Clinical and Morphologic Characteristics of ERK Inhibitor-Associated Retinopathy.

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Investigate clinical and morphologic characteristics of serous retinal disturbances in patients taking extracellular signal-regulated kinase (ERK) inhibitors.Of 61 patients receiving ERK inhibitors for treatment of metastatic cancer, this study included 40 eyes of 20 patients with evidence of retinopathy confirmed by optical coherence tomography (OCT).Single center, retrospective study of prospectively collected data METHODS: Clinical exam, fundus photography and OCT were used to evaluate ERK inhibitor retinopathy. The morphology, distribution and location of fluid foci were serially evaluated for each eye. Visual acuity and choroidal thickness measurements were compared at baseline, fluid accumulation and resolution.Characteristcs of treatment-emergent choroid and retinal OCT abnormalities as compared to baseline OCT, and the impact of toxicity on visual acuity and final visual acuity.Of 20 patients with retinopathy the majority of patients had fluid foci that were bilateral (100%), multifocal in each eye (75%) and at least one focus involving the fovea (95%). All subretinal fluid foci occurred between the interdigitation zone and an intact retinal pigment epithelium. There was no statistical difference in choroidal thickness at fluid accumulation and resolution compared to baseline. 45% eyes had evidence of concomitant intraretinal edema localized to the outer nuclear layer. At the time of fluid accumulation, 57.5% eyes had a decline in visual acuity (mainly by 1-2 lines from baseline). For all eyes with follow-up, the subretinal fluid and intraretinal edema was reversible and resolved without medical intervention; and best-corrected visual acuity at fluid resolution was not statistically different from baseline. Concomitant intraretinal fluid was not associated with worsening of visual acuity. No patient discontinued or decreased drug dose on account of their retinopathy.This study shows ERK inhibitors may cause subretinal fluid foci with unique clinical and morphologic characteristics. The observed foci are similar to MEK inhibitor associated retinopathy and distinct from central serous chorioretinopathy. However, unlike MEK inhibitors, there appears to be an increased occurrence of concomitant intraretinal fluid without significant additive visual impact. In this series, ERK inhibitors did not cause irreversible loss of vision or serious eye damage: retinopathy was self-limited and did not require medical intervention.

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Authors: Jasmine H Francis, Julia Canestraro, Dianna Haggag-Lindgren, James J Harding, Eli L Diamond, Alexander Drilon, Bob T Li, Iyer Gopakumar, Alison M Schram, David H Abramson