Adaptive Optics Scanning Laser Ophthalmoscopy (AOSLO) Measures in MERTK-Related Retinal Degenerations

Abstract

Purpose : Mutations in the MERTK gene cause autosomal recessive rod-cone degeneration that results in impaired outer segment phagocytosis followed by photoreceptor death. We measured the area of cone coverage and cone density in patients with MERTK-related rod-cone degeneration using adaptive optics scanning laser ophthalmoscopy (AOSLO), a non-invasive method to visualize cones with high resolution.

Methods : Seven eyes of four patients with MERTK-related rod-cone degeneration were studied with visual acuity, optical coherence tomography (OCT), fundus autofluorescence (FAF), OCT angiography (OCTA) and AOSLO. AOSLO images were obtained from six eyes with stable fixation. Twelve-month follow up images were taken in four eyes of two patients and density was calculated at one region in each eye at baseline and at month twelve. The area of cone coverage was measured by tracing the visible and contiguous cones in and around the fovea using ImageJ. Cone density was measured in one region near the fovea by a single grader. AOSLO cone spacing was converted to Z-scores, or standard deviations from the normal mean. We analyzed choriocapillaris flow deficit percent (CC FD%) from 6x6mm OCTA scans in the better eye of each patient. CC FD% was the ratio of area with FD, defined as greater than one standard deviation below mean values from a normal database. Average CC FD% was compared between subjects and controls.

Results : Visual acuity ranged from 0.5 to bare hand motion. At twelve months, the area with visible and contiguous cone mosaics decreased from 3.7 deg² ± 1.9 to 1.0 deg² ± 0.52 (mean ± std dev). Mean cone density near the fovea decreased from 1391.7 cones/deg² to 922.2 cones/deg² and spacing increased from 1.7 arcmin to 2.1 arcmin. Cone spacing Z-scores were abnormal (23.2 ± 9.7). For three of four patients, the CC FD% was within normal limits (9.9 ± 3.8). The patient with the most advanced disease showed abnormally increased mean CC FD % (21.7 ± 12.9).

Conclusions : Cones persist at the fovea but the area with contiguous cones decreases over time in MERTK-related rod-cone degeneration. Cone density is reduced below normal and decreases over time. Choriocapillaris flow is preserved even in regions with increased cone spacing until advanced stages of rod-cone degeneration. AOSLO and OCTA may provide sensitive measures of disease progression over one year in patients with MERTK-related rod-cone degeneration.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.