Abstract
Purpose :
Gene-based therapies for numerous inherited retinal degenerations (IRD) are on the horizon, and current experience with RPE65 gene therapy suggests that treatment given early in life may be most beneficial. We aimed to identify and register all children in the Netherlands with IRD, and determined the genetic cause and risk profile of patients most suitable for future therapies.
Methods :
Clinical and genetic data from IRD patients (N=767, 62% male) aged 0-20 years were collected from medical charts from the 5 centers participating in the national RD5000 study group in the Netherlands over a mean follow-up period of 5.95 ± 4.0 years. Patients were stratified in 2 groups: progressive retinal dystrophies and stable retinal dysfunction disorders. Outcome measures were prevalence of diagnosis, causal genes, mean best-corrected visual acuity (BCVA) in LogMAR at age categories 0-5 years, 5-10 years, 10- 15 years and 15 -20 years. Wilcoxon signed Rank Test was used to analyze differences between groups.
Results :
Mean age at diagnosis was 6.75 ± 5.0 yrs. Among patients with a progressive retinal dystrophy, retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) (together N=249; 52%) and X-linked retinoschisis (XLRS; N=63; 13%) were most prevalent. Within the stable retinal dysfunction group, achromatopsia (N= 62; 53%) and congenital stationary night blindness (CSNB; N=49; 41%) were most prevalent. Almost half of the patients (367/767; 48%) were genetically solved. Most frequently reported disease-causing genes for progressive retinal dystrophies were CEP290 (N=33) and RPE65 (N=15) and RS1 (N=29); most frequent disease-causing genes for stable retinal dysfunctions were CNGB3 (N=22) and CACNA1F (N=15). For RP and LCA cases (122 eyes), mean BCVA was 0.73 ± 0.52 at 0-5 years compared to 0.59 ± 0.49 at 5-10 years (p=0.002), 0.40 ± 0.40 at 10-15 years (p=0.014), and 0.32 ± 0.35 at 15-20 years (p=0.028).
Conclusions :
In the Netherlands, CEP290 and RS1 are the most frequently identified genetic causes of progressive retinal dystrophies in children, and CNGB3 and CACNA1F the most frequently identified causes of stable retinal dysfunction disorders. The Dutch national RD consortium will be an important source for selection of patients most suitable for future gene-based therapies.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.