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

Abstract

Immune checkpoint inhibitors (ICIs) are novel immunotherapy-based drugs that have become increasingly popular in the treatment of lung cancer. Researchers have recognized ocular immune-related adverse events (irAEs) secondary to ICIs because of their vision-threatening characteristics. However, they are incompletely characterized and no studies have reported the ICI-related ocular irAEs in lung cancer. Therefore, we aimed to comprehensively illustrate the clinical characteristics, contributory factors, diagnosis, and management of ICI-related ocular irAEs in lung cancer, based on previously reported 79 patients. Ophthalmoplegia (40.51%), uveitis (20.25%), and dry eye (17.72%) were the most common ICI-related ocular irAEs in lung cancer. Ptosis was the most common (36.71%) and the highest mortality (23.33%) of ophthalmoplegia. Patients in Asia and patients who underwent combination therapy with programmed cell death-1 and cytotoxic T-lymphocyte-associated antigen 4 inhibitors demonstrated significantly higher frequency of ophthalmoplegia than other ocular irAEs. Most ICI-related ophthalmoplegia and uveitis in lung cancer were observed in the first 10 weeks following the initiation of ICIs. Furthermore, the onset time of dry eye and other ocular irAEs was much longer. In addition, 92.31% of the patients with ocular irAEs other than ophthalmoplegia could be remised. In conclusion, ocular irAEs secondary to ICIs in lung cancer are non-negligible, particularly ophthalmoplegia. Ethnicity and the type of ICIs play important roles in the distribution of ocular irAEs. ICI-related ophthalmoplegia in lung cancer presented with early onset and worse prognosis features, thus necessitating further attention.

Anti-PD-1 sintilimab-induced bilateral optic neuropathy in non-small cell lung cancer: A case report and literature review

“…The relatively rare ophthalmic irAEs have been only reported in less than 5% of patients treated with anti-PD-1 antibody-containing regimens ( 15 ). The optic neuritis was the fifth most common ICI-related ocular adverse event in lung cancer, and most of the patients with ocular irAEs other than ophthalmoplegia could be relieved after drug withdrawal and glucocorticoid treatment ( 17 , 27 ). Optic neuritis is one of the ophthalmic emergencies and may lead to permanent vision damage if left inappropriately treated ( 16 ).…”

“…A comprehensive review reported that ophthalmoplegia (40.51%), uveitis (20.25%), dry eye (17.72%), retinopathy (5.06%), conjunctivitis (5.06%), and optic neuritis (3.80%) were the most common immune checkpoint inhibitor (ICI)-related ocular adverse events in lung cancer ( 17 ). A recent report showed that pembrolizumab might lead to inflammatory optic neuritis, which could reverse by the cessation of ICI and the use of corticosteroids ( 18 ).…”

Holistic Approach to Immune Checkpoint Inhibitor-Related Adverse Events

“…irAEs of the eye are rare and occur in <1% of patients treated with ICIs ( 212 , 213 ). Uveitis can be a complication of ICI treatment ( 214 ).…”

Atezolizumab induced immune-related adverse event mimicking conjunctival metastatic disease

“… 2 According to recent literature reviews, ocular irAEs occur in an estimated 1–4% of patients with dry eye disease (1–24%) and uveitis (1%) being most common. 3 , 4 , 5 , 6 …”