Purpose: To evaluate foveal function in patients with inherited retinal degenerations (IRD) by measuring visual acuity (VA) after correction of higher-order aberrations. Methods: Adaptive optics scanning laser ophthalmoscopy (AOSLO) was used to image cones in 4 healthy subjects and 15 patients with IRD. The 840-nm scanning laser delivered an “E” optotype to measure AOSLO-mediated VA (AOSLO-VA). Cone spacing was measured at the preferred retinal locus by two independent graders and the percentage of cones below the average density of 47 age-similar healthy subjects was computed. Cone spacing was correlated with best-corrected VA measured with the Early Treatment of Diabetic Retinopathy Study protocol (ETDRS-VA), AOSLO-VA, and foveal sensitivity. Results: ETDRS-VA significantly correlated with AOSLO-VA (ρ = 0.79, 95% confidence interval [CI] 0.5–0.9). Cone spacing correlated with AOSLO-VA (ρ = 0.54, 95% CI 0.02–0.7), and negatively correlated with ETDRS letters read (ρ = −0.64, 95% CI −0.8 to −0.2). AOSLO-VA remained ≥20/20 until cones decreased to 40.2% (CI 31.1–45.5) below normal. Similarly, ETDRS-VA remained ≥20/20 until cones were 42.0% (95% CI 36.5–46.1) below normal. Cone spacing z scores negatively correlated with foveal sensitivity (ρ = −0.79, 95% CI −0.9 to −0.4) and foveal sensitivity was ≥35 dB until cones were 43.1% (95% CI 39.3–46.6) below average. Conclusions: VA and foveal cone spacing were weakly correlated until cones were reduced by 40% to 43% below normal. The relationship suggests that VA is an insensitive measure of foveal cone survival; cone spacing may be a more sensitive measure of cone loss.

Purpose: Leber congenital amaurosis due to CEP290 mutations (LCA10) is an inherited retinal disease that often results in severe visual impairment or blindness in early childhood. Currently, there are no approved treatments, highlighting the considerable unmet medical need associated with LCA10. We aimed to review the clinical characteristics of LCA10, its impact on patients and society, and the investigational treatment strategies currently in development. Methods: Review of the current literature. Results: LCA10 is an autosomal recessive ciliopathy, for which the CEP290 intronic variant c.2991+1655A>G (p.Cys998X) is the most common mutation. Usually diagnosed in early childhood, most patients with LCA10 have severe visual impairment during their first decade of life, which significantly affects the quality of life and development. LCA10 also has a significant societal burden (direct and indirect costs). RNA editing using antisense oligonucleotides or Staphylococcus aureus CRISPR-associated protein-9 nuclease is currently under investigation for treatment of p.Cys998X LCA10. Specifically, the antisense oligonucleotide therapy QR-110 (sepofarsen) has demonstrated encouraging safety and efficacy data in a first-in-human trial; a phase 3 clinical trial is ongoing. Conclusion: Interventions that can preserve or improve vision in patients with LCA10 have considerable potential to improve the patient quality of life and reduce burden of disease.