Bharat Protocol” (pilot study). Indian J Ophthalmol 2023;71:3203‑9. 46. Mazzott C, Romani A, Burroni A, et al. Pachymetry-based accelerated cross-linking: The “M Nomogram” for standardized treatment. Int J Keratoconus Ectatic Corneal Dis 2018;7:137-44. 47. Jacob S, Kumar DA, Agarwal A, Basu S, Sinha P, Agarwal A. Contact lens‑assisted collagen cross‑linking (CACXL): A new technique for cross-linking thin corneas. J Refract Surg 2014;30:366-72. 48. Filippello M, Stagni E, O’Brart D. Transepithelial corneal collagen crosslinking: Bilateral study. J Cataract Refract Surg 2012;38:283-91. 49. Luca Gualdi, MD; Federica Gualdi, MD; Veronica Cappello, MD; and Massimo Gualdi, MD. Iontophoresis Assisted CXL. CRSTEUROPE; 288 Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023

Dhar, et al.: Evolving trends in corneal surgery 2015. 50. Mazzotta C, Bagaglia SA, Vinciguerra R, Ferrise M, Vinciguerra P. Enhanced‑fluence pulsed‑light iontophoresis corneal cross‑linking: 1-year morphological and clinical results. JRefract Surg 2018;34:438-44. 51. Guhan S, Peng SL, Janbatian H, Saadeh S, Greenstein S, Al Bahrani F, et al. Surgical adhesives in ophthalmology: History and current trends. Br J Ophthalmol 2018;102:1328-35. 52. Grau AE, Durán JA. Treatment of a large corneal perforation with a multilayer of amniotic membrane and TachoSil. Cornea 2012;31:98-100. 53. Darian-Smith E, Gouvea L, Gendler S, Alshaker S, Din N, Weill Y, et al. KAMRA presbyopic inlay refractive outcomes: a Canadian perspective. Can J Ophthalmol. 2022:S0008-4182(22)00342-8. 54. Korah S, Selvin SS, Pradhan ZS, Jacob P, Kuriakose T. Tenons patch graft in the management of large corneal perforations. Cornea 2016;35:696-9. 55. Deshmukh R, Stevenson LJ, Vajpayee R. Management of corneal perforations: An update. Indian J Ophthalmol 2020;68:7-14. 56. Walkden A. Amniotic membrane transplantation in ophthalmology: An updated perspective. Clin Ophthalmol 2020;14:2057-72. 57. Mehta JS, Kocaba V, Soh YQ. The future of keratoplasty: Cell-based therapy, regenerative medicine, bioengineering keratoplasty, gene therapy. Curr Opin Ophthalmol 2019;30:286-91. 58. Kinoshita S, Koizumi N, Ueno M, Okumura N, Imai K, Tanaka H, et al. Injection of cultured cells with a ROCK inhibitor for bullous keratopathy. N Engl J Med 2018;378:995-1003. 59. Rafat M, Jabbarvand M, Sharma N, Xeroudaki M, Tabe S, Omrani R, et al. Bioengineered corneal tissue for minimally invasive vision restoration in advanced keratoconus in two clinical cohorts. Nat Biotechnol 2023;41:70-81. Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023 289

Abstract Review Article Introduction Myopia, a refractive error, is now being referred to as an “explosive epidemic” or pandemic. Any myopia of >−5 D is referred to as high myopia resulting in complications such as glaucoma, cataracts, retinal detachment, and choroidal neovascularization that can lead to visual impairment and vision loss.[1] Progression of myopia happens when with time, there is an increase in axial length or negative sphere dioptric power. It can occur in both simple myopia and in pathological myopia. A chemical cascade of neurotransmitters signals the eye to elongate when, peripheral light rays focus behind the retina, creating hyperopic defocus.[2] There are numerous ways, in which we can slow the progression of myopia-environmental modifications, and optical and pharmaceutical interventions. In this review, we have highlighted recent research on the latest treatment options available for slowing the progression of myopia. Environmental and Lifestyle Modification Multiple environmental factors playing a major role in axial length growth and myopia progression include time spent outdoors, indoor lighting, near work, sleep patterns, and nutrition. Although the environmental and lifestyle modifications may not solely help us to control myopia progression, they act as an add-on mechanism to various optical and pharmacological interventions which have been mentioned below. The impact of various environmental and lifestyle techniques is summarized in Table 1. Repeated Low‑level Red‑light Therapy for Myopia Progression Repeated low‑level red‑light (RLRL) therapy is an effective and emerging modality for the control of myopia progression with no documented functional or structural damage. According to a study by Jiang et al.,[15] around 40% of RLRL-treated children showed axial length shortening of >0.05 mm. Changes in choroidal thickness did not fully account for this shortening, indicating some other mechanism at play. After 2 years, the results for axial length control are more in line with other optical interventions and 0.05% atropine. Optical coherence tomography did not show any changes at fovea. Although clinical trial terms the modality to be a safe technique, a single case of retinal damage resulting in bilateral darkened fovea after RLRL therapy in a 12-year-old girl has been reported after RLRL therapy.[16] Myopia is now an emerging global public health challenge that significantly affects an individual’s quality of life and hence requires appropriate interventions to delay or arrest the onset and progression. The current concepts in myopia have come up with studies that mainly focus on control strategies, lifestyle modifications, and pharmaceutical and optical management options being taken into consideration. This article summarizes current updates on myopia control strategies. Keywords: Atropine, myopia, myopia control, myopia progression Address for correspondence: Dr. Nilima Khochikar, Department of Paediatric Ophthalmology, MM Joshi Eye Institute, Hubli, Karnataka, India. E‑mail: [email protected] This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non‑commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. For reprints contact: [email protected] How to cite this article: Joshi D, Khochikar N, Krishnaprasad R. Clinical trials in myopia control: A Review. Delhi J Ophthalmol 2023;33:290-5. Clinical Trials in Myopia Control: A Review Deepti Joshi, Nilima Khochikar, R. Krishnaprasad Department of Paediatric Ophthalmology, MM Joshi Eye Institute, Hubli, Karnataka, India Access this article online Quick Response Code: Website: https://journals.lww.com/djo DOI: 10.4103/DLJO.DLJO_187_23 Submitted: 06-Dec-2023 Revised: 27-Dec-2023 Accepted: 28-Dec-2023 Published: 15-Jan-2024 290 © 2024 Delhi Journal of Ophthalmology | Published by Wolters Kluwer - Medknow

Joshi, et al.: Studies of myopia Pharmaceutical Intervention Of all the drugs used in stopping myopia progression, low-dose atropine has been the safest and successful drug. Although atropine acts on ocular accommodation, yet the main mechanism by which atropine acts in myopia progression has been by a nonaccommodation mechanism. The most acceptable mechanism is thought to be through modulation of dopamine release, which in turn alters the rate of axial eye growth.[17,18] Various pharmaceutical trials such as atropine for the treatment of myopia (ATOM) 1, ATOM2, CHAMPS, and LAMP studies mainly aim to find out the best concentration of atropine which is effective yet safe for slowing myopia progression. Atropine for the treatment of myopia-1 trial ATOM-1 study by Chua et al. [19] aimed to compare the efficacy of 1% atropine drops with placebo. Following 2-year treatment, there was an approximately 77% mean reduction of myopia progression in the treatment group compared with the placebo group [Table 2]. Although the study did prove 1% atropine to be a successful modality in slowing myopia progression, yet the major concerns were the side effects of 1% atropine. Moreover, a rebound phenomenon was observed following the cessation of atropine eye drops administration. The drawbacks prompted a search for low-dose atropine, leading to the ATOM 2 study. Atropine for the treatment of myopia-2 trial The ATOM-2 trial[20] compared the efficacy of 0.5%, 0.1%, and 0.01% concentrations of atropine in slowing myopia progression [Table 2]. Over 2 years of the treatment period, the mean myopia progression noted was −0.30 (0.60) D in the 0.5% group, −0.38 (0.60) D in the 0.1% group, and −0.49 (0.63) D in the 0.01% group. The axial elongation was 0.27 (0.25) mm, 0.28 (0.28) mm, and 0.41 (0.32) mm in the 0.5%, 0.1%, and 0.01% atropine groups, respectively. Rebound of myopia was observed in 0.5% and 0.1% atropine groups. However, it was relatively less in 0.01% groups.[21] ATOM2 study concluded that 0.01% atropine was better in treatment-to-side effect balance considering a fewer side effects and rebound following atropine cessation. Low concentration atropine for myopia progression study LAMP[22] study was conducted at Hong Kong to study the efficacy and safety of 0.05%, 0.025%, and 0.01% atropine eye drops for long-term myopia control over 1-year period. They found, after 1 year, spherical change was −0.27 ± 0.61 D, −0.46 ± 0.45 D, −0.59 ± 0.61 D, and −0.81 ± 0.53 D in the 0.05%, 0.025%, and 0.01% atropine groups and placebo groups, respectively (P < 0.001). Axial length was 0.20 ± 0.25 mm, 0.29±0.20mm, 0.36 ±0.29mm, and 0.41 ±0.22mm(P<0.001). The study concluded that 0.05% atropine was most effective in controlling myopia progression over 1 year. What new did LAMP study prove? a. First year of this trial demonstrated that, compared to placebo, 0.01% atropine significantly reduced refractive progression but had a nonsignificant effect on eye elongation b. However, 0.05% atropine significantly reduced both the rate of refractive progression and eye elongation over the 1-year period and demonstrated superior efficacy to 0.025% and 0.01% at the end of 2 years c. Rebound effect after stopping atropine 0.05% was small and was labeled “clinically insignificant” (0.04 mm faster progression over 1 year), while 0.025% and 0.01% groups did not experience any “rebound effect” d. Despite the study favoring 0.05% to be a better dose of atropine, yet 0.01% is significantly used because Cooper et al. [23] suggested in their study that any concentration above 0.02% is likely to produce clinical symptoms which may pose a barrier for clinical use [Table 3]. CHAMP trial The CHAMP study was a double-masked, placebo-controlled study which compared 0.01% and 0.02% atropine. 0.01% dose of atropine was associated with a significantly slower progression of spherical equivalent refraction and axial elongation. Paradoxically, the effect of the 0.02% dose on responder proportion and SER progression was not statistically significant, but the treatment was associated with slower axial elongation. No serious ocular adverse effects were noted.[24] Optical Interventions Glasses and contact lenses have been used since ages for inhibiting myopia progression. Many clinical trials have been conducted to study the effect of various types of optical aids on myopia progression. Most of the research is based on the Table 1: Environmental and lifestyle modifications for slowing myopia progression Outdoor time and natural light[3-7] Indoor lightings[8-10] Near work[11-13] Important points from studies Sunlight exposure stimulates retinal ganglion cells causing dopamine release and reducing eye growth Pupillary miosis decreases peripheral defocus, delaying progression UV light exposure upregulates myopia suppression gene (EGR1)[7] Lighting levels >3000 lux produced a protective factor for myopia in Chinese students[8] It was found that students who used LED lamps had larger myopic refractive errors and longer axial lengths when compared to students who used incandescent or fluorescent lamps[10] Close working distance (20–25 cm), a head tilt when reading, continuous reading for >45 min and prolonged digital usage are all associated with greater odds of myopia progression Clinical implications IMI now recommends a minimum of 2 h/day of outdoor time for the prevention of myopia onset[14] Higher indoor illumination Yellow halogen bulbs preferred over LED bulbs Maintaining adequate distance (>30 cm) while reading, breaks between readings and digital abstinence LED: Light-emitting diode, UV: Ultraviolet, IMI: International Myopia Institute Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023 291

Joshi, et al.: Studies of myopia theory that myopic progression causes accommodative lag and peripheral hyperopic defocus. Optical intervention methods for both theories, therefore, aim to reduce hyperopic defocus, either centrally during near work or in the peripheral visual field [Figure 1]. The major studies pertaining to optical interventions to slow myopia progression have been highlighted below. Under correction of myopia In a randomized study by Chung et al.,[25] children in the experimental group were assigned to wear spectacle lenses that were under-corrected by 0.50–0.75 D whereas children in the control group were prescribed their full correction. After 2 years, the under-correction group had greater myopia progression of −1.00 D as compared to the control group who progressed by −0.77 D. Clinical Implication - Under correction of myopia to be withheld as much as possible to prevent myopia progression. Progressive addition lens spectacle-COMET 2 study[26] PALs have been assessed in well‑sized, randomized (between PALs and single‑vision spectacles), double‑masked, multicenter trials with robust testing procedures. The studies used +2 D near additions over each participant’s distance refraction and monitored progression over 3 years. Findings included: • There was statistically significantly slower myopia progression in the PAL group in the 1st year, followed by equivalent progression between PAL and single-vision spectacles • In a subset of children with high accommodative lag and near esophoria, there was a statistically significant reduction in myopia progression in the PAL spectacles group compared to the single-vision spectacles group. PALs are definitely a preferable option for myopic children with accommodative lag and esophoria. Defocus incorporated multiple segments spectacle lens [Figure 2] Defocus incorporated multiple segment (DIMS) lens‑a new kid on the myopia for myopia progression control comprises a central optical zone for correcting refractive error and multiple segments of constant myopic defocus (+3.50 D) surrounding the central zone. It combines the principle of simultaneous vision with myopia defocus for myopia control. Trials comparing the efficacy of single-vision lenses to that of DIMS showed 52% lesser myopia progression and 62% lesser axial elongation with DIMS compared to children wearing single-vision spectacle lenses over 2 years.[27] Table 3: Summary of low-concentration atropine for myopia progression study 0.01% 0.025% 0.05% Pupil dilatation +0.5 +0.8 +1 Refractive progression reduction (%) 27 43 66 Axial length growth reduction (%) 12 29 51 Table 2: Summary of atropine for the treatment of myopia study Myopia progression (D) Percentage reduction ATOM 1 Placebo −1.20 77 Atropine 1% −0.28 ATOM 2 Atropine 0.5% −0.30 75 Atropine 0.1% −0.35 68 Atropine 0.01% −0.49 59 What did we learn from ATOM study? Atropine eye drops slows down myopia progression in dose-dependent manner Higher the dose, the higher were side effects and rebound phenomenon on drop cessation Best therapeutic index was 0.01% ATOM: Atropine for the treatment of myopia 292 Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023 Figure 1: Optical interventions to slow myopia progression. H.A.L.T.: Highly aspherical lenslet target, DIMS: Defocus incorporated multiple segments, DOT: Diffusion optics technology

Joshi, et al.: Studies of myopia Contact lens and myopia progression study The CLAMP study is a randomized clinical trial that examines the effects of rigid gas permeable (RGP) contact lenses on myopia progression.[28] CLAMP study indicates that RGPs significantly slow the progression of myopia in children. The questionable part was on the probable temporary aspect of results as the treatment effect is likely to be due to corneal flattening which may be reversible; the decreased refractive error progression is not accompanied by slowed axial growth; and the initial treatment effect does not continue to accrue during the entire study. Orthokeratology Orthokeratology (ortho‑k) is defined as a reduction, modification, or elimination of a refractive error by programmed application of contact. Rigid contact lens worn in night temporarily flattens the front surface of the corneas during the night, resulting in flattening of the central cornea and a steepening of the mid-peripheral cornea, accompanied by changes in the epithelial thickness.[29] Although these lenses were designed for refractive error correction, studies have revealed a secondary advantage of slowing myopic progression[30] by creating peripheral myopic defocus secondary to epithelial reshaping. A number of studies have shown a 30%–71% reduction in axial elongation compared with the control.[31] Cheung et al. [32] suggest that ideal candidates for orthokeratology might be children around 6–9 years of age with fast myopic progression (increase in the axial length of ≥0.20 mm/7 months or the spherical equivalent of ≥1 diopter/year). Soft bifocal, peripheral gradient, and extended depth of focus contact lenses The newer contact lens not just corrects myopia but controls myopia progression too [Figure 3]. The Bifocal Lenses In Nearsighted Kids(BLINKs) randomized clinical trial[33] has recently determined the role of soft multifocal lenses in slowing myopia progression in children, comparing high‑add power (+2.50 D) with medium‑add power (+1.50 D) and single‑vision contact lenses. This demonstrated that treatment with high-add power multifocal contact lenses significantly reduced the rate of eye elongation compared with medium-add power multifocal and single-vision contact lenses. Extended depth of focus(EDOF) contact lenses were tested in a 3-year prospective, double-blind trial[34] that demonstrated their efficacy in slowing myopia progression. A total of 508 children with the cycloplegic spherical equivalent −0.75 to −3.50 were enrolled and randomized in one of the five groups: one group Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023 293 Figure 3: Contact lens to achieve myopia control adapted from Andrea Russo et al. [34] Figure 2: Mechanism of action of DIMS glasses. DIMS: Defocus incorporated multiple segments

Joshi, et al.: Studies of myopia with single vision, two groups with bifocal, and two groups with EDOF contact lenses(configured to offer EDOF of up to +1.75 D and +1.25 D). At 2 years, the two groups of EDOF lenses slowed myopia by 32% and 26% and reduced axial length elongation by 25% and 27%, respectively. However, efficacy was not significantly different between the bifocal and EDOF lens groups. Recent studies have observed a rising trend of myopia in most populations worldwide, with prevalence reaching up to 69% by the age of 15 years in the urban population of East Asia.[35] Several independent studies confirm a greater predisposition for myopia in Chinese ethnicity than in the white population.[35] Among Caucasians, the estimated prevalence of myopia ranges from approximately 26% in the United States and Western Europe to 16% in Australia and has superseded hyperopia as the most prevalent refractive error.[35] In India, nearly, doubling of myopia prevalence, that is, from 7.4% to 13.1%, was observed when compared with the previous decade in urban schools of Delhi.[35] A recent meta-analysis of the last four decades from India reports a rising trend of myopia in the country with narrowing of the urban–rural gap in myopia prevalence.[35] Young age and female gender are found to be at higher risk. Gender predisposition, although not noted in many studies, is mostly explained by the fact that girls engage less in outdoor activities compared to boys.[35] Conclusion Myopia is an emerging global public health issue with high prevalence. Literature suggests multiple options for myopia progression control. All the options mentioned above exhibit varying degrees of efficacy and the results may vary in each individual. As a treating physician, it becomes our responsibility to customize and deliver the most suitable progression prevention method to every myopic individual. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. References 1. IAPB: WHO – Global Initiative for the Elimination of Blindness. Available from: https://www.iapb.org/resources/who-global-initiativefor-the-elimination-of-blindness/. 2. Holden BA, Fricke TR, Wilson DA, Jong M, Naidoo KS, Sankaridurg P, et al. Global prevalence of myopia and high myopia and temporal trends from 2000 through 2050. Ophthalmology 2016;123:1036-42. 3. Zhang J, Deng G. Protective effects of increased outdoor time against myopia: A review. J Int Med Res 2020;48:300060519893866. 4. Leng L, Zhang J, Xie S, Ding W, Ji R, Tian Y, et al. Effect of sunshine duration on myopia in primary school students from Northern and Southern China. Int J Gen Med 2021;14:4913-22. 5. Rose KA, Morgan IG, Ip J, Kifley A, Huynh S, Smith W, et al. Outdoor activity reduces the prevalence of myopia in children. Ophthalmology 2008;115:1279-85. 6. Rose KA, Morgan IG, Smith W, Burlutsky G, Mitchell P, Saw SM. Myopia, lifestyle, and schooling in students of Chinese ethnicity in Singapore and Sydney. Arch Ophthalmol 2008;126:527-30. 7. Read SA, Collins MJ, Vincent SJ. Light exposure and physical activity in myopic and emmetropic children. Optom Vis Sci 2014;91:330-41. 8. Wen L, Cao Y, Cheng Q, Li X, Pan L, Li L, et al. Objectively measured near work, outdoor exposure and myopia in children. Br J Ophthalmol 2020;104:1542-7. 9. Hua WJ, Jin JX, Wu XY, Yang JW, Jiang X, Gao GP, et al. Elevated light levels in schools have a protective effect on myopia. Ophthalmic Physiol Opt 2015;35:252-62. 10. Pan CW, Wu RK, Liu H, LiJ, Zhong H. Types of lamp for homework and myopia among Chinese school-aged children. Ophthalmic Epidemiol 2018;25:250-6. 11. Li SM, Li SY, Kang MT, Zhou Y, Liu LR, Li H, et al. Near work related parameters and myopia in Chinese children: The Anyang childhood eye study. PLoS One 2015;10:e0134514. 12. Charman WN. Myopia, posture and the visual environment. Ophthalmic Physiol Opt 2011;31:494-501. 13. Mccrann S, Loughman J, Butler JS, Paudel N, Flitcroft DI. Smartphone use as a possible risk factor for myopia. Clin Exp Optom 2021;104:35-41. 14. Resources – Myopia Institute. Available from: https://myopiainstitute. org/resources. [Last accessed on 2023 Jun 30]. 15. JiangY, ZhuZ, Tan X, Kong X, Zhong H, Zhang J, et al. Effect of repeated low-level red-light therapy for myopia control in children: A multicenter randomized controlled trial. Ophthalmology 2022;129:509-19. 16. Liu H, Yang Y, Guo J, Peng J, Zhao P. Retinal damage after repeated low-level red-light laser exposure. JAMA Ophthalmol 2023;141:693-5. 17. Read SA, Alonso-Caneiro D, Vincent SJ, Collins MJ. Longitudinal changes in choroidal thickness and eye growth in childhood. Invest Ophthalmol Vis Sci 2015;56:3103-12. 18. Trier K, Munk Ribel-Madsen S, Cui D, Brøgger Christensen S. Systemic 7-methylxanthine in retarding axial eye growth and myopia progression: A 36-month pilot study. J Ocul Biol Dis Infor 2008;1:85-93. 19. Chua WH, Balakrishnan V, Chan YH, Tong L, Ling Y, Quah BL, et al. Atropine for the treatment of childhood myopia. Ophthalmology 2006;113:2285-91. 20. Wu PC, Chen CT, Lin KK, Sun CC, Kuo CN, Huang HM, et al. Myopia prevention and outdoor light intensity in a school-based cluster randomized trial. Ophthalmology 2018;125:1239-50. 21. Chia A, Chua WH, Cheung YB, Wong WL, Lingham A, Fong A, et al. Atropine for the treatment of childhood myopia: Safety and efficacy of 0.5%, 0.1%, and 0.01% doses (atropine for the treatment of myopia 2). Ophthalmology 2012;119:347-54. 22. Yam JC, Jiang Y, Tang SM, Law AK, Chan JJ, Wong E, et al. Lowconcentration atropine for myopia progression (LAMP) study: A randomized, double-blinded, placebo-controlled trial of 0.05%, 0.025%, and 0.01% atropine eye drops in myopia control. Ophthalmology 2019;126:113-24. 23. Cooper J, Eisenberg N, Schulman E, Wang FM. Maximum atropine dose without clinical signs or symptoms. Optom Vis Sci 2013;90:1467-72. 24. Zadnik K, Schulman E, Flitcroft I, Fogt JS, Blumenfeld LC, Fong TM, et al. Efficacy and safety of 0.01% and 0.02% atropine for the treatment of pediatric myopia progression over 3 years: A randomized clinical trial. JAMA Ophthalmol 2023;141:990-9. 25. Chung K, Mohidin N, O’Leary DJ. Undercorrection of myopia enhances rather than inhibits myopia progression. Vision Res 2002;42:2555-9. 26. Correction of Myopia Evaluation Trial 2 Study Group for the Pediatric Eye Disease Investigator Group. Progressive-addition lenses versus single-vision lenses for slowing progression of myopia in children with high accommodative lag and near esophoria. Invest Ophthalmol Vis Sci 2011;52:2749-57. 27. Lam CS, Tang WC, Tse DY, Lee RP, Chun RK, Hasegawa K, et al. Defocus incorporated multiple segments (DIMS) spectacle lenses slow myopia progression: A 2-year randomised clinical trial. Br J Ophthalmol 2020;104:363-8. 28. Walline JJ, Mutti DO, Jones LA, Rah MJ, Nichols KK, Watson R, et al. The contact lens and myopia progression (CLAMP) study: Design and baseline data. Optom Vis Sci 2001;78:223-33. 29. Kerns RL. Research in orthokeratology. Part I: Introduction and background. J Am Optom Assoc 1976;47:1047-51. 294 Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023

Joshi, et al.: Studies of myopia 30. Kang P. Optical and pharmacological strategies of myopia control. Clin Exp Optom 2018;101:321-32. 31. Sankaridurg P. Contact lenses to slow progression of myopia. Clin Exp Optom 2017;100:432-7. 32. Cheung SW, Boost MV, Cho P. Pre-treatment observation of axial elongation for evidence-based selection of children in Hong Kong for myopia control. Cont Lens Anterior Eye 2019;42:392-8. 33. Walline JJ, Walker MK, Mutti DO, Jones-Jordan LA, Sinnott LT, Giannoni AG, et al. Effect of high add power, medium add power, or single-vision contact lenses on myopia progression in children: The BLINK randomized clinical trial. JAMA 2020;324:571-80. 34. Sankaridurg P, Bakaraju RC, Naduvilath T, Chen X, Weng R, Tilia D, et al. Myopia control with novel central and peripheral plus contact lenses and extended depth of focus contact lenses: 2 year results from a randomised clinical trial. Ophthalmic Physiol Opt 2019;39:294-307. 35. Dhiman R, Rakheja V, Gupta V, Saxena R. Current concepts in the management of childhood myopia. Indian J Ophthalmol 2022;70:2800-15. Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023 295

Original Article Introduction Digital devices are used by people of all ages, genders, races, and educational levels for work, education, entertainment, and contact with others.[1] According to studies, the excessive use of digital devices affects eye health.[1,2] The eye can be affected by the screen’s luminance, especially at night.[1] Lacrimation, blurred vision, itching, headache, eye strain, exhausted eyes, burning, redness of the eye, and double vision are among the symptoms that users of these devices have experienced.[1] Dry eye is a complex, diverse condition that affects the preocular tear film and causes ocular surface illness, which is characterized by tear film instability and inflammation and may harm the ocular surface.[3] The sophisticated and steady system that the tear film and ocular surface form might become unbalanced due to a variety of frightening Abstract Background: With the increasing prevalence of digital gadget usage, there has been a noticeable impact on ocular health, including conditions such as dry eye attributed to prolonged digital device use and issues related to binocularity or convergence insufficiency. The objective of our research was to conduct a comparative analysis and correlate between scores obtained from the ocular surface disease index (OSDI) and the convergence insufficiency symptom score (CISS). Methods: This study was a prospective, cross-sectional, quantitative approach through a questionnaire-based study conducted in various optometry institutes from August 2022 to May 2023. The participants comprised students from optometry colleges in Gujarat, with a total of 329 individuals included in the study. Two validated questionnaires, namely the OSDI and the convergence insufficiency symptoms score (CISS), were administered. Data collection utilized a Digital Google form. Subsequently, groups were formed based on digital usage, CISS symptom scores, and OSDI scores. Results: Among the total of 329 participants, 31% were male, and 69% were female, with a mean age of 20.26 ± 1.86. The average duration of digital device usage was 4.08 ± 1.95 h. The overall OSDI score was 17.72 ± 17.04, and the CISS score was 11.23 ± 11.27. The study identified a significant and positive correlation between OSDI and CISS scores (r = 0.719, P < 0.01). The one‑way analysis of variance indicated a notable increase in OSDI scores corresponding to CISS scores, F (3, 325) = 71.45, P < 0.05. On the normal ocular surface, the mean CISS score was 5.54 ± 6.57, while on the mild OSDI score, it was 11.16 ± 8.89, on the moderate OSDI score, it was 17.51 ± 9.26, and on the severe OSDI score, it was 24.96 ± 13.66. Conclusion: We conclude that OSDI and CISS questionnaire is simple, efficient, and affordable treatment for screening. The study concludes there is increase in CISS score with severe OSDI score or vice versa. The current study suggests evaluating both dry eye and binocular vision assessment where students use digital usage for more than 3 h. Awareness campaign to be carried out on limited use of digital devices. Keywords: CISS questionnaire, convergence insufficiency, dry eye, ocular surface disease index questionnaire Address for correspondence: Dr. Niravkumar Mehta, Hari Jyot College of Optometry, Rotary Eye Institute, Dudhia Talav, Navsari ‑ 396 445, Gujarat, India. E‑mail: [email protected] This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non‑commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. For reprints contact: [email protected] How to cite this article: Mehta N, Desai R, Ajudiya J. Correlate ocular surface disease index with convergence insufficiency symptom score among optometry students. Delhi J Ophthalmol 2023;33:296-300. Correlate Ocular Surface Disease Index with Convergence Insufficiency Symptom Score Among Optometry Students Niravkumar Mehta1 , Rupam Desai2 , Jainisha Ajudiya1 Departments of 1 Optometry and 2 Ophthalmology, Rotary Eye Institute, Navsari, Gujarat, India Access this article online Quick Response Code: Website: https://journals.lww.com/djo DOI: 10.4103/DLJO.DLJO_175_23 Submitted: 13-Nov-2023 Accepted: 28-Nov-2023 Published: 15-Jan-2024 296 © 2024 Delhi Journal of Ophthalmology | Published by Wolters Kluwer - Medknow

Mehta, et al.: OSDI and CISS survey in optometry students causes.[3] When dry eye symptoms appear, quality of life will eventually decrease.[3] Dryness, burning, and sand-gritty eye irritation that grows worse throughout the day are common symptoms of dry eyes.[4,5] Other symptoms are itchy, stinging, or tired eyes, pain, redness, a pulling sensation, and pressure behind the eye.[4,6] The resulting harm to the surface of the eye makes people more sensitive to bright light and uncomfortable.[4,7] Dry eyes can result from spending too much time using computers, smartphones, tablets, or other digital devices.[8] The normal human blinking rate is 15 times per minute. However, research indicates that while using laptops and other digital screen devices, we only blink 5–7 times per minute.[8] The eye obtains the necessary wetness for its surface by blinking.[8] Other causes include dry eye occurs with increasing age, after laser-assisted in situ keratomileusis and other refractive surgeries, after a long time wearing contact lenses, eyelid disorders and abnormalities of the mucin tear layer caused by Vitamin A deficiency, and certain topical medications are also causes of dry eye.[9] Ocular surface disease index (OSDI) score evaluates the symptoms of dry eye and how they have affected the patient’s ability to see during the previous week.[10] A survey of adolescents found that those using digital devices 4 h/day or more had significantly more convergence insufficiency symptoms, near exophoria, negative fusional vergence, negative relative accommodation, and reduced accommodation amplitude than those using digital devices for <4 h daily.[11] To achieve separate and slightly distinct images that appear in each eye to be seen as one cohesive image during the process of fusion, binocular single vision demands the coordinated employment of both eyes.[12,13] The retinal images for the two eyes must be well-focused and identical in size and form for efficient single‑binocular vision to occur.[12] This is indicated by the accommodative and vergence systems operating properly, as well as by the absence of any eye alignment issues and sensory anomalies.[11] Symptoms related to binocular vision problems are classified into different categories such as VISUAL SYMPTOMS (sore eyes, eye strain, blurry vision at near or far distances, difficulty with close‑up vision, trouble with night vision, and eye achene), EFFECTS ON READING (eye fatigue when reading, trouble concentrating, difficulty with reading comprehension, skipping lines when reading, seeing letters shimmering or moving, words appearing to run together, headaches, and eye movements hurt) and BINOCULAR VISION SYMPTOMS (blurry, shadowed, or double vision, trouble holding eye contact, poor hand-eye coordination, poor depth perception, light sensitivity, difficulty with glare or reflection, and covering or squinting one eye to enhance vision).[14] The symptoms relating to binocular function can be evaluated using the CISS questionnaire after calculating the CISS score.[15-17] This study aims to calculate both OSDI and CISS scores. Due to the increased use of digital gadgets, recent years have seen a decline in eye health. The study aimed to find the relationship between OSDI and convergence insufficiency symptom score (CISS) with digital usage. Methods A prospective, cross-sectional, quantitative, questionnaire-based study was carried out at different optometry institutes in Gujarat between August 2022 and May 2023. The study protocol (REIEC/03/2023) was been reviewed by the Ethics committee of the Rotary Eye Institute, which adherence to the principles outlined in the Helsinki Declaration. Seven optometry schools in Gujarat were. Before initiating contact with the students, permission was taken from school heads to conduct the research. Participants who were studying in an optometry institute within the age range of 17–25 years were included in the study. All students, regardless of whether they were wearing glasses or not were included in the study. Participants who had omitted the question or filled it inaccurately or were absent during that day were excluded from the study. Validated OSDI and CISS surveys were created in Google form. Consents were taken from participants with demographic details, question regarding digital devices usage, OSDI questionnaire, and CISS questionnaire were addressed. The questionnaire was filled in directly in the classroom in the presence of the class teacher as shown in Figure 1. Ocular surface disease index OSDI questionnaire were ocular symptoms-based questions, functionality-based symptoms, and environmental-based symptoms were included. The score was recorded based on the severity rate of these symptoms. For OSDI questionnaire: 0 = “NONE OF THE TIME,” 1 = “SOME OF THE TIME,” 2 = “HALF OF THE TIME,” 3 = “MOST OF THE TIME,” 4 = “ALL OF THE TIME.” Calculation of OSDI score = (Sum of scores for all questions answered) × 100 ÷ (Total number of questions answered) × 4. OSDI scores were further categorized as normal ocular surface (OSDI score 0–12), mild (OSDI score 13–22), Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023 297 Figure 1: Students filling out OSDI and CISS survey in their classroom under supervision of Investigator

Mehta, et al.: OSDI and CISS survey in optometry students moderate (OSDI score 23–32), and severe (OSDI score 33–100).[16,18] Convergence insufficiency symptom score (CISS) CISS questionnaire was fatigue-based questions, concentration, comprehension- and memory-based questions, and reading speed-based questions were included. CISS score = Sum of all questions’ answers. A total of 36 questions were asked in this survey. The frequency of questions was assessed using a Likert scale, which was used to evaluate the frequency of the symptoms. For CISS questionnaire: 0 = “NEVER,” 1 = “INFREQUENTLY/NOT VERY OFTEN,” 2 = “SOMETIMES,” 3 = “FAIRLY OFTEN,” 4 = “ALWAYS” CISS score is also categorized as normal (CISS score 0–20), mild (CISS score 21–24), moderate (CISS score 25–34), and severe (CISS score >34). Results A total of 329 individual participated in this study, 102 (31%) of who were male, and 227 (69%) of whom were female. Mean ± standard deviation age between 20.26 ± 1.86 [Table 1]. The impact of digital usage on OSDI and CISS total scores was examined using a one-way analysis of variance (ANOVA). For OSDI, F (2, 326) = 7.91, P < 0.05, indicating a significant effect. Mean OSDI scores were 11.98 for students using digital devices for <3 h, 17.94 for 3–5 h, and 23.78 for more than 6 h [Graph 1]. Similarly, CISS showed a significant impact with F (2, 326) = 4.38, P < 0.05. Mean CISS scores were 7.90, 11.76, and 13.38 for students using digital devices for <3 h, 3–5 h, and more than 6 h, respectively [Graph 2]. One-way ANOVA showed OSDI score increase with CISS scores, F (3, 325) = 71.45, P < 0.05. On the normal ocular surface, the mean CISS score was (5.54 ± 6.57), while on the mild OSDI score, it was (11.16 ± 8.89), on the moderate OSDI score, it was (17.51 ± 9.26), and on the severe OSDI score it was(24.96 ± 13.66). According to the Games–Howell post-HOC test, CISS scores were significantly different in mild (11.16 ± 8.89, P < 0.05), moderate (17.51 ± 9.26, P< 0.05), and severe OSDI(24.96 ± 13.66, P< 0.05) categories compared to the normal ocular surface (5.54 ± 6.57), mild OSDI score (11.16 ± 8.89), and moderate OSDI score (17.51 ± 9.26). There was a significant correlation between the OSDI score and CISS in optometry students N = 329, r = 0.719, R2 = 0.52, P < 0.01, mean OSDI score 17.72 ± 17.04 and mean CISS score 11.23 ± 11.27 as shown in Graph 4. Discussion The digital environment is now ubiquitous in our daily lives. A lifestyle epidemic: ocular surface disease, which was undertaken to establish the direct and indirect impacts that everyday lifestyle choices and challenges have on ocular surface health. The study aimed to find the relationship between OSDI and convergence insufficiency symptom score (CISS) with digital usage. People worldwide spend 6 h, 58 min every day in front of a screen.[19] 298 Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023 Graph 2: Analysis of variance test: Comparison of CISS score with digital device usage Graph 1: Analysis of variance test: Comparison of ocular surface disease index score with digital device usage Graph 3: Analysis of variance test: Comparison of CISS score with ocular surface disease index groups

Mehta, et al.: OSDI and CISS survey in optometry students Over the past few years, there has been an increase in digital device use with implications for adults’ or college students’ eye health.[2] In our study, the average time spent on digital devices was 4.08 ± 1.95 h. In the current study, students spent on digital devices was 18% spent >5 h, 61% spent 3–5 h, and 21% spent <3 h on digital screen per day. Participants who used digital gadgets for <3 h had mean OSDI and CISS scores were (11.98 ± 14.98) and (7.90 ± 10.02), respectively. The mean OSDI and CISS scores for individuals who spent time on digital devices for 3–5 h were (17.94 ± 15.94), (11.76 ± 11.22), and for those who used them for >5 h were (23.78 ± 20.72), (13.38 ± 12.19), respectively as shown in Graphs 2 and 3 which suggests that the OSDI and the CISS score got higher by increasing the usage time of the digital devices. Mean OSDI score was 17.72 ± 17.04 and CISS score was 11.23 ± 11.27. Our study suggests that the OSDI score was higher than the CISS score. This finding indicates that those who participated in the study experienced symptoms associated with dry eyes with greater frequency than symptoms related to binocular vision problems. In our study, CISS score in the normal, mild, moderate, and severe groups. Out of 329 participants, 80% had normal, 7% had mild, and 13% had moderate-to-severe CISS scores. In the previous study, they suggested that the OSDI and CISS scores among participants were positively correlated (r = 0.71, P < 0.01)[20] which was similar to our study. Our study also proves the OSDI and CISS scores were strongly correlated (r = 0.719, P < 0.01). The study’s primary drawback was the absence of an optometric evaluation, which made it challenging to determine whether the OSDI score or CISS score was caused by ocular surface issues or binocular vision problems. Conclusion We conclude that OSDI and CISS questionnaire is simple, efficient, and affordable treatment for screening. The study concludes that there is increase in CISS score with severe OSDI score. The study suggests all students should be evaluated with comprehensive dry eye evaluation and binocular vision assessment where CISS score is more than 20 and having severe OSDI score. The current study suggests evaluating both dry eye and binocular vision assessment where students use digital usage of more than 3 h. Awareness campaign to be carried out on limited use of digital devices. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. References 1. Ahmed Alamri A, Alhibshi N, Alnefaie M, Alzhrani W, Almaymuni A, Mosli M. Patterns of digital device usage and its related health effects on elementary and middle school students: An instrument development and regression analysis. Electron Physician 2018;10:7333-40. 2. Usgaonkar U, Shet Parkar S, Shetty A. Impact of the use of digital devices on eyes during the lockdown period of COVID-19 pandemic. Indian J Ophthalmol 2021;69:1901. 3. Lee AJ, Lee J, Saw SM, Gazzard G, Koh D, Widjaja D, et al. Prevalence and risk factors associated with dry eye symptoms: A population based study in Indonesia. Br J Ophthalmol 2002;86:1347-51. 4. Foster CS. Dry eye disease (keratoconjunctivitis sicca). Medscape [homepage Internet] Available from https//emedicine medscape com/ article/1210417-overview [Last accessed on 2019 Oct 01]. 5. Boyd K Computers, digital devices and eye strain. American Academy of Ophthalmology 2020. 6. Tabbara KF, Sharara N. Dry eye syndrome. Drugs Today (Barc). 1998;34:447-53. doi: 10.1358/dot.1998.34.5.485243. PMID: 15010707. 7. Dougherty BE, Nichols JJ, Nichols KK. Rasch analysis of the Ocular Surface Disease Index (OSDI). Invest Ophthalmol Vis Sci 2011;52:8630‑5. Table 1: Frequency distribution Count (%) Mean±SD Gender total 329 - Male 102 Female 227 Mean age 20.26±1.86 Digital usage groups (h) Group 1: <3 69 1.81±0.39 Group 2: 3–5 202 3.92±0.80 Group 3: >5 58 7.35±1.55 OSDI OSDI: Normal (0–12) 169 (51) 5.51±4.28 Mild (13–22) 64 (20) 18.16±3.03 Moderate (23–32) 47 (14) 28.01±2.37 Severe (33–100) 49 (15) 49.36±15.86 CISS CISS: Normal (0–19) 262 (80) 6.52±5.70 Mild (20–24) 22 (7) 22.14±1.49 Moderate (25–34) 30 (9) 29.03±2.90 Severe (>34) 15 (4) 42.07±7.06 OSDI: Ocular Surface Disease Index, CISS: Convergence insufficiency symptom score, SD: Standard deviation Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023 299 Graph 4: Correlation: Scatterplot CISS score with ocular surface disease index scores

Mehta, et al.: OSDI and CISS survey in optometry students 8. Maharjan U, Rijal S, Jnawali A, Sitaula S, Bhattarai S, Shrestha GB. Binocular vision findings in normally‑sighted school aged children who used digital devices. PLoS One 2022;17:e0266068. 9. Stidwill D, Fletcher R. Normal Binocular Vision: Theory, Investigation and Practical Aspects. John Wiley & Sons; 2017. 10. O’Connor AR, Birch EE, Anderson S, Draper H, FSOS Research Group. The functional significance of stereopsis. Invest Ophthalmol Vis Sci 2010;51:2019-23. 11. García-Muñoz Á, Carbonell-Bonete S, Cacho-Martínez P. Symptomatology associated with accommodative and binocular vision anomalies J Optom 2014;7:178-192. 12. Darko-Takyi C, Owusu-Ansah A, Boampong F, Morny EK, Hammond F, Ocansey S. Convergence insufficiency symptom survey (CISS) scores are predictive of severity and number of clinical signs of convergence insufficiency in young adult Africans. J Optom 2022;15:228-37. doi:10.1016/j.optom.2021.05.001. 13. Rueff EM, Sinnott LT, Bailey MD, King-Smith PE. The similarity between symptoms of binocular vision disorders and dry eye. Invest Ophthalmol Vis Sci 2014;55:1990. doi:10.4103. 14. Schiffman RM, Christianson MD, Jacobsen G, Hirsch JD, Reis BL. Reliability and validity of the ocular surface disease index. Arch Ophthalmol 2000;118:615-21. 15. Al-Mohtaseb Z, Schachter S, Shen Lee B, Garlich J, Trattler W. The relationship between dry eye disease and digital screen use. Clin Ophthalmol 2021;15:3811-20. 16. Bade A, Boas M, Gallaway M, Mitchell GL, Scheiman M, Kulp MT, et al. Relationship between clinical signs and symptoms of convergence insufficiency. Optom Vis Sci 2013;90:988‑95. 17. Mohan A, Sen P, Shah C, Datt K, Jain E. Binocular accommodation and vergence dysfunction in children attending online classes during the COVID‑19 pandemic: Digital Eye Strain in Kids (DESK) study‑2. J Pediatr Ophthalmol Strabismus 2021;58:224-31. 18. Miller KL, Walt JG, Mink DR, Satram-Hoang S, Wilson SE, Perry HD, et al. Minimal clinically important difference for the ocular surface disease index. Arch Ophthalmol 2010;128:94-101. 19. Howarth J. Alarming Average Screen Time Statistics (2023). Explore Topics; 2023. Available from: https://explodingtopics.com/blog/screentime-stats. [Last accessed on 2023 Jun 20]. 20. Jaiswal S, AsperL, Long J, LeeA, HarrisonK, GolebiowskiB. Ocular and visual discomfort associated with smartphones, tablets and computers: What we do and do not know. Clin Exp Optom 2019;102:463-77. 300 Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023

Abstract Original Article Introduction Good community participation is an essential component of any health promotion program.[1] Over the past two decades, increasing emphasis has been placed on health communication strategies that are collaboratively designed, implemented, and evaluated.[2,3] Creating awareness of the disease and its effects on millions of people in an area is critically important. In particular, people aware of a disease in their proximity can take measures to reduce their susceptibility. Changes in behavior in response to the disease can alter its progression. Even if no centralized information is provided about the presence of a disease; such awareness can arise through first‑hand observation and word of mouth. Most causes of childhood blindness are either treatable or avoidable.[4] Blindness decreases the quality of life of a child. Childhood blindness places a burden on the healthcare system. Awareness about children’s eye care is low in India.[5] To enhance community awareness of eye care is one of the objectives of the National Programme for Control of Blindness in India.[6] School teacher training, school screening, training of primary health-care workers, and opening of vision centers are the main strategies for providing primary eye care in India. All these strategies have long been thought to increase awareness, knowledge, and beliefs about children’s eye care. Parents are the first and best teachers for their children.[7] Background: A high proportion of visual impairment is avoidable. Parent’s eye care-seeking behavior about children’s eye diseases plays a crucial role in eradicating avoidable causes of blindness in children. Aim: The study aims to determine the eye care-seeking behavior of parents and their knowledge about common eye diseases. Methods: This cross-sectional study was conducted. The questionnaire consists of demographic information, questions to assess eye care-seeking behavior, and knowledge about eye diseases. Each correct response was given a score of one. An individual score of more than six was considered to have adequate knowledge, and a score of less than or equal to six was considered to have poor knowledge about eye diseases. Binary logistic regression was performed to ascertain the effect of the gender of the child, location, number of children in the family, previous eye examination, respondent (mother/father), family history of eye diseases, and socioeconomic status on the likelihood that participants have adequate knowledge about eye diseases. Results: The sample included 384 parents with 384 children from the pediatric eye care clinic at CL Gupta Eye Institute, Moradabad (India). Of them, 203 (52.9%) children had a previous examination by an eye care professional. Awareness of parents about common eye problems was: Cataracts(81.3%), strabismus(74%), night blindness (73.2%), and glaucoma (59.1%). Family history of visual impairments, mother respondent, and higher socioeconomic status were found associated with adequate knowledge of parents about eye diseases. Conclusion: Eye care-seeking behavior in the study region was low. The findings of the study suggest that parent awareness can be considered as a first step to bringing the child with eye care needs to the eye care facility. Keywords: Awareness, children eye care, common eye disease, eye care seeking behavior, knowledge level, parents Address for correspondence: Mr. Lokesh Chauhan, Department of Clinical and Public Health Research, CL Gupta Eye Institute, Ram Ganga Vihar, Phase 2 (Ext), Moradabad ‑ 244 001, Uttar Pradesh, India. E‑mail: [email protected] This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non‑commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. For reprints contact: [email protected] How to cite this article: Maan V, Agarwal P, Chauhan L. Parental eye care seeking behavior and knowledge of common eye diseases. Delhi J Ophthalmol 2023;33:301-8. Parental Eye Care Seeking Behavior and Knowledge of Common Eye Diseases Veenu Maan1 , Pradeep Agarwal1 , Lokesh Chauhan2 1 Department of Pediatric Ophthalmology, Strabismus and Neuro‑Ophthalmology, CL Gupta Eye Institute, Moradabad, Uttar Pradesh, India, 2 Department of Clinical and Public Health Research, CL Gupta Eye Institute, Moradabad, Uttar Pradesh, India Access this article online Quick Response Code: Website: https://journals.lww.com/djo DOI: 10.4103/DLJO.DLJO_125_23 Submitted: 25-Jul-2023 Revised: 16-Aug-2023 Accepted: 21-Aug-2023 Published: 15-Jan-2024 © 2024 Delhi Journal of Ophthalmology | Published by Wolters Kluwer ‑ Medknow 301

Maan, et al.: Eye care‑seeking behavior of parents Empowering the parents is thus an essential goal of any disease eradication program. Parents are responsible for the medical care of their children.[8] Awareness of parents about children’s eye disease has a direct impact on children’s eye health in any region. Studies about awareness of eye conditions have been conducted in the past.[8,9] Moreover, little research has been conducted on parents’ knowledge about children’s eye disease.[5,8,10] Many of these studies used interviews to qualitatively assess parental knowledge. Based on the above-mentioned background, we decided to design this study to assess parents’ knowledge level about eye diseases using a validated quantitative questionnaire consisting of knowledge-based questions. Methods It was a cross-sectional study conducted among parents/ guardians of children who attended the pediatric eye care unit of CL Gupta Eye Institute. The study was approved by the institutional ethics committee and followed the tenets of the Declaration of Helsinki for biomedical research. Prior informed consent was taken from each participant (a total of 384 parents) included in the study. Sample size determination Due to the lack of published literature investigating the knowledge level of parents regarding eye diseases in India as well as in the study area, the present study calculated the maximum possible sample size. With 5% margin of error, 95% confidence interval a sample size was 377 ( ( ) ) ( ) 2 2 2 2 Z ×P 1-P / e Sample size = Z ×P 1-P 1 + e N             Study questionnaire The study tool was a self-administered questionnaire. It was developed with the help of experienced faculty and a literature search.[10] Questionnaires consist of demographic/ socioeconomic status information and questions to assess the eye care-seeking behavior, and knowledge about eye diseases such as amblyopia, cataract, refractive error, glaucoma, strabismus, and night blindness. Apart from demographics and socioeconomic status (Q1–Q5) questionnaire had seven (Q6–Q12) questions to assess eye care‑seeking behavior, one question to assess awareness (Q13), and nine questions (Q14–Q22) to assess knowledge about various eye diseases. There were two questions for cataract (Q14–Q15), one question for glaucoma (Q16), two questions for amblyopia (Q17–Q18), three questions for refractive error (Q19, Q20, and Q21), and one question for night blindness (Q22) [Annexure 1]. The questionnaire was pretested on 36 parents to assess its ease of implementation and internal consistency. However, the data generated during pretesting was not included in the final analysis. Statistical analysis Demographic data were presented as mean, standard deviation, and percentage. All respondents were categorized into different socioeconomic classes according to the Kuppuswamy scale. For questionnaire analysis, each correct response (Q14–Q22) was given a score of 1, and a wrong response, or do not know response a score of 0. The maximum score that one can achieve was nine and the minimum score was zero. An individual score of 6 or more was considered to have adequate knowledge, a score of 4–5 was considered to have moderate knowledge, and a score of ≤3 was considered to have inadequate knowledge about eye diseases. The Mann–Whitney test and Chi‑square test were used to find differences in knowledge score by each category (gender, type of respondent, literacy, location, educational level, family history of eye diseases, and socioeconomic status). Fisher’s exact test was used if expected frequencies were <5. For comparative analysis, adequate and moderate knowledge levels were combined and presented as adequate knowledge levels. Binary logistic regression was performed to ascertain the effect of the gender of the child, religion, location, number of children in the family, previous eye examination, respondent (mother/father), family history of eye diseases, and socioeconomic status on the likelihood that participants have adequate knowledge about eye diseases. A Hosmer–Lemeshow test was used to test the goodness of fit of the model. Results A total of 384 parents presented to our pediatric unit agreed to participate in the study. Of them, 213 (55.5%) belonged to rural locations and 171 (44.5%) to urban locations. Of all respondents, 202 (52.6%) were fathers of children, and 182 (47.4%) were mothers. The mean age of children whose parents were included in this study was 10.3 ± 4.9 years and 187 of them were male children. Other demographic and socioeconomic characteristics of parents are presented in Table 1. According to the Kuppuswamy scale, 6 (1.6%) respondents belonged to the lower class, 131 (34.1%) to the Table 1: Demographic characteristics of study participants Characteristic Category n (%) Location Rural 213 (55.5) Urban 171 (44.5) Siblings Yes 330 (85.9) No 54 (14.1) Gender of child Male 187 (48.7) Female 197 (51.3) Previous eye examination Yes 203 (52.9) No 181 (47.1) Socioeconomic status Lower class 6 (1.6) Lower middle class 131 (34.1) Upper lower class 129 (33.6) Upper middle class 94 (22.2 Upper class 24 (6.3) Lower class 6 (1.6) 302 Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023

Maan, et al.: Eye care‑seeking behavior of parents lower middle class, 129 (33.6%) to the upper lower class, 94 (24.2%) to the upper middle class and 24 (6.3%) to the upper class. A total of 54 (14.1%) parents had a single child. Eye care-seeking behavior A total of 203 (52.9%) children have attended a previous examination by an eye care professional. Parents of 177 (46.1%) children have not visited an eye care facility for routine eye examination of their child. Out of the male children, 89 (47.6%) have attended previous eye examinations, while among the female children, 114 (57.9%) have also attended previous eye examinations. This difference is statistically significant with a p-value of 0.04. Of all, 92 (24%) children have undergone an eye examination by a pediatric ophthalmologist previously. A total of 282 (73.4%) parents believed that children’s vision screening should be done before preschool. Of all, 21 (5.5%) parents brought eye medicines from a pharmacy without consulting an ophthalmologist. There was no difference in seeking eye care for a child based on the gender of the child [Table 2]. Awareness and knowledge level Among all 81.3%, 74%, 73.2%, 59.1%, and 14.3% of parents were aware of the cataract, strabismus, night blindness, glaucoma, and amblyopia, respectively [Figure 1]. Adequate knowledge level about eye disease was reported in 12 (3.1%) parents, moderate knowledge level in 195 (50.8%), and inadequate knowledge level in 177 (46.1%) parents. Of all, 159 (41.4%) parents know the cause of night blindness, 32 (8.3%) parents know what cataract and 214 (55.7%) know how cataract has been treated. Of all respondents, 54 (14.1%) know what refractive error is, 254 (66.1%) know at least one symptom of refractive error and 194 (50.5%) know at least one treatment option available. In all, 12 (3.1%) know about glaucoma and 15 (3.9%) about amblyopia. Answers to each question are presented in Table 2. The mean knowledge score of male parents was 2.3 ± 1.8 and of female parents was 2.5 ± 1.8 (P = 0.32; Mann–Whitney test). The mean knowledge score of literate parents was 2.81 ± 1.6 and of illiterate parents 1.95 ± 1.9 (P = 0.00; Mann–Whitney test). A total of 101 (72.6%) parents with family history of eye diseases had adequate knowledge level as compared to 43.2% (n = 106/249) parents who did not have family history of eye diseases (P = 0.00, Chi‑square test). Similarly, 19 (74.5%; 19/24) parents who belong to upper, and upper middle socioeconomic classes had adequate knowledge levels as compared to 77 (6.2%; 77/137) parents who belonged to lower, and lower middle class (P = 0.00, Chi‑square test). The logistic regression model was statistically significant, χ2 = 131.9, P < 0.00. The model correctly classified 74.2% of cases. Family history of visual impairments, mother respondent, and higher socioeconomic status was found associated with adequate knowledge of parents about eye diseases. A Hosmer–Lemeshow goodness of fit test showed that the binary regression model was a good fit for the data (P = 0.48) [Table 3]. Discussion In the present study, authors developed a structured questionnaire to assess parent awareness quantitatively in a different geographical location. The relationship between different socioeconomic classes (according to the Kuppuswamy socioeconomic scale) and the knowledge level about eye disease of parents was also assessed. It was found that before this visit almost half of the parents never visited an eye care practitioner for their child’s eye examination. Most of the parents said that they would visit an eye doctor only if their child had any vision problems. This shows the low acceptance of parents regarding routine eye examinations of their children’s eyes in the study area. Parents were not Table 2: Eye care seeking behavior of parents Questions Yes, n (%) No, n (%) Has your child ever had an eye examination by an eye care practitioner? 203 (52.9) 181 (47.1) Reason for not taking their children for routine eye examination Financially unable 4 (2.2) The child has no problem 177 (97.7) Has you ever visited a pediatric ophthalmologist for your child’s eye examination? 92 (24) 292 (76) At what age did this child have their first eye examination? 0–2 years of age 31 (8.1) 3–6 years of age 43 (11.2) 7–10 years of age 65 (16.9) 11–15 years of age 51 (13.3) 16 years and above 9 (2.3) Never 185 (48.2) Has this child been screened and referred for further eye evaluation by a health-care professional 158 (41.1) 226 (58.8) Do you believe children should have a vision screening before starting preschool (between ages 3 and 5)? 282 (73.4) 102 (106.6) Has you ever bought eye medicine from pharmacy without consulting an ophthalmologist 21 (5.5) 363 (94.5) Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023 303 Figure 1: Awareness of various eye diseases among parents

Maan, et al.: Eye care‑seeking behavior of parents aware of the importance of routine eye examinations in their child’s eye health. Only 8.1% (n = 31/382) of children had their first eye examination before completing 2 years of age. These results are consistent with other previously reported studies.[11-15] Literate parents had significantly higher knowledge than illiterate parents. Mothers had significantly higher knowledge about eye diseases than fathers. However, there was no significant difference between their literacy levels. There is a need to change this behavior by generating awareness of routine eye examinations through educational campaigns. School teachers, community health workers, and vision technicians can play a key role in changing this behavior as they are the most accessible person in areas with limited availability of eye care services. In all, 24% of parents consulted with a pediatric ophthalmologist for their child’s eye examination. This may be due to lack of awareness, accessibility, affordability, and low eye care-seeking behavior of parents towards their child’s eye diseases. The limited availability of pediatric ophthalmologist in the study area is also a contributing factor. Parents usually present to a pediatric ophthalmologist after being referred from elsewhere either by a vision technician, school screening, community screening, or by another nearby general ophthalmologist. There was no difference in parents’ eye care-seeking behavior in terms of number of children in family, religion, location (rural/urban), gender of child, and socioeconomic class. He et al. reported that awareness of vision difficulties in parents was associated with older child age, greater visual impairment, and higher parental education.[16] The prevalence of self-medication reported in this study was found to be low as compared to other published studies from India and elsewhere. Gupta et al. reported that 18.2% of respondents were using ophthalmic medications without consulting an ophthalmologist.[17] Kumar et al. reported 92.8% prevalence of self-medication in Delhi (India).[18] However, in their study respondent had not taken self-medication for eye diseases. Marquez et al. reported 25.6% prevalence of self-medication in ophthalmology in Argentinean population.[19] Approximately 50% of parents had good knowledge about eye diseases. Parents with a family history of eye diseases had good knowledge as compared to parents without any family history of eye diseases. In parents with family history of eye diseases, there may be a bias toward knowledge of cataract, strabismus, night blindness, and glaucoma as they also commonly occur in adults. Most of the parents were aware about cataract, night blindness, and strabismus. Knowledge level regarding amblyopia and glaucoma was very low as compared to refractive error and night blindness. Majority of the respondents know at least one symptom and one treatment option for refractive error. He et al. also reported 80% parental awareness regarding refractive error in their children.[16] Only few parents know the cataract correctly; however, more than 50% of them were aware about its treatment. Most of the respondents were aware about eye diseases. Very few of them exactly know about the disease and its treatment options. This low knowledge level of parent may be contributing to the low eye care-seeking behaviors in terms of their children’s eye health. Senthilkumar et al. also reported that the causative factors for ocular diseases were not well understood by parents.[5] In our study, 15 parents were aware about amblyopia however in reports by Senthilkumar et al.,[5] and Ebeigbe and Emedike[20] only one parent quoted amblyopia as an eye problem. In India, distant areas still remain underserved in terms of health care. Parent’s awareness and their knowledge about any disease are the most important and effective means to prevent and treat that disease in children. Parents’ awareness to seek eye care can be considered as a first step which can definitely help to bring the child with eye care needs to the eye care facility. The present study implies to the need of means of educating parents and to make them aware about common eye diseases in children. It is very important because early detection and early treatment can prevent children from developing irreversible vision loss. Dandona et al. also suggested to increase parental awareness that symptoms in a child suggestive of poor vision such as bringing books very close to the face or colliding with objects frequently should prompt them to consult an ophthalmologist.[21] Although this study makes many important contributions, the findings are subject to few limitations. Data on parental awareness in this study were based on self-report questionnaires, which may be subject to recall and other biases. The study population is selected from parents visiting a pediatric eye care facility in one city. Thus, the results may have overestimated the knowledge level of parents. This study is an attempt to investigate a little-explored facet of vision screening in India. Conclusion This study contributes quantitative data from northern India on eye seeking behavior of parents and their knowledge about Table 3: Multivariate analysis indicating associations between several variables and the knowledge level of parents Variable OR SE Wald P 95% CI Lower Upper Previous eye check-up 0.83 0.24 0.56 0.46 0.52 1.34 Family history of eye diseases 0.31 0.26 19.75 0.00 0.18 0.52 KU-score 1.21 0.03 47.37 0.00 1.15 1.28 Location 1.54 0.26 2.79 0.09 0.93 2.54 Religion 0.70 0.28 1.56 0.21 0.41 1.22 Respondent 1.94 0.26 6.27 0.01 1.15 3.25 Age 1.01 0.03 0.04 0.83 0.96 1.06 Gender of child 2.58 0.28 11.76 0.00 1.50 4.43 Siblings 0.94 0.41 0.02 0.88 0.42 2.12 Number of children 1.07 0.08 0.73 0.39 0.91 1.26 Constant 0.06 0.69 16.29 0.00 OR: Odds ratio, CI: Confidence interval, SE: Standard error 304 Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023

Maan, et al.: Eye care‑seeking behavior of parents common eye disease. To increase parental knowledge and skills, educational interventions should be provided. This will help them recognize their child’s eye care needs. It can further aid to formulate a region‑specific approach for bringing more awareness and constituting effective programs for pediatric eye care. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. References 1. Dineen B. Health promotion and community participation in eye care services. Community Eye Health 1999;12:35-6. 2. Nutbeam D. Health literacy as a public health goal: A challenge for contemporary health education and communication strategies into the 21st century. Health Promot Int 2000;15:259-67. 3. Mahmud AJ, Olander E, Eriksén S, Haglund BJ. Health communication in primary health care -a case study of ICT development for health promotion. BMC Med Inform Decis Mak 2013;13:17. 4. Resnikoff S, Pascolini D, Etya’ale D, Kocur I, Pararajasegaram R, Pokharel GP, et al. Global data on visual impairment in the year 2002. Bull World Health Organ 2004;82:844-51. 5. Senthilkumar D, Balasubramaniam SM, Kumaran SE, Ramani KK. Parents’ awareness and perception of children’s eye diseases in Chennai, India. Optom Vis Sci 2013;90:1462-6. 6. VermaR, Khanna P, Prinja S, Rajput M, AroraV. The national programme for control of blindness in India. Australas Med J 2011;4:1-3. 7. Serbin LA, Hubert M, Hastings PD, Stack DM, Schwartzman AE. The influence of parenting on early childhood health and health care utilization. J Pediatr Psychol 2014;39:1161-74. 8. Nirmalan PK, Sheeladevi S, Tamilselvi V, Victor AC, Vijayalakshmi P, Rahmathullah L. Perceptions of eye diseases and eye care needs of children among parents in rural South India: The Kariapatti pediatric eye evaluation project (KEEP). Indian J Ophthalmol 2004;52:163‑7. 9. Dandona R, Dandona L, John RK, McCarty CA, Rao GN. Awareness of eye diseases in an urban population in Southern India. Bull World Health Organ 2001;79:96-102. 10. Kemmanu V, Giliyar SK, Shetty BK, Singh AK, Kumaramanickavel G, McCarty CA. Parental inability to detect eye diseases in children: Barriers to access of childhood eye-care services in South India. Eye (Lond) 2018;32:467‑8. 11. Göransson A, Dahlgren LO, Lennerstrand G. Changes in conceptions of meaning, effects and treatment of amblyopia. A phenomenographic analysis of interview data from parents of amblyopic children. Patient Educ Couns 1998;34:213-25. 12. Karlica D, Matijević S, Galetović D, Znaor L. Parents’ influence on the treatment of amblyopia in children. Acta Clin Croat 2009;48:427-31. 13. Rahi JS, Manaras I, Barr K. Information sources and their use by parents of children with ophthalmic disorders. Invest Ophthalmol Vis Sci 2003;44:2457-60. 14. Su Z, Marvin EK, Wang BQ, van Zyl T, Elia MD, Garza EN, et al. Identifying barriers to follow-up eye care for children after failed vision screening in a primary care setting. J AAPOS 2013;17:385-90. 15. Sugg JH, Enzenauer RW, Yarbrough L. Public survey of pediatric eye disease and eye care. Invest Ophthalmol Vis Sci 2003;44:4848. 16. He M, Xu J, Yin Q, Ellwein LB. Need and challenges of refractive correction in urban Chinese school children. Optom Vis Sci 2005;82:229-34. 17. Gupta N, Vashist P, Tandon R, Gupta SK, Kalaivani M, Dwivedi SN. Use of traditional eye medicine and self-medication in rural India: A population-based study. PLoS One 2017;12:e0183461. 18. Kumar V, Mangal A, Yadav G, Raut D, Singh S. Prevalence and pattern of self-medication practices in an urban area of Delhi, India. Med J Dr DY Patil Univ 2015;8:16. 19. Marquez GE, Torres VE, Sanchez VM, Gramajo AL, Zelaya N, Peña FY, et al. Self-medication in ophthalmology: A questionnaire-based study in an Argentinean population. Ophthalmic Epidemiol 2012;19:236-41. 20. Ebeigbe JA, Emedike CM. Parents’ awareness and perception of children’s eye diseases in Nigeria. J Optom 2017;10:104-10. 21. Dandona L, Gilbert CE, Rahi JS, Rao GN. Planning to reduce childhood blindness in India. Indian J Ophthalmol 1998;46:117-22. Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023 305

Maan, et al.: Eye care‑seeking behavior of parents Annexure Annexure 1: Study Questionnaire to assess the eye care-seeking behavior and knowledge about eye diseases. Name: Age: Mobile Number: (a) Demographics/socioeconomic 1. Family history of visual impairments or eye disease? a. Yes b. No 2. Please specify your relationship to the child a. Mother b. Father c. Grandparent d. Legal Guardian e. Other –List 3. Education a. Professional or honors b. Graduate or postgraduate c. Intermediate or posthigh school diploma d. High school certificate e. Middle School certificate f. Primary School certificate g. Illiterate 4. Occupation a. Professional b. Semi-Professional c. Clerical, shop owner, farmer d. Skilled worker e. Unskilled worker f. Unemployed 5. What is your household income (INR)? a. ≥42,876 b. 21,438–42,875 c. 16,078–21,437 d. 10,719–16,077 e. 6431–10,718 f. 2165–6430 g. ≤2164 (b) Eye care‑seeking behavior 6. Has your child ever had an eye examination by an eye care practitioner? a. Yes b. No 7. If not, select the most appropriate reason a. Passed pediatrician screening b. Passed school screening c. Financially unable d. Child has no problem e. Lack of transportation f. Other 8. Has you ever visited a pediatric ophthalmologist for your child’s eye examination? a. Yes b. No 306 Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023

Maan, et al.: Eye care‑seeking behavior of parents 9. At what age did this child have their first eye examination? a. 0–2 years of age b. 3–6 years of age c. 7–10 years of age d. 11–15 years of age e. 16 and up f. Never 10. Has this child been screened and referred for further eye evaluation by a health‑care professional (vision technician, school teacher, and pediatrician)? a. Yes b. No 11. Do you believe children should have a vision screening before starting preschool (between ages 3 and 5)? a. Yes b. No 12. Have you ever brought eye medicine from a pharmacy without consulting an Ophthalmologist? a. Yes b. No (c) Awareness about children’s eye diseases? 13. Have you heard about these eye diseases? a. Amblyopia b. Cataract c. Glaucoma d. Night blindness e. Strabismus f. Vitamin A deficiency (d) Knowledge about common eye diseases? 14. What is a cataract? a. A white spot in the eye b. A lens change where the lens become opaque c. A white membrane growing over the eye d. A age-related process leading to decrease in vision e. Do not know 15. How is it treated? a. By medicine b. By surgery c. Do not know 16. What is glaucoma? a. High pressure inside the eye b. Eye protrudes outside because of high pressure c. Eye deviate inside or outside d. A age related process leading to decrease in vision e. Do not know 17. What is Amblyopia? a. A disease where nerve of eye become weak b. A age-related process leading to decrease in vision c. Vision development disorder in which an eye fails to achieve normal vision/lazy eye d. A disease in which shape of your eye does not bend light correctly, resulting in a blurred image e. Do not know Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023 307

Maan, et al.: Eye care‑seeking behavior of parents 18. When would it occur? a. At any age b. From 9 to 15 years c. Till 7–8 years of age d. Do not know 19. What is refractive error? a. Vision development disorder in which an eye fail to achieve normal vision b. A disease where nerve of eye become weak c. A age-related process leading to decrease in vision d. A disease in which shape of your eye does not bend light correctly, resulting in a blurred image e. None of the above f. Do not know 20. What are the signs and symptoms of refractive errors? a. Double Vision b. Haziness c. Headaches d. Eye strain e. All of the above f. None of the above g. Do not know 21. How are refractive errors treated? a. Eyeglasses b. Contact lenses c. By Surgery d. All of the above e. None of the above f. Do not know 22. What is common cause of night blindness? a. Vitamin A deficiency b. Malnutrition c. Diarrhea d. Do not know 308 Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023

Abstract Original Article Introduction Dry eye disease (DED) is a multifactorial disease of tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface. It can greatly affect the quality of life. The prevalence of DED has been reported to be between 5% and 50%.[1] Reports from Western India show dry eye prevalence according to severity as 47.98% mild, 31.82% moderate, and 20.20% severe disease.[2] Thus, dry eye, a chronic disease, has a significant impact on quality of life. Definition of dry eye as described in TFOS DEWS 2 definition and classification report goes by “Dry eye is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles.”[1] There are two major classes of DED: aqueous tear‑deficient dry eye and evaporative dry eye. The tear film is composed of three layers, the lipid, aqueous, and mucin component.[3] Mucins are key actors in tear film quality and tear film stability. Both secreted and membrane-bound mucins are essential to maintain the wettability of the ocular surface.[4] Alteration of membrane-bound mucin expression on corneal and conjunctival epithelial cells and/or gel-forming mucin secretion by goblet cells (GCs) occurs in ocular surface diseases and DED. Changes in the mucin layer may lead to tear film instability eventually contributing to tear hyperosmolarity which has been associated with ocular surface inflammation. Inflammatory mediators in turn may have a negative impact Purpose: Dry eye disease (DED) is a multifactorial disease of tears and ocular surface. The tear film is composed of three layers – lipid, aqueous, and mucin. Loss of mucin and goblet cell atrophy due to Vitamin A deficiency contributes to the instability of tear film secondary to mucin abnormality leading to dry eye. Our aim is to study the effect of short‑term oral Vitamin A supplementation on tear film in patients with dry eye. Methods: This is a cross-sectional interventional study of 42 patients undertaking treatment at a tertiary health-care center in Western India. A total of 42 patients meeting the dry eye diagnostic criteria were enrolled. After taking informed consent, history, anterior segment examination, tests specific for DED were performed. Patients were graded as per dry eye severity and supplemented with oral Vitamin A as per regimen. All tests were repeated at 1 month and at 3 months. Results: Statistical analysis was done using analysis of variance test to compare the outcome of 3 values, i.e., on presentation, 1 month, and 3 months post supplementation for different DES parameters, and P value was analyzed for each of them. Out of 42 patients, 18 were mild, 16 were moderate, and 8 were severely symptomatic. The mean symptom score improved from 7.95 ± 3.74 to 4.38 ± 2.99 at 3 months whereas Ocular Surface Disease Index score improved from 22.81 ± 7.89 to 17.17 ± 7.39 at 3 months. The mean Schirmer’s grade improved from 2.20 ± 0.95 to 1.61 ± 0.74 at 3 months whereas ferning (TF) grade improved from 2.59 ± 0.92 to 1.37 ± 0.77 at 3 months. Conclusion: Oral Vitamin A improves tear ferning due to improved mucin production. Keywords: Dry eye, tear ferning, Vitamin A Address for correspondence: Dr. Vaibhavi Gulabbhai Patel, A‑301, Sahjanand Park, Kudasan, Gandhinagar ‑ 382 421, Gujarat, India. E‑mail: [email protected] This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non‑commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. For reprints contact: [email protected] How to cite this article: Jadeja JN, Patel VG, Garasiya TR. Effect of short-term oral vitamin A on ocular tear film in dry eye. Delhi J Ophthalmol 2023;33:309-13. Effect of Short-Term Oral Vitamin A on Ocular Tear Film in Dry Eye Jagruti Navalsinhji Jadeja, Vaibhavi Gulabbhai Patel, Tejal Rameshbhai Garasiya Department of Ophthalmology, M and J Institute of Ophthalmology, B. J. Medical College, Ahmedabad, Gujarat, India Access this article online Quick Response Code: Website: https://journals.lww.com/djo DOI: 10.4103/DLJO.DLJO_126_23 Submitted: 26-Jul-2023 Revised: 28-Sep-2023 Accepted: 09-Nov-2023 Published: 15-Jan-2024 © 2024 Delhi Journal of Ophthalmology | Published by Wolters Kluwer - Medknow 309

Jadeja, et al.: Effect of oral vit-A on TF in DED on GCs’ differentiation, proliferation, and mucin secretion. This sheds new light on the position of GCs in the vicious circle of DED.[4] Tear ferning is a simple noninvasive test to assess mucus alteration or deficiency.[5] This test is based on the physical characteristics of mucus to crystallize and form ferns(arborization) when dried at room temperature on a clean smooth surface which can be observed under microscope.[6,7] Thus, tear ferning is not only an indicator of mucins but also of tear osmolarity and quality of the tear film. Mucin deficiency leads to tear film hyperosmolarity and thus alters the tear ferning pattern.[7] Vitamin A is an essential nutrient present naturally in tear film of healthy eyes. Vitamin A plays an important role in production of the mucin layer, the innermost lubricating layer of tear film that is crucial for a healthy tear film.[8] Mild Vitamin A deficiency may result in changes in the conjunctiva (Bitot’s spots) and also causes xerophthalmia. Loss of mucin and GC atrophy due to Vitamin A deficiency contributes to the instability of tear film secondary to mucin abnormality and leads to consequent DED.[9] Literature review did not reveal the effect of Vitamin A supplementation on mucin production and tear ferning pattern. Most of the studies have demonstrated the effect of Vitamin A supplementation on tear film quality, quantity, and other dry eye parameters. Hence, in the present study, we decided to assess whether short-term oral Vitamin A supplementation could improve tear film stability, especially tear ferning pattern along with symptoms and clinical parameters of DES. Methods and Study Design This is a cross-sectional and interventional study of 42 patients undertaking treatment at a tertiary health-care center in Western India. Approval of the institutional ethics committee was taken. Only those who consented to undergoing tests, taking interventional treatment, and coming for follow-up visits were included in the study which was conducted over a 2-year period from June 2019 to June 2021. Inclusion criteria Patients diagnosed with DED and who consented and could comply with the study questionnaire and tests pre and post supplementation were included in this study. Exclusion criteria Any ocular affection which could affect ocular surface and tear film such as lid disorders, ocular anatomical and contour distortion, preexisting ocular infection, allergic conjunctivitis, infective/noninfective keratoconjunctivitis, chemical burns, prosthesis use like contact lens, ocular laser treatment, ocular surgery, patients on antiglaucoma treatment or other systemic medications causing dry eye, medical systemic conditions, pregnant or lactating mothers, and patients who did not give consent were excluded from the study. Demographic data along with detailed history were taken from each patient including presenting ocular complaints and their duration, frequency of symptoms, any precipitating or relieving factors, history of wear of spectacles, previous ocular treatment, any history of allergies or cosmetic use, previous surgery, systemic illness and its duration, and family history of ocular disease and were noted. Grading of each symptom was done subjectively by asking the patients to grade on a scale of 0–3 with 0 corresponding to “absent” and 3 corresponding to “always present.” A validated Ocular Surface Disease Index (OSDI) questionnaire of ocular symptoms related to dry eyes was used to grade the ocular surface as normal (0–12 points) or as having mild (13–22 points), moderate (23–32 points), and severe (33–100 points) disease. The unaided, aided, and pinhole visual acuity using Snellen’s test type was noted. A detailed anterior segment slit-lamp examination was done, and the following parameters were recorded – tear ferning test (TFT), Schirmer’s 1, tear film breakup time (TBUT), tear film height (TFH), ocular surface fluorescein stain, and conjunctival stain with Lissamine green. For TFT, tear film was collected by asking the patient to look up and placing a capillary tube in the inferior fornix near the lateral canthus. Teardrops were transferred on a sterile glass slide and allowed to air dry at room temperature. The sample was then examined under microscope at ×5 and ×40 magnification for ferning pattern [Figure 1] and graded as per Rolando grading, as shown in Table 1. [10] Schirmer’s 1 test was performed, and any value <10 mm at the end of 5 min was considered an indicator of dry eye.[1] TBUT is defined as the time, in seconds, between the last blink and the appearance of the first random dry spot on the Table 1: Ronaldo classification of tear ferning pattern[10] Grade Ferning pattern Grade 1 Closely packed fern with no gaps Grade 2 Small ferns with gap in between Grade 3 Incomplete fern with no branching, wide gap Grade 4 No ferning 310 Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023 Figure 1: Tear ferning pattern[10]

Jadeja, et al.: Effect of oral vit-A on TF in DED cornea. TBUT <10 s was considered abnormal.[1] Tear film meniscus height was measured immediately after TBUT by measuring the tear film collection at the lower lid margin using a slit-lamp micrometer.[1] TFH measuring <0.25 mm was considered significant. Fluorescein staining of the cornea was done and graded according to the Oxford grading.For assessing conjunctival damage, Lissamine green staining was done and a score of more than 9 conjunctival spots was considered as positive stain.[1] After performing all the tests, patients were graded in accordance with the severity of DED to mild, moderate, and severe, as shown in Table 2, as per DEWS II.[1] After this detailed assessment and grading of patients, they were given oral Vitamin A supplementation at a dosage of 2 lac IU per capsule on days 0, 1, 14, and 28. Symptomatic topical treatment in the form of lubricating eye drop carboxymethyl cellulose (0.5%) was given 4 times a day to all mild dry eye patients and 6 times a day to all moderate and severe dry eye patients. Follow-up was scheduled at 1 month and 3 months from the 28th day of Vitamin A supplementation (the last dose of the course). On each follow‑up visit, all of the above‑mentioned tests were repeated and documented. Statistical analysis was done using analysis of variance test to compare the outcome of 3 values, i.e., on presentation, 1 month, and 3 months post supplementation for different DES parameters, and P value was analyzed for each of them. Results In our study out of 42 patients, 24 (57.14%) were female and 18 (42.85%) were male patients with a mean age of 42.52 years, ranging from 21 to 58 years. Among all, 18 (42.85%) were mildly symptomatic, 16 (38.09%) were moderate, and 8 (19.04%) were severely symptomatic. Nearly half, i.e., 19 (45.23%) patients, had mild OSDI score, while 13 (30.95%) had moderate OSDI score and 7 (16.66%) had severe OSDI score [Figure 2] and the rest 3 patients had normal OSDI score. There was a significant improvement in DED parameters pre and post supplementation, as shown in Table 3. As shown in Figure 3, the mean TFT grade was 2.59 ± 0.92 on presentation, which significantly improved up to 1.71 ± 0.75 1 month and 1.37 ± 0.77 at 3 months post supplementation. For Schirmer’s 1, the mean score changed from 2.14 ± 0.96 on presentation, 1.73 ± 0.77 at 1 month, and 1.61 ± 0.70 at 3 months with significant P < 0.0001, as shown in Figure 4. The mean score for TBUT improved from 1.86 ± 0.93 on presentation, 1.42 ± 0.59 at 1 month, and 1.19 ± 0.40 at 3 months with significant P < 0.0001. The mean score for ocular surface stain improved from 1.83 ± 1.04 on presentation, 1.61 ± 0.81 at 1 month, and 1.42 ± 0.54 at 3 months with significant P < 0.0001. The TFH mean score improved from 1.86 ± 0.91 on presentation to 1.45 ± 0.50 at 3 months with significant P < 0.0001. The Lissamine green conjunctival stain was positive for 4 eyes of severe dry eye patients, which turned negative at 3 months post Vitamin A supplementation. Discussion Dry eye syndrome is a common ocular surface disorder which not only impacts the vision but also has an adverse impact on the patient’s quality of life. It is caused by either abnormal tear production or tear film instability. Vitamin A is known to regulate the proliferation and differentiation of corneal epithelial cells and conjunctival GCs, increase mucin production and thus improves tear film stability. It has been Table 2: Classification of dry eye disease[1] Dry eye severity level Mild Moderate Severe Very severe Symptom score Mild (0–6) Moderate (7–12) Severe (13–18) Constant or disabling (>18) Visual symptoms Grade 1 None or mild fatigue Grade 2 Annoying or activity limiting Grade 3 Annoying, chronic or constant activity limiting Grade 4–5 Constant or possibly disabling OSDI score (points) 13–22 23–32 33–50 50–100 Meibomian gland dysfunction Grade 1 Grade 2 Grade 3 Grade 4 Tear fern test Close packed ferns Small ferns Incomplete ferning No ferning Schirmer’s 1 test (mm/5 min) >1 <10 <5 <2 TBUT (s) >10 <10 <5 Immediate Fluorescein stain Grade 1 None to mild Grade 2 Variable Grade 3 Marked central Grade 4 Severe punctate erosions Tear film height (mm) >0.3 <0.3–0.2 <0.2–0.1 <0.1 Lissamine green stain Absent Occasional/some spots <9 spots >9 spots TBUT: Tear film breakup time, OSDI: Ocular Surface Disease Index Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023 311 Figure 2: A age‑wise distribution as per severity of Ocular Surface Disease Index score

Jadeja, et al.: Effect of oral vit-A on TF in DED used in the treatment of DED at different doses for some time. In the present study, we decided to evaluate the effect of short-term oral Vitamin A supplementation and study its consequent effect on tear film quality, quantity, and other DES parameters including tear ferning pattern. In a hospital-based study done by Shilpy and Patel,[2] the prevalence of DED in Western India was 34.26%. The mean age of patients with DED was 50.63 ± 18.69 years. Females (54.04%) were more commonly affected compared to males(45.96%). The prevalence of DED as per OSDI score was 47.98% mild, 31.82% moderate, and 20.20% severe DED. In our study, the mean age of patients with DED was 42.52 ± 9.82. Females(57.14%) were more commonly affected as compared to males (42.85%). The prevalence of DED as per OSDI score was 45.23% mild, 30.95% moderate, and 16.66% severe DED. Patients who suffer from dry eye syndrome suffer from symptoms such as burning, eye fatigue, sensitivity to light, blurred vision, and stringy mucous which can have a significant impact on their quality of life. Astudy done by Ziada[11] showed a statistical decrease in photophobia with P < 0.05 at 3 months post Vitamin A supplementation (3000 IU daily for 6 months). In our study, the mean symptom score on presentation was 7.95 ± 3.74 which reduced up to 4.38 ± 2.99 (3 months post supplementation) with P < 0.0001. Kim et al. [12] studied the efficacy of topical Vitamin A 0.05% (retinyl palmitate) and cyclosporine 0.05% eye drop in DED and observed that ODSI score had become statistically significant with P value of 0.735, 0.226, and 0.004 at 0 month, 3 months, and 6 months, respectively. In our study, the mean OSDI score changed from 22.81 ± 7.89 on presentation to 20.05 ± 7.53 at 1 month with significant P = 0.003 and 17.17 ± 7.39 at 3 months with significant P < 0.0001 as shown in figure 5. Alanazi et al. [13] studied the effect of oral Vitamin A supplementation 1500 mg for 3 consecutive days on tear ferning and other DES parameters. TFT grades improved from 2.4 ± 0.5 to 1.4 ± 0.5. Selek et al. [14] studied the effect of 0.01% trans retinoic acid oral emulsion and observed a significant change in mucus ferning grade with P < 0.05 with clearing of mucus debris. In our study, oral Vitamin A was given for 1 month (as per regimen) and TFT improved from 2.59 ± 0.92 on presentation to 1.71 ± 0.75 at 1 month post supplementation and up to 1.37 ± 0.77 3 months post supplementation with significant P < 0.0001 [Figure 3]. As shown in Figure 6, TFT pattern showed a grossly positive improvement possibly due to increased mucin production due to Vitamin A supplementation. Selek et al. [14] studied the effect of 0.01% trans retinoic acid oral emulsion, and the mean Schirmer value improved from 6.32 ± 3.3 ± 0 mm up to 7.32 ± 4.16 mm at 2 months. In our study, the mean Schirmer’s value increased from 8 ± 3.95 mm on presentation to 9.82 ± 4 mm at 1 month and 10.43 ± 3.95 mm at 3 months post supplementation, as shown in Figure 4. Iwuagwu et al. [15] gave oral Vitamin A (50,000 I.U) supplementation for 7 consecutive days and studied its effect on TBUT in young adults 20 days post supplementation. After 20 days, the range becomes 16–31 s and a mean TBUT of 21.79 s. Our study demonstrated an improvement in mean TBUT grade score from 1.86 ± 0.94 on presentation to 1.2 ± 0.41 at 3 months post supplementation with significant P < 0.0001. Kim et al. [12] compared 0.05% retinyl palmitate versus 0.05% cyclosporine in dry eye patients and observed that there was a statistically significant decrease in ocular surface staining in both groups (from 2.18 ± 0.74 mm to 1.95 ± 0.35 mm) at 3 months. In our study, ocular surface staining with fluorescein stain showed an improvement with mean 1.83 ± 1.04 on presentation to 1.45 ± 0.59 at 3 months with significant P < 0. Table 3: Improvement in various dry eye disease parameters post supplementation Mean±SD Presentation (pre supplementation) 1 month (post supplementation since last dose) 3 months (post supplementation since last dose) Symptom score 7.95±3.74 6.17±3.20 4.38±2.99 OSDI score 22.81±7.89 20.05±7.53 17.17±7.39 Tear ferning grade 2.59±0.92 1.71±0.75 1.37±0.77 Schirmer’s grade 2.20±0.95 1.76±0.77 1.61±0.74 TBUT grade 1.86±0.94 1.42±0.6 1.2±0.41 F stain 1.81±0.7 1.62±0.83 1.38±0.49 Tear film height 1.88±0.9 1.57±0.6 1.47±0.51 Lissamine green stain Positive Positive Negative TBUT: Tear film breakup time, OSDI: Ocular Surface Disease Index, SD: Standard deviation 312 Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023 Figure 3: Change in tear ferning Grade, pre and post supplementation

Jadeja, et al.: Effect of oral vit-A on TF in DED 0001. In our study, TFH showed that a mean increase of 0.6 mm ± 0.2 mm was noted at 3 months post supplementation. Limitation Due to the COVID-19 pandemic, a smaller number of dry eye patients could be recruited during the study period, and few of them (11 patients) did not return for follow‑up examination. Due to the COVID-19 pandemic, we could not design our study for longer follow‑up duration (more than 3 months) post supplementation. Conclusion The findings of our study suggest that short‑term oral Vitamin A supplementation at the studied dose (2 lac IU on days 0, 1, 14, and 28) improves tear ferning pattern which is suggestive of improved mucin content which in turn suggests enhanced GC performance especially in patients with moderate-to-severe DED. As compared to topical therapy, oral supplementation at this dose is well tolerated, has minimal adverse effect, is cost-effective, and has better patient compliance as only 1 capsule (2 lac IU/capsule) has to be taken each time for 4 doses. Thus, short-term oral Vitamin A supplementation has an improving effect on tear film quality, quantity, and tear film stability in patients with dry disease. Financial support and sponsorship Nil. Conflicts of interest The manuscript has been read and approved by all the authors. Each author believes that the manuscript represents honest work. There is no conflict of interest. References 1. Craig JP, Nichols KK, Akpek EK, Caffery B, Dua HS, Joo CK, et al. TFOS DEWS II definition and classification report. Ocul Surf 2017;15:276-83. 2. Shilpy N, Patel D. Prevalence of dry eye disease in Western India. Int J Contemp Med Res [IJCMR]2019;6:7.37. [doi: 10.21276/ijcmr. 2019.6.7.]. 3. Dartt DA, Willcox MD. Complexity of the tear film: Importance in homeostasis and dysfunction during disease. Exp Eye Res 2013;117:1-3. 4. Baudouin C, Rolando M, Benitez Del Castillo JM, Messmer EM, Figueiredo FC, Irkec M, et al. Reconsidering the central role of mucins in dry eye and ocular surface diseases. Prog Retin Eye Res 2019;71:68-87. 5. Masmali AM, Al-Bahlal JM, El-Hiti GA, Akhtar S, Purslow C, Murphy PJ, et al. Repeatability and diurnal variation of tear ferning test. Eye Contact Lens 2015;41:262-7. 6. Pearce EI, Tomlinson A. Spatial location studies on the chemical composition of human tear ferns. Ophthalmic Physiol Opt 2000;20:306-13. 7. Masmali AM, Purslow C, Murphy PJ. The tear ferning test: A simple clinical technique to evaluate the ocular tear film. Clin Exp Optom 2014;97:399-406. 8. Smith J, Steinemann TL. Vitamin A deficiency and the eye. Int Ophthalmol Clin 2000;40:83-91. 9. Gilbert C. The eye signs of Vitamin A deficiency. Community Eye Health 2013;26:66-7. 10. Rolando M, Baldi F, Calabria GA. Tear mucus ferning in keratoconjunctivitis sicca. In: Holly FJ, editor. The Preocular Tear Film in Health, Disease and Contact Wear. Lubbock, Tex: Dry Eye Institute; 1986. p. 203e9. 11. Ziada H. Oral Vitamin A- including antioxidant formula versus topical Vitamin A added to lubricant eye drops in treatment of dry eye syndrome; a comparative study. Int J Ophthalmic Res 2017;3:252-8. Available from: https://www.ghrnet.org/index.php/ijor/article/view/. 12. Kim EC, Choi JS, Joo CK. A comparison of Vitamin A and cyclosporine a 0.05% eye drops for treatment of dry eye syndrome. Am J Ophthalmol 2009;147:206-13.e3. 13. Alanazi SA, El-Hiti GA, Al-Baloud AA, Alfarhan MI, Al-Shahrani A, Albakri AA, et al. Effects of short-term oral Vitamin A supplementation on the ocular tear film in patients with dry eye. Clin Ophthalmol 2019;13:599-604. 14. Selek H, Unlü N, Orhan M, Irkeç M. Evaluation of retinoic acid ophthalmic emulsion in dry eye. Eur J Ophthalmol 2000;10:121-7. 15. Iwuagwu FO, Agu GC, Azuamah Y, Okolie U. The effects of Vitamin A on tear break-up time of young adults. J Niger Med Assoc 2011;10:19-24. Figure 5: Change in Ocular Surface Disease Index score, pre and post supplementation Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023 313 Figure 6: Improvement in tear ferning grade of the same patient with grade 4 dry eye disease (DED) to grade 1 DED, pre and post oral Vitamin A supplementation Figure 4: Change in Schirmer’s test, pre and post supplementation

Abstract Original Article Introduction Developmental delay (DD) denotes a significant delay in one or more developmental domains. The developmental domains included are gross motor, fine motor, speech or ocular and social development. Significant delay is said to be present if the development or ability is two standard deviations or more below the mean on accepted developmental testing such as the Denver developmental screening test. The presence of DD is a major problem in the pediatric population in developing countries. In the world, around 1.5%–2% pediatric population has DD. Approximately 85% of children with DD are from developing countries. There is reported evidence of increased incidence of visual abnormalities among children with mental and DD. These ocular signs are often missed due to the presence of coexisting handicaps in other functional domains. In India, as per 2011 census, out of 78 lakh children with DD, 14 lakh (17%) have visual impairment.[1,2] Many ocular disorders are treatable. Hence, early detection and intervention of the disease is helpful in restoring useful vision. In addition, psychological and economic burdens in the form of increased blind years due to the associated visual impairment can be reduced by giving these children a near-normal social life. This study was conducted to determine various ocular Aim: This study aims to study the various ocular and systemic manifestations in children with developmental delay (DD) and its association with development quotient. Materials and Methods: A total of 192 children between the age group of 1–5 years with DD were enrolled in the study at a pediatric care tertiary teaching hospital. All these children underwent detailed ocular and systemic examination along with psychometric development quotient calculation. Along with this, a detailed antenatal and postnatal history was also noted. Results: DD was more common in males and lower socioeconomic class. The most common ocular manifestations were refractive error (64.6%) followed by strabismus (34.4%), temporal disc pallor (16.6%), nystagmus (7.9%), optic atrophy (2.6%), congenital nasolacrimal duct obstruction (1.0%), and cataract (0.5%). Hypoxic ischemic encephalopathy (75%) was the most common systemic association followed by hearing and speech impairment (70.8%), cerebral palsy (53.1%), and seizure disorder (46.8%). Delayed cry at birth was found to have a significant association with lower Developmental Quotient (DQ) (P = 0.021) and higher incidence of refractive error (P = 0.036). Refractive error was more prevalent in children with cerebral palsy (P = 0.006). Children with seizure disease had lower visual potential (P < 0.001). Children with severe MRI findings were found to have lower DQ. Conclusion: The incidence of ocular co-morbidities in children with DD is high. Many of them are treatable. Among these, refractive errors are the most common cause of visual impairment followed by strabismus and optic atrophy. Early detection and intervention can help these children to restore useful vision and help in their rehabilitation. Keywords: Cerebral palsy, development quotient, global developmental delay Address for correspondence: Dr. Meenakshi Wadhwani, Guru Nanak Eye Centre, New Delhi ‑ 110 031, India. E‑mail: [email protected] This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non‑commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. For reprints contact: [email protected] How to cite this article: Wadhwani M, Malhotra S, Dhingra D, Manika M, Kursange S, Singh R, et al. Association of disability quotient with ocular and systemic manifestations in children with developmental delay. Delhi J Ophthalmol 2023;33:314-8. Association of Disability Quotient with Ocular and Systemic Manifestations in Children with Developmental Delay Meenakshi Wadhwani1 , Sehzadi Malhotra2 , Dhulika Dhingra3 , Manika Manika4 , Shubhangi Kursange4 , Rahul Singh4 , Sneha Kumari4 , Amit Kumar4 1 Guru Nanak Eye Centre, New Delhi, India, 2 Clinical Psychologist, IHBAS, New Delhi, India, Departments of 3 Pediatrics and 4 Ophthalmology, Chacha Nehru Bal Chikitsalaya, New Delhi, India Access this article online Quick Response Code: Website: https://journals.lww.com/djo DOI: 10.4103/DLJO.DLJO_129_23 Submitted: 27-Jul-2023 Revised: 29-Nov-2023 Accepted: 09-Dec-2023 Published: 15-Jan-2024 314 © 2024 Delhi Journal of Ophthalmology | Published by Wolters Kluwer - Medknow

Wadhwani, et al.: Asssociation of DQ with ocular manifestations in children with GDD and systemic manifestations along with associated risk factors in children with DD and its association with development quotient (DQ). Materials and Methods This prospective and observational cross-sectional study was conducted in tertiary care pediatric hospital from January 2019 to December 2019 after obtaining clearance from the institutional ethics committee. All children in the age group of 1–5 years with delayed developmental milestones attending the outpatient department of ophthalmology, pediatric, or psychiatric and diagnosed with DD (DQ <70) after developmental screening test were enrolled in the study. All children with neurodegenerative disorders despite being presenting as DD were excluded from the study. The children with DD were included in the study after all appropriate written and informed consent from the patient’s legal guardians. The following details were noted for each child: age at presentation, presenting complaints, visual acuity, cycloplegic refraction, ocular alignment and motility, head posture, and anterior and posterior segment findings. Visual acuity assessment was done using any of the following criteria: fixation and following light, ambulatory freely, reach out to objects, child’s ability to recognize parents, preferential looking test (Cardiff acuity cards), Landolt C‑Chart (if the child was cooperative). All children with significant refractive errors after cycloplegic correction were given spectacles as per the AAO guidelines for the prescription of glasses.[3] Children with strabismus and cataract were advised surgical intervention after anesthetic fitness. Besides this, a detailed antenatal and postnatal history was elicited from the attending parent or guardian along with a history of systemic factors, previous medical history, birth history, and past surgical interventions. All the children were referred to the psychiatry department for the assessment of development quotient (DQ) using developmental assessment scales for Indian infants for age <2.5 years and Pandey’s cognitive development test for preschoolers for age >2.5 years.[4,5] Patients who needed higher investigations such as visual evoked potential (VEP), electroencephalography, magnetic resonance imaging (MRI), and computed tomography were carried out at the same institute. Results A total of 192 children with DD were enrolled in the study which consisted of 131 (68.2%) males and 61 (31.8%) females. Out of total of 192 cases, 114 (59.4%) were within 1–2 years, 41 (21.3%) in 2.1–3 years, 18 (9.4%) in 3.1–4 years, and 19 (9.9%) in 4.1–5 years of age group with a mean age of 2.25 ± 1.20 years [Table 1]. Systemic associations and risk factors Antenatal history Fever or infection (upper respiratory tract infection or gastroenteritis or urinary tract infection) was the most common risk factor in 29 (15.1%) followed by pregnancy‑induced hypertension in 26 (13.5%), per vaginal leak in 13 (6.8%) mothers, multiple X‑ray exposure was present in 3 (1.6%), and drug exposure in one (0.5%) mother. Thirty‑one (16.1%) mothers had obstructed labor, and 39 (20.3%) had prolonged labor. Postnatal history Amongst these 192 children, a history of consanguinity was present in 44 (22.9%) children, normal birth weight in 162 (84.37%), and low birth weight in 29 (15.10%). Delayed cry at time of birth was present in 159 (82.8%) children. One hundred and eighty‑one (94.3%) children were born term, 14 (7.3%) children were preterm. One hundred and seventeen children had no complication during labor. One hundred and five (54.7%) had prolonged intensive care unit (ICU) stay, 40 (20.8%) had exposure to 100% oxygen concentration and meconium aspiration was present in 31 (16.1%) children. Out of 192,184 (95.8%), children had healthy siblings, 6 (3.1%) had a history of dead siblings during the infantile period, siblings of 2 (1.04%) children had heart disease, and 1 (0.1%) had a sibling with DD. Ocular examination Amongst these 192 children, the highest cause for ocular morbidity was refractive error (122 [63.5%] OD and 124 [64.6%] OS), followed by strabismus in 66 (34.4%), 32 (16.6%) with temporal pallor of disc, nystagmus in 15 (7.9%), 5 (2.6%) with optic atrophy, congenital nasolacrimal duct obstruction (CNLDO), and retinal dystrophy in 2 (1.0%) cases each [Table 2]. Anterior segment: Normal in 174 (90.6%) children, nystagmus noted in 15 (7.9%), CNLDO in 2 (1.0%), cataract and pseudophakia in 1 (0.5%) case each. Posterior segment: retinal examination was normal in 153 (79.7%) children; temporal optic disc pallor was noticed in 32 (16.7%) children, complete optic atrophy in 5 (2.6%) children and 2 (1.0%) cases of retinal dystrophy. Ocular alignment: ocular alignment was normal in 126 (65.6%) children, exotropia was noted in 32 (16.7%), and esotropia in 34 (17.7%) children. Systemic manifestations Various investigations VEP was done in 15 cases; of these, 3 (20%) children showed no response. Delayed latency was noted in 12 (80%) cases. MRI was done in 81 children. It was found to be normal in 20 (24.7%) children. Hypoxic ischemic encephalopathy (HIE) sequelae was a common finding seen in 18 (22.2%) cases followed by periventricular leukomalacia found in 13 (16.0%), encephalomalacia in 9 (11.1%), cerebral atrophy in 8 (9.9%), hydrocephalus in 7 (8.6%), arachnoid cyst in 2 (2.5%), cerebral Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023 315

Wadhwani, et al.: Asssociation of DQ with ocular manifestations in children with GDD hematoma in 2 (2.5%), hemosiderin deposits in 1 (1.2%), and hypoplasia in 1 (1.2%) children [Table 3]. There was a significant association of lower DQ with the severity of MRI findings (P = 0.021). There was a significant association of seizure disorder with lower visual potential in children with DD (P < 0.001). Cerebral palsy was also found associated with refractive error (P = 0.006 and P = 0.004 in the right and left eyes, respectively) [Table 4]. In this study, we tried to find association between incidence of ocular anomaly in DD children with antenatal insult(pregnancy‑induced hypertension/X‑ray exposure/history of fever/infection during pregnancy/history of drug exposure), perinatal insult (time of cry after birth/obstructed labor/ prolonged labor/MSL/PROM), postnatal events (prolonged ICU stay/O2 exposure/meconium aspiration), consanguinity, age of mother at time of birth, birth order, birth history (term or preterm/birth weight), sibling history, and socioeconomic status. None of the antenatal and postnatal factors were found to be associated with DQ significantly. Out of all perinatal factors, only delayed cry was found significantly associated with DQ (P = 0.021) and refractive error (P = 0.036). Discussion Children with DD have a wide spectrum of disabilities including visual disability. The various causes for visual impairment in children with DD are cerebral visual impairment (CVI), strabismus, refractive errors, cataract, nystagmus, and optic atrophy. CVI is defined as visual dysfunction due to brain damage in otherwise normal ocular examination. CVI is a leading cause of childhood blindness with the incidence of Table 2: Various ocular features in developmental delay children n (%) Visual potential No fixation to light 51 (26.6) Fix and follow torch light 133 (69.3) Ambulate freely 45 (23.4) Reach out to objects 98 (51.0) Cardiff card test 15 (7.8) Identifies parents 67 (34.8) Anterior segment Normal 174 (90.6) Nystagmus 15 (7.9) Congenital nasolacrimal duct obstruction 2 (1.0) Cataract 1 (0.5) Posterior segment Normal 153 (79.7) Temporal pallor 32 (16.7) Complete optic atrophy 5 (2.6) Retinal dystrophy 2 (1.0) Ocular alignment Normal 126 (65.6) Exotropia 32 (16.7) Esotropia 34 (17.7) Refractive error Emmetropia 69 (35.9) Myopia 9 (4.7) Hypermetropia 47 (24.4) Myopic astigmatism 36 (18.8) Compound myopic astigmatism 30 (15.7) Hyperopic astigmatism 1 (0.5) Table 1: Demographic distribution of children with global developmental delay Age and gender distribution (years) Male, n (%) Female, n (%) Total, n (%) 1–2 (Group 1) 79 (41.1) 35 (18.2) 114 (59.4) 2–3 (Group 2) 31 (16.1) 10 (5.2) 41 (21.3) 3–4 (Group 3) 4 (2.1) 14 (7.3) 18 (9.4) 4–5 (Group 4) 17 (8.9) 2 (1.1) 19 (9.9) Total 131 (68.2) 61 (31.8) 192 Birth order, n (%) First 88 (45.8) Second 63 (32.9) Third 35 (18.2) Fourth and more than fourth 6 (3.1) Socioeconomic status (Kuppuswamy Scale)[6], n (%) Upper lower 94 (48.9) Lower middle 74 (38.6) Upper middle 23 (12) Lower 1 (0.5) Age of mother at time of birth (years), n (%) <20 13 (6.7) 20–25 85 (44.3) 26–30 77 (40.1) >30 17 (8.9) 316 Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023

Wadhwani, et al.: Asssociation of DQ with ocular manifestations in children with GDD 2/1000 live birth in term and 19/1000 live birth in preterm neonates.[6] The brain damage causing CVI could be at the cortical or subcortical level (visual processing is a complex cerebral activity with the involvement of a major portion of the central nervous system). Henceforth, children with neurodevelopmental disabilities have visual deficits[7] Cerebral palsy is the leading cause of visual deficits. Children with birth asphyxia particularly with HIE have involvement in not only motor pathways but also various visual pathways.[2,8] The present study was done in 192 children with DD. The prevalence of DD in this study was found to be more in male children as compared to female children. Ninety percent of the study children belonged to lower socioeconomic class. Improper hygiene, less awareness among parents/caregivers, and poor accessibility to medical care further add to poor prognosis in these children as by Lai et al. [9] There was a positive history of consanguinity in parents of 44 (22.9%) children, though this was statistically insignificant with DQ (P = 0.728) in the present study in contrast to studies conducted by Maheshwari and Wadhwa and Fan et al. respectively,[10,11] they reported higher incidence of seizure disorder and DD in children born from the consanguineous marriage. There was no significant association of DD in children with higher birth order or more maternal age at the time of birth. The most common systemic manifestations in the present study were birth asphyxia causing HIE (75%) followed by hearing and speech impairment (70.8%), cerebral palsy (53.1%), and seizure disorder (46.8%). Similar findings were reported by Lanka et al. 2015[12] who reported birth asphyxia in 45% of cases and (Joshi et al., 2018), they found cerebral palsy as the most common association (64%) followed by down syndrome (22%) and autism (7%).[12,13] Delayed cry leading to birth asphyxia is the leading cause of neonatal death (23%) that causes acute and subacute brain injury presenting as neurodevelopmental disabilities and majority of these children present with visual disabilities. In the present study, delayed crying at birth was present in 159 (82.8%) children. Among all antenatal and postnatal risk factors, only these children with delayed cry at birth were found to have lower DQ (P = 0.021) and higher incidence of refractive error (P = 0.036). On comparing the results for ocular manifestations in the last decade, the results of our study are comparable to the other studies. These studies[1,13-18] also reported refractive error as the most common finding followed by strabismus and optic nerve head anomalies in the form of atrophy or temporal pallor [Table 5]. There was no significant association of DQ with refractive error and ocular alignment. Refractive error was also found to be more in children with cerebral palsy (P = 0.006). Children with seizure disorder were found to have lower visual potential compared to others (P < 0.001). MRI Table 3: Association of systemic anomalies in developmental delay children Other associated anomalies n (%) HIE 144 (75) Seizure disease 90 (46.8) Cerebral palsy 102 (53.1) Hearing and speech impairment 136 (70.8) Microcephaly 10 (5.2) Low serum ferritin 1 (0.5) Down syndrome 1 (0.5) VSD 1 (0.5) Head nodding 1 (0.5) Hydrocephalus 1 (0.5) HIE: Hypoxic ischemic encephalopathy, VSD: Ventricular septal defect Table 4: Distribution of children according to development quotient Category n (%) Mild 51 (37.2) Moderate 54 (39.4) Severe 31 (22.6) Profound 1 (0.8) Total 137 (100) anomalies in the form of periventricular leukomalacia, cerebral atrophy, gliosis, and encephalomalacia were associated with lower DQ (P = 0.06). This periventricular leukomalacia is known to be due to the involvement of pyramidal pathways and other visual pathways leading to the typical fundus appearance of a pale optic disc due Table 5: Presentation of various ocular findings in different studies done on global developmental delay Studies Ocular manifestations Reena et al. [14] Ocular manifestations: 64.6%, refractive error (41.3%), strabismus (40%), optic atrophy (9.3%), nystagmus (4.6%), ROP (4%), CVI (6%), cataract (2.6%) Solomon et al. [15] Refractive error (51.2%), optic atrophy (21.6%), strabismus (18.4%), CVI (11.2%) Vora et al. [1] Refractive error (58.5%) Joshi et al. [13] Refractive error (79.9%), strabismus (46.4%) Wu and Tsai[16] Ocular manifestation in 56.1%, most common was optic atrophy and strabismus Nielsen et al. [17] Refractive error in 46.7% and strabismus in 26.8% significant correlation of lower IQ with ocular manifestation, decreased contrast sensitivity Smitha et al. [18] Ocular manifestation in 83.6%, refractive error in 59.7%, strabismus 8.6%, optic atrophy in 9.7%, ptosis in 1.08% Present study Ocular manifestations in 64.6% children - refractive error in 123 (64.6%) followed by strabismus in 66 (34.4%), temporal pallor of disc 32 (16.6%), nystagmus in 15 (7.9%), optic atrophy in 5 (2.6%), CNLDO and retinal dystrophy in 2 (1.0%) each, and one (0.5%) case of cataract CVI: Cerebral visual impairment, IQ: Intelligence quotient, CNLDO: Congenital nasolacrimal duct obstruction, ROP: retinopathy of prematurity Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023 317

Wadhwani, et al.: Asssociation of DQ with ocular manifestations in children with GDD to transsynaptic degeneration reflecting an unusual form of optic disc hypoplasia.[2] Higher incidence of refractive errors noted in DD is due to disturbance in visual feedback mechanism. Compliance with spectacle use is poor but early correction of refractive error is found to be beneficial in the development of these children.[19] Surgical correction of strabismus was done in 4 children, there were numerous problems associated in the form of noncompliance to patching, noncooperation for preoperative measurement, and risk of general anesthesia due to associated systemic conditions although over corrections are more, surgical correction in these children is well tolerated and effective.[20] Conclusion The incidence of ocular comorbidities in children with DD is high. Many of them are treatable. Among these, refractive errors are the most common cause of visual impairment followed by strabismus and optic atrophy. Early detection and intervention can help these children to restore useful vision and help in rehabilitation. Hence, a multispecialty approach is needed for the comprehensive management of these children. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. References 1. Vora U, Khandekar R, Natrajan S, Al-Hadrami K. Refractive error and visual functions in children with special needs compared with the first grade school students in Oman. Middle East Afr J Ophthalmol 2010;17:297-302. 2. Fazzi E, Signorini SG, LA Piana R, Bertone C, Misefari W, Galli J, et al. Neuro-ophthalmological disorders in cerebral palsy: Ophthalmological, oculomotor, and visual aspects. Dev Med Child Neurol 2012;54:730-6. 3. AAO Pediatric Eye Evaluation PPP – 2017. 4. Beran TN, Elliott CD. Differential ability scales (2nd ed.). San Antonio, TX: Harcourt assessment. Can J Sch Psychol 2007;22:128‑35. 5. Pandey H. Pandey’s Cognitive Development Test for Preschoolers Manual. Kacher Ghat, Agra: National Psychological Corporation, The Psychological Corporation; 1992. p. 1-15. 6. Wani RT. Socioeconomic status scales‑modified Kuppuswamy and Udai Pareekh’s scale updated for 2019. J Family Med Prim Care 2019;8:1846-9. 7. McDonald L, Rennie A, Tolmie J, Galloway P, McWilliam R. Investigation of global developmental delay. Arch Dis Child 2006;91:701-5. 8. Kozeis N. Brain visual impairment in childhood: Mini review. Hippokratia 2010;14:249-51. 9. Lai DC, Tseng YC, Guo HR. Characteristics of young children with developmental delays and their trends over 14 years in Taiwan: A population-based nationwide study. BMJ Open 2018;8:e020994. 10. Maheshwari K, Wadhwa L. Role of consanguinity in pediatric neurological disorder. Int J Contemp Pediatr 2016;3:939-42. 11. Fan YS, Ouyang X, Peng J, Sacharow S, Tekin M, Barbouth D, et al. Frequent detection of parental consanguinity in children with developmental disorders by a combined CGH and SNP microarray. Mol Cytogenet 2013;6:38. 12. Lanka UV, Dasari N, Siva C. A cross sectional study of factors influencing severity of developmental delay and its co morbidities. Int J Innov Res Dev 2015;4:33-41. 13. Joshi MS, Telang OJ, Morepatil VG. Ocular disorders in children with developmental delay. J Evid Based Med Healthc 2017;4:4065-70. 14. Reena A, Lekshmy SR, Lekshmi H, Appukuttan BK. Ophthalmic manifestations in children with delayed milestones- a clinical study. Kerala J Ophthalmol 2009;21:264-9. 15. Solomon CG, Bindu N, Raju KV, George M. Ocular associations in children with developmental delay. Kerala J Ophthalmol 2011;22:367-71. 16. Wu HJ, Tsai RK. Ocular manifestations in children with developmental delay preliminary report. Kaohsiung J Med Sci 2000;16:422-8. 17. Nielsen LS, Skov L, Jensen H. Visual dysfunctions and ocular disorders in children with developmental delay. I. Prevalence, diagnoses and aetiology of visual impairment. Acta Ophthalmol Scand 2007;85:149-56. 18. Smitha KS, Harshavardhan P, Patil SB, Bhagyajyoti BK, Sheetal VG, Kathyayini SV, et al. Prevalence of ocular manifestations in children with developmental delay. Med Innovatica 2014;3:42-4. 19. Smitha KS, Patil VD, Kamate MD, Prabhu M, Harakuni U, Rakshitha OP. Impact of refractive error correction on mental and visual development in children with global developmental delay. Indian J Health Sci Biomed Res 2019;12:117-22. 20. Liu G, Ranka MP. Strabismus surgery for children with developmental delay. Curr Opin Ophthalmol 2014;25:417-23. 318 Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023

Abstract Case Report Introduction Of all cutaneous cysts, epidermal inclusion cysts(EIC) are the most prevalent. Epidermoid cyst, epidermal cyst, infundibular cyst, inclusion cyst, and keratin cyst are only a few of the names for EIC that are well-known. These cysts can develop anywhere on the body, usually appear as nodules under the patient’s skin, and frequently feature a central punctum that is clearly apparent. These cysts can range in diameter from a few millimeters to several centimeters. Lesions might not change over time, or they might get bigger. It is impossible to anticipate with any degree of accuracy whether an epidermal inclusion cyst will grow, swell, or remain dormant.[1] Case Report A 56-year-old female came for the excision of asymptomatic, recurrent swelling in both upper lids. The patient had a normal visual check-up and was in good health. She had undergone multiple surgeries (four times) in the past 6 years on the conjunctival side, probably being diagnosed with chalazion. However, each time, there was a recurrence within 2–3 weeks, after which the swelling progressively enlarged in size. Clinically, on inspection, it was a round mass the size of a pea in the upper eyelids of both eyes. The mass was located away from the lid margin over the tarsal plate. It resulted in moderate mechanical ptosis in both eyes. There were no visible puncta, and the overlying skin was healthy with a normal lid crease. The protrusion of the cyst on the cutaneous side was more noticeable than the conjunctival side, which was unlike chalazion. On palpation, it was nontender, soft, and fluctuant. It was located superficially, just deep into the skin, measuring 1.5 cm × 1 cm × 1 cm with an almost spherical shape. It became more prominent with forceful lid closure, indicating that it was superficial to the orbicularis muscle. It was movable over the tarsal plate, although not freely. Cysts in both lids showed no signs of infection or inflammation. The underlying conjunctiva showed a linear scar from previous surgeries. Because of the recurrence and unusual presentation, an excision biopsy was planned. After infiltration of a local anesthetic agent, the cyst was excised through a horizontal skin incision over the lid crease. Intraoperatively, care was taken not to breach the Epidermal cysts are benign, slow-growing tumors resulting from the proliferation of epidermal cells. A cyst of the eyelid typically presents as a solitary, elevated, round, and freely mobile subcutaneous mass with smooth, overlying skin during adolescence and late adulthood. Usually, cysts are asymptomatic; however, they may become inflamed or secondarily infected. Here, we are reporting a case of bilateral symmetrical epidermal inclusion cyst of the upper eyelid in a 56-year-old female, though epidermal cysts are more common in men. She gave a history of recurrent surgical removal of cysts in both eyes in the past after being misdiagnosed as chalazion. Keywords: Bilateral, epidermal inclusion cyst, symmetrical, upper lid Address for correspondence: Dr. Rajwinder Kaur, Department of Ophthalmology, Adesh Institute of Medical Sciences and Research, Bathinda, Punjab, India. E‑mail: [email protected] This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non‑commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. For reprints contact: [email protected] How to cite this article: Kaur R, Dahiya P, Baghla P, Roychoudhary AK. Bilateral epidermal inclusion cysts with unusual symmetrical presentation and review. Delhi J Ophthalmol 2023;33:319-21. Bilateral Epidermal Inclusion Cysts with Unusual Symmetrical Presentation and Review Rajwinder Kaur1 , Priyanka Dahiya1 , Panku Baghla1 , Arnav Kr Roychoudhary2 1 Department of Ophthalmology, Adesh Institute of Medical Sciences and Research, Bathinda, Punjab, India, 2 Department of Pathology, Adesh Institute of Medical Sciences and Research, Bathinda, Punjab, India Access this article online Quick Response Code: Website: https://journals.lww.com/djo DOI: 10.4103/DLJO.DLJO_160_23 Submitted: 26-Sep-2023 Revised: 16-Nov-2023 Accepted: 24-Nov-2023 Published: 15-Jan-2024 © 2024 Delhi Journal of Ophthalmology | Published by Wolters Kluwer - Medknow 319

Kaur, et al.: Symmetrical bilateral epidermal inclusion cysts: Case report with unusual presentation and brief review of literature capsule of the cyst. Intraoperatively, the cysts were found in the subcutaneous plane with orbicularis fibers split over them, placed anterior to the levator attachment over the tarsus, and superficial to the orbital septum. In both cases, the cysts were found adherent to the underlying tarsus at some point. A part of the tarsal tissue had to be excised to remove the cyst in toto. Both cysts were removed after an intervening period of 2 weeks. Excised cysts were sent for histopathology. The size of the excised right upper lid cyst was 1 cm × 0.7 cm × 0.3 cm. The size of the left upper lid cyst was 1.4 cm × 0.9 cm × 0.3 cm. Microscopic examination of the section studied showed a cyst lined by keratinized stratified squamous epithelium. The wall of the cyst was fibrocollagenous with mild chronic inflammation. The lumen of the cyst showed numerous keratin flakes. The overlying epidermis was unremarkable. Findings were consistent with EIC in both eyes [Figure 1]. After 2 months, there are no signs of recurrence. Table 1: Differential diagnosis of epidermal inclusion cyst Epidermal inclusion - cyst Chalazion Pilomatrixoma Hidrocytoma Squamous papilloma Sebaceous cyst Presentation Nodule underneath the skin with visible punctum Deep-seated nodule away from the lid margin Superficial nodules in the dermis with white overlying epidermis Cystic (translucent, compressible) with smooth underlying skin Soft skin colored round pedunculated lesion Intradermal creamy plaques Mobility Freely mobile Fixed Fixed Freely mobile Stuck on skin appearance Pathology Implantation of epidermal elements into the dermis commonly due to blocked follicular orifice Sterile granulomatous inflammation of the tarsal meibomian gland Calcifying epithelioma arising from hair follicle matrix Cystic lesion of ducts of eccrine and apocrine glands (sweat glands) Benign hyperplasia of superficial epithelium Due to obstruction of the sebaceous gland not associated with eyelashes Histology Lined by stratified squamous epithelium with keratin center Sterile granuloma with lipid‑filled giant cells Islands of epithelial cells (basophilic and ghost cells) and areas of calcification Simple cuboidal cell wall lining the cyst and vacuolization in intercellular space Fibrovascular core with overlying hyperkeratosis acanthosis and focal parakeratosis Contains epithelial cells, keratin fats, and cholesterol crystals Table 2: Case reports with review of literature Case report authors Patient age/sex Eyelid involved Laterality Surgical technique Vagefi et al. [11] 78/male Right upper eyelid Unilateral Lid crease Lucarelli et al. [3] 3 cases Upper lids Unilateral Lid crease Majumdar et al. [12] 35/male Right upper lid Unilateral Lid crease with transconjunctival suturing due to extent of lesion Bubanale et al. [13] 32/male Right upper lid Unilateral Lid crease Mandal et al. [14] 45/male Right upper lid Unilateral in eviscerated eye Temporal approach as orbital extension was present Kim et al. [15] 11 cases (31–71 years) 5 males 6 females Upper lid Unilateral one with multiple lesions Both transcutaneous and transconjunctival Panditrao et al. [16] 65/female Right upper lid Unilateral Lid crease Behera and Panja[2] 65/male Right upper lid Unilateral Lid crease Ban et al. [17] 16/female Left upper lid Unilateral Lid crease Mathur and Saxena[18] 55/male Right upper lid Unilateral Lid crease Shah et al. [19] 69/male Left lower lid Unilateral Lid crease Kronish and Dortzbach[9] 24 children, 8 months–7 years Upper eyelid cysts Unilateral Surgical technique described for removing eyelid cysts 320 Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023 Figure 1: (a) Bilateral epidermal inclusion cyst involving both upper lid. (b) After the excision biopsy, (c) Cyst removed in toto, (d and e) Histopathology shows cyst lined by keratinized stratified squamous epithelium. The wall of the cyst was fibrocollagenous with mild chronic inflammation. The lumen of the cyst showed numerous keratin flakes, thus confirming the diagnosis of epidermal inclusion cyst c d a b e

Kaur, et al.: Symmetrical bilateral epidermal inclusion cysts: Case report with unusual presentation and brief review of literature Discussion An epidermal inclusion cyst demonstrates the implantation of epidermal elements into the dermis of the skin. It may be congenital or acquired. The acquired form is usually at a site of prior trauma (including surgical trauma), which causes occlusion of the orifice of the hair follicle. Epidermoid cysts are frequently seen to involve the upper eyelid, conjunctiva, and skin.[2] They are usually freely mobile over the tarsus, rarely adherent to the tarsus. In our case, both cysts were adherent to the tarsal plate. Recurrent prior surgeries on the conjunctival side may have resulted in this adhesion. Lucarelli et al. [3] reported cases of intrastromal EIC that were initially diagnosed as chalazion and for which incision and curettage were done, like in our case. However, bilateral symmetrical occurrences of epidermal inclusion bodies are rarely reported in the literature. Differential diagnosis includes chalazion, sebaceous cyst, lipoma, and dermoid cysts [Table 1]. Chalazion is a lipogranulomatous inflammation that lacks the epithelial cyst lining. A sebaceous cyst is a most common benign cyst that appears as an elevated, smooth, pale yellow, and painless swelling beneath the skin near or around hair follicles. Sebaceous cysts are caused by blockage of the pilosebaceous duct on the skin. Sebaceous cysts do not gradually change with time. Whereas epidermoid or dermoid cysts arose from the infundibulum of hair follicles. Histology shows that the epidermal cyst features a lining of benign keratinizing stratified epithelium with a granular layer and contains keratinaceous debris in the core in the absence of adnexal structures. Epidermoid and dermoid cysts are embryologically derived cysts that arise from the infundibulum of the hair follicle or sweat gland in conjunction with benign stratified squamous epithelial cyst lining. Eccrine hidrocystomas are caused by obstruction of eccrine sweat glands and are histologically identified by a dual layer of bland and cuboidal epithelial cells. Apocrine hidrocystomas are caused by obstruction of apocrine sweat glands and are histologically identified by the presence of an inner layer of elongated epithelial cells with apical snouts and decapitation secretions. Pilomatrixoma, which presents as a superficial nodule overlying the epidermis, is also an important differential diagnosis. Epidermoid cyst formation can be due to occlusion of the pilosebaceous follicles or surface epidermis. It can be due to the implantation of epidermal elements secondary to trauma or surgery.[4,5] Recently, associations with the human papillomavirus and chronic ultraviolet exposure have been published.[6] Complications associated with epidermoid cysts include recurrence (recurrence rate 1% to 8%) secondary infection, malignant transformation into basal cell carcinoma or squamous cell carcinoma (1%)[7,8], and spontaneous rupture or traumatic rupture leading to leakage of their keratin contents into the surrounding tissues may lead to a localized, granulomatous inflammatory reaction[9], and rarely abscesses. Small as well as asymptomatic epidermoid cysts can be managed with intralesional triamcinolone injection (Lubis R. R.). Incision and drainage may be performed if the cyst wall is inflamed. Injection of triamcinolone into the tissue surrounding the inflamed cyst results in faster resolution. However, it does not eradicate the cyst. Alarge, symptomatic cyst should be excised in toto, as in our case. This removal can be done under local anesthesia in small forms [Table 2].[10] Clinical importance An excision biopsy must be done in any cyst that is recurrent and unusual in presentation. Histopathology should be done on all excised cysts to rule out malignancy. Cyst excision in toto is of paramount importance to minimize recurrence. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. References 1. Zito PM, Scharf R. Epidermoid cyst. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2023. Available from: https://www.ncbi.nlm.nih. gov/books/NBK499974/. [Last updated on 2023 Aug 08]. 2. Behera M, Panja M. Epidermal cyst of upper eyelid: A case report with literature review. J Clin Exp Ophthalmol 2016;7:2. 3. Lucarelli MJ, Ahn HB, Kulkarni AD, Kahana A. Intratarsal epidermal inclusion cyst. Ophthalmic Plast Reconstr Surg 2008;24:357-9. 4. Shields JA, Bakewell B, Augsburger JJ, Donoso LA, Bernardino V. Space-occupying orbital masses in children. Areview of 250 consecutive biopsies. Ophthalmology 1986;93:379-84. 5. Kronish JW, Sneed SR, Tse DT. Epidermal cysts of the eyelid. Arch Ophthalmol 1988;106:270. 6. Egawa K, Egawa N, Honda Y. Human papillomavirus-associated plantar epidermoid cyst related to epidermoid metaplasia of the eccrine duct epithelium: A combined histological, immunohistochemical, DNA-DNA in situ hybridization and three-dimensional reconstruction analysis. Br J Dermatol 2005;152:961-7. 7. Jakobiec FA, StagnerAM, Freitag SK, Yoon MK. Unusual eyelid dermal keratinous cysts of pilosebaceous origin. Ophthalmic Plast Reconstr Surg 2016;32:93-7. 8. Ikeda I, Ono T. Basal cell carcinoma originating from an epidermoid cyst. J Dermatol 1990;17:643-6. 9. Kronish JW, Dortzbach RK. Upper eyelid crease surgical approach to dermoid and epidermoid cysts in children. Arch Ophthalmol 1988;106:1625-7. 10. Adella AC, editor. Stem Cell Oncology: Proceedings of the International Stem cell and Oncology Conference (ISCOC, 2017), December 1‑2, 2017. Medan, Indonesia: CRC Press; 2018. p. 27. 11. Vagefi MR, Lin CC, McCann JD, Anderson RL. Local anesthesia in oculoplastic surgery: Precautions and pitfalls. Arch Facial Plast Surg 2008;10:246-9. 12. Majumdar M, Khandelwal R, Wilkinson A. Giant epidermal cyst of the tarsal plate. Indian J Ophthalmol 2012;60:211-3. 13. Bubanale SC, Harakuni U, Patil H, Arora V. A rare site of epidermoid cyst of the eyelid. J Sci Soc 2013;40:47-8. 14. Mandal SK, Mandal A, Bandyopadhya A. Post surgical giant epidermal inclusion cyst of the lid and orbit- a rare case. JClin Diagn Res 2015;9:D01-3. 15. Kim JA, Kim N, Choung HK, Lee MJ, Lee C, Khwarg SI. Clinical features of intratarsal keratinous cysts. Eye (Lond) 2016;30:59‑63. 16. Panditrao K, Bhalke VB, Naik RR. A Case of Eyelid Epidermoid Cyst. Sch J Med Case Rep 2016;4:228-30. 17. Ban A, Pendkar A, Vasava K, Rathod K, Makada M, Bahri N. Epidermoid cyst at lateral canthus of eye. 2018. [doi: 10.1594/ EURORAD/CASE.15477]. 18. Mathur R, Saxena S. Epidermoid cyst of the eyelid-a case report and review of literature. IOSR JDMS 2018;17:1-3. 19. Shah K, Thacker M, Mehta K, Vora C, Gogadani V. Acase of epidermoid cyst of eyelid. GAIMS J Med Sci 2023;3:84-6. Delhi Journal of Ophthalmology ¦ Volume 33 ¦ Issue 4 ¦ October-December 2023 321