Purpose: To describe a case of bilateral, multiple branch retinal artery occlusions (BRAO) in a woman on pembrolizumab immunotherapy for metastatic uterine cancer. Methods: Case report of one patient and literature review. Case Presentation: A female in her mid-40s with obesity, hypertension, type 2 diabetes, and metastatic uterine cancer status post chemotherapy, debulking surgery, and whole-brain radiation presented with bilateral worsening of vision and a symptomatic scotoma in her right eye. Ten months prior to presentation, she was found to have recurrence of her cancer and was started on immunotherapy with pembrolizumab and lenvatinib. Dilated fundus examination showed vascular tortuosity, intraretinal hemorrhages, microaneurysms, and macular edema in both eyes. The macular edema was attributed to diabetic retinopathy and was treated with intravitreal bevacizumab. Although there was improvement of edema on optical coherence tomography, her vision did not significantly improve. Over sixteen months, her vision worsened from 20/40 and 20/50 to 20/200 and 20/150 in the right and left eye, respectively. Fluorescein angiography was performed and revealed multiple, bilateral branch retinal artery occlusions, symmetrically involving the superior arterial vessels in both eyes. Extensive imaging and laboratory work-up was negative. Her BRAOs were attributed to pembrolizumab. Conclusion: Pembrolizumab can be associated with multiple branch retinal artery occlusions. Fluorescein angiography is a useful tool in distinguishing between etiologies of retinal vascular disease. Oncologic and ophthalmologic providers should be cognizant of this rare cause of vision loss and screen appropriately. Plain Language Summary: This case reports an unusual ophthalmic complication attributed to an immune checkpoint inhibitor (ICI), a class of medications which are increasingly used to treat refractory solid organ tumors. In this case, our patient had been on an ICI for sixteen months with excellent response of her metastatic uterine cancer. However, her vision progressively worsened in both eyes. Additional ophthalmic testing with fluorescein angiography, a test that highlights the vasculature in the posterior segment of the eye, revealed multiple branch retinal artery occlusions. ICIs are more commonly known to cause autoimmune and inflammatory conditions within the eye, more broadly termed uveitis. They have rarely been reported in association with retinal vascular occlusion, which could potentially be related to vasculitis and occlusion of the retinal arterial lumen. The case presented here shows multiple branch retinal artery occlusions in both eyes, which could not be associated with another ophthalmic condition and ultimately was attributed to her ICI. This report highlights the need for providers to refer appropriately for patients on ICIs with vision loss and for ophthalmologists to consider additional imaging for patients on ICIs with unexplained vision loss. Keywords: Immune checkpoint inhibitor, immunotherapy, PD-1 inhibitor, PD-1/PD-L1 immunotherapy, retinal artery occlusions
Zhao et al. (Sun,) studied this question.