Immune checkpoint inhibitor-associated orbital inflammation: a systematic review

Immune checkpoint inhibitors (ICIs) are increasingly used across a growing range of malignancies. ICI-associated orbital inflammation is a rare immune-related adverse event (irAE) that remains poorly characterised despite its potential for substantial visual morbidity.

A systematic search of PubMed, Ovid MEDLINE, Embase, Scopus, and Google Scholar was performed in September 2026. Studies reporting orbital inflammatory disease during or following ICI therapy were included.

Fifty-seven studies reporting 81 patients were included. The median age at presentation was 65.6 years (IQR, 55.5-77.0), and 63% were male. Melanoma was the most common malignancy (40.7%). The median time to onset of orbital inflammation following ICI initiation was 6.0 weeks (IQR, 3.5-11.3). Concurrent non-orbital irAEs occurred in 67.9% of patients, most commonly systemic myositis (37.0%) and myocarditis (23.5%). The most common clinical features were ophthalmoplegia (70.4%) and proptosis (29.6%), with bilateral disease in 76.5% of cases. Extraocular muscle inflammation predominated (82.7%), followed by diffuse orbital inflammation (32.1%), while dacryoadenitis (4.9%) and optic nerve involvement (6.2%) were rare. Thyroid eye disease-like orbitopathy was described in 17.3% of patients, most of whom were euthyroid (78.6%). Corticosteroids were administered in 92.6% of patients, with 39.5% requiring additional immunomodulatory therapy. Complete or partial resolution occurred in 88.3% of patients and disease recurrence occurred in 9.9%.

ICI-associated orbital inflammation demonstrates a distinct phenotype characterised by early onset, bilateral disease, extraocular muscle predominance, and frequent overlap with systemic myositis and myocarditis. Recognition should prompt immediate multidisciplinary assessment and evaluation for systemic irAEs.