Biomarkers to monitor progression in MERTK retinopathy

Abstract

Purpose : MERTK, a tyrosine kinase receptor protein expressed by the retinal pigment epithelium (RPE), is mutated in a rare group of autosomal retinitis pigmentosa (RP) patients. The purpose of this study is to investigate biomarkers in MERTK-RP patients.

Methods : Medical records for MERTK genetically confirmed patients attending the Save Sight Institute 2014 - 2019 were reviewed. Best corrected visual acuity (BCVA) and spectral domain optical coherence tomography (SD-OCT) central macular thickness (CMT) and ellipsoid zone (EZ) length were assessed. Ultra-widefield fundus autofluorescence (UW-FAF) identified patterns of change by qualitative grading (Hypo-AF/Hyper-AF areas). Semi-automated kinetic perimetry (SKP) used III4e and V4e stimuli. ISCEV standard full field electroretinogram (ffERG) and pattern electroretinogram (pERG) were analysed.

Results : Ten eyes from 5 subjects (2 siblings) mean age 25.2 yrs (19-45.9). Mean follow-up 51.7 months (24.6-66.9). BCVA mean at presentation 0.88 ± 0.83 range 0.30 to 2.40 logMar. Mean BCVA at last visit 1.10 ±0.87. Mean reduction in acuity was 0.22 LogMar equivalent to 0.05 logMar units per year. This rate of loss will lead to BCVA progressing to legal blindness for all eyes in approximately 14 years. All patients had a myopic refraction. Mean CMT at presentation 184.7µ ± 32.9, mean last visit CMT 152.6µ±17, mean reduction in CMT 32.1±21µ with a rate of -7.45 µ per year. OCT showed shortening of the EZ then disruption into discrete hyperreflective bodies which migrated to the outer nuclear layer. EZ could be measured in 8 eyes at initial visit (mean 1297±416µ) and 7 eyes at last visit (mean 784±285µ). ffERG confirmed a rod-cone dystrophy. PERG was identifiable in only one patient. AF showed several different phenotypes, but each had a central macular speckled hyperAF correlating with macular atrophy, a diffuse mid peripheral hyperAF in addition 2 had a hypoAF areas corresponding to the retinal vascular arcades. SKP (III4e and V4e) was normal in 2 eyes, restricted nasal field in four eyes, superior wedge defect in 2 eyes and undetectable in 2 eyes.

Conclusions : In this young cohort visual loss (BCVA) occurred early due to macular dysfunction with CMT and EZ line decline. Visual field assessment (SKP) showed relative peripheral field preservation. This study identifies the relatively rapid decline in BCVA in MERTK -RP patients providing guidance to timing for intervention with therapeutic clinical trials.

This is a 2020 ARVO Annual Meeting abstract.