Abstract
Purpose :
To compare cone structure and function in patients with autosomal dominant-cone rod dystrophy (AD-CRD) due to genetic mutations in retinal guanylate cyclase (GUCY2D), which encodes a protein that modulates calcium metabolism, and in the homeodomain transcription factor (CRX) that regulates photoreceptor differentiation.
Methods :
Refractive error, best corrected visual acuity, short-wavelength autofluorescence fundus photos, and spectral domain optical coherence tomography (SD-OCT) were obtained from all subjects. Confocal and split-detector adaptive optics scanning laser ophthalmoscopy (AOSLO) images were acquired from one patient each with GUCY2D and CRX mutations and stable fixation. Cone spacing was calculated using a density recovery profile method and Z-scores were used to report standard deviation (std dev) from the normal mean at the eccentricity of the measured cones; < 2 was within normal limits. Differences between groups were assessed by Student’s t-test (GraphPad PRISM-9 software).
Results :
Our cross-sectional study included 14 eyes of 7 AD-CRD patients (3 with GUCY2D and 4 with CRX mutations); the groups were not different in age (GUCY2D mean ± std dev: 51.3 ± 17.8 years, and CRX 41.0 ± 3.8, P = 0.3). Though both groups displayed reduced visual acuity and central scotomas, CRX patients had better visual acuity (P = 0.013) and less myopic refractive error (P = 0.0075) than GUCY2D patients. Fundus autofluorescence revealed retinal pigment epithelial mottling in early stages and bull’s eye maculopathy in advanced disease in both groups. SD-OCT revealed outer retinal layer thickness loss with foveal atrophy in all but one GUCY2D patient and ellipsoid zone irregularity in CRX patients. AOSLO images showed no evidence of cone structure at the anatomical fovea for either CRX- or GUCY2D-related AD-CRD. In the eyes with CRX-related AD-CRD, cone spacing Z scores were within normal limits (0.76 ± 0.70; n=3 regions), while in the eyes with GUCY2D-related AD-CRD, Z-scores were abnormal (5.2 ± 5.3; n=10 regions).
Conclusions :
AD-CRD differs in disease severity as evidenced by worse visual acuity, greater myopic refractive error and more abnormal cone spacing in GUCY2D patients relative to similarly aged CRX patients. High resolution retinal imaging showed cone loss in all imaged patients and may aid in diagnosis and disease severity monitoring in patients with GUCY2D and CRX-related AD-CRD.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.