The ocular surface is mainly composed of conjunctiva and corneal epithelium covered by a thin layer of tear film. Proper eyelid function, lacrimal gland tear production, meibomian gland function and sensorineural factors are essential for homeostasis. ^[1] Even one dysfunction can make permanent ocular surface problems, which lead to blindness, or ocular surface failure. Ocular surface failure is classified to the two major types; the first is limbal stem cell deficiency (LSCD), in which the corneal epithelium is replaced by conjunctival epithelium and  the second is

squamous metaplasia, in which the corneal or conjunctival epithelium exhibits keratinization and loss of mucosal epithelial characteristics including the expression of goblet cells. ^[2] Although there are some options to treat the ocular surface failure, both two types eventually give birth to the dreadful result, blindness. ^[3]

Steven-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) is a hypersensitivity mucocutaneous disease triggered mostly by medication and infection. They have a direct effect on the skin and no fewer than two mucous membranes including the eye and sometimes can be life-threatening. ^[4] SJS and TEN are variants belonging in the same class and are defined based upon the amount of epidermal detachment; SJS, 10% or less of total body surface area involvement, TEN, 30% or greater involvement and SJS/TEN overlap, involvement between 10-30%. ^[5] Clinical findings include a prodromal symptom of fever and malaise, followed by the development of a generalized, tender cutaneous eruption consisting of a variety of morphologic macules, papules, atypical target lesions and vesicles or bullae. ^[6] Serious dermatologic manifestations may make a physician overlook ocular sequelae, which are irreversible and fatal to visual acuity by the destruction of the ocular surface. The incidence of SJS and TEN are 9.2 and 1.9 per million person-years, respectively. ^[7]

This is a prospective study conducted in the Department of Dermatology at Tertiary Care Teaching Hospital over a period of 1 year.

The data included information on gender, presenting age, causative medications/diseases, and systemic treatments. Regarding disease chronicity, Shanbhag et al. have defined the acute phase as the period between symptom onset of SJS/TEN up to 2 months later; the subacute phase was defined as 2–6 months after symptom onset; and the chronic phase was defined as more than 6 months after symptom onset.

Based on clinical parameters, observed on ocular slit-lamp examination, the severity of involvement at the time of presentation was determined as mild, moderate, and severe, as per the classification described by Power et al. Mild ocular involvement comprised of eyelid skin involvement in the form of desquamation and denudation, eyelid edema, mild corneal involvement, mild conjunctival injection, mucous discharge, or chemosis. Moderate cases were the ones with membranous conjunctivitis, epithelial defects with more than 30% healing with medical treatment, corneal ulceration, or corneal infiltrates. Severe manifestations comprised of acquired eyelid malposition, formation of symblepharon, nonhealing corneal epithelial defects, complete or partial visual loss, or foreshortening of conjunctival fornix.

Statistical Analysis

All statistics were calculated using SPSS software version

• for Windows (SPSS, , Chicago, IL, USA). Continuous variables are presented as the mean and standard deviation (SD). A p < 0.05 was deemed to be statistically significant.

All experimental procedures were conducted in accordance with the principles set forth in the Helsinki Declaration.

A total of 40 patients were included in the study during the study period, of which 19 were males and 21 females in Table 1.

Table 1: Distribution of Gender

Table 2: Distribution of Gender

Out 40 of these, 22 were SJS or SJS/TEN overlap and 8 were TEN patients in Table 2.

Table 3: Causative agents of SJS/TEN

All cases were drug-induced, except one, in which no history of any drug intake prior to the appearance of lesions could be elicited [Table 3]. All patients had bilateral ocular findings.

Table 4: Classification of ocular involvement based on severity

All the patients having ocular involvement, presented to us in the acute phase, with symptoms such as redness, burning, watering, discharge, swelling, and sloughing of skin over lids and so on. The acute manifestations were classified as mild, moderate, or severe using the classification system described above. About 30.0% (12 patients) had mild involvement, 55.0% (22 patients) had

moderate involvement, and 15.0% (6 patients) had severe involvement [Table 4].

Table 5: Ocular findings in the acute stage based on structures involved: Lids, Conjunctiva, and Cornea

All patients were treated with topical antibiotics, topical corticosteroids, and tear substitutes in the acute phase.

Table 6: Long-term ocular sequelae after the end of 6 months

At the end of the study period, 8 patients (29.6%)

developed chronic sequelae of ocular manifestations [Table 6]. Out of these patients, 3 patients developed severe dry eye disease, 2 patients developed trichiasis, 2 patients had a diminution of vision, and 1 patient developed severe photophobia. Patients of SJS and SJS- TEN overlap had mild-to-moderate whereas patients of TEN had moderate to severe ocular manifestations. It was observed that delayed complications are more common in patients with initial severe eye involvement. More diffuse cutaneous and oral mucous membrane damage was associated with a greater risk of ocular manifestations.

Stevens-Johnson syndrome is a noteworthy cause of ophthalmic morbidity. Most patients who develop SJS/TEN consult a physician or a dermatologist in the acute phase. They consult ophthalmologists only after the resolution of skin lesions and are later referred to tertiary eye-care centers. This explains why none of our patients presented in the acute stage of the disease.

Several studies have shown that drugs are the most common cause of SJS/TEN. ^[8] In our study drugs were the cause in all the cases similar to the findings in some studies and Phenytoin drugs was the most common etiological agent. This remains a cause of concern. Specific drug cause could not be ascertained in 5 (50%) patients who had taken mixture of several drugs prior to development of SJS/TEN.

Based on severity, the ocular involvement in SJS/ TEN can be classified into mild, moderate, or severe. Mild ocular involvement is characterized by eyelid skin involvement in the form of desquamation and denudation, eyelid edema, mild corneal involvement, mild conjunctival injection, mucous discharge, or chemosis. Moderate cases present with membranous conjunctivitis, epithelial defects with more than 30% healing with medical treatment, corneal ulceration, or corneal infiltrates. Severe manifestations comprise of acquired eyelid malposition, formation of symblepharon, non-healing corneal epithelial defects, complete or partial visual loss, or foreshortening of conjunctival fornix. All our patients presented with severe manifestation. This is contrast with the study by Abrol et al ^[9] where moderate involvement was seen in most patients (62.9%), followed by mild involvement 25.9% and severe 11.1% 1

The goal of treatment in SJS/TEN is survival and recovery from the systemic disease as well as the prevention of cicatricial complications in the affected organ systems. ^[10] The major aim of early ophthalmologic intervention in the acute stage of SJS/TEN is to prevent cicatricial complication and in late stages of the disease is reconstruction of ocular surface to correct the effects chronic inflammation. The management of late sequelae remains a challenge because of the irreversible alteration in the ocular surface. ^[11] Most of our patients did not have early ophthalmic intervention. This may account for the severe late complications seen in them. ^[12-15]

Prophylactic antibiotic and topical steroids have been reported to improve the outcome of care and have become an acceptable practice. Topical steroid drops plus ointment for the lid margin is recommended only after microbial keratitis has been excluded. A symblepharon ring can be used with copious lubrication to prevent adhesions in the fornix. ^[17] Various surgical options are available for care of patients with SJS/TEN depending on the nature of ophthalmic complications. Mucus membrane transplantation and amniotic membrane grafting are increasingly being used to mitigate complications and the reconstruction the ocular surface in patients with SJS/TEN. Amniotic membrane tends to reduce ocular surface inflammation, form a scaffold for re-epithelialization, and prevent symblepharon formation, thus mitigating the long- term sequelae of the disease. ^[18]

Stevens-Johnson syndrome and toxic epidermal necrolysis are complex immunological syndrome that can result in devastating complications of ocular surface scarring and keratinization leading to blindness. Early ophthalmic assessment and management as well as regular follow up care are key factors to recovery and prevention of ocular complications.

1. Ezeanosike E, Ezeanosike OB. Current trends in the management of Stevens – Johnson syndrome: a call for paradigm shift I ophthalmic care in Niger J Ophthalmol 2018; 26:1-7
2. Morales ME, Purdue GF, Verity SM, Arnoldo BD, Blomquist PH. Ophthalmic manifestations of Stevens–Johnson syndrome and toxic epidermal necrolysis and relation to Am J Ophthalmol 2010; 150:505-510
3. Van Zyl, , Carrara, H., & Lecuona, K. Prevalence of chronic ocular complications in Stevens-Johnson syndrome and toxic epidermal necrolysis. Middle East African journal of ophthalmology 2014; 21(4): 332 -335.
4. Ukponmwan CU, Njinaka I, Ehimiyen Ocular complications of Stevens – Johnson Syndrome and Toxic epidermal necrolysis. Trop Doct. 2010; 40(3): 167 – 168.
5. Kang Ocular manifestations of Stevens- Johnson syndrome and toxic epidermal necrolysis. Hanyang Med Rev 2016; 36:174181.
6. Jain R, Sharma N, Basu S, Iyer G, Ueta M, Sotozono C, et Stevens-Johnson syndrome: the role of an ophthalmologist. Surv Ophthalmol 2016; 61(4): 369 – 399.
7. Swamy NN, Tasneem A case series on ocular manifestations in Steven Johnson Syndrome and their varied presentationReview of literature. J Clin Res Ophthalmol 2020; 7(1): 004-007.
8. Okonkwo SN, Ezeh EI, Megbelayin Bilateral Levator Aponeurosis Disinsertion Following Stevens – Johnson Syndrome: Case report. Sch J Med Case Rep, 2021; 9(6): 687-689.

9. Abrol A, Gulanikar A, Thakre S, Patel A. Study of ocular manifestations of Stevens‐Johnson syndrome/toxic epidermal Indian Dermatol Online J 2020; 4: 570 – 574.
10. Meller D, Pauklin M, Thomasen H, Westekemper H, Steuhl KP: Amniotic membrane transplantation in the human eye. Dtsch Arztebl Int 2011; 108(14): 243–248.
11. Stevens AM, Johnson FC. A new eruptive fever associated with stomatitis and ophthalmia: report of two cases in Arch Pediatr Adolescent Med 1922; 24: 526-33.
12. Roujeau Stevens-Johnson syndrome and toxic epidermal necrolysis are severity variants of the same disease which differs from erythema multiforme. J Dermatol 1997; 24: 726-9.
13. Leonard J, Dart J. The skin and the eyes. Rook's Textbook of 8th ed. USA: Blackwell publishing; 2004, p. 1-37.
14. Gueudry J, Roujeau JC, Binaghi M, Soubrane G, Muraine M. Risk factors for the development of ocular complications of Stevens- Johnson syndrome and toxic epidermal necrolysis. Arch Dermatol 2009; 145: 157-62.
15. Power WJ, Ghoraishi M, Merayo-Lloves J, Neves RA, Foster CS. Analysis of the acute ophthalmic manifestations of             the       erythema multiforme/Stevens-Johnson syndrome/toxic epidermal necrolysis disease Ophthalmol 1995; 102: 1669-76.
16. Sotozono C, Ueta M, Kinoshita The management of severe ocular complications of stevens-johnson syndrome and toxic epidermal necrolysis. Arch Dermatol 2009; 145: 1336-7; author reply 7-8.
17. Hazin R, Ibrahimi OA, Hazin MI, Kimyai-Asadi
    38. Stevens-Johnson syndrome: pathogenesis, diagnosis, and management. Ann Med 2008; 40: 129-38.
18. Mockenhaupt M, Viboud C, Dunant A, Naldi L, Halevi S, Bouwes Bavinek JN, et al. Stevens- Johnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed The EuroSCAR-study. J Invest Dermatol 2008; 128: 35-44.