Abstract
Purpose :
To report the spectrum of ophthalmic adverse events related to immune checkpoint inhibitor (ICI) therapy with attention to external manifestations.
Methods :
The WHO VigiLyze database of individual case safety reports (ICSRs) was queried for reported eye disorders associated with ICIs (ipilimumab, pembrolizumab, nivolumab, avelumab, atezolizumab, durvalumab, and tremelimumab) from 2009 to April 15, 2018. ICSRs were further categorized as ocular, external, or visual disturbances only. Events categorized as external exclude any globe involvement (eyelid, extraocular muscle, and orbital disease) and were further analyzed.
Results :
A total of 846 patients with ophthalmic ICSRs were identified, of which 165 (19.5% of the total) had external manifestations. Of these 165 patients, 54 (32.7%) experienced diplopia, 47 (28.5%) had ptosis, 14 (8.5%) suffered ocular myasthenia like disorders, and 50 (30.3%) suffered a variety of other ailments including non-specific eyelid and orbital disorders, nystagmus, and strabismus. Over 90% of patients had sex recorded, and of those 89 (58.6%) were males and 63 (41.4%) were females. The average age of patients with external manifestations was 65 years (range 27-86 years). Most patients received nivolumab (N=76, 46.1%), pembrolizumab (N=42, 25.5%), ipilimumab (N=33, 20.0%), or a combination of ipilimumab and nivolumab (N=7, 4.2%). Patients with external manifestations were under treatment for fourteen different primary malignancies the most common of which where cutaneous melanoma (N=55, 33.3%), lung cancer (N=46, 27.9%), and renal cancer (N=10, 6.1%).
Conclusions :
ICIs are increasingly used for metastatic malignancies; however, the frequency and spectrum of ophthalmic adverse events has not been fully described. While ocular adverse events like uveitis and dry eye are most commonly reported, our work highlights that a much broader spectrum of ophthalmic adverse events occurs, including complications beyond the globe. We advocate for establishing ophthalmic screening guidelines for patients receiving these medications to allow early diagnosis of these ophthalmic manifestations.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.