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.