Genotypic and phenotypic findings in GUCA1A-associated retinopathy

Abstract

Purpose : To report the range of findings in a cohort of patients with GUCA1A-associated retinopathy.

Methods : The electronic patient record from a single large centre (Moorfields Eye Hospital in London) was retrospectively searched for patients with disease associated with heterozygous variants in GUCA1A. Genotypic data and phenotypic data were analysed, including age, sex, recorded visual symptoms, findings on multimodal retinal imaging and international standard pattern and full-field electroretinogram (PERG; ERG) recordings.

Results : Eighteen patients (6 females, 12 males) from 14 families were included. The p.Tyr99Cys variant was found in 10 families; p.Leu84Phe, p.Ile107Thr, p.Glu111Ala, p.Leu176Phe were found in 1 family each. Mean (SD) age at first visit was 36 (15) years (ranging from 9 to 68 years; median 33.5 years). Mean (SD) right eye LogMAR acuity at first visit was 0.70 (0.61), ranging from 0.18 to light perception (median 0.54). Mean (SD) age at last visit was 47 (15) years (ranging from 24 to 70 years; median 51 years). Mean (SD) right eye LogMAR acuity at last visit was 0.97 (0.58), ranging from 0.12 to light perception (median 0.95). Most patients described progressive problems with central vision, colour vision and photophobia. Across all patient visits, there was a positive correlation between LogMAR visual acuity and age (R² of 0.21 for right and for left eyes). Spectral domain optical coherence tomography revealed outer retinal abnormalities (including irregularity or loss of the ellipsoid zone line) in all eyes in the central macula; no patients had macular oedema. Central macular autofluorescence abnormalities were also observed. On ultra-widefield imaging, a few patients showed peripheral degeneration. ERGs were available in 12 patients: these were consistent with cone dystrophy (n=11) or macular dystrophy (n=1; ERG normal) with PERG P50 evidence of severe macular dysfunction in all but 1 of the 12 cases tested (ages 16-68 years). Five of the 6 oldest cases had the mildest ERG abnormalities.

Conclusions : We present findings from the largest single centre cohort of patients with GUCA1A-associated disease. Most patients had problems with central vision and photophobia, and showed a decline in vision with time. A minority of patients had additional peripheral degeneration evident on imaging. ERGs revealed cone dystrophy in most, including some older cases with mild disease.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.