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Updated: Feb 17, 2026
Technique of Conjunctival Biopsy and Direct Immunofluorescence for Diagnosing Mucous Membrane Pemphigoid
Published on: June 17, 2025
Mucous Membrane Pemphigoid with Ocular Involvement: The Clinical Phenotype and Its Relationship to Direct
Hon Shing Ong1, Jane F Setterfield2, Darwin C Minassian3
1Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom; National Institute of Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, United Kingdom; Singapore National Eye Centre and Singapore Eye Research Institute, Singapore.
Purpose:
This study explored the validity of the First International Consensus on Mucous Membrane Pemphigoid (MMP) guidance, which recommends that clinically indistinguishable patients, who have direct immunofluorescence (DIF)-negative biopsies, be excluded from a diagnosis of MMP. Misdiagnosis, or delayed diagnosis, of MMP with ocular involvement leads to the inappropriate use of topical therapy, the standard of care for causes of cicatrising conjunctivitis other than MMP, rather than systemic immunomodulatory therapy, resulting in irreversible clinical deterioration in patients with MMP.
Design:
Prospective, cross-sectional study.
Participants:
Patients meeting the clinical criteria of ocular MMP, including those with positive and negative DIF findings.
Methods:
A case report form was used to collect the demographic details, the clinical history, and the results of a detailed clinical assessment by ophthalmologists, otolaryngologists, dermatologists, and oral medicine specialists. All anatomic sites potentially affected by MMP were examined apart from the esophagus (and larynx in a subset). The DIF results were recorded.
Main Outcome Measures:
Differences between DIF-positive and -negative patients in demography, sites of involvement, and disease severity as determined by the degree of conjunctival scarring (using Tauber staging), central corneal disease (vascularization, scarring, ulceration, and conjunctivalization), history of conjunctival or lid surgery, and requirement for systemic immunotherapy at the time of screening.
Results:
A total of 73 patients with ocular MMP were recruited, of whom 20 of 73 (27.4%) had ocular-only disease. There was no significant demographic or clinical difference between patients with positive and negative DIF results. This finding included differences in disease severity for which the only significant difference was that of more severe central corneal disease in DIF-negative patients. Asymptomatic disease at different sites was frequent.
Conclusions:
These findings do not support the classification of DIF-negative patients, meeting the clinical criteria for ocular MMP, as having a different disease. This category of patients should be accepted as having DIF-negative MMP, for clinical management purposes, with patients having inflamed eyes being treated with systemic immunomodulatory therapy. The frequent finding of asymptomatic ocular, oral, and nasopharyngeal MMP is clinically significant and implies that these sites should be routinely screened in asymptomatic patients.
