MEK INHIBITOR-ASSOCIATED RETINOPATHY (MEKAR) IN A PEDIATRIC PATIENT WITH AN OPTIC PATHWAY GLIOMA

Abstract Pediatric low-grade glioma (LGG) and plexiform neurofibroma (PN) universally have up-regulation of the RAS-mitogen-activated protein kinase (MAPK) pathway. Recent phase I and II clinical trials evaluating MEK inhibitors for the treatment pediatric LGG and PN report efficacy and tolerable side effects, including no reported ophthalmologic toxicity. Contrary to the pediatric experience, adult trials using MEK inhibitors describe several ophthalmologic side effects, including MEK inhibitor-associated retinopathy (MEKAR), also termed central serous-like retinopathy. MEKAR is defined as accumulation of subretinal fluid. It occurs in up to 90% of adults on MEK inhibitors, usually causing minimal to no symptoms, and typically resolving without MEK inhibitor dose adjustment. We report a case of MEKAR in a 15 year old boy with an optic pathway pilocytic astrocytoma with duplication of BRAF (7q34). Baseline ophthalmic exam showed 20/20 vision in his right eye with loss of the temporal hemifield and no light perception vision in the left eye. Nine months into treatment with Selumetinib his ophthalmologic exam and optical coherence tomography (OCT) showed asymptomatic bilateral subretinal fluid. Selumetinib was held for 2 weeks resulting in resolution of the subretinal fluid. Selumetib was resumed at the prior dose and MEKAR recurred 2 weeks later but then permanently resolved 4 weeks later despite remaining on Selumetib. Review of the literature discovered a single publication of 2 pediatric patients with optic pathway glioma who developed MEKAR around 6-7 months after initiating Selumetinib, which resolved after stopping Selumetinib. One patient was symptomatic and despite resolution of symptoms, Selumetinib was not resumed. The other patient was asymptomatic and resumed Selumetib, but redeveloped MEKAR 8 months after restarting Selumetinib. Based on adult experience and the limited pediatric experience outlined above, we recommend pediatric patients with asymptomatic and mild-moderate symptomatic MEKAR undergo close monitoring without Selumetinib dose interruption or modification unless symptoms progress.