Tear Fluid Indirect Immunofluorescence for Assessing Disease Activity in Ocular Mucous Membrane Pemphigoid: First Report of a New Method for Monitoring Disease Progression

Ocular mucous membrane pemphigoid (MMP) presents a significant diagnostic challenge because of the typically low positivity rate of serum antibody. While direct immunofluorescence (DIF) of conjunctival biopsies yields a high positivity rate, its invasiveness limits routine application. To address this, we explored tear fluid—which contains detectable immunoglobulin G (IgG) and can be collected safely and minimally invasively—as an alternative sample source for immunological testing. This pilot study reports the first case of tear fluid–based indirect immunofluorescence (IIF) using oral mucosal tissue to evaluate disease activity in ocular MMP. A man in his 60s presented with ocular pain, conjunctival hyperemia, and erosions. He had a prior MMP diagnosis based on low‐titer serum anti‐BP180NC16a antibody, histopathology, DIF, and serum IIF. During the second exacerbation, serum anti‐BP180NC16a antibody was negative, and serum‐based IIF showed no linear deposition of IgG and C3. Tear fluid testing revealed linear IgG deposition along the basement membrane zone (BMZ) of oral mucosa, with titers of 1:20 (left eye) and 1:320 (right eye), correlating with clinical asymmetry. Control testing yielded negative results. Following remission, tear fluid–based IIF showed no IgG reactivity, indicating a correlation with disease activity. Notably, serum‐based IIF using oral mucosa was negative, while tear fluid–based IIF demonstrated clear IgG positivity, suggesting higher sensitivity in detecting ocular disease. In conclusion, tear fluid–based IIF using oral mucosa represents a novel and potentially more sensitive method for evaluating ocular MMP, warranting further validation.