Dear Editors, Ocular mucous membrane pemphigoid (OcMMP) denotes the subtype of the rare blistering autoimmune disease mucous membrane pemphigoid (MMP) that affects only the ocular mucosa. OcMMP manifests as chronic conjunctivitis, with subepithelial blistering and fibrotic changes, which can lead to symblepharon, trichiasis, and eventually blindness.1-3 The diagnosis of OcMMP is challenging as the sensitivity of direct immunofluorescence (DIF) and serology is lower than in non-ocular MMP.4, 5 Data on patients with isolated ocular involvement remain limited. Here, we present nine patients with OcMMP treated at our medical center. Patients with MMP treated in the departments of ophthalmology and dermatology of the University Medical Center Göttingen between 01/2004 and 04/2025 were retrospectively identified using the ICD-10 code L12.1, and all patients with isolated ocular involvement were included. A total of nine patients with OcMMP were included, whose characteristics, clinical features, and diagnostic findings are presented in Table 1. As diagnostic procedures, histological examination was performed in five patients and was consistent with OcMMP in two cases. DIF showed positive results in four out of eight patients. Serological autoimmune diagnostics were positive in five of nine patients; in four of these five patients, autoantibodies against BP180 domains were identified by immunoblot, while Enzyme-Linked Immunosorbent Assay (ELISA) was negative in all patients (for details see Table 1). In one patient, only indirect immunofluorescence assay on NaCl-separated human split skin was positive, while a target antigen could not be identified. In two patients, the diagnosis of OcMMP was based solely on clinical findings. Regarding systemic treatment, eight of nine patients received one or more systemic therapies. All eight patients received glucocorticoids (GCS) as intravenous (IV) pulse therapy and/or oral therapy (Table 2). As GCS sparing agents, GCS were combined with immunosuppressants. Treatment timelines are shown in Figure 1. In the four patients with a follow-up of more than a year, mycophenolate mofetil (MMF) maintained disease control as monotherapy in one patient and in combination with oral GCS in a second patient. In another patient, disease control was achieved after adding rituximab to MMF and GCS, and in the fourth patient after adding intravenous immunoglobulins (IVIG) to the combination of rituximab and GCS. Azathioprine (AZA) was given as first steroid-sparing agent in two patients but was discontinued due to side effects within two months. 3x synechiolysis 1x laser dacryoplasty 4 (57.1) 2 (33.3) 2 (40.0) 1 (33.3) 1 (50.0) 0 (0.0) 2 (100) 0 (0.0) 0 (0.0) 1 (20.0) 1 (33.3) 1 (50.0) 1 (100) 0 (0.0) 2 (28.6) 3 (50.0) 1 (20.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) OcMMP presents unique diagnostic and management challenges. MMP has an incidence of 1.3–2.0 cases per million population per year,6 and ocular involvement occurs in about 70 % of all MMP cases.7, 8 Disease strictly limited to the eyes is even rarer,8, 9 and OcMMP patients are at risk for delayed diagnosis and potentially worse outcomes.10 Diagnosis of OcMMP can be made on the basis of a compatible clinical presentation even in the absence of positive DIF or serological findings, provided that differential diagnoses have been excluded by routine conjunctival histopathology and clinical examination.4 The reported sensitivity of conjunctival DIF (60 %) is lower than in MMP with extraocular involvement.5, 7, 11 Serological autoimmune diagnostics likewise show limited sensitivity in OcMMP,12 which was also reflected in our cohort, with positive findings in five of nine patients. In line with previous reports, immunoblot proved more sensitive than ELISA in OcMMP,5, 12, 13: None of our patients was positive for BP230 or BP180 NC16A by ELISA, whereas four of five tested positive for BP180 domains by immunoblot. Overall, negative DIF and serology are more common in OcMMP than in MMP patients with additional extraocular involvement.5 Regarding systemic therapy, current European S3 guidelines for MMP recommend a stepwise approach in OcMMP with escalation according to disease severity and activity.14 In our retrospective study, GCS, IV and/or orally, were used as initial acute therapy, either in direct combination with immunosuppressive agents or followed shortly by their subsequent addition. Among steroid-sparing agents, AZA was discontinued due to adverse events that have been reported to be frequent, particularly in older patients.15 MMF was well tolerated in our patients and was part of the long-term therapy regimen in three out of four patients with a follow-up of more than a year. Rituximab and IVIG helped to achieve stable disease in another two patients. This is consistent with previous reports16-18 where rituximab and IVIG were effective in allowing reduction of systemic GCS and concomitant immunosuppressants, and represents a promising option for advanced or refractory OcMMP. Given the risk of progressive disease and irreversible damage, larger studies are needed to better characterize OcMMP and to support the development of individualized, optimized treatment strategies. Open access funding enabled and organized by Projekt DEAL. J. Mohr has been an advisor and/or received grants and/or participated in clinical trials for Abbvie, Allmirall, Biogen IDEC GmbH, Böhringer-Ingelheim, Celgene, Janssen-Cilag GmbH, Leo Pharma GmbH, Eli Lilly and Company, MSD SHARP & DOHME GmbH, Novartis Pharma GmbH, Pfizer GmbH, and UCB. R. Mössner has been an advisor and/or received speakers’ honoraria and/or received grants and/or participated in clinical trials of the following companies: Abbvie, Almirall, Biogen IDEC, Böhringer-Ingelheim, Celgene, Janssen-Cilag, Leo Pharma, Lilly, Moonlake, MSD SHARP & DOHME, Novartis Pharma, Pfizer, and UCB. C. van Oterendorp has been an advisor and/or received speakers’ honoraria and/or received grants and/or participated in clinical trials of the following companies: Abbvie, Bayer, Heidelberg Engineering, Johnson&Johnson, Novartis, Santen. N. Cramer reports no conflicts of interest.
Cramer et al. (Mon,) studied this question.