Veatriki Athanasiou
Ocular cicatricial pemphigoid (OCP) is a chronic autoimmune scarring disorder of the conjunctiva that may progress to severe visual morbidity. This review provides an overview of its clinical features, underlying immunopathology, diagnostic evaluation, and current management strategies, highlighting the importance of early recognition and systemic therapy.
Definition
Ocular cicatricial pemphigoid (OCP) is an uncommon but clinically significant autoimmune disorder marked by chronic, progressive scarring of the conjunctiva and ocular surface (1). It forms part of the mucous membrane pemphigoid spectrum, a group of conditions capable of affecting multiple mucosal sites, including the oral and nasal cavities (1). A central pathological feature of OCP is the presence of autoantibodies directed against components of the epithelial basement membrane zone, resulting in subepithelial blistering and persistent inflammatory activity (2).
Aetiology and Risk Factors
OCP arises through autoantibody recognition of basement membrane proteins such as BP180, BP230, laminin-332 and the α6β4 integrin complex (3). These autoantibodies promote complement activation and downstream inflammatory cascades, ultimately contributing to fibrosis of the conjunctival tissue (3). Genetic predisposition plays a recognised role, with HLA-DQB1*0301 identified as a significant susceptibility allele (4). A number of environmental and iatrogenic factors, including topical agents such as timolol, pilocarpine and sulphonamides, as well as previous ocular surgery, have been associated with disease onset or exacerbation (5). The condition typically presents in individuals over the age of 60 and is more frequently observed in women (1).
Signs and Symptoms
Early manifestations are often subtle and may resemble chronic conjunctivitis. Patients commonly report erythema, tearing, foreign body sensation and photophobia, symptoms that can lead to delayed recognition (6). As fibrosis becomes more established, characteristic clinical signs develop, including symblepharon formation, shortening of the conjunctival fornix, trichiasis and, in advanced cases, ankyloblepharon (5). Progressive ocular surface instability may lead to corneal vascularisation, surface keratinisation and, ultimately, significant visual impairment or blindness (7).
Classification and Staging
The Foster system identifies four stages of increasing severity (5,8):
- Stage I – subepithelial fibrosis
- Stage II – ≤25% reduction in fornix depth
- Stage III – symblepharon formation
- Stage IV – ankyloblepharon with corneal involvement
To complement this qualitative scheme, Mondino and Brown developed an objective measurement system for assessing fornix depth, which is particularly useful for monitoring disease progression (9).
Investigations
A diagnosis of OCP relies on clinical suspicion supported by appropriate immunopathological testing. Conjunctival biopsy with direct immunofluorescence remains the gold standard, typically demonstrating linear deposition of IgG, IgA or C3 along the basement membrane zone (3). Additional investigations, including indirect immunofluorescence and ELISA-based assays, may identify circulating autoantibodies and clarify antigen specificity (10). Assessment of ocular surface function, such as Schirmer’s test, tear osmolarity analysis and impression cytology, provides valuable information regarding associated surface disease and tear film instability (10).
Management
The principal goals of treatment are suppression of inflammation and prevention of irreversible conjunctival scarring. In milder cases, dapsone may be effective, provided glucose-6-phosphate dehydrogenase deficiency has been excluded (6). More advanced disease often requires systemic immunosuppression, typically involving corticosteroids in combination with agents such as azathioprine, mycophenolate mofetil or cyclophosphamide (5,10). For refractory disease, biologic therapies, including rituximab or intravenous immunoglobulin, may provide additional benefit (11).
Supportive measures for ocular surface health play an important adjunctive role. Preservative-free lubricants and topical calcineurin inhibitors help stabilise the ocular surface and reduce symptomatic burden (12). In selected cases, surgical intervention such as amniotic membrane transplantation or mucous membrane grafting may be required, although these procedures should only be undertaken once inflammatory activity is adequately controlled (13).
Complications
If inadequately controlled, OCP can result in profound conjunctival fibrosis, severe dry eye disease, corneal vascularisation, keratinisation and irreversible visual loss (7). Long-term systemic immunosuppression, while often essential, carries risks including haematologic and hepatic toxicity, necessitating regular monitoring and careful dose adjustment (14).
Prognosis
Early identification and initiation of systemic therapy are crucial to preserving ocular function (10). Prompt treatment can slow disease progression and reduce the risk of long-term complications, whereas delays in diagnosis or insufficient immunosuppression substantially increase the likelihood of irreversible blindness (1). Given its chronic and relapsing nature, lifelong follow-up is required to manage disease activity, detect recurrences and monitor treatment-related adverse effects (2).
References
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3. Chan LS, Ahmed AR, Anhalt GJ, et al. Diagnostic immunopathology of mucous membrane pemphigoid. Clin Dermatol. 2015;33(4):451–457.
4. Setterfield JF, Shirlaw PJ, Bhogal BS, et al. Genetic susceptibility in mucous membrane pemphigoid. Br J Dermatol. 2017;177(1):110–117.
5. Foster CS. Cicatricial pemphigoid: Diagnosis and management. Trans Am Ophthalmol Soc. 1986;84:527–663.
6. Sullivan BR, Heffernan MP. Mucous Membrane Pemphigoid. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2021.
7. American Academy of Ophthalmology. Mucous Membrane Pemphigoid with Ocular Involvement. EyeNet Magazine. 2023.
8. Foster CS, et al. Cicatricial pemphigoid classification and grading. Trans Am Ophthalmol Soc. 1986;84:527–663.
9. Mondino BJ, Brown SI. Ocular cicatricial pemphigoid: Quantification of fornix depth. Ophthalmology. 1981;88(8):952–957.
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13. Melles RB, Djalilian AR, Holland EJ. Ocular surface reconstruction in cicatricial pemphigoid. Cornea. 2019;38(6):698–704.
14. Saw VPJ, Dart JK, Rauz S, et al. Ocular cicatricial pemphigoid: Current and emerging treatment strategies. Br J Ophthalmol. 2020;104(9):1210–1216.