A natural history study of autosomal dominant GUCY2D-associated cone-rod dystrophy

Purpose To describe the natural history of autosomal dominant (AD) GUCY2D-associated cone-rod dystrophies (CRDs), and evaluate associated structural and functional biomarkers.Method Retrospective analysis was conducted on 16 patients with AD GUCY2D-CRDs across two sites. Assessments included central macular thickness (CMT) and length of disruption to the ellipsoid zone (EZ) via optical coherence tomography (OCT), electroretinography (ERG) parameters, best corrected visual acuity (BCVA), and fundus autofluorescence (FAF).Results At first visit, with a mean age of 30 years (range 5-70 years), 12 patients had a BCVA below Australian driving standard (LogMAR >= 0.3 bilaterally), and 1 patient was legally blind (LogMAR >= 1). Longitudinal analysis demonstrated a deterioration of LogMAR by - 0.019 per year (p < 0.001). This accompanied a reduction in CMT of - 1.4 mu m per year (p < 0.0001), lengthened EZ disruption by 42 mu m per year (p = < 0.0001) and increased area of FAF by 0.05 mm(2) per year (p = 0.027). Similarly, cone function decreased with increasing age, as demonstrated by decreasing b-wave amplitude of the light-adapted 30 Hz flicker and fused flicker (p = 0.005 and p = 0.018, respectively). Reduction in CMT and increased EZ disruption on OCT were associated with functional changes including poorer BCVA and decreased cone function on ERG.Conclusion We have described the natural long-term decline in vision and cone function associated with mutations in GUCY2D and identified a set of functional and structural biomarkers that may be useful as outcome parameters for future therapeutic clinical trials.

Automated summary

This study describes the natural history of GUCY2D-associated cone-rod dystrophies, identifies structural and functional biomarkers associated with the disease, and evaluates their correlation with vision and cone function decline.