Abstract
Purpose :
To quantify the density of macular cone photoreceptors in children receiving subretinal gene therapy (voretigene neparvovec-rzyl) for RPE65–related Leber’s Congenital Amaurosis (LCA).
Methods :
Prospective observational study of four children (8 eyes, Age Range: 10 - 14 years) who underwent adaptive optics imaging (rtx1, Imagine Eyes). Ten to 12 eccentricities (4 °x 4 °field) were imaged: (i) prior to gene therapy, and (ii) 6 to 12 months and (iii) 18 months after treatment. Foveal cone density (0 °, 0 °), and average cone density at other eccentricities were analyzed. The injection site was away from the fovea but within the arcades, and the blebs created encroached to the central fovea. Images with poor quality acquisition due to optical aberrations or motion artifacts, and images from the injection sites were excluded from analysis.
Results :
At baseline, the mean foveal cone density (7 eyes) was 14,945/ mm2 (Range: 10,609–19,806/mm2), whilst at other eccentricities (8 eyes) the mean cone density was 15,433/ mm2 (Range: 5,919–21,210/mm2). Two patients (twins) had the 18-month follow-up. In Twin 1, the foveal cone density decreased from 16,697/mm2 (baseline) to 13,117/mm2 (18 months) in the right eye (RE), and from 16,349/mm2 (baseline) to 12694/mm2 (18 months) in the left eye (LE). The mean cone density at other eccentricities also decreased from baseline (RE: 14,930/mm2, LE: 14,764/mm2) to 18 months (RE: 14,755/mm2, LE: 9,944/mm2). The best corrected visual acuity (BCVA) remained stable at 0.30 and 0.39 log MAR in the RE and LE, respectively during the study. In Twin 2, the LE foveal cone density decreased from 10,609/mm2 (baseline) to 9663/mm2 (18 months). The mean cone density at other eccentricities decreased from baseline (RE: 16,858/mm2, LE: 15,881/mm2) to 18 months (RE: 14,159/mm2, LE: 13,638/mm2, Range). The BCVA remained stable at 0.49 log MAR in either eye during the study. In the twins, foveal cone density significantly decreased at 18 months (Anova F= 4.098 p= 0.04).
Conclusions :
Our preliminary results indicate progressive cone photoreceptor loss following subretinal gene therapy for RPE65-related LCA. Further studies are needed to ascertain if this finding is due to continued cone loss despite gene therapy or if this may be related to surgical procedure.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.