Ophthalmic Aspects of Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis: A Narrative Review

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TL;DR

This narrative review summarizes current knowledge on Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), emphasizing that acute ocular involvement affects 50–80% of patients and nearly 90% develop chronic ocular disease. Early diagnosis, timely amniotic membrane transplantation, and aggressive topical management in the acute phase are critical to prevent severe chronic complications such as limbal stem cell deficiency and blindness. The review highlights limited treatment options and the need for multidisciplinary care, including regular ophthalmic examinations from the acute phase onward.

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**Background:** Stevens–Johnson syndrome (SJS) and its severe form, toxic epidermal necrolysis (TEN), are rare, immune-mediated, mucocutaneous diseases with significant mortality and potential for devastating ocular sequelae, including bilateral blindness. The review aims to summarize current literature on epidemiology, aetiology, pathology, clinical appearance, and treatment of SJS/TEN, with a focus on ophthalmic aspects.

**Methods:** This is a narrative review based on previously published studies. It does not include new studies with human participants or animals. The authors synthesized existing knowledge on SJS/TEN, covering epidemiology, aetiology, pathophysiology, clinical manifestations (acute and chronic phases), diagnosis, and management strategies.

**Key Results:** - **Epidemiology:** Annual incidence per million people varies: 0.93 in Germany, 5.76 in the UK, 12.35 in the USA. Incidence is 100× higher in Africa (linked to HIV), 30× higher in cancer patients, 1.5× higher in females, and 14× higher during pregnancy. Acute ocular signs affect 50–80% of patients, severe early ocular complications affect ~50%, and nearly 90% develop chronic ocular disease. Overall lethality in Europe is 34% (24% for SJS, 49% for TEN). - **Aetiology:** Medicines cause 75% of cases; infections (viral, *Mycoplasma pneumoniae*) and idiopathic causes account for 25%. Common triggers: antibiotics (53.2%), anticonvulsants (35.7%), NSAIDs (15.9%), and antineoplastic agents. Specific drugs include fluoroquinolones (8.5%), carbamazepine, phenytoin, paracetamol (6.2%), and nimesulide (2.8%). - **Pathophysiology:** SJS/TEN is a T-cell-mediated type IV hypersensitivity reaction involving CD8+ cytotoxic T cells and NK cells, with key mediators like granulysin, perforin, and Fas ligand. Genetic associations include HLA-B*1502 (carbamazepine), HLA-B*5801 (allopurinol), and HLA-A*0206 (NSAIDs). - **Clinical Manifestations:** Acute phase develops 4–28 days after trigger, with prodrome (fever, cough) followed by mucosal inflammation and skin lesions. Ocular signs include bilateral conjunctivitis, corneal epithelial defects, eyelid margin necrosis, and pseudomembrane formation. Chronic phase (3–6 months after acute) involves eyelid (meibomian gland destruction, trichiasis), conjunctival (symblepharon, scarring), and corneal complications (limbal stem cell deficiency, neovascularization, keratinization). Grading systems by Gregory (acute) and Sotozono et al. (chronic) are described. - **Management:** Acute phase requires multidisciplinary care, discontinuation of causative agent, and ophthalmic examination within 1–2 days. Topical therapy includes antibiotic-steroid ointment, levofloxacin/moxifloxacin, corticosteroids, cyclosporine, and preservative-free lubricants. Amniotic membrane transplantation (AMT) within 10 days is recommended for severe cases to prevent chronic complications. Systemic therapies (corticosteroids, IVIG, cyclosporine, TNF inhibitors) have equivocal evidence. Chronic phase management focuses on ocular surface protection: artificial tears, autologous serum drops, punctal occlusion, scleral contact lenses/PROSE, mucous membrane grafting (MMG), and keratoprosthesis for advanced cases. COMET (autologous cultivated oral mucosal epithelial transplantation) is preferred over limbal stem cell transplantation.

**Clinical Implications:** Early recognition and aggressive ophthalmic management in the acute phase are essential to prevent or mitigate chronic ocular complications. AMT should be performed as early as possible. In chronic SJS/TEN, PROSE combined with MMG is recommended for lid margin keratinization. Randomized studies are needed to establish optimal therapies.