Features
Despite the increasing prevalence of melanoma worldwide, the mortality from this disease entity continues to decline due to improved and targeted therapies. Specifically in the case of metastatic disease, the use of novel immunomodulatory therapies has shown great promise, significantly improving progression-free survival.
Immune checkpoint inhibitors, which serve to “release the brakes” on the immune system and enzyme inhibitors that have specific molecular targets, have been reported to have significant systemic side effects. Ocular immune-related adverse events, although less common, have also been reported.
Immune checkpoint inhibitors:
Anti-CTLA-4 monoclonal antibody: ipilimumab.
Anti-PD-1 antibodies: nivolumab and pembrolizumab.
Anti-PDL-1 antibodies: atezolizumab, avelumab, and durvalumab.
Enzyme inhibitors:
BRaf enzyme inhibitors: vemurafenib and dabrafenib.
MEK pathway inhibitors: binimetinib, trametinib, and cobimetinib.
The imaging features of retinopathy from these immune modulators are similar given they all reflect the hallmark feature of subretinal fluid with or without inflammation. However, the pathophysiology is postulated to be different. The immune checkpoint inhibitor antibody drugs likely act via an increase in inflammation as they lead to T-cell activation and secretion of proinflammatory molecules, which is believed to cause leakage of vessels from the choroidal circulation. In contrast, the BRAF and MEK inhibitors disrupt the FGFR-MAPK pathway, which is responsible for maintaining the integrity of the retinal pigment epithelium (RPE) cells, affecting their ability to maintain fluid balance as well as deal with oxidative stress, thus resulting in fluid accumulation and possible retinal vein occlusions.
91.1.1 Common Symptoms
Common symptoms are blurred vision (usually bilateral), photophobia, and eye pain or foreign body sensation.
91.1.2 Exam Findings
Inflammation may range from none to mild anterior chamber and/or vitreous cell. Blunted foveal reflexes indicate subretinal or intraretinal fluid. Multifocal serous retinal detachments are possible. In rare cases associated with combined ipilimumab and nivolumab, concurrent choroidal detachment with secondary angle closure was observed. Retinal vein occlusion is seen particularly with MEK pathway and BRaf inhibitors.
91.2 Key Diagnostic Tests and Findings
91.2.1 Optical Coherence Tomography
Optical coherence tomography demonstrates multifocal areas of neurosensory retinal detachment with or without intraretinal edema and possible undulation of the RPE if there are associated choroidal detachments (▶ Fig. 91.1).
Fig. 91.1 (a) Right and (b) left eyes of a patient on MEK inhibitor therapy with small pockets of subretinal fluid.
(Images courtesy of Jasmine Francis, MD and Irina Belinsky, MD)
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