We read with great interest the perspective by Kate and associates regarding the role of conjunctival biopsy in the diagnosis and management of ocular mucous membrane pemphigoid (oMMP). We concur with the authors’ central conclusion that a negative direct immunofluorescence (DIF) result should not deter clinicians from initiating appropriate immunomodulatory therapy in patients with clinically progressive cicatrizing conjunctivitis highly suggestive of oMMP. Indeed, the limited sensitivity of conjunctival DIF has been well documented. Accordingly, treatment decisions should ultimately be guided by the totality of findings rather than by immunopathologic results alone.
However, we believe that the value of conjunctival biopsy extends beyond the confirmation of oMMP and warrants further emphasis. In his landmark American Ophthalmological Society thesis on cicatricial pemphigoid, Foster advocated for a clinicopathologic approach, in which biopsy findings are interpreted within the broader clinical context rather than viewed solely through the lens of DIF. In our experience at the Foster Center for Ocular Immunology and Inflammation at Duke University School of Medicine, a high-volume tertiary referral center, biopsy has, not infrequently, identified other disorders, including ocular surface squamous neoplasia, chronic infectious conjunctivitis, other types of inflammatory disorders such as atopy or sarcoidosis, and lymphoproliferative disorders in patients referred for presumed oMMP. Although the authors acknowledge that histopathologic evaluation may occasionally identify diagnoses other than oMMP, diagnostic function of conjunctival biopsy deserves greater awareness. ,,
Furthermore, reserving biopsy only for clinically “atypical” presentations presupposes that alternative diagnoses can be reliably recognized before tissue acquisition and workup, a judgment that may vary with clinician experience. This distinction is particularly relevant because the systemic immunomodulatory therapies often used in oMMP are associated with potentially serious adverse effects. A comprehensive evaluation therefore represents an important patient safety measure, minimizing the risk of missed malignancy, infection, or alternative inflammatory disorders while reducing the likelihood of unnecessary exposure to long-term systemic immunosuppression.
In addition, conventional histopathologic assessment may provide information beyond just diagnosis. Evaluation with hematoxylin and eosin and, in select cases, additional histochemical and immunohistochemical stains can help characterize the relative contributions of cellular elements of active inflammation vs established fibrosis, thereby offering insights into disease stage and potentially informing therapeutic intensity. For this reason, we believe that routine light microscopic examination should accompany DIF whenever conjunctival biopsy is performed for cicatrizing conjunctivitis, even in cases with seemingly classic clinical features.
We applaud the authors for highlighting the limitations of DIF in oMMP and emphasizing clinical judgment. We advocate for a comprehensive diagnostic approach incorporating medical and medication history, clinical findings, and full laboratory workup.
CRediT authorship contribution statement
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
