Objectives Peripheral ulcerative keratitis (PUK) is a severe corneal condition associated with uncontrolled rheumatoid arthritis (RA). Tocilizumab (TCZ) is used to control RA, however, episodes of paradoxical ocular inflammation have been reported in TCZ-treated patients. We report a case series of PUK in TCZ-treated RA patients with ophthalmological and systemic findings and discuss the potential underlying mechanisms. Methods Four patients (6 eyes), aged 47–62 years were included. At the onset of PUK, the median duration of RA was 13 years (3–13), and the median treatment with TCZ was 9 months (3–14). Two patients had active disease (DAS 28 > 3.2) and the disease was controlled in 2 patients (DAS 28 ≤ 3.2). Results TCZ was initially replaced by another immunomodulatory treatment in all patients and later reintroduced in 2 patients without PUK recurrence. Corneal inflammation was controlled in all cases with local and systemic treatments, with severe visual loss in one eye. Conclusion To summarize, PUK may occur in patients with long standing RA after a switch to TCZ and can be interpreted, depending on the context, as insufficient efficacy or a paradoxical manifestation. These cases highlight the urgent need for reliable biomarkers of the efficacy/paradoxical reactions for biologics.

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