Sep-Oct 2023

www.dosonline.org/dos-times DOS Times Volume 29, Number 5, September-October 2023 DOS TIMES 49 microscopic and macroscopic level. No single therapy has been found that conclusively targets the pathogenesis of the disease. Topical insulin and its effects on ocular surface have been studied extensively, probably more than any other available treatment modality. Its role in the migration and proliferation of the epithelial cells including the conjunctival, limbal, corneal, lacrimal gland and in maintaining ocular homeostasis has been proven time and again. This modality of treatment is ought to be game changer in ophthalmology especially in our country where other expensive, invasive, difficult to procure treatment options prove to be a barrier in the optimal care of the patients with OSDs. References 1. Morthen MK, Magno MS, Utheim TP, Snieder H, Hammond CJ, Vehof J. The physical and mental burden of dry eye disease: a large population-based study investigating the relationship with healthrelated quality of life and its determinants. The Ocular Surface. 2021 Jul 1;21:107-17. 2. Rosenthal P, Cotter JM, Baum J. Treatment of persistent corneal epithelial defect with extended wear of a fluid-ventilated gaspermeable scleral contact lens. American journal of ophthalmology. 2000 Jul 1;130(1):33-41. 3. Vaidyanathan U, Hopping GC, Liu HY, Somani AN, Ronquillo YC, Hoopes PC, Moshirfar M. Persistent corneal epithelial defects: a review article. Medical Hypothesis, Discovery and Innovation in Ophthalmology. 2019;8(3):163. 4. Rocha EM, Cunha DA, Carneiro EM, Boschero AC, Saad MJ, Velloso LA. Identification of insulin in the tear film and insulin receptor and IGF-I receptor on the human ocular surface. Investigative ophthalmology & visual science. 2002 Apr 1;43(4):963-7. 5. Van Ort SR, Gerber RM. Topical application of insulin in the treatment of decubitus ulcers: a pilot study. Nursing Research. 1976 Jan 1;25(1):9-12. 6. Aynsley TR. The use of insulin in the treatment of corneal ulcers. The British Journal of Ophthalmology. 1945 Jul;29(7):361. 7. 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. 8. Alves M, Calegari VC, Cunha DA, Saad MJA, Velloso LA, Rocha EM. Increased expression of advanced glycation end-products and their receptor, and activation of nuclear factor kappa-B in lacrimal glands of diabetic rats. Diabetologia. 2005;48:2675–81. 9. Cruz-Cazarim ELC, Cazarim MS, Ogunjimi AT, Petrilli R, Rocha EM, Lopez RFV. Prospective insulin-based ophthalmic delivery systems for the treatment of dry eye syndrome and corneal injuries. Eur J Pharm Biopharm. 2019;140:1–10. doi:10.1016/j.ejpb. 2019.04.014. 10. Ding J, Liu Y, Sullivan DA. Effects of insulin and high glucose on human meibomian gland epithelial cells. Invest Ophthalmol Vis Sci. 2015;56:7814-20. 11. Dias AC, Batista TM, Roma LP, Módulo CM, Malki LT, Dias LC, et al. Insulin replacement restores the vesicular secretory apparatus in the diabetic rat lacrimal gland. Arq Bras Oftalmol. 2015;78:158–63. 12. Nishida T, Chikama T, Morishige N, et al. Persistent epithelial defects due to neurotrophic keratopathy treated with a substance p-derived peptide and insulin-like growth factor 1. Jpn J Ophthalmol 2007;51:442-7 55. 13. Chen DK, Frizzi KE, Guernsey LS, Ladt K, Mizisin AP, Calcutt NA. Repeated monitoring of corneal nerves by confocal microscopy as an index of peripheral neuropathy in type-1 diabetic rodents and the effects of topical insulin. J Peripher Nerv Syst. 2013;18:306- 15. 14. Wang AL, Weinlander E, Metcalf BM, Barney NP, Gamm DM, Nehls SM, Struck MC. The use of topical insulin to treat refractory neurotrophic corneal ulcers. Cornea. 2017 Nov;36(11):1426. 15. Soares RJ, Arêde C, Neves FS, da Silva Fernandes J, Ferreira CC, Sequeira J. Topical insulin—utility and results in refractory neurotrophic keratopathy in stages 2 and 3. Cornea. 2022 Aug 1;41(8):990-4. 16. Priyadarsini S, Whelchel A, Nicholas S, Sharif R, Riaz K, Karamichos D. Diabetic keratopathy: Insights and challenges. Survey of ophthalmology. 2020 Sep 1;65(5):513-29. 17. Alves MD, Carvalheira JB, Módulo CM, Rocha EM. Tear film and ocular surface changes in diabetes mellitus. Arquivos brasileiros de oftalmologia. 2008;71:96-103. 18. Kern TS. Contributions of inflammatory processes to the development of the early stages of diabetic retinopathy. Exp Diabetes Res. 2007;95:103. 19. Habib T, Hejna JA, Moses RE, Decker SJ. Growth factors and insulin stimulate tyrosine phosphorylation of the 51C/SHIP2 protein. J Biol Chem. 1998;273(29):18605-9. 20. Bastion ML, Ling KP. Topical insulin for healing of diabetic epithelial defects?: A retrospective review of corneal debridement during vitreoretinal surgery in Malaysian patients. Med J Malaysia. 2013 Jun 1;68(3):209. 21. Azmi NA, Bastion ML. Short-term results of trial of topical insulin for treatment of dry eyes in diabetics. Eye & contact lens. 2020 Jan 1;46:S25-32. 22. Ljubimov AV, Saghizadeh M. Progress in corneal wound healing. Progress in retinal and eye research. 2015 Nov 1;49:17-45. 23. Nakamura M, Nagano T, Chikama T, et al. Up-regulation of phosphorylation of focal adhesion kinase and paxillin by combination of substance P and IGF-1 in SV-40 transformed human corneal epithelial cells. Biochem Biophys Res Commun 1998;242: 16–20. 24. Diaz-Valle D, Burgos-Blasco B, Gegundez-Fernandez JA, GarciaCaride S, Puebla-Garcia V, Peña-Urbina P, Benitez-del-Castillo JM. Topical insulin for refractory persistent corneal epithelial defects. European Journal of Ophthalmology. 2021 Sep;31(5):2280-6. 25. Diaz‐Valle D, Burgos‐Blasco B, Rego‐Lorca D, Puebla‐Garcia V, Perez‐Garcia P, Benitez‐del‐Castillo JM, Herrero‐Vanrell R, Vicario‐ de‐la‐Torre M, Gegundez‐Fernandez JA. Comparison of the efficacy of topical insulin with autologous serum eye drops in persistent epithelial defects of the cornea. Acta Ophthalmologica. 2022 Jun;100(4):e912-9. 26. Sun Q, Li J, Gao F. New insights into insulin: The anti-inflammatory effect and its clinical relevance. World journal of diabetes. 2014 Apr 4;5(2):89. 27. Aljada A, Saadeh R, Assian E, Ghanim H, Dandona P. Insulin inhibits the expression of intercellular adhesion molecule-1 by human aortic endothelial cells through stimulation of nitric oxide. J Clin Endocrinol Metab 2000; 85: 2572-75. 28. Balal S, Din N, Ashton C, Ahmad S. Healing of Chemical Injury– Related Persistent Corneal Epithelial Defects With Topical Insulin. Cornea. 2022 May 13:10-97. 29. Bartlett JD, Slusser TG, Turner-Henson AN, Singh KP, Atchison JA, Pillion DJ. Toxicity of insulin administered chronically to human

DOS Times Volume 29, Number 5, September-October 2023 www.dosonline.org/dos-times DOS TIMES 50 eye in vivo. Journal of Ocular Pharmacology and Therapeutics. 1994;10(1):101-7. 30. Bartlett JD, Turner-Henson AN, Atchison JA, Woolley TW, Pillion DJ. Insulin administration to the eyes of normoglycemic human volunteers. Journal of Ocular Pharmacology and Therapeutics. 1994;10(4):683-90. Dr. Avani Hariani, MS, DNB, FICO Guru Nanak Eye Center, Delhi. Corresponding Author:

www.dosonline.org/dos-times DOS Times Volume 29, Number 5, September-October 2023 DOS TIMES 51 Follicular Conjunctivitis - An Overview Anchal Thakur, MBBS, MS, FICO, Chintan Malhotra, MBBS, MS Advanced Eye Centre, Post Graduate Institute of Medical Education and Research, Chandigarh. Abstract: Objective: This article aims to provide a structured overview of the clinical presentation, aetiology, diagnosis, management, and recent advancements in the understanding of follicular conjunctivitis. Methods: A systematic literature search conducted in major medical databases, including PubMed and Google Scholar, using relevant keywords revealed 634 articles related to follicular conjunctivitis. Results: Follicular conjunctivitis is a distinctive form of conjunctival inflammation characterized by the presence of lymphoid follicles on the conjunctival surface. It can be caused by various infectious and non-infectious agents, including viruses, bacteria and ocular allergens. Clinical presentation includes redness, itching, discharge, and photophobia. Diagnosis involves a thorough clinical examination and microbiological tests when necessary. Treatment options range from symptomatic relief to addressing the underlying cause with topical and/or systemic medications depending on the severity and chronicity. Differences between follicular conjunctivitis and childhood folliculosis are highlighted and features of COVID-19 related conjunctivitis discussed. Conclusion: Follicular conjunctivitis is a multifaceted condition with diverse aetiologies and clinical manifestations. A precise diagnosis and tailored management plan are essential for optimal patient outcomes. Further research is warranted to explore emerging treatments and deepen our understanding of this common yet intriguing ocular disorder. Introduction Follicular conjunctivitis is one of the most common forms of conjunctivitis seen in clinical practice, since it encompasses all forms of viral conjunctivitis including the common eye flu.[1] Basically, it is an inflammation of the conjunctiva with collection of immune cells/round lymphoid cells underlying it. (Figure-1) Another term described in the year 1923 was “school folliculosis,” “simple folliculosis,” or “folliculosis of the conjunctiva.” It can also be called as uncomplicated folliculosis implying no underlying inflammation of the conjunctiva.[2] Since this disease entity usually has an uncomplicated course, limited studies have been published in this regards. This article describes the aetiologies and description of the common causes of follicular conjunctivitis including viral conjunctivitis e.g. adenovirus and coronavirus, toxic conjunctivitis, childhood folliculosis and trachoma. Certain typical clinical signs may lead to a definitive diagnosis and appropriate management in a large majority of the cases. What is a follicle? Can it be physiological? What is the difference between a follicle and a papilla? Literally the word follicle means a small cavity, sac or gland; and conjunctivitis is the inflammation of the conjunctiva. Thus, it is conjunctivitis associated with hypertrophic lymphoid tissue clinically seen as pinkish round bodies in the conjunctival fornices.[3] These “follicles” appear as grey-white, round to oval elevations measuring between 0.5 to 1.5mm in diameter and are not physiological. On the other hand the word papillae means rounded protuberance on a part. In the conjunctiva, they are localized swellings in the tarsal conjunctiva due to dilated conjunctival capillaries surrounded by oedema and inflammatory infiltrates. (Figure-1) Is a follicle always fornicial or can it be limbal as well? Although the most common site is the inferior fornix, limbal follicles are not uncommon and can be seen in acute trachoma.[4] Acute active inflammation at the limbus presents as limbal follicles which at the later stages form Herbert pits/ scars commonly seen in many elderly patients. Interestingly, an isolated rare case has been published of a patient with bilateral multiple limbal and palpebral conjunctival follicles in a glaucoma patient being treated with brimonodine and dorzolamide.[5] Figure 1: Diagrammatic representation showing the basic architecture of a follicle. and a papilla.

DOS Times Volume 29, Number 5, September-October 2023 www.dosonline.org/dos-times DOS TIMES 52 Figure 2: The major causes of Infectious or non-infectious follicular conjunctivitis. Table 1: Causes of acute and chronic follicular conjunctivitis. Acute conjunctivitis (onset < 3 weeks) Chronic conjunctivitis (onset > 3 weeks) Adenoviral conjunctivitis Trachoma Herpetic conjunctivitis Inclusion conjunctivitis Parinaud oculo-glandular syndrome Molluscum contagiosum Toxic follicular conjunctivitis Histopathology A follicle comprises nodules of lymphocytes comprising reactive germinal centers and composed of immature large B-cells, surrounded by a mantle of smaller mature B-cells.[6] These nodules are present in the substantia propria and cause a smooth bulge of the overlying epithelium. The three layers of a follicle are: 1. Corona: The outer layer, composed of darker blue, mature lymphocytes and plasma cells. 2. Stroma: The middle layer, composed of lymphocytes and plasma cells. 3. Germinal Center: The inner layer, which is typically pale, and full of immature lymphocytes. Pathophysiology : Why do follicles form? The hypothesis is that the follicle-stimulating substance is soluble in nature such that it is able to pass through the epithelium into the subepithelial tissues causing a follicular reaction e.g. in viral conjunctivitis, trachoma, inclusion conjunctivitis, and molluscum contagiosum. It has been observed that if the stimulus is of low intensity, follicular hypertrophy is the chief conjunctival reaction, but if the stimulus is intense, papillary hypertrophy accompanies the follicle formation, and if it is very intense, conjunctival pseudo-membranes or even true membranes may result, e.g., in epidemic keratoconjunctivitis. In all types of follicular conjunctivitis and in folliculosis and trachoma, the histological nature of the follicles is identical, but the prominent degenerative changes in the follicle of trachoma differentiate it from all non-trachomatous follicles. The typically soft, easily expressible, so-called “sago-grain follicles” of trachoma contain numerous macrophages (Leber cells) and fragmented cells with bare nuclei.[7] Etiology and Clinical Features 1. Viral Conjunctivitis: Almost all viral conjunctivitis present with a watery discharge, lid edema and characteristically follicles in the inferior fornix. A. Adenoviral Conjunctivitis: The leading cause of acute viral conjunctivitis is human adenovirus (15–70% of all conjunctivitis cases worldwide)[1]. It a biphasic disease that begins with an infective phase that is then followed by an inflammatory phase, which tends to begin 7–10 days after the initial infection as the virus continues to shed. The patient remains infectious for up to 2–3 weeks. More than 50 different adenovirus serotypes have been identified and divided into six distinct subgroups. The most common types of adenoviral conjunctivitis include EKC (epidemic keratoconjunctivitis; the most common), PCF (pharyngoconjunctival fever) and nonspecific follicular conjunctivitis (simple adenoviral conjunctivitis). EKC typically starts with a unilateral foreign body sensation and then develops, within a few hours or days, into bilateral keratoconjunctivitis with marked lid oedema, chemosis, epiphora, and photophobia.[8,9] Figure-3 shows a patient with left eye conjunctivitis, with lid oedema, congestion and classical inferior follicles. Visual impairment can persist or recur because of subepithelial corneal infiltrates causing irregular astigmatism or development of pseudomembranes.[10] In general, EKC typically occurs in the 20-40 year age group, whereas PCF typically occurs in children.

www.dosonline.org/dos-times DOS Times Volume 29, Number 5, September-October 2023 DOS TIMES 53 Figure 3: A patient presenting with acute adenoviral conjunctivitis showing typical lid edema with follicles. Figure 4: A patient with acute haemorrhagic conjunctivitis, note the deep red subconjunctival haemorrhages in both the eyes. B. Acute Haemorrhagic Conjunctivitis: Although most of the outbreaks of red eye have been reported to be caused by adenovirus, acute haemorrhagic conjunctivitis (AHC) has been known to cause isolated epidemic outbreaks. This type is mainly attributed to enterovirus family especially Enterovirus 70 and Coxsackie A24 variant.[13] These are non-enveloped single stranded RNA viruses belonging to the genus Enterovirus from the family Picornaviridae. Symptoms of AHC include ocular pain, redness, swelling of the eyelids, irritation and eye discharge. The diagnostic sign is the presence of small petechial haemorrhages mostly noticed in the inferior fornix along with an intense follicular reaction (Figure-4). Trachomatous Inflammation (TF) The presence of 5 or more follicles (>0.5 mm) in the upper tarsal conjunctiva Trachomatous Inflammation (TI) Inflammatory thickening of the tarsal conjunctiva that obscures more than half of the deep normal vessels Trachomatous Scarring (TS) The presence of scarring in the tarsal conjunctiva Trachomatous Trichiasis (TT) At least one lash rubs on the eyeball or evidence of recent removal of inturned lashes Corneal Opacity (CO) Easily visible corneal opacity over the pupil Table 2: WHO classification of Trachoma for grading the disease. C. COVID Conjunctivitis: Coronavirus can cause conjunctivitis like all other viruses. The incidence of COVID-19 associated conjunctivitis is 1.1% which can range from as low as 0.8% to 31.6%.[14] Symptoms may appear as early as 2 days or may be delayed till 14 days after the systemic infection. Rarely it can be the only manifestation. A case series by Scalinci reported it to be the sole presentation of COVID-19.[15] D. Other Causes: Herpetic conjunctivitis is fairly common among these causes. Often the primary herpetic infection goes unnoticed as the patient is generally asymptomatic. Other causative viral causes include molluscum contagiosum (most common cause of unilateral follicular conjunctivitis), measles, mumps, Moraxella and Newcastle’s Disease.[16] 2. Bacterial A. Chlamydia Trachomatis: Trachoma, caused by Chlamydia trachomatis was a leading infectious cause of blindness in previous decades. It is transmitted via personal contact with infected ocular and nasal secretions by hands, fomites and eye- seeking flies. Active trachoma is more common among children aged 1 to 9 years. The diagnosis of active trachoma is a clinical diagnosis based on the World Health Organization (WHO) grading system. (Table-2). Trachomatous inflammation - follicular (TF) and Trachomatous inflammation- Intense (TI) are indications of active trachoma. In our clinical practice it is actually hard to find a case of active trachoma due to better hygiene practices nowadays. Also, it is no longer a public health problem in India according to a survey conducted in the 10 districts though late complications like trichiasis, lid thickening and faint nebulomacular corneal opacities are still frequently seen in a lot of village based population in our country and contributes significantly as a cause of corneal blindness.[11,12] 3. Toxic conjunctivitis/Ocular surface medicamentosa This is due to chronic exposure to topical medications, eye makeup and various environmental pollutants. The pathophysiology is the ability of certain drugs to act as nonantigenic mitogens that induce mitotic and lymphoblastic transformations of lymphocytes by nonimmunologic means.[17,18] Mostly, true lymphoid follicles with germinal centers containing lymphoblasts are present. The patients typically presents with mild-severe congestion with ocular discomfort with prominent follicles in the lower fornix and inferior palpebral conjunctiva.

DOS Times Volume 29, Number 5, September-October 2023 www.dosonline.org/dos-times DOS TIMES 54 Antiviral Idoxuridine Vidarabine Trifluorothymidine Antiglaucoma Pilocarpine Echothiophate Epinephrine Dipivefrin Epinephrine Carbachol Apraclonidine Brimonidine tartrate Cycloplegics Atropine Homatropine Table 3: Topical ocular medications causing toxic conjunctivitis. absorbed, the surface of the conjunctiva returns to normal without any adverse visual effects as contrasted with the cicatrization and impairment of vision occurring with trachoma. Management Treatment of follicular conjunctivitis is largely determined by the cause. The management of viral conjunctivitis includes symptomatic treatment mainly in the form of cold compresses, lubricants and oral anti-inflammatory agents. Topical steroids are reserved for severe adenoviral conjunctivitis if there are corneal sub-epithelial infiltrates or formation of pseudomembranes. WHO recommendation for acute trachoma is oral azithromycin as well as tetracycline ointment. For molluscum related conjunctivitis excision of molluscum lesion, is the treatment of choice. Discontinuation of the offending agent reverses the follicles in case of toxic conjunctivitis. The acute type responds faster as compared to the chronic type which may take weeks to resolve. References 1. Azari AA, Barney NP. Conjunctivitis: a systematic review of diagnosis and treatment. JAMA. 2013:23;310:1721-9. 2. Milton V. Veldee. (1923). An Epidemiological Study of Folliculosis of the Conjunctiva. Public Health Reports. 1923;38:2877–2887. 3. Basic and Clinical Science Course, Section 8: External Disease and Cornea. San Francisco: American Academy of Ophthalmology, 2015. 4. Dawson CR, Juster R, Marx R, Daghfous MT, Ben Djerad A. Limbal disease in trachoma and other ocular chlamydial infections: risk factors for corneal vascularisation. Eye (Lond). 1989;3:204-9. 5. Al-Hashimi M, Fu L, Gomaa A. Bilateral Limbal Follicles in Antisynthetase Syndrome. Ophthalmology. 2019;126:354. 6. Mudhar HS. Update on conjunctival pathology. Indian J Ophthalmol. 2017;65:797-807. 7. Thygeson P. Etiology and differential diagnosis of non-trachomatous follicular conjunctivitis. Bull World Health Organ. 1957;16:995-1011. 8. Jhanji V, Chan TC, Li EY, Agarwal K, Vajpayee RB. Adenoviral keratoconjunctivitis. Surv Ophthalmol 2015; 60:435-43. 9. O’Brien TP, Jeng BH, McDonald M, Raizman MB. Acute conjunctivitis: truth and misconceptions. Curr Med Res Opin. 2009; 25:1953-61. 10. Chintakuntlawar AV, Chodosh J. Cellular and tissue architecture of conjunctival membranes in epidemic keratoconjunctivitis. Ocul Immunol Inflamm 2010;18:341-5. 11. Gupta N, Vashist P, Senjam SS, Gupta V, Wadhwani M, Manna S, Grover S, Bhardwaj A. Current status of trachoma in India: Results from the National Trachoma Prevalence Survey. Indian J Ophthalmol. 2022;70:3260-3265. 12. U. Trachoma and Inclusion Conjunctivitis. Common Eye Infections. InTech; 2013. (Book Chapter) 13. Maitreyi RS, Dar L, Muthukumar A, Vajpayee M, Xess I, Vajpayee RB, Seth P, Broor S. Acute hemorrhagic conjunctivitis due to enterovirus 70 in India. Emerg Infect Dis. 1999 Mar-Apr;5:267-9. 14. Peng Y, Zhouu YH. Is novel Coronavirus disease (COVID-19) transmitted through conjunctiva? J Med Virol 2020. 4. Childhood Folliculosis Unlike follicular conjunctivitis, the term childhood folliculosis referes to a non-infectious benign condition affecting younger children. The affected population can be completely asymptomatic or can present with mild foreign body sensation. Veldee in 1923 conducted the largest epidemiological survey of Folliculosis of the Conjunctiva.[2,7] This study conducted in 7146 school children and 200 adults showed that the highest rate of occurrence was in the younger age group between 5-6 years; only 2% of children between 16-18 years had folliculosis. The pathophysiology behind this disease entity is linked to hypertrophy of the lymphoid tissue since children with folliculosis had an association with the tonsil hypertrophy. The salient features of this disease differentiating it from trachoma follicles are: a. Childhood folliculosis will not show signs of palpebral thickening, though there may be a fullness of the eyelids. b. The lymphoid follicles retain their smooth glistening appearance and are transparent. There is no tendency to bleed. The retention of normal elasticity, the absence of hypertrophy in the body of the conjunctiva, the absence of the so-called trachoma granules, and the fact that the blood vessels remain clearly visible constitute the essential points in differentiating the two conditions. c. The colour of the follicles is white to pink, similar to the normal conjunctiva. d. No secretions in the cul de sac and no matting of the lashes is seen in cases of folliculosis, unlike in trachoma where there is mucoid or mucopurulent discharge. e. Unlike trachoma, folliculosis is not associated with any conjunctival cicatrisation. As the follicles are gradually Table-3 lists some of the topical ocular medications associated causing follicular conjunctivitis.

www.dosonline.org/dos-times DOS Times Volume 29, Number 5, September-October 2023 DOS TIMES 55 15. Scalinci SZ, Battagliola ET. Conjunctivitis can be the only presenting sign and symptom of COVID-19. IDCases.2020;20;e00774. 16. Trott, D. G., & Pilsworth, R. (1965). Outbreaks Of Conjunctivitis Due To The Newcastle Disease Virus Among Workers In Chicken-Broiler Factories. The British Medical Journal, 2(5477), 1514–1517 17. Wilson FM II. Toxic and allergic reactions to topical ophthalmic medications. 18. RC. Grayson’s diseases of the cornea. 3rd ed. Mosby: St Louis; 1991. Prof. Chintan Malhotra, MBBS, MS Professor, Advanced Eye Centre, Post Graduate Institute of Medical Education and Research, Chandigarh. Corresponding Author:

DOS Times Volume 29, Number 5, September-October 2023 www.dosonline.org/dos-times DOS TIMES 56 Predictive Analysis of Ultrasound Biomicroscopy Guidance in Cases of Anterior Staphyloma Undergoing ScleroCorneal Transplantation - A Pilot Study Shreya Thatte[1], MS, Chhavi Gupta Narula[2], MS 1. Prof. at SAMC and PGI Indore. 2. Fellow Oculoplasty and Ocular Oncology, Shroff’s Charity Eye Hospital, New Delhi. Abstract: Purpose: To evaluate the utility of Ultrasound Bio-microscopy (UBM) in predicting status of anterior segment structures in cases of anterior staphyloma undergoing sclero-corneal transplantation surgery. Method: Twelve eyes of 12 patients with anterior staphyloma that underwent sclero-keratoplasty were evaluated preoperatively by performing UBM in all meridians 360 degrees. UBM findings related to corneal thickness with anterior chamber depth (ACD in mm), extent of synechiae, iris details, lens and zonular status were taken into consideration by the operating surgeon. Pre-operative predictions were made, and they were rectified intraoperatively. Results: Full thickness sclero-corneal transplantation surgery was planned as per findings seen on UBM. 100% positive predictions could be made for graft size and trephination depth. Positive predictions for corneal thickness estimation and anterior chamber entry were 83.33%. Accuracy for iris reconstruction was positively predicted in 55.55% and negatively overpredicted in 33.33% and underpredicted in 11.11%. Observed need of cataract extraction in 33.33%, IOL implantation or replacement in 33.33%. Major complication was spontaneous lens extrusion and loss of iris causing aniridia in 16.66 % of cases which was underpredicted in 1 case (8.33%). Conclusion: In anterior staphyloma, UBM findings are accurate (75 to 100%) in planning surgical modalities to improve surgical techniques. Keywords: Anterior staphyloma, Sclero-keratoplasty, Ultrasound Bio-microscopy, Anterior segment. Introduction Corneal pathologies leading to anterior staphyloma can create intraoperative problems to due to unidentified status of anterior segment structures. Strategizing a reconstructive surgery of the anterior segment along with corneal transplantation in the presence of anterior staphyloma can be a challenge and knowledge about preoperative status of anterior segment structure can help to increase surgical success in such cases. Ultrasound bio-microscopy (UBM) is a modality that works on the principle of high frequency ultrasound waves.[1,2,3] It uses 35- 40 MHz probe which has a resolution of 40 microns and depth penetration of 4mm that can penetrate through opaque media easily and provide better visualization to give useful information about anterior segment structures.[4,5] Although, techniques like AS-OCT and Penta-cam that work on the principle of light waves with advantage of being noncontact with better resolution, they fail to visualize structures in opaque corneal lesions. In the present study, we evaluated the role of UBM in predicting status of anterior segment structures in cases of anterior staphylomas to plan and execute sclero-keratoplasties without intra-operative surprizes. Research Design: An observational pilot study. Methods The study was conducted in accordance with the health Helsinki law after its approval from Institutional ethics committee [IEC no. SAIMS/IEC/2019/38]. Patients with anterior staphyloma undergoing full thickness sclero corneal transplantation, who consented for the study were included. Patients who had demonstrable posterior segment pathology and advanced glaucoma were excluded. All patients had undergone a complete ocular examination with visual acuity in both eyes and slit lamp bio-microscopy for assessment of cornea and anterior segment structure. An ultrasound bio-microscopy (UBM) was performed using a commercially available system (Optos OTI scan 3000) with a 50-MHz transducer for detailed analysis of the anterior segment.[3] All scans were performed with standard settings [35 MHz (34’’ probe settings), biometry option for corneal thickness and ACD, callipers for other measurements like iridocorneal touch in all 360-degree meridians (in transverse, axial and longitudinal mode)] were scanned by placing the

www.dosonline.org/dos-times DOS Times Volume 29, Number 5, September-October 2023 DOS TIMES 57 probe in appropriate position. All parameters with comorbidities describing their severity, extent, depth, and location were noted down. Photographs and videos were taken to document the UBM findings. Corneal thickness (at locations: CT0- at the centre, CTp- 2mm away from scleral spur, CT2.5- 2.5mm away from the centre of cornea) based on reflectivity of the layers, anterior chamber depth maximum (ACD in mm), anterior and posterior synechiae along with quadrants involved and extent of iris adherence (Irido corneal touch, adherent leucoma, iris incarceration) were analysed. Status of lens and zonular status were meticulously recorded. Quadrants were divided into 4 depending on area of involvement (Quadrant I- 12 to 3’o clock, quadrant II – 3-6’o clock, quadrant III – 6 to 9’o clock, quadrant IV- 9 to 12’ o clock). All these findings were taken into consideration by the operating surgeon preoperatively before performing sclero-corneal transplantation, UBM findings were broadly categorised into 3 groups: 1. Status of cornea 2) Status of AC 3) Status of lens and zonules. Technique: Majority of the cases surgery was performed under local anaesthesia. Only in cases of elderly, uncooperative patients or children, general anaesthesia was used. Trephination: Size and depth of trephination was planned as per UBM data of corneal thickness and size of pathology, accordingly partial trephination of sclero-corneal rim was performed, to prevent direct damage to iris and angle structures. Managing AC: Site (quadrant) for AC entry was planned as per predicted on UBM, with maximum AC depth. AC was entered with a side port blade. Synechiae Release: Visco-elastic was instilled in AC to deepen it. Using curved corneal scissors, corneal button was excised along visible AC. Adherence of iris was separated as predicted by extent, depth and adherence of iris on UBM examination- with stiff bud in contact synechia, iris repositor in adherent leucoma and cutting with blunt scissors in iris incarceration. In contact synechia and adherent leucoma iris damage could be prevented, but in incarceration of iris, damage to the iris and even aniridia in extensive incarceration was suspected as projected on UBM. Lens Management: Lens management was completed as per UBM predictions. 1. Lens closure to opacity - care was taken not to damage the lens capsule, while removing button. 2. According to cataract grading on UBM, cataract extraction was planned and IOL was implanted. 3. In case of predicted aniridia and spontaneous lens expulsion, anterior vitrectomy was planned. Managing Iris: Peripheral buttonhole iridectomy was done (1-2 in number) depending on graft size. In case of iris distortion, repair of iris and pupil was undertaken with 10-0 prolene suture with a straight needle. Graft Management: Up to 9mm of recipient button size donor graft was kept 0.5mm larger and 1mm larger was preferred in 10mm and more graft size. Graft was sutured with 10-0 monofilament nylon interrupted sutures with buried knots towards the limbus AC was formed with an air bubble. Subconjunctival 0.40ml gentamycin (20-40mg/ml) and 0.4ml dexamethasone (4mg/ml) were given. Preoperative UBM predictions were rectified with intraoperative findings and were divided into positive predictions (intra operative findings same as preoperative UBM findings) and negative predictions which were further divided into overestimation (pre-operative UBM findings over estimating) and under-estimation (pre-operative UBM finding underestimating a comorbidity). Results Of 12 patients that underwent UBM guided corneal transplantation surgery, 8 were males and 4 were females with an age range of 18-70 years. Aetiology in this case series was mainly of infective origin in 10 (83.33%) cases out of which one (8.33%) patient had history of trauma with branch of a plant. Two (16.66%) cases were not able to explain the exact cause for the disease. The mean central corneal thickness (CT) of 625.583±33 microns. 2.5mm away from centre, the average corneal thickness was 610.75mm and 2mm away from scleral spur, the average corneal thickness was 598.167mm. Case Corneal Thickness CT 0 CT 2.5 CT p (2mm from Scleral Spur) Trephination Depth into Host Button 1 522 510 509 ½ 2 720 718 709 ¾ 3 710 708 698 ¾ 4 512 500 498 ½ 5 522 516 509 ½ 6 609 598 577 ½ 7 788 712 700 ¾ 8 525 509 478 ¼ 9 609 617 600 ¾

DOS Times Volume 29, Number 5, September-October 2023 www.dosonline.org/dos-times DOS TIMES 58 Case Corneal Thickness CT 0 CT 2.5 CT p (2mm from Scleral Spur) Trephination Depth into Host Button 10 702 698 655 ¾ 11 676 632 622 ¾ 12 612 611 623 ¾ Case A C D Quadrant Involved (Anterior Synechaie) Posterior Synechaie Prediction for Quadrant of Entry into AC Predictive Value 1 1.22 at 2’o clock III, IV sectoral 8-12’o clock Absent I at 2’o clock Positive - accurate 2 0.55 at 8’o clock I membrane at pupillary region Absent III at 8’o clock Negative as AC was shallow for entry at 8 o clock hours and entry was made from 10 o clock hours. 3 1.76 at 4’o clok IV, I sectoral 11-1’o clock Absent II at 4’o clock Positive - accurate 4 1.54 at 11’o clock II membrane at pupillary region IV at 11’o clock Positive - accurate 5 2.33 at 8’o clock I membrane at pupillary region Absent III at 7’o clock Positive - accurate 6 1.43 at 4’o clock IV, I sectoral 9-1’o clock Absent II at 4’o clock Positive - accurate 7 1.22 at 5’o clock IV sectoral 9-12’o clock Absent II at 5’o clock Positive - accurate 8 2.23 at 6’o clock IV sectoral 9-12’o clock Absent II at 6’o clock Positive - accurate 9 2.55 at 1’o clock III, IV sectoral 8-10’o clock Absent I at 1’o clock Positive - accurate 10 0.78 at 9’o clock I membrane at pupillary region Absent III at 9’o clock Positive - accurate 11 0.65 2. III sectoral 8-9’o clock Absent I at 2’o clock Positive - accurate 12 1.89 at 8’o clock I membrane at angles Absent III at 8’o clock Positive - accurate Table 1: Showing corneal thickness at 0, 2.5 and 2mm from scleral spur along with trephination depth into host button. Table 2: Showing prediction for quadrant entry into AC based on iris involvement. Out of 12 cases 50% (6) had ACD of between 1 to 2mm and 25% (3) patients had less than 1mm and more than 2mm, respectively. Involvement of quadrant IV was seen in 50% of cases.

www.dosonline.org/dos-times DOS Times Volume 29, Number 5, September-October 2023 DOS TIMES 59 Figure 1: (a),(b) Pre-operative clinical photograph of a post infective anterior staphyloma along with (c) its UBM picture showing dense iris incarceration with a deep AC and a cataractous lens.

DOS Times Volume 29, Number 5, September-October 2023 www.dosonline.org/dos-times DOS TIMES 60 Prediction for entry into AC was accurate in 83.33% while 16.66% had negative prediction as entry into AC was not able to perform through predicted position. Case Quadrant Involvement Anterior Synechiae Pre-Operative Findings on UBM Surgical Prediction Intraoperative Execution Diction Value Aniridia 1 III, IV sectoral 8-12’o clock Irido-corneal adhesions. Use of Iris repositor Adhesions broken using Iris repositor 100% positive - 2 I membrane at pupillary region Contact synechaie Easy removal of membrane Stiff swab usage Membranectomy done and Iris salvaged Checked by stiff cotton swab 100% positive - 3 IV, I sectoral 11-1’o clock Irido corneal dense adhesions Iris distortion may occur May need scissors to cut/ iris repositor for synechiolysis Adhesions broken using Iris repositor 100% positive - 4 II membrane at pupillary region Irido corneaal adhesions present. Damage may occur. Iris repositor needed to break adhesions Membranectomy and synechioysis done. Iris reconstruction done 100% positive - 5 I membrane at pupillary region Irido corneal adhesions = Need for iris reconstruction Membrane removed. Iris salvaged as they were not adhesions. Checked by stiff cotton swab. Negative prediction - 6 IV, I sectoral 9-1’o clock Iris incarceration Pupillary distortion may occur Need for iris reconstruction. Pupillary distortion Synechiolysis done Reconstruction of pupil done scissors and repositor and with 10-0 prolene suture 100% positive - 7 IV sectoral 9-12’o clock Extensive incarceration. May need reconstruction. Iris destruction with spontaneous extrusion of iris. Negative prediction Aniridia seen 8 IV sectoral 9-12’o clock Irido corneal adhesions Need for reconstruction. Adhesions broken using scissors and repositor. Iris salvaged and iris reconstruction done. 100% positive -

www.dosonline.org/dos-times DOS Times Volume 29, Number 5, September-October 2023 DOS TIMES 61 Case Quadrant Involvement Anterior Synechiae Pre-Operative Findings on UBM Surgical Prediction Intraoperative Execution Diction Value Aniridia 9 III, IV sectoral 8-10’o clock Iris incarceration. Separation using repositor and scissors. Need for reconstruction of iris. Iris Separation done using scissors and repositor. Reconstructed using 10-0 prolene sutures. 100% positive - 10 I membrane at pupillary region Contact synechaie No damage to iris Use stiff swab to check the irido corneal touch. Stiff sab used for separation and membrane peeled. Iris salvaged 100% positive - 11 III sectoral 8-9’o clock Extensive irido corneal adhesions. Aniridia possible. Iris couldn’t be salvaged 100% positive Aniridia seen 12 I membrane at angles and pupillary area Posterior synechiae seen. Angles obscured. Iris reconstruction required No adhesions seen. Membraned peeled Posterior synechiae – contact synechaie- no adhesions. Negative prediction - Table 3: Showing prediction of iris adhesions based on UBM findings and intraoperative execution of the same. Iris adhesions were found in maximum in quadrant III and IV. Contact synechia recorded in 16.66% (2) cases were 100% accurately predicted for separation of synechia with stiff swab. Adhesion of iris was seen in 25% (3) cases with 100% accurate prediction for use of iris repositor to separate synechia. 58.33% (7) cases showed dense adhesion and incarceration of iris and predicted for requirement of iris repositor and corneal scissors, out of these 7 cases, 42.85% (3) cases showed negative prediction as 14.28 % (1) case could be managed with stiff swab only as thick membrane obscured iris position. Another case 14.28% showed requirement of both the instruments iris repositor and corneal scissors but iris adhesions could be separated by iris repositor only. The 3rd case predicted for iris adhesion to be solved by both iris repositor and corneal scissors but prediction was negative as there was extensive adhesions and after entry into AC there was spontaneous expulsion of iris and lens leading to aniridia and aphakia. Prediction for iris reconstruction was projected in 75% (9) cases. and same could be executed in 55.55% (5) cases. Remaining 44.44% (4) cases had negative prediction as 33.33% (3) cases had no iris damage (over predicted) hence no iris reconstruction was required and 11.11% (1) case had spontaneous lens and iris expulsion which could not be predicted on UBM (underpredicted). Figure 2: (a),(b) Pre-operative clinical photograph of a post corneal perforation resulting in anterior staphyloma along with (c) its UBM photo showing irido-corneal incarceration and a cataractous lens.

DOS Times Volume 29, Number 5, September-October 2023 www.dosonline.org/dos-times DOS TIMES 62 Case Lens status Cataractous/ Non Cataractous Zonules Posterior Capsule Prediction Execution 1 Phakic Non Cataractous Intact Present - Sclerokeratoplasty with synechiolysis 2 Phakic Cataractous - Early Cortical Intact Present - Sclerokeratoplasty with membranectomy with cataract extraction and PCIOL (AFTER 2 YEARS) 3 Phakic Non Cataractous Intact Present - Sclerokeratoplasty with synechiolysis 4 Phakic Non Cataractous Intact Present - Sclerokeratoplasty with synechiolysis (iris reconstruction) 5 Phakic Cataractous- Nuclear Sclerosis with cortical Cataract Intact Present Cataract extraction with PCIOL Sclerokeratoplasty with membranectomy with cataract extraction and PCIOL 6 Pseudophakic In the Bag Intact Present - Sclerokeratoplasty with synechiolysis (iris reconstruction) 7 Phakic Non Cataractous dialysis 9-11’o clock Absent at central part Lens extraction Sclerokeratoplasty with synechiolysis with spontaneous extrusion of iris and lens resulting in aniridia and aphakia 8 Phakic Non Cataractous Intact Present - Sclerokeratoplasty with synechiolysis (iris reconstruction) 9 Phakic Non Cataractous Intact Present - Sclerokeratoplasty (iris reconstruction) 10 Phakic Cataractous- Nuclear Sclerosis with Cortical Cataract Intact Present Cataract extraction with PCIOL Sclerokeratoplasty with membranectomy with cataract extraction with PCIOL 11 Phakic Cataractous- Nuclear Sclerosis with Cortical Cataract Intact Present Cataract extraction with PCIOL Sclerokeratoplasty with aniridia with cataract extraction and aniridic IOL 12 Phakic Cataractous- Nuclear Sclerosis with Cortical Cataract Intact Present Cataract extraction with PCIOL Sclerokeratoplasty with membranectomy with cataract extraction and PCIOL Table 4: Showing lens status, zonular status, and presence of posterior capsule along with surgery done. Only one patient (8.33%) was pseudophakic, all other 11 cases (91.66%) were phakic, out of which 4 cases (33.33%) showed significant lens changes in the form of nuclear sclerosis and cortical changes and all were 100% accurately predicted and planned for simultaneous cataract extraction and IOL implantation. One patient (8.33%) had just cortical changes on UBM and was planned for only sclero-keratoplasty without cataract surgery. Rest 5 cases were not showing any cataractous changes and were left as such. Another phakic patient without any cataractous change showed zonular-dialysis and not clear posterior capsule, suspecting absent posterior capsule, and had extensive irido-corneal incarceration. In this case surgeon was prepared for spontaneous lens extraction, aniridia and need for vitrectomy as per UBM findings and same could be performed without further complication.

www.dosonline.org/dos-times DOS Times Volume 29, Number 5, September-October 2023 DOS TIMES 63 No Age/ Sex Cause of Corneal Opacity CCT Extent of Synechiae Maximum AC Depth Lens/Zonule Status VA Post op Surgery 1 38/M post infective abscess (6months back) 522 III, IV 1.22 Phakic Non Cataractous PL+PR accurate in all 4 quadrants Sclerokeratoplasty (12.5mm graft) with synechiolysis With graft failure (opaque graft) after 1 year 2 40/F H/O trauma with plant branch followed by corneal ulcer (8-10 years back) 720 I 0.55 Phakic Early Cortical Changes VA 5/60 After cataract surgery with PCIOL VA 6/24 Sclerokeratoplasty (9.5mm graft size) with membranectomy followed by cataract extraction with PCIOL (after 2 years) 3 68/M Post infective corneal perforation (1 year back) 710 IV, I 1.76 Phakic Non Cataractous PL+PR accurate in all 4 quadrants Sclerokeratoplasty (12mm graft size) with synechiolysis leading to graft failure in 6 months. 4 50/M Post infective corneal thinning (3 years back) 512 II 1.54 Phakic Non Cataractous VA 6/24 on 2 years follow up Sclerokeratoplasty (10mm graft size) with synechiolysis (iris reconstruction) 5 48/M Post infective corneal opacity (1 year back) 522 I 2.33 Phakic Cataractous VA 6/36 Sclerokeratoplasty (9mm graft size) with membranectomy with cataract extraction and PCIOL 6 70/F Post corneal ulcer perforation anterior staphyloma (20 years back) 609 IV, I 1.43 Pseudophakic VA 6/18 Sclerokeratoplasty (10.5mm graft size) with synechiolysis (iris reconstruction) 7 56/F Corneal ulcer leading to abscess formation and then large adherent leucoma with staphyloma (8 months back) 788 Iv 1.22 Phakic- non cataractous, irido dialysis and zonular diaysis noted at 9-11’o clock Fc 2 feet (unaided) BCVA- +10D sph and +2.5 cyl 30 degrees 6/12 Sclerokeratoplasty (9mm graft size) with synechiolysis with spontaneous expulsion of lens and iris leading to aniridia and aphakia 8 62/M Large Anterior staphyloma since many years History Unknown 525 IV 2.23 Phakic Non Cataractous VA 6/24 Sclerokeratoplasty (9mm graft size) with synechiolysis (iris reconstruction) 9 18/F Since 8 years – central anterior staphyloma -probably infective etiology 609 III, IV 2.55 Phakic Non cataractous VA 6/12 Sclerokeratoplasty (9mm graft size) (iris reconstruction) with clear graft 10 38/M As per historyPost corneal ulcer adherent leucoma Duration of pathology approximately 5 to 6 years 702 I 0.78 Phakic Cataractous VA 6/18 Sclerokeratoplasty (9mm graft size) with membranectomy with cataract extraction with PCIOL

DOS Times Volume 29, Number 5, September-October 2023 www.dosonline.org/dos-times DOS TIMES 64 No Age/ Sex Cause of Corneal Opacity CCT Extent of Synechiae Maximum AC Depth Lens/Zonule Status VA Post op Surgery 11 48/M Corneal perforation resulting in anterior staphyloma 1 year 676 III 0.65 Phakic Cataractous VA 2/60 Sclerokeratoplasty (11.5mm graft size) with aniridia with cataract extraction and aniridic IOL 12 56/M Exact history not available, redness followed by white opacity almost 10 years 612 I 1.89 Phakic Cataractous lens VA 6/60 Sclerokeratoplasty (10 mm graft size) with membranectomy with cataract extraction and PCIOL Table 5: Combined table of all cases. Iris adhesion to cornea was noted in 8 (66.66%) cases in one quadrant, 4 (33.33%) cases showed two quadrants involvement. IV quadrant (from 9 to 12’o clock quadrant) was involved in most of the cases (50%). Maximum available AC depth was recorded, it was seen that 3 (25%) cases with less than 1mm, 6 (50%) cases had less than 2mm and 3 (25%) cases showed more than 2mm of AC depth. Central corneal thickness was variable, less than 600, 700 and 800 micron was recorded in each 4 (33.33%) cases. Discussion Corneal pathologies with distorted anterior segment where details are not visualized properly, need to be evaluated preoperatively before planning for surgery. Multiple imaging modalities are available but UBM is the only modality that works on the principle of ultrasound waves and its ability to penetrate through the opaque structures of the eye and provide depth perception and extension of lesions has improved our ability to preoperatively strategize surgeries and improve our surgical outcome. Most of the studies done previously were either single case report studies[6,7,8,9] or studies done to differentiate staphyloma from other scleral pathologies.[10] Study done by Madhavan et al[11] was similar to our study where they established the efficacy of UBM in preoperative planning for penetrating keratoplasty but it differed on the fact that it was blind folded study in which the surgeon was unaware of the findings of the UBM and they were corelated later only after surgeon had given out the findings on his/her own intraoperatively. Our pilot study is different with a case series of 12 anterior staphyloma undergoing large diameter sclero-keratoplasties. The operating surgeon studied the UBM findings, predicted anterior segment comorbidities and planned the already complicated surgery accordingly, which was helpful in achieving less surgical surprises by overshadowing the unforeseen disastrous complications. Figure-4 Various UBM pictures that helped in evaluating the anterior segment status of different kinds of anterior staphylomas. We could modify our surgical steps at every level according to the UBM findingsGraft Size UBM was extremely helpful in all the cases planned for reconstructive sclero-keratoplasty as the prediction of graft size ranging from 8-13mm could be made positively in all cases (100%). Large grafts were needed for these sclero-keratoplasty based on the extension of these pathologies involving both central and eccentric cornea. Availability of large trephines can Figure 3: (a) Pre-operative clinical photograph of a post corneal ulcer perforation anterior staphyloma along with its (b) UBM photo depicting irido corneal adhesions, variable AC and pseudophakia. (c) Post-operative photograph showing a healthy sclero-corneal graft.

www.dosonline.org/dos-times DOS Times Volume 29, Number 5, September-October 2023 DOS TIMES 65 be arranged and ensured preoperatively. Study by Umiya et al[12] mentioned the same but they were not specific as they had included all the different indications for sclero-keratoplasties. Figure 4: Various UBM pictures that helped in evaluating the anterior segment status of different kinds of anterior staphylomas. Site and Depth of Trephination Maximum available anterior chamber depth (ACD) at the area of involvement (quadrants) of corneal pathology helped us deciding the trephination site and the corneal thickness (CT) along the vicinity of the diseases cornea could be measured and according to this value, the depth of trephination was estimated. This helped us in avoiding damage to the underlying structures such as lens and iris and made easy space for further dissection and manipulation. Prediction for entry into AC was positive in 83.33% while 16.66% had negative prediction as entry into AC was not performed through predicted position (both cases were underestimated- one case had a shallow AC depth at predicted entry site and in another case iris injury occurred while doing trephination. This type of prediction for trephination and AC entry in sclero-keratoplasties has not been commented upon by any of the previously done studies. Such high value of positive prediction (>80%) makes UBM a reliable tool in establishing site, size, and depth of trephination in conducting sclero-keratoplasties. Iris Management Location and Type of Synechiae Anterior synechiae were present in all cases (100%) out of which 58.33% showed clear cut extension/involvement into different quadrants of cornea and in the remaining 41.67% cases iris was not directly incarcerated. There was a fibrinous membrane to which iris was adhered. Posterior synechiae were only seen in 8.33% of the cases. During intraoperative evaluation, 100% accurate rectification of preoperative UBM findings was done. In a similar study by Madhavan et al[14] positive predictive value of anterior synechiae was 55.6% (5/9, PAS was 73.1% (19/26) and posterior synechiae was 80% (12/15). Zhang et al in their congenital staphyloma study also demonstrated the clock hours and locations of lens-iris–corneal touch, which was like our study.[13] No other studies have mentioned about extent or course of synechiae in such details before. Prediction of iris reconstruction and aniridia as per estimated iris distortion As per reflectivity of the structures of cornea and iris, anterior and posterior synechiae could be estimated whether it was mere touch/contact synechiae, adhesions, or incarceration of iris. Prediction for iris reconstruction was projected in 75% (9) cases and same could be executed in 55.55% (5) cases. Remaining 44.44% (4) cases had negative prediction as 33.33% (3) cases had no iris damage (over predicted) hence no iris reconstruction was required and 11.11% (1) case which had dense iris incarceration underwent spontaneous lens and iris expulsion leading to aniridia and aphakia which could not be predicted on UBM (underpredicted). Aniridia Cases No aniridia was expected in 11 cases. Our positive predictability for this was 91.6%. Only 1 was predicted for aniridia due to dense irido corneal adhesions and was 100% positively predicted. Aniridia was expected in this surgically challenging case and same was explained to the patient beforehand. Preoperative mannitol was given to lower the IOP and sclero-keratoplasty with aniridia with cataract extraction and aniridic IOL implantation was done successfully with rigorous vitrectomy. Out of 11 and one was underestimated/not predicted (8.33%). This phakic patient without any cataractous change showed irido-zonulardialysis and unclear posterior capsule was noticed which were accurately predicted. No vitreous was seen in the anterior segment. This complicated case had a spontaneous iris and lens expulsion and needed to be managed by careful dissection and vitrectomy. The patient was left aphakic with aniridia. None of the studies done previously have predicted aniridia and managed them successfully. Lens and Posterior Capsule Status Prediction about lens status was also 100% positively documented. Only one patient (8.33%) was pseudophakic. All other 11 cases (91.66%) were phakic, out of which 4 cases (33.33%) showed cataractous changes and were 100% positively predicted and planned for simultaneous cataract extraction and IOL implantation. PC (posterior chamber) status predictability in the form of presence of absence and zonular status which was 100% accurate. Madhavan et al[11] gave positive prediction value of posterior capsule (PC) in the form of presence of PC/PC remnants which was 92.9% (13/14). Status of pseudophakia in the form of - presence, centration, location in anterior chamber or posterior chamber. Presence of crystalline lens was also predicted by 100% (4/4) by them along with cataractous changes in anterior part of lens by 50% (1/2). Utilisation of UBM for zonular details and evaluating haptic status has also been done similarly in studies by Rutnin et al[14] and Pavlin et al[15]

DOS Times Volume 29, Number 5, September-October 2023 www.dosonline.org/dos-times DOS TIMES 66 UBM is an ancillary tool in meticulously scanning cases of post corneal pathology anterior staphylomas and to note anterior segment architecture. Management of anterior staphylomas are complicated as the anterior segment is in total darkness due to the opaque cornea. If surgeon knows pre-operatively the complications hiding behind this opaque cornea and can estimate the extent of the lesion, AC depth, angle details, iris synechiae, lens and zonular status, these cases can be managed with appropriate pre-operative planning. This will help in predicting complications, in execution and overall surgical outcome and success of the surgeon. The cumulative positive prediction was 88.423% and negative prediction was only 11.57%. Our findings of the UBM like graft size; size, site and depth of trephination, entry into the AC, location and type of synechiae; need for iris reconstruction, lens, zonular and posterior capsule status that were predicted by the ophthalmologist were rectified intra-operatively and surgeries were executed with minimal manipulation by the surgeon by maintaining anterior chamber and not disturbing anterior segment details. Guarded visual prognosis was explained to the patient and follow up was recommended accordingly. Limitation of our study was that it was a small study with limited number of cases. References 1. Pavlin CJ, Sherar MD, Foster FS. Subsurface ultrasound microscopic imaging of the intact eye. Ophthalmology 1990;97:244–50. 2. Pavlin CJ, Harasiewicz K, Sherar MD, Foster FS. Clinical use of ultrasound biomicroscopy. Ophthalmology 1991;98:287–95. 3. Umiya Agraval, Wilma Kincaid, Sanjay Mantry, Kanna Ramaesh; Predicting Anterior Segment Surgical Anatomy: Application of Ultrasound Biomicroscopy (UBM) in Surgical Intervention. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4847. 4. Konstantopoulos A, Hossain P, Anderson DF Recent advances in ophthalmic anterior segment imaging: a new era for ophthalmic diagnosis British Journal of Ophthalmology 2007;91:551-557. 5. Bhat DC. Ultrasound biomicroscopy: An overview. J Clin Ophthalmol Res 2014;2:115-23. 6. Nischal KK, Naor J, Jay V, MacKeen LD, Rootman DS. Clinicopathological correlation of congenital corneal opacification using ultrasound biomicroscopy. Br J Ophthalmol. 2002;86(1):62–69. doi:10.1136/bjo.86.1.62. 7. Leff SR, Shields JA, Augsburger JJ, Sakowski AD Jr, Blair CJ. Congenital corneal staphyloma: clinical, radiological, and pathological correlation. Br J Ophthalmol. 1986 Jun;70(6):427-30. doi: 10.1136/ bjo.70.6.427. PMID: 3718906; PMCID: PMC1041034. 8. Salour H, Owji N, Sadeghipour A. Congenital corneal staphyloma. J Ophthalmic Vis Res. 2009;4:182–4. 9. Verschooten R, Foets B, De Ravel T, Van Ginderdeuren R, Lombaerts R, Casteels I. Clinical spectrum of congenital corneal staphyloma: a case report. Bull Soc Belge Ophtalmol. 2011;(318):7-10. PMID: 22003758. 10. Pavlin CJ, Easterbrook M, Hurwitz JJ, Harasiewicz K, Eng P, Foster FS. Ultrasound biomicroscopy in the assessment of anterior scleral disease. Am J Ophthalmol. 1993;116(5):628-635. doi:10.1016/s0002- 9394(14)73207-6. 11. Madhavan C, Basti S, Naduvilath TJ, Sangwan VS. Use of ultrasound biomicroscopic evaluation in preoperative planning of penetrating keratoplasty. Cornea. 2000 Jan;19(1):17-21. doi: 10.1097/00003226- 200001000-00004. PMID: 10632002. 12. Umiya Agraval, Wilma Kincaid, Sanjay Mantry, Kanna Ramaesh; Predicting Anterior Segment Surgical Anatomy: Application of Ultrasound Biomicroscopy (UBM) in Surgical Intervention. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4847. 13. Zhang, Y., Zhou, J. & Zhu, D. J Med Ultrasonics (2016) 43: 291. https://doi.org/10.1007/s10396-015-0675-8. 14. Rutnin SS, Pavlin CJ, Slomovic AR, Kwartz J, Rootman DS. Preoperative ultrasound biomicroscopy to assess ease of haptic removal before penetrating keratoplasty combined with lens exchange. J Cataract Refract Surg. 1997 Mar;23(2):239-43. doi: 10.1016/s0886- 3350(97)80347-1. PMID: 9113575. 15. Pavlin CJ, Buys YM, Pathmanathan T. Imaging Zonular Abnormalities Using Ultrasound Biomicroscopy. Arch Ophthalmol. 1998;116(7):854–857. doi:10.1001/archopht.116.7.854. Prof. Shreya Thatte, MS Professor, SAMC and PGI Indore. Corresponding Author:

www.dosonline.org/dos-times DOS Times Volume 29, Number 5, September-October 2023 DOS TIMES 67 Evolution of Corneal Cross-Linking Jyotsana Sharma, MBBS, Nikunj Gupta, MBBS, Tushar Grover, MBBS, MS, FICO, FAICO Vision Eye Centres, New Delhi. Abstract: Corneal cross-linking is a minimally invasive procedure aimed at halting the progression of corneal ectasia by increasing the biomechanical strength of the cornea. Conventional CXL has the limitation of being utilized in eyes with a corneal thickness of at least 400 microns after de-epithelization. With newer advancements, the cross-linking process has been optimized to improve refractive outcomes even in thin corneas. These include newer riboflavin formulations, utilization of reduced fluence protocol and customized epithelial debridement procedure in moderate to advanced cases. The use of cross-linking for pathological myopia, and infective keratitis is likely the road ahead. This review aims to highlight the evolving arms of the cross-linking process and its wide applications. Introduction In 1998, corneal collagen cross-linking was first proposed as a treatment modality to stabilize the ectatic cornea.[1] Corneal collagen Cross-linking is a well-known physiological process based on the phenomenon of forming new cross-links on the surface of the collagen fibrils and within the proteoglycan using the interaction between riboflavin and UVA radiation in which riboflavin acts as photosensitizer. Riboflavin in the presence of UVA light induces the formation of covalent bonds by biochemical reactions which involve both aerobic conditions and anaerobic conditions leading to the formation of radical ions, inducing cross link bonds at corneal stroma. The creation of inter and intra-fibrillary collagen crosslinks by this process increases the biomechanical rigidity of the cornea by up to 300%.[2] Conventional CXL, also known as the “Dresden protocol,” involves epithelial debridement followed by corneal soakage with riboflavin solution. The cornea is then exposed to UVA radiation (370 nm) at 3 mW/cm2 for 30 min to achieve a surface dose of 5.4 J/cm2 . [3] Accelerated Cross-Linking In the present scenario, the accelerated protocols of CXL, have evolved in an attempt to overcome the limitations of conventional cross-linking (i.e. long intraoperative time), while maintaining the efficacy of results. The accelerated protocol of cxl (A-CXL), is based on the Bunsen Roscoe law of reciprocity. The various settings for A-CXL are at 9 mW/cm2 for 10 min, 30 mW/cm2 for 3 min, 18 mW/cm2 for 5 min, and 45 mW/cm2 for 2 min and all deliver a constant energy dose of 5.4 J/cm[4] According to a study by Vinciguerra et al, around 25% of keratoconus patients have a pachymetry of <400 microns at initial presentation. It has also been reported that corneal thickness significantly reduces intraoperatively during CXL owing to possible corneal desiccation and dehydration during the prolonged period of UVA exposure.[5] CXL In Thin Cornea Hypo-Osmolar Riboflavin Normal swelling pressure of corneal stroma is 50–60 mm Hg Field.[6] It can swell up to double its thickness when exposed to a hypo-osmolar solution.[7] Hafezi et.al revealed that after inducing corneal de-epithelialization when isotonic riboflavin was applied to the cornea every 3 min for 30 min, and five repetitive measurements were taken at the thinnest point of the de-epithelialized cornea using ultrasound pachymetry. Following that, Hypo-osmolar riboflavin (without dextran) was instilled every 20 still the corneal thickness increased to a minimum of 400 microns and then irradiated the eye with UVA radiation at 3 mW/cm2 . So, when this method was used in 20 eyes stabilization of the keratectasia was noted at 6 months of follow-up. An absolute increase in pachymetry using hypo-osmolar riboflavin ranged from 36 to 110 microns in their study.[8] Schmidinger et al. proposed that with the use of hypo-osmolar riboflavin, the thinnest corneal thickness was <400 microns due to corneal desiccation during the irradiation phase.[9] This limitation was addressed and resolved using the accelerated protocol of CXL using 9 mW/cm2 for 10 min which could effectively halt the progression of keratoconus in thin corneas.[10] Transepithelial Crosslinking Conventional CXL can cause irreversible endothelial damage in thin corneas with epithelial debridement.[11] Corneal collagen CXL without epithelial debridement allows thinner corneas to be treated. Riboflavin which is a high molecular weight, hydrophilic molecule, has to be combined with, substances like ethylenediaminetetraacetic acid (EDTA), benzalkonium chloride (BAC), gentamicin, and trometamol to increase its permeability through the epithelium.[12][13]

DOS Times Volume 29, Number 5, September-October 2023 www.dosonline.org/dos-times DOS TIMES 68 Since epithelium is intact in transepithelial crosslinking it decreases the risk of infective keratitis, improves patient comfort, and reduces stromal haze, and intraoperative corneal thinning.[14] Filippello et al. reported that there was a significant improvement in UDVA, BDVA, Kmax, and higher-order aberrations after using riboflavin with dextran, EDTA, and trometamol in 20 eyes.[14] One of the proven disadvantages of an intact epithelium is diminished oxygen diffusion into the stroma, attenuating the effect of CXL[15] and the depth of stromal demarcation line in cases of transepithelial CXL which is approximately 200 microns indicating that the actual CXL effect might be less as compared to the standard protocol.[16] Lontophoresis-Assisted Crosslinking (I-CXL) Riboflavin is a negatively charged molecule, ideal for iontophoresis.[17] Iontophoresis is a non-invasive technique wherein a small electric current is used to facilitate penetration of an ionized substance in a tissue.[18] In this method, the passive electrode (anode) is placed on the cervical vertebrae or on the patient’s forehead. The active electrode is applied to the cornea using a suction ring. The annular suction ring of the iontophoresis device is irrigated with 0.1% riboflavin in distilled water. A small current of 1 mA is given for 5 min and UVA exposure is given.[17,19] Vinciguerra et al. reported that iontophoresis CXL effectively stabilises the progression of keratoconus in 20 eyes when followed up to 1 year.[20] Customised Epithelial Debridement Technique It is a technique that involves epithelial debridement of the cornea with keratoconus sparing the epithelium over the apex of the cone.[21] An island of epithelium is left intact and is soaked with riboflavin, it acts as a protective shield over the thinnest corneal point and the paracentral cornea, where epithelium is removed, which allows better riboflavin penetration resulting in increased biomechanical stiffening effect as compared to trans-epithelial CXL. Cagil et al., demonstrated in 19 eyes, that there was a halt in the progression of keratoconus at 12 months and a significant endothelial cell loss after this procedure.[22] Mazzotta and Ramovecchi reported that the depth of the CXL effect in the epithelium-on area was 150 microns compared to 250 microns in the epithelium-off area indicating a lower CXL effect under the intact epithelium.[23] Lenticule-Assisted Crosslinking This technique made use of the stromal lenticule removed from patients undergoing small incision lenticule extraction (SMILE) for myopic correction. A stromal lenticule of appropriate thickness was placed over the patient’s cornea (centre of lenticule placed over apex of cone) after epithelial debridement. Reduction in the availability of oxygen for CXL was a limitation. There is a need for further studies in order to establish the safety of this procedure.[24] King Contact Lens-Assisted Crosslinking (CACXL) For corneas having pachymetry of 350-400 microns after epithelial removal Jacob et al. in their study of 14 eyes described the use of bandage contact lens having a thickness of approximately 0.9 mm, soaked in 0.1% iso-osmolar riboflavin for 30 min further when intraoperative pachymetry was confirmed to be >400 microns, UVA irradiance was given. They found this technique to be effective.[25] The advantage is no dependency on the swelling properties of the cornea. However, the riboflavin-soaked contact lens reduces oxygen availability and absorbs UVA radiation to reduce the surface irradiance level by 40–50%.[26] CXL in Ultrathin Corneas (“Sub400” Protocol) A study conducted by Farhad Hafezi et al.in 39 progressive keratoconic eyes in the year 2020 dealt with the corneal thickness ranging from 214 -398 microns (sub 400). The study discusses individualised fluence cross-linking in which irradiation time was individually adapted to stromal thickness (corneal tomography). Results were encouraging in the manner that 90% of the subjects showed halting progression of KC as evidenced by corneal tomography over the period of 12 months.[27] Newer Directions For CXL In Future Photorefractive intrastromal cross-linking (PiXl) for reduction of low myopia Is a novel application of corneal collagen cross-linking (CXL) which aims to correct mild refractive error. this modality is based on zonal application of ultraviolet-A (UVA) light unlike conventional CXL, which utilizes broad-beam UVA light. PiXL is a tailor-made approach based on patient characteristics such as corneal topography and refractive error. It is performed through the delivery of specific patterns and intensities of UVA irradiation, which results in localized corneal strengthening and flattening to induce predictable refractive changes.[28] A study done by Stodulka et al and Wee Kiak Lim et al. results were significantly good for a low degree of myopia and a low degree of hyperopia but results need to be validated by further studies as both the prior studies have a limited number of patients in their case series.[29][30] Scleral cross-linking for axial myopia (SXL) Scleral thinning and weakening result in progressive myopia and axial length elongation. Scleral cross-linking (SXL) with photosensitiser and blue light potentially strengthens the sclera which may prevent progression in axial length elongation for severe myopia. Kwok et al. described the use of flexible optical waveguides for periscleral crosslinking.[31] They demonstrated efficient and uniform stiffening of a 5 mm wide equatorial band of scleral tissue.[32]

www.dosonline.org/dos-times DOS Times Volume 29, Number 5, September-October 2023 DOS TIMES 69 Photoactivated chromophore for infectious keratitis-corneal collagen cross-linking (PACK CXL) UV irradiation alone is used as an antimicrobial procedure for disinfection of water, surfaces and air. Its damaging effect on the DNA and RNA of pathogens including bacteria and viruses is well known.[33] The use of photo-activated riboflavin to inactivate pathogens has been described along with its antimicrobial effect.[34] An antimicrobial effect of photo-activated riboflavin on agar plates inoculated with Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumonia and Candida albicans. Inhibition was found to be much more in the plates treated with photo-activated riboflavin than those treated with UVA alone.[35] Infectious keratitis in 2008, by Iseli et al, was the first reported in which CXL with standard Dresden protocol was used and it reported healing in 4 out of 5 cases of mycobacterial and fungal corneal melting unresponsive to conventional therapy. [36] Said et al, in 2014, in a large prospective clinical trial on infective keratitis compared 21 eyes, that were treated with antimicrobial therapy and CXL, with 19 eyes that were treated with antimicrobial therapy alone. It was concluded that CXL can be an important adjuvant therapy in preventing the need for emergency keratoplasty.[37] In a randomised study by Tawfeek et al, a higher proportion of patients, with bacterial keratitis who received an adjuvant PACK-CXL with topical antibiotics, experienced complete resolution ulcers.[38] A recently performed trial by Torres Netto et al demonstrated that PACK-CXL alone is as efficient in small ulcers up to 4mm in size.[39] In a randomised control trial by Prajna et al in patients with fungal keratitis, no difference was found in culture positivity at 24 hours, re-epithelisation rates or scar size. Moreover, the best corrected visual acuity deteriorated at 3 weeks and 3 months in patients treated with PACK-CXL.[40] In a study by Wei et al, CXL in combination with antifungals was demonstrated to provide an accelerated duration of ulcer healing and significantly reduce the maximum ulcer depth post-treatment.[41] Rose Bengal Photodynamic Therapy (RB-PDAT) in a pilot study by Naranjo et al, was studied as an alternative, and shown to have avoided the need for therapeutic penetrating keratoplasty.[42] Combined Procedures CXL and photorefractive keratectomy(PRK)- Early studies in 2009 by Kymionis et al showed that transepithelial PRK with CXL for keratoconus offers better visual acuity and corneal stability.[43] A recent study by Kontadakis et al demonstrated uncorrected distance visual acuity at the end of 3 years to be significantly better in eyes treated with topography-guided transepithelial photorefractive keratectomy and CXL compared to CXL alone.[44] Athens protocol involves performing topography-guided transepithelial PRK followed by CXL. Kanellopoulos et al. proposed an enhanced Athens protocol wherein a customised topography-guided UVA irradiation is incorporated to maximise refractive normalisation of the cornea with lesser stromal tissue removal compared to the standard Athens protocol.[45] CXL and transepithelial phototherapeutic keratectomy(tPTK)- Cretan protocol involves performing these 2 procedures together. Kymionis et al reported a case treated with the Cretan protocol in 2010 whose uncorrected and best spectacle-corrected visual acuity improved along with keratoconus stabilisation.[46] Kymionis et al later in a clinical trial demonstrated that the Cretan protocol achieves a significant improvement in post-op visual acuity at the end of 12 months which is not the case with the Dresden protocol.[47] Grentzelos et al in a 3-year prospective study demonstrated that a reduction in mean corneal astigmatism is achieved post-operatively in patients treated with the Cretan protocol.[48] Intrastromal corneal ring segment implantation (ICRS) with CXL- Intrastromal corneal ring segment implantation is studied as a treatment modality for corneal ectasias. Kim et al reported that intrastromal corneal ring implantation followed by CXL within a month had a greater improvement in visual acuity and reduction in keratometry values compared to either of the procedures done alone.[49] In a large prospective study of 542 eyes conducted by Singal et al, it was concluded that CXL with ICRS may be more effective in eyes to treat irregular astigmatism with worse visual acuity. In contrast, CXL with PRK may be more effective in eyes with irregular astigmatism but good visual acuity.[50] Topography-guided custom ablation treatment (T-CAT) is a procedure which involves limited ablation of the cornea using an excimer laser and is designed to attain corneal symmetry without attempting to correct spherical or regular astigmatism. This procedure involves the removal of the epithelium, similar to photorefractive keratectomy (PRK) so, the terminology of topography-guided-PRK (TPRK) can be used interchangeably with T-CAT. TPRK flattens part of the cone apex, similar to an eccentric partial myopic PRK and also simultaneously flattens an arcuate, broader area of the cornea away from the cone, this ablation pattern resembles hyperopic treatment and will lead to some amount of steepening or elevation adjacent to the cone, that effectively normalizes the cornea.[51] References 1. Spoerl E, Huhle M, Seiler T. Induction of cross-links in corneal tissue. Exp Eye Res 1998;66(1):97–103. 2. Dhawan S, Rao K, Natrajan S. Complications of Corneal Collagen Cross-Linking. J Ophthalmol 2011;2011:869015. 3. Wollensak G. Crosslinking treatment of progressive keratoconus: new hope. Curr Opin Ophthalmol 2006;17(4):356–60. 4. Anitha V, Ravindran M. Commentary: Bunsen-Roscoe reciprocity – Is it still valid? Indian J Ophthalmol 2022;70(8):2936. 5. Vinciguerra P, Albè E, Mahmoud AM, Trazza S, Hafezi F, Roberts CJ. Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking. J Refract Surg Thorofare NJ 1995 2010;26(9):669–76.

DOS Times Volume 29, Number 5, September-October 2023 www.dosonline.org/dos-times DOS TIMES 70 6. DOHLMAN CH, HEDBYS BO, MISHIMA S. The Swelling Pressure of the Corneal Stroma. Invest Ophthalmol Vis Sci 1962;1(2):158–62. 7. Maurice DM, Giardini AA. Swelling of the Cornea in vivo after the Destruction of its Limiting Layers. Br J Ophthalmol 1951;35(12):791– 7. 8. Hafezi F, Mrochen M, Iseli HP, Seiler T. Collagen crosslinking with ultraviolet-A and hypoosmolar riboflavin solution in thin corneas. J Cataract Refract Surg 2009;35(4):621–4. 9. Schmidinger G, Pachala M, Prager F. Pachymetry changes during corneal crosslinking: Effect of closed eyelids and hypotonic riboflavin solution. J Cataract Refract Surg 2013;39. 10. Koç M, Uzel MM, Koban Y, Tekin K, Taşlpnar AG, Ylmazbaş P. Accelerated Corneal Cross-Linking With a Hypoosmolar Riboflavin Solution in Keratoconic Thin Corneas: Short-Term Results. Cornea 2016;35(3):350–4. 11. Wollensak G, Spörl E, Reber F, Pillunat L, Funk R. Corneal endothelial cytotoxicity of riboflavin/UVA treatment in vitro. Ophthalmic Res 2003;35(6):324–8. 12. Chang SW, Chi RF, Wu CC, Su MJ. Benzalkonium chloride and gentamicin cause a leak in corneal epithelial cell membrane. Exp Eye Res 2000;71(1):3–10. 13. Majumdar S, Hippalgaonkar K, Repka MA. Effect of chitosan, benzalkonium chloride and ethylenediaminetetraacetic acid on permeation of acyclovir across isolated rabbit cornea. Int J Pharm 2008;348(1–2):175–8. 14. Filippello M, Stagni E, O’Brart D. Transepithelial corneal collagen crosslinking: bilateral study. J Cataract Refract Surg 2012;38(2):283– 91. 15. Hersh PS, Lai MJ, Gelles JD, Lesniak SP. Transepithelial corneal crosslinking for keratoconus. J Cataract Refract Surg 2018;44(3):313– 22. 16. Wollensak G, Iomdina E. Biomechanical and histological changes after corneal crosslinking with and without epithelial debridement. J Cataract Refract Surg 2009;35(3):540–6. 17. Transepithelial corneal collagen cross‐linking by iontophoresis of riboflavin - Bikbova - 2014 - Acta Ophthalmologica - Wiley Online Library [Internet]. [cited 2023 Oct 10]; Available from: https:// onlinelibrary.wiley.com/doi/full/10.1111/aos.12235 18. Cassagne M, Laurent C, Rodrigues M, Galinier A, Spoerl E, Galiacy SD, et al. Iontophoresis Transcorneal Delivery Technique for Transepithelial Corneal Collagen Crosslinking With Riboflavin in a Rabbit Model. Invest Ophthalmol Vis Sci 2016;57(2):594–603. 19. Jia HZ, Pang X, Fan ZJ, Li N, Li G, Peng XJ. Iontophoresis-assisted corneal crosslinking using 0.1% riboflavin for progressive keratoconus. Int J Ophthalmol 2017;10(5):717–22. 20. Vinciguerra P, Randleman JB, Romano V, Legrottaglie EF, Rosetta P, Camesasca FI, et al. Transepithelial iontophoresis corneal collagen cross-linking for progressive keratoconus: initial clinical outcomes. J Refract Surg Thorofare NJ 1995 2014;30(11):746–53. 21. Kymionis GD, Diakonis VF, Coskunseven E, Jankov M, Yoo SH, Pallikaris IG. Customized pachymetric guided epithelial debridement for corneal collagen cross linking. BMC Ophthalmol 2009;9:10. 22. Cagil N, Sarac O, Can GD, Akcay E, Can ME. Outcomes of corneal collagen crosslinking using a customized epithelial debridement technique in keratoconic eyes with thin corneas. Int Ophthalmol 2017;37(1):103–9. 23. Mazzotta C, Ramovecchi V. Customized epithelial debridement for thin ectatic corneas undergoing corneal cross-linking: epithelial island cross-linking technique. Clin Ophthalmol Auckl NZ 2014;8:1337–43. 24. Sachdev MS, Gupta D, Sachdev G, Sachdev R. Tailored stromal expansion with a refractive lenticule for crosslinking the ultrathin cornea. J Cataract Refract Surg 2015;41(5):918–23. 25. 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 Thorofare NJ 1995 2014;30:366-72. 26. Chen X, Stojanovic A, Eidet JR, Utheim TP. Corneal collagen crosslinking (CXL) in thin corneas. Eye Vis 2015;2:15. 27. Hafezi F, Kling S, Gilardoni F, Hafezi N, Hillen M, Abrishamchi R, et al. Individualized Corneal Cross-linking With Riboflavin and UV-A in Ultrathin Corneas: The Sub400 Protocol. Am J Ophthalmol 2021;224:133–42. 28. Kanellopoulos AJ. Novel myopic refractive correction with transepithelial very high-fluence collagen cross-linking applied in a customized pattern: early clinical results of a feasibility study. Clin Ophthalmol Auckl NZ 2014;8:697–702. 29. Lim WK, Soh ZD, Choi HKY, Theng JTS. Epithelium-on photorefractive intrastromal cross-linking (PiXL) for reduction of low myopia. Clin Ophthalmol Auckl NZ 2017;11:1205–11. 30. Pavel S, Zuzana H, Slovak M, Šramka M, Karel L, Polisensky J. Photorefractive intrastromal corneal crosslinking (PiXL) for correction of hyperopia - 12 month results. J Cataract Refract Surg 2020;46:1. 31. Kwok SJJ, Kim M, Lin HH, Seiler TG, Beck E, Shao P, et al. Flexible Optical Waveguides for Uniform Periscleral Cross-Linking. Invest Ophthalmol Vis Sci 2017;58(5):2596–602. 32. Iseli HP, Körber N, Koch C, Karl A, Penk A, Huster D, et al. Scleral cross-linking by riboflavin and blue light application in young rabbits: damage threshold and eye growth inhibition. Graefes Arch Clin Exp Ophthalmol Albrecht Von Graefes Arch Klin Exp Ophthalmol 2016;254(1):109–22. 33. Tabibian D, Richoz O, Hafezi F. PACK-CXL: Corneal Cross-linking for Treatment of Infectious Keratitis. J Ophthalmic Vis Res. 2015;10:77– 80. doi: 10.4103/2008-322X.156122. 34. Goodrich RP. The use of riboflavin for inactivation of pathogens in blood products. Vox Sang. 2000;78:211–5. 35. Martins SA, Combs JC, Noguera G, Camacho W, Wittmann P, Walther R, et al. Antimicrobial efficacy of riboflavin/UVA combination (365 nm) in vitro for bacterial and fungal isolates: a potential new treatment for infectious keratitis. Invest Ophthalmol Vis Sci. 2008;49(8):3402–8. doi: 10.1167/iovs.07-1592. 36. Iseli HP, Thiel MA, Hafezi F, Kampmeier J, Seiler T. Ultraviolet A/ riboflavin corneal cross-linking for infectious keratitis associated with corneal melts. Cornea. 2008;27:590–4. doi: 10.1097/ ICO.0b013e318169d698. 37. Said DG, Elalfy MS, Gatzioufas Z, El-Zakzouk ES, Hassan MA, Saif MY, et al. Collagen cross-linking with photoactivated riboflavin (PACK-CXL) for the treatment of advanced infectious keratitis with corneal melting. Ophthalmology. 2014;121:1377–82. doi: 10.1016/j. ophtha.2014.01.011. 38. Tawfeek, M., Ammar, K., Hosny, M., and Enany, H. (2020). “Photoactivated Chromophore for Keratitis (PACK-CXL) as Adjunctive

www.dosonline.org/dos-times DOS Times Volume 29, Number 5, September-October 2023 DOS TIMES 71 Therapy for Infectious Keratitis: A Prospective Study,” in 38th Congress of the European Society of Cataract and Refractive Surgeons. Available at: https://www.escrs.org/ amsterdam2020/programme/ free-papers-details.asp?id36752. 39. Torres-Netto, E. A., Shetty, R., Knyazer, B., Chen, S., Hosny, M., Gilardoni, F., et al. (2020). “Corneal Cross-Linking for Treating Infectious Keratitis: Final Results of the Prospective Randomized Controlled Multicenter Trial,” in 38th Congress of the ESCRS. Available at: https://www.escrs.org/amsterdam2020/programme/ posters-details.asp?id35943. 40. Prajna, N. V., Radhakrishnan, N., Lalitha, P., Austin, A., Ray, K. J., Keenan, J. D.,et al. (2020). Cross-Linking-Assisted Infection Reduction. Ophthalmology 127, 159–166. doi:10.1016/j.ophtha.2019.08.029. 41. Wei, A., Wang, K., Wang, Y., Gong, L., Xu, J., and Shao, T. (2019). Evaluation of Corneal Cross-Linking as Adjuvant Therapy for the Management of Fungal Keratitis. Graefes Arch. Clin. Exp. Ophthalmol. 257, 1443–1452. doi:10.1007/s00417-019-04314-1. 42. Naranjo, A., Arboleda, A., Martinez, J. D., Durkee, H., Aguilar, M. C., Relhan, N.,et al. (2019). Rose Bengal Photodynamic Antimicrobial Therapy for Patients with Progressive Infectious Keratitis: A Pilot Clinical Study. Am. J. Ophthalmol. 208, 387–396. doi:10.1016/j. ajo.2019.08.027. 43. Kymionis, G. D., Kontadakis, G. A., Kounis, G. A., Portaliou, D. M., Karavitaki, A. E., Magarakis, M., et al. (2009). Simultaneous Topography-Guided PRK Followed by Corneal Collagen CrossLinking for Keratoconus. J. Refract Surg. 25, S807–S811. doi:10.392 8/1081597X-20090813-09 44. Kontadakis, G. A., Kankariya, V. P., Tsoulnaras, K., Pallikaris, A. I., Plaka, A., and Kymionis, G. D. (2016). Long-Term Comparison of Simultaneous Topography- Guided Photorefractive Keratectomy Followed by Corneal Cross-Linking Versus Corneal CrossLinking Alone. Ophthalmology 123, 974–983. doi:10.1016/j. ophtha.2016.01.010. 45. Kanellopoulos, A. J. (2019). Management of Progressive Keratoconus with Partial Topography-Guided PRK Combined with Refractive, Customized CXL – A Novel Technique: The Enhanced Athens Protocol. Opth 13, 581–588. doi:10.2147/OPTH.S188517. 46. Kymionis, G. D., Grentzelos, M. A., Karavitaki, A. E., Kounis, G. A., Kontadakis, G. A., Yoo, S., et al. (2010). Transepithelial Phototherapeutic Keratectomy Using a 213-nm Solid-State Laser System Followed by Corneal Collagen Cross-Linking with Riboflavin and UVA Irradiation. J. Ophthalmol. 2010, 1–3. doi:10.1155/ 2010/146543. 47. Kymionis, G. D., Grentzelos, M. A., Kounis, G. A., Diakonis, V. F., Limnopoulou, A. N., and Panagopoulou, S. I. (2012a). Combined Transepithelial Phototherapeutic Keratectomy and Corneal Collagen Cross-Linking for Progressive Keratoconus. Ophthalmology 119, 1777–1784. doi:10.1016/ j.ophtha.2012.03.038. 48. Grentzelos, M. A., Liakopoulos, D. A., Siganos, C. S., Tsilimbaris, M. K., Pallikaris, I. G., and Kymionis, G. D. (2019). Long-term Comparison of Combined T-PTK and CXL (Cretan Protocol) Versus CXL with Mechanical Epithelial Debridement for Keratoconus. J. Refract Surg. 35, 650–655. doi:10.3928/ 1081597X-20190917-01. 49. Kim, C. Y., and Kim, M. K. (2019). Effect of Sequential Intrastromal Corneal Ring Segment Implantation and Corneal Collagen Crosslinking in Corneal Ectasia. Korean J. Ophthalmol. 33, 528–538. doi:10.3341/kjo.2019.0088. 50. Singal, N., Ong Tone, S., Stein, R., Bujak, M. C., Chan, C. C., Chew, H. F., et al. (2020). Comparison of Accelerated CXL Alone, Accelerated CXL-ICRS, and Accelerated CXL-TG-PRK in Progressive Keratoconus and Other Corneal Ectasias. J. Cataract Refract. Surg. 46, 276–286. doi:10.1097/ j.jcrs.0000000000000049. 51. Shetty R, D’Souza S, Srivastava S, Ashwini R. Topography-guided custom ablation treatment for treatment of keratoconus. Indian J Ophthalmol 2013;61(8):445. Dr. Jyotsana sharma, MBBS PG Resident, Vision Eye Centres, New Delhi. Corresponding Author:

DOS Times Volume 29, Number 5, September-October 2023 www.dosonline.org/dos-times DOS TIMES 72 Importance of Posterior Segment Screening Before Corneal Refrective Surgery Sanjeev Kumar Nainiwal, MD, DNB, MNAMS, Kavita Bajiya, MBBS, Sunil Kumar Gurjar, MBBS, Mansi Sonwar, MBBS, Prithvi Raj, MS Department of Ophthalmology, Sawai Man Singh Medical College & Hospital, Jaipur, Rajasthan, India. Introduction Many young adults have moderate to severe visual impairment because they do not correct their refractive errors.[1] Refractive errors seen in day-to-day clinical practice include myopia, hyperopia, astigmatism, and presbyopia. Myopia is the most common one.[2] Patients who are myopic have steep cornea or a longer axial length or both. Since the past several decades, surgical correction of refractive errors, particularly myopia, is on the rise. There are different types of refractive surgical techniques used in the treatment of myopia include surface ablation techniques like photorefractive keratotomy, laser in situ keratomileusis (LASIK), femtosecond LASIK and intraocular procedures like intrastromal corneal ring segments, phakic intraocular lens (phakic IOL) and elective refractive lens exchange. Peripheral retina Degenerations are common in myopes and studies have shown a higher prevalence with increasing grades of myopia. [3-6] Lattice degeneration, snail track degeneration, retinal tears/ holes, degenerative retinoschisis, cystic retinal tufts, and, rarely, zonular traction tufts, can result in a rhegmatogenous retinal detachment (RRD) and its associated morbidity.[7] Another problem that myopes may have is, PVD that present at a much younger age.[8] The rapid increase and then decrease in IOP could theoretically stretch the vitreous base and the acoustic shock waves from the laser could play a role in the development of a posterior vitreous detachment. Highly myopic eyes undergoing phakic IOL procedures are at risk of retinal detachment from the underlying high myopia as well as from the intraocular surgery. A retinal detachment rate of 4.8% was reported in a study of phakic IOLs used to correct high myopia. PVD can lead to retinal tears and an RRD. Therefore it is very important for myopes to have their retina examination before and after surgery to find and treat any retinal degeneration prophylactic ally.[7] There are no framed guidelines for screening of patients but a general screening protocol which one could follow. Before having refractive surgery, people should have their retina examination by a retina specialist. Peripheral retinal lesions can be screened by using an ultra-wide field fundus camera. This modality has moderate sensitivity (about 57%) and high specificity (>99%) for screening of peripheral lesions. Patients who have peripheral lesions and do not treat before surgery have 10 times higher chances of developing an RD than those who are administered prophylactic laser photocoagulation. Therefore it is better to treat these retinal degenerations before surgery with laser. These lesions according to review article are: (1) asymptomatic patients with peripheral lesions when monitoring is not possible (learning disability, living in remote area, etc.); (2) areas of retinal weakness if symptomatic/only-eye/retinal detachment in fellow eye; (3) symptomatic breaks or persistent vitreoretinal traction; (4) operculated holes where vitreous is adherent to the hole margin; (5) horseshoe tears/giant tears/retinal dialysis. Or one could follow the Wilkinson CP recommendations for treatment (Table 1). It is also important to stress the fact that some studies show a lack of efficacy for prophylactic treatment to areas of peripheral degeneration. But that is not the case, as it has been observed that RDs that developed post-laser are not related to previous lesions but to newer lesions that develop or a PVD that may theoretically induce a tear at edge of a treated area. Requisite for Retinal Examination Patients with high myopia should be counselled that refractive surgery corrects only the refractive aspect of the myopia and not the natural history of the highly myopic eye with its known complications. Such patients remain at risk of retinal tears and detachment throughout their lives, despite refractive surgery. The presence of pre-existing retinal tears or holes, new retinal breaks secondary to PVD in pre-existing peripheral retinal degenerations and rarely development of new retinal breaks post surgery are predisposing factors for retinal detachment in patients undergoing refractive surgery. Thus, a complete dilated retinal examination with indentation is necessary to identify any 1. All symptomatic and asymptomatic horse-shoe tears, operculated holes, lattice degeneration with retinal holes, atrophic holes, treat promptly. 2. All symptomatic lattice degeneration without retinal holes and atrophic holes, Treatment is usually recommended. 3. All asymptomatic lattice degeneration without retinal holes, pigmented lattice degeneration, and atrophic holes, Can be observed. 4. Eyes with atrophic holes or lattice degeneration where the fellow eye has already developed retinal detachment can be considered for treatment. Table 1: Recommendations for treatment of peripheral retinal degenerations for patients undergoing refractive surgery.

www.dosonline.org/dos-times DOS Times Volume 29, Number 5, September-October 2023 DOS TIMES 73 retinal degeneration that needs treatment prior to any refractive surgery. Refractive Surgery in Previous Operated RD Surgery Patients Patients who have had prior sclaral buckle surgery or vitrectomy may seek refractive surgery due to resultant myopia. Prior RD surgery can result in a myopic shift due to axial elongation of the eye from indentation of the sclaral buckle. Refractive surgery can be considered in selected cases that have symptomatic anisomatropia with good BCVA. Preoperative pathology including pre-existing macular pathology will continue to limit UCVA and BCVA after refractive surgery. Both the patient and the surgeon should realize that the final visual results may not be as predictable as after other refractive surgeries. Patients should also be aware that if the sclaral buckle needs to be removed, the refractive error could change dramatically. Retinal Examination Ideally screening for retinal degeneration and PVD status, should be done by an experienced retinal specialist after dilating the pupil with indirect ophthalmoscope. Another way to examine retina without dilating pupil is to use ultra wide field fundus camera.[9-10] Sometimes, an ocular ultrasound can also use to see PVD.[11] Prophylaxis for retinal breaks before refractive surgery Before refractive surgery, it is recommended to treat any predisposing retinal lesions with prophylactic laser photocoagulation. Time interval between the laser photocoagulation and refractive surgery Laser photocoagulation produces a strong adhesive bond between the neurosensory retina and retinal pigment epithelium. Now, after treatment with laser photocoagulation, the adhesive force of the retina reduces by 50% at the 8 hrs, but then it increases by 140% (beyond the normal) by 24 hours and becomes twice the normal between 3 days and 4 weeks.[12-13] Hence, after retinal laser photocoagulation, it is better to wait for at least 1 week before having refractive surgery. Follow-Up Retinal Examination Following microtome assisted LASIK or femtosecond assisted LASIK, a PVD can occur as soon as two days after surgery in 16% of cases and in up to 85% within a month.[11] Also, in various studies[14] it was observed that most RDS occur around a period of about 11 months. So, even if the surgery goes well, the patient may still get an RD. Patients with increased floaters and/ or flashes should be evaluated by a retinal specialist at the earliest to check for the development of PVD, retinal tears, or retinal detachment. Despite a low incidence of retinal detachment after post refractive surgery, it can happen at any time after surgery.[15] Since myopic patients are at a risk for vision threatening macular complications like progressive thinning and atrophy, choroidal neovascular membranes, retinoschisis, macular hole, pigment epithelial detachments, and foveal detachments, a long term follow up is mandatory after refractive surgery. Conclusion In conclusion, patients who want to have refractive surgery need a thorough retinal examination to find any peripheral lesions. They need to treat, any predisposing degenerative retinal lesions with Prophylactic barrage laser photocoagulation, at least 1 week before surgery. Retinal examination should be done at regular intervals for a long term to check for the development or progression of PVD, retinal tears, retinal detachment, and macular pathologies. Sometimes, it may be hard to examine every patient well at a high-volume center. But, it is very important to do so and to tell the patients about the risks of retinal detachment and what to do if they see flashes or floters. This can help the patients accept the treatment better and take timely treatment if needed. This can lead to better results. We want to end this discussion with a real example: A myopic patient who was going to have LASIK changed her mind a week before. The next day, she called the doctor because she could not see well in one eye. The doctor found out that her retinal detachment.[16] What would happen if this patient came to you and did not examine her retina well or tell her about the risks? That is why this discussion is important. References 1. Flaxman SR, Bourne RRA, Resnikoff S, Ackland P, Braithwaite T, Cicinelli MV, et al. Global causes of blindness and distance vision impairment 1990-2020: A systematic review and meta-analysis Lancet Glob Health 2017;5:e122134. 2. Sheeladevi S, Seelam B, Nukella PB, Borah RR, Ali R, Keay L. Prevalence of refractive errors, uncorrected refractive error, and presbyopia in adults in India: A systematic review. Indian J Ophthalmol 2019;67:583-92. 3. Lam DSC, Fan DSP, Chan W-M, Tam BSM, Kwok AKH, Leung ATS, et al. Prevalence and characteristics of peripheral retinal degeneration in Chinese adults with high myopia: A cross-sectional prevalence survey. Optom Vis Sci Off Publ Am Acad Optom 2005;82:235-8. 4. PierroL, Camesasca FI, Mischi M, Brancato R. Peripheral retinal changes and axial myopia. Retina Phila Pa 1992;12:12-7. 5. Martín Sánchez MD, Roldán Pallarés M. Myopia: Frequency of latticedegeneration and axial length. Arch Soc Espanola Oftalmol 2001;76:291-6. 6. Gözüm N, Cakir M, Gücukoglu A, Sezen F. Relationship between retinal lesions and axial length, age and sex in high myopia. Eur J Ophthalmol 1997;7:277-82. 7. Lewis H. Peripheral retinal degenerations and the risk of retinal detachment. AmJ Ophthalmol 2003;136:155-60. 8. Yonemoto J, Ideta H, Sasaki K, Tanaka S, Hirose A, Oka C. The age of onset of posterior vitreous detachment. Graefes Arch Clin Exp Ophthalmol Albrecht Von Graefes Arch Klin Exp Ophthalmol 1994;232:67-70. 9. Liu L,Wang F, Xu D, Xie C, Zou J. The application of wide-field laser ophthalmoscopy in fundus examination before myopic refractive surgery. BMC Ophthalmol 2017;17:250.

DOS Times Volume 29, Number 5, September-October 2023 www.dosonline.org/dos-times DOS TIMES 74 10. Yang D, Li M, Wei R, Xu Y, Shang J, Zhou X. Optomap ultrawide field imaging for detecting peripheral retinal lesions in 1725 high myopic eyes before implantable collamer lens surgery. Clin Experiment Ophthalmol 2020. doi: 10.1111/ceo.13809. 11. Gavrilov J-C, Gaujoux T, Sellam M, Laroche L, Borderie V. Occurrence of posterior vitreous detachment after femtosecond laser in situ keratomileusis: Ultrasound evaluation. J Cataract Refract Surg 2011;37:1300-4. 12. Yoon YH, Marmor MF. Rapid enhancement of retinal adhesion by laser photocoagulation. Ophthalmology 1988;95:13858. 13. Folk JC, Sneed SR, Folberg R, Coonan P, Pulido JS. Early retinal adhesion from laser photocoagulation. Ophthalmology 1989;96:1523- 5. 14. Srinivasan R, Jain S, Jaisankar D, Raman R. Incidense and risk factor for retinal detachment following laser assisted in-situ keratomileusis. Indian J Ophthalmol 2021;69:1856-60. 15. Arevalo JF, Lasave AF, Torres F, Suarez E. Rhegmatogenous retinal detachment after LASIK for myopia of up to -10 diopters: 10 years of follow-up. Graefes Arch Clin Exp Ophthalmol Albrecht Von Graefes Arch Klin Exp Ophthalmol 2012;250:963-70. 16. Mannis, M. J., & Holland, E. J. (2022). Cornea: Fundamental, diagnosis and Management, Elsevier. Dr. Sanjeev Kumar Nainiwal, MD, DNB, MNAMS Senior Professor Ophthalmology, Sawai Man Singh Medical College & Hospital, Jaipur Rajasthan India. Corresponding Author:

www.dosonline.org/dos-times DOS Times Volume 29, Number 5, September-October 2023 DOS TIMES 75 Patient Satisfaction in Modern Eye Care System: A Perspective Sonia Singh, DNB, M S Ravindra, MS, Karthik R Meda, DNB Karthik Netralaya Institution of Opthalmology, Bangalore, Karnataka, India. Patient satisfaction can be considered as a final outcome for evaluating and improving health care services[1] and an indicator of quality of health care that consequently affects the patient trust, outcome and loyalty. Though research on patient satisfaction dates back to the late 1960s[2], there is no clear consensus in literature about the definition. Most literature describe patient satisfaction in health care as a reaction to, or outcome of an interaction between patients and healthcare providers.[3] In recent times there has been a change in the attitude and profile of the patients. The awareness of varied options of care and treatment choices has led people to demand their entitlement to better services.[4] There are certain specific factors pertaining to eye hospitals that need emphasis. Most ophthalmic surgeries and procedures are day care procedures with short recovery time. In-patient treatment and prolonged patient stay is infrequently required. There is a growing number of elective refractive procedures.[5] Now a days, cataract surgery is also considered as a refractive surgery. This leads to higher expectation in terms of results and gratification regarding postoperative functional outcomes.[6] With advent of antiVEGF agents, many retinal conditions need regular prolonged treatment and follow ups with recurring expenses which can result in patient dissatisfaction & poor compliance. Increased competition in the eye care sector has also led to a greater appreciation for the need to understand patient desires.[7] Certain strategies that can be adopted to improve patient satisfaction are being discussed in this article. Treat them as Guests and not as Patients Health care revolves around many factors like physical, financial, social, temporal and emotional status of the elements in the society. Treating the patient with warmth and ensuring comfortable experience when in the hospital goes a long way in building good bonding with them. Taking special care of the vulnerable group of patients by giving them priority, providing necessary assistance, wheel chair, feeding rooms etc. makes them and their family feel taken care of. Get Accreditation Getting your institution accredited has multiple benefits as various accreditation agencies like International Organization for Standardization (ISO), National Accreditation Board for Hospitals (NABH), Joint Commission International (JCI) etc all focus on quality service issues.[8] It certifies that the quality of care and processes being followed is standardized. It inculcates the confidence in patient and insurance providers and helps institute to develop, analyze and streamline the processes and stimulate continuous improvements. Efficient Telephone and Help Desk Hospital telephone and information desk are the most important zones for making a good impression of the hospital. The staff designated for handling phone calls should be smart, knowledgeable, helpful, friendly and should be able to converse well in multiple languages. Make sure that the missed calls are returned, inform in case of cancellation or rescheduling of appointments, send reminder and confirmation messages and calls, provide necessary instructions beforehand about scheduled procedures, and inform the probable cost of procedure so that the patient is prepared. Keep the Premises Clean and Tidy Cleanliness in a health care facility has both medical and aesthetic importance. A neat and clean well-maintained facility with good ventilation, lighting and comfortable furnishing is important. Make a schedule for housekeeping staff for cleaning furniture, fixtures, fans, bathrooms etc. Providing dust bins, sanitizers, clean potable drinking water in required areas is a must. Various studies have found that cleanliness has a positive effect on patient satisfaction.[9,10] Minimize Waiting Monitor the total hospital stay of patients, and ensure that their stay in the hospital is not only pleasant but is brief. In case there is going to be a delay, inform the patients so, with viable reasons and offer alternatives. Look for any bottle necks in the patient flow in the clinics like refraction and visual testing areas. Identify multitasking staff, train and mobilize them and streamlining the appointments to reduce hardship. Go through daily statistics and see which days are busier and what process is causing increase in wait times. Scheduling appointments accordingly will help minimize waiting. A proper communication by the staff to patients and families regarding expected and unexpected waits may lead to an increase in patient satisfaction.[11] Make sure they have a comfortable waiting area with things to do like a TV, magazines etc. Staff Interaction and Behaviour Before meeting a doctor, the patient interacts with several staff. Socially skilled, well dressed and well-behaved staff achieve a great impact. Organize frequent training programs to improve BEYOND OPHTHALMOLOGY

DOS Times Volume 29, Number 5, September-October 2023 www.dosonline.org/dos-times DOS TIMES 76 soft skills of employees which will help in improving patient satisfaction and loyalty.[12] Hospital management should monitor the staff behaviour and make sure they keep up a positive and friendly attitude. Doctor-Patient Interaction Doctor consultation is the main reason why the patient visits the hospital. Results of a research by Dawn and Lee revealed that ophthalmology patients do expect communication and explanation of medical information regarding diagnosis and prognosis, psychosocial support, and therapeutic listening.[13] Most of the doctors can only offer a limited time within which they need to understand the patient, analyze their symptoms, examine, diagnose and suggest appropriate treatment. Polite words, smiling face and kind gestures puts the anxious and nervous patient at ease. Talking in their language, learning about their social and personal situation helps to build a good rapport. Suggest cost effective treatment, explain all the available options, set the right expectations about the treatment and inform about the risks and alternatives. Communication is the Key In today’s world, the patients are informed and educated. It is important that the communications, be it with staff, para medics, technicians, insurance executives, nurses, or doctors, should be clear, identical and precise. Various methods can be employed to educate patients about their condition and treatment. Counselors, handouts, brochures, videos, groupbased education, online meetings etc. can be used to provide necessary information. Display patient rights and responsibilities and tariff lists appropriately. Grievance Redressal An unsatisfied patient has a higher probability to share his experience more than a satisfied patient. Patients should know the mechanism and their right to complaint. Allot a senior and experienced staff to handle an unsatisfied and agitated patient with patience and politeness. Try to offer an acceptable solution. Keep the documentation complete so as to keep yourself legally safe. Reviews in digital media will not always be pleasant. Do quickly and firmly respond to a negative comment with your view points. Never request them to remove such a comment! Take Feedback Patient feedback in the form of survey or questionnaire is a good tool for monitoring the performance and improving the quality of services.[14,15] The information obtained can be used to improve the care given to the patients. Was the process pleasant, quick and easy, cleanliness, experience with staff and doctors, counselling, medical conditions and treatment details, post treatment care and how likely will they refer their friends etc. are some of the feedback questions. Satisfied patients are more likely to continue using healthcare services and comply with care regimens.[16] Patient satisfaction is a good indicator of overall hospital performance. In the era of online reviews and ratings, this parameter has become even more important. Ultimately patient satisfaction not only makes everyone happy but also provides value to the hospital and motivation to the employees. This can be summarized as “there is no better advertising than a happy patient’s word of mouth”. References 1. Sitzia J, Wood N: Patient satisfaction: a review of issues and concepts. Soc Sci Med 1997,45:1829-1843. 2. Hall JA, Dornan MC: Meta analysis of satisfaction with medical care: description of research domain and analysis of overall satisfaction levels Sci Med 1988, 27:637-644. 3. Goodrich GW, Lazenby JM. Elements of patient satisfaction: An integrative review. Nurs Open. 2023 Mar;10(3):1258-1269. doi: 10.1002/nop2.1437. Epub 2022 Oct 28. PMID: 36306415; PMCID: PMC9912404. 4. Wong, EL, Coulter, A, Cheung, AW, (2013), “Validation of inpatient experience questionnaire”. International Journal Quality Health Care Vol.25(4), pp.443–451. 5. Dawn AG, Lee PP. Patient expectations for medical and surgical care: a review of the literature and applications to ophthalmology. Surv Ophthalmol. 2004 Sep-Oct;49(5):513-24. doi: 10.1016/j. survophthal.2004.06.004. PMID: 15325196. 6. Tielsch JM, Steinberg EP, Cassard SD, et al: Preoperative functional expectations and postoperative outcomes among patients undergoing first eye cataract surgery. Arch Ophthalmol 113:1312–8, 1995. 7. Houtman DM. Managing patient expectations. Int Ophthalmol Clin. 2000; 40:29-34. 13. Maller BS. Market trends in refractive surgery. Int Ophthalmol Clin. 2000; 40:11-19. 8. IL: JCAHO: Oak Brook Terrace; 1992. Joint commission Accreditation of Health care Organizations: Accreditation Manual for Hospitals. 9. Westbrook, K. W., Babakus, E., & Grant, C. C. (2014). Measuring patient-perceived hospital service quality: Validity and managerial usefulness of HCAHPS scales. Health Marketing Quarterly, 31(2), 97–114.https://doi.org/10.1080/07359 683.2014.907114. 10. Persai D, Balu RK, Singh K, Prabhu RR, Lahoti S, Rout S, Panda R. Patient Satisfaction with Quality of Primary Care Health servicesfindings from India. Int J Health Plann Manage. 2022 Jul;37(4):2256- 2265. doi: 10.1002/hpm.3467. Epub 2022 Apr 2. PMID: 35368115. 11. Godley M, Jenkins JB. Decreasing Wait Times and Increasing Patient Satisfaction: A Lean Six Sigma Approach. J Nurs Care Qual. 2019 Jan/Mar;34(1):61-65. doi: 10.1097/NCQ.0000000000000332. PMID: 29889720. 12. Kazemi, Nasim & Ehsani, Parisa & Abdi, Farshid & Bighami, Mohammad. (2013). Measuring hospital service quality and its influence on patient satisfaction: An empirical study using structural equation modelling. Management Science Letters. 3. 2125-2136. 10.5267/j.msl.2013.06.005. 13. Dawn AG, Lee PP. Patient expectations for medical and surgical care: a review of the literature and applications to ophthalmology. Surv Ophthalmol. 2004 Sep-Oct;49(5):513-24. doi: 10.1016/j. survophthal.2004.06.004. PMID: 15325196. 14. Jenkinson C, Coulter A, Bruster S, Richards N, Chandola T. Patients’ experiences and satisfaction with health care: results of a questionnaire study of specific aspects of care. Qual Saf Health Care. BEYOND OPHTHALMOLOGY

www.dosonline.org/dos-times DOS Times Volume 29, Number 5, September-October 2023 DOS TIMES 77 2002 Dec;11(4):335-9. doi: 10.1136/qhc.11.4.335. PMID: 12468693; PMCID: PMC1757991. 15. Sudhan A, Khandekar R, Deveragonda S, Devi S, Jain BK, Sachan R, Singh V. Patient satisfaction regarding eye care services at tertiary hospital of central India. Oman J Ophthalmol. 2011 May;4(2):73- 6. doi: 10.4103/0974-620X.83657. PMID: 21897622; PMCID: PMC3160073. 16. Hooker, R.S., Moloney-Johns, A.J. and McFarland, M.M. (2019) Patient Satisfaction with Physician Assistant/Associate Care: An International Scoping Review. Human Resources for Health, 17, Article No. 104. https://doi.org/10.1186/s12960-019-0428-7. Dr. Sonia Singh, DNB Karthik Netralaya, 89, 7th Cross Rd, Near Bull Temple Road, CK Nagar, NR Colony, Basavanagudi, Bengaluru, Karnataka, India. Corresponding Author: BEYOND OPHTHALMOLOGY

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DELHI OPHTHALMOLOGICAL SOCIETY A-23, 1st Floor, Green Park Main, New Delhi - 110016 Email: [email protected] / [email protected] Web: www.dosonline.org