Buccal Biopsy Appropriate for Suspected Ocular Cicatricial Pemphigoid

Ocular mucous membrane pemphigoid
Ocular mucous membrane pemphigoid
Buccal mucosal biopsy with direct immunofluorescence proposed as “silver standard” to diagnose ocular cicatricial pemphigoid (OCP).

Ocular cicatricial pemphigoid (OCP) is a fibrotic autoimmune disease, challenging to diagnose, in part because gold standard conjunctival biopsy is only intermittently positive — thus, clinicians may offer immunosuppressive therapy for patients who present with highly OCP-suspicious clinical signs despite negative direct immunofluorescence (DIF). Since multiple conjunctival biopsies also introduce the risk for complication, a less invasive method is necessary, investigators report. A study published in Ophthalmology shows that, despite absence of buccal lesion, buccal mucosal biopsies increase the number of individuals who can be treated as DIF-positive.

The chart review included all individuals evaluated for cicatrizing conjunctivitis at University of Texas Southwestern Medical Center (UTSW) from September 2011 to the end of August 2019, and who attended follow-up for 6 months or longer. After excluding cases with involvement outside the eye and diagnoses other than OCP, the cohort comprised 41 participants, mean age 67 years, with a range of 43 to 85 years. Care included examinations by an ophthalmologist and dermatologist specialist, and all were offered an initial conjunctival or buccal mucosal biopsy.

Of the 41, 18 chose conjunctival biopsy, and 12 of these were positive. Additionally, 4 individuals with 2 consecutive negative conjunctival tests later had buccal DIF positive results. All participants underwent 1, 2, or 3 buccal biopsies.

In the buccal samples, 22 were positive: 14 exhibited positive DIF on the first buccal biopsy, followed by an additional 8 after the second round. The amount of positive buccal tests may not at first appear striking, but it is notable, as a rate of approximately 54% positivity or greater is comparable with that found with conjunctival tissue samples, the analysis explains. Almost all, 21 with positive buccal results showed immunoglobulin G (IgG) in the basement membrane.

After 17 patients obtained negative conjunctival biopsies, a positive buccal test allowed them to be reclassified to DIF-positive. Further, 13 more could be treated without having conjunctival testing, and 4 additional individuals were freed from a second ocular procedure. Also, no buccal samples were positive in individuals with low clinical suspicion for OCP.

Prior research has established that mucous membrane pemphigoid (MMP) lesions may appear in different locations or mucosal surfaces. And like MMP, OCP may also show intermittent DIF-positive results, the investigators wrote. As such, a patient may need more than one biopsy, and buccal sampling has been associated with fewer complications. Further, testing the buccal region may ultimately boost cases from DIF-negative to DIF-positive status, potentially enabling more individuals with OCP to obtain earlier, consistent therapy and obtain insurance approval for immunosuppressives — thus, a “silver standard“ option in sight-threatening cases. 

In this analysis, conjunctival biopsies were analyzed by Massachusetts Eye Research and Surgery Institution (MERSI), and buccal DIF performed at UT Southwestern Cutaneous Immunopathology lab. The retrospective design limited this study, as well as a non-diverse cohort of 83% White individuals. Also, since participants could receive immunosuppressive therapy after a positive buccal biopsy — waiving conjunctival testing — the 2 biopsies were not directly compared for sensitivity and specificity. The investigation’s strength was in demonstrating positive DIF by buccal mucosal biopsy without an oral lesion in patients with ocular-only autoimmune disease.


Lopez SN, Cao J, Casas de Leon S, Dominguez AR. Utility of direct immunofluorescence using buccal biopsies in those with suspected isolated ocular mucous membrane pemphigoidOphthalmol. Published online June 7, 2022. doi:10.1016/j.ophtha.2022.06.001