Ophthalmic adverse effects of immune checkpoint inhibitors: the Mayo Clinic experience

Abstract

Background/AimsTo investigate immune-related ophthalmic side effects of systemic checkpoint inhibitors and compare side effect frequency and requirement for cessation of immunotherapy by checkpoint target.MethodsPatients taking immune checkpoint inhibitors at a single centre from January 1, 2010 to February 29, 2020 were retrospectively reviewed for clinical characteristics, treatments and concurrent systemic adverse effects.ResultsOf 996 patients, 28 (2.8%) experienced an ophthalmic side effect that came to the attention of an eye care provider. Mean age at presentation of the side effect was 63 years (median 64, range 25–88). The checkpoint inhibitor most often preceding side effects was pembrolizumab in 12 (43%). The most common side effect was dry eye in 16 (57%), followed by uveitis in 4 (14%) patients, and singular cases of ptosis and binocular diplopia, among others. Ocular surface adverse effects occurred more frequently with programmed death ligand-1 (PD-L1) targeting therapy. There were no significant differences in the frequency of orbit/ocular adnexa and uveitis or retinal side effects based on checkpoint targets. Follow-up was available in 13 (46%) patients, with mean duration of 20 months (median 16, range 2–52 months). Of these patients, the ophthalmic side effects were controlled without discontinuing therapy in 12 (92%). Checkpoint inhibitor cessation was required in one patient with panuveitis.ConclusionOphthalmic immune-related adverse events are rare but could be more common than previously estimated. PD-L1-directed checkpoint inhibitors may have a slight predilection for ocular surface adverse effects. Most ophthalmic events can be treated with targeted therapy without discontinuation of life-prolonging immunotherapy.

Ocular adverse events associated with immune checkpoint inhibitors: a novel multidisciplinary management algorithm

“…Ocular IrAEs occur with an estimated prevalence of 1–3% of all treated patients. 8 , 9 While the spectrum of severity is broad, they are highly significant as they can threaten vision. Reports of ocular IrAEs associated with CPIs are limited to small, single-digit case series and individual case reports, which principally report patients experiencing varying degrees of uveitis.…”

Ocular Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors in Lung Cancer

“…In 2018, uveitis and dry eye had been reported as the most frequent ICI-related ocular side effects. Ocular irAEs were reported in 2.80% patients in a cohort of 996 patients with ICIs reported in Mayo clinic ( 31 ). Dry eye was observed in 57.14% of the patients with ocular irAEs, followed by uveitis in 14.28% of the patients ( 31 ).…”

“…Ocular irAEs were reported in 2.80% patients in a cohort of 996 patients with ICIs reported in Mayo clinic ( 31 ). Dry eye was observed in 57.14% of the patients with ocular irAEs, followed by uveitis in 14.28% of the patients ( 31 ). In relation to ICI-associated ocular surface toxicity, dry eye, conjunctivitis, and keratitis were reportedly the most common irAEs in a previous review involving 29 studies ( 32 ).…”

“…Researchers have also identified differences in the distribution and incidence of ocular irAEs. Ocular surface adverse effects occur more frequently with PD-L1 ( 31 ). Uveitis is more likely to occur in patients following ICI therapy with CTLA-4 inhibition than in those with PD1 inhibition ( 14 , 30 , 136 ).…”

Corneo-Uveal-Retinal Adverse Effects after Single Course of Targeted Anti-Cancer Therapy: Case Report and Review of Literature

“…Those targeted anticancer drugs have become an increasingly important tool in the oncologic armamentarium but have also been associated with a diverse spectrum of side effects [4,5].…”