Journal
RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
Volume 39, Issue 3, Pages 502-513Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/IAE.0000000000002027
Keywords
MEK; hydroxychloroquine; interdigitation zone; outer segments; optical coherence tomography; central serous retinopathy; cutaneous melanoma; BRAF inhibition; MEK inhibition; photoreceptors; subretinal fluid
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Funding
- National Institutes of Health [NEI-K12EY015398-10]
- Hope for Vision
- Foundation Fighting Blindness
- Macula Vision Research Foundation
- Paul and Evanina Bell Mackall Foundation Trust
- Pennsylvania Lions Sight Conservation and Research Foundation
- Research to Prevent Blindness
- NATIONAL CANCER INSTITUTE [P50CA174523, R01CA198015, P01CA114046] Funding Source: NIH RePORTER
- NATIONAL EYE INSTITUTE [K12EY015398] Funding Source: NIH RePORTER
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Purpose: To assess the potential ocular toxicity of a combined BRAF inhibition (BRAFi) + MEK inhibition (MEKi) + hydroxychloroquine (HCQ) regime used to treat metastatic BRAF mutant melanoma. Methods: Patients with stage IV metastatic melanoma and BRAF V600E mutations (n = 11, 31-68 years of age) were included. Treatment was with oral dabrafenib, 150 mg bid, trametinib, 2 mg/day, and HCQ, 400 mg to 600 mg bid. An ophthalmic examination, spectral domain optical coherence tomography, near-infrared and short-wavelength fundus autofluorescence, and static perimetry were performed at baseline, 1 month, and q/6 months after treatment. Results: There were no clinically significant ocular events; there was no ocular inflammation. The only medication-related change was a separation of the photoreceptor outer segment tip from the apical retinal pigment epithelium that could be traced from the fovea to the perifoveal retina noted in 9/11 (82%) of the patients. There were no changes in retinal pigment epithelium melanization or lipofuscin content by near-infrared fundus autofluorescence and short-wavelength fundus autofluorescence, respectively. There were no inner retinal or outer nuclear layer changes. Visual acuities and sensitivities were unchanged. Conclusion: BRAFi (trametinib) + MEKi (dabrafenib) + HCQ causes very frequent, subclinical separation of the photoreceptor outer segment from the apical retinal pigment epithelium without inner retinal changes or signs of inflammation. The changes suggest interference with the maintenance of the outer retinal barrier and/or phagocytic/pump functions of the retinal pigment epithelium by effective MEK inhibition.
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