Spontaneous Corneal Perforation Due To Nivolumab Associated Peripheral Ulcerative Keratitis

To present a case of Immune checkpoint inhibitor, nivolumab, induced peripheral corneal ulcer leading to corneal perforation: successfully managed by withdrawing Nivolumab, corneal gluing, and systemic corticosteroids to control surface inflammation.

 Tertiary care hospital -Corneal and external disease services, Department of Ophthalmology, University Hospital Coventry and Warwickshire, Coventry, United Kingdom

Retrospective case report.

A 77-year-old gentleman with inoperable oral cavity squamous cell carcinoma was started on palliative nivolumab by oncologists.3 months after starting nivolumab, he presented with painless vision loss and redness in right eye for 4 days.

On examination, corneal perforation with peripheral corneal thinning in inferotemporal quadrant and mild surface inflammation was seen. No infective agent found on corneal swabs. Autoimmune screen revealed raised ESR, CRP, rheumatoid factor and CCP. Positive ENA and ANA with indeterminate ANCA pattern (MPO and PR3 negative). Although patient had some deformities in both hands, he denied any joint pain/ stiffness. He was previously not known to have rheumatologic/ autoimmune disease.

After oncology and rheumatology review patient was diagnosed with right perforated peripheral ulcerative keratitis thought to be exacerbated by nivolumab. It was difficult to comment whether rheumatoid arthritis (RA)was pre-existing or patient had nivolumab related inflammatory arthritis mimicking RA

Corneal perforation was glued with cyanoacrylate glue requiring multiple revisions.

Nivolumab was withdrawn and three courses of IV methylprednisolone pulse dose followed by oral prednisolone in tapering doses was started.

  At 5 months review, corneal glue was holding well, corneal thinning and inflammation have settled. Patient declined DMARD/immunomodulators and is under low dose maintenance oral prednisolone with close clinical monitoring.

Immune checkpoint inhibitors like nivolumab are being increasingly used for treatment of solid head and neck tumours. These agents can cause a number of ocular immune related adverse events (IRAE)including corneal perforation. Immune arthritis resembling rheumatoid arthritis is also an adverse reaction of these agents which can be confused with autoimmune rheumatoid arthritis.

Prompt recognition of the condition by ophthalmologists and close liaison with oncologists and rheumatologists is required to manage the condition. Withdrawal from nivolumab with high-dose systemic steroid treatment needs to be judiciously considered, balancing risk of stopping anticancer treatment and the severity of ocular adverse reactions from such treatment