Relationship between genotype, phenotype, and refractive status in patients of inherited retinal degeneration

Abstract

Background: To elucidate the relationship between inherited retinal disease, visual acuity and refractive error development in Asian patients.

Subjects: Five hundred phakic eyes with refractive data were analysed in this retrospective cohort. Diseases were categorized by clinical phenotypes, and the prevalent genotypes identified in the Taiwan Inherited Retinal Degeneration Project were analysed. Consecutive surveys in Taiwan have provided the rates of myopia in the general population.

Results: No differences were observed among the disease phenotypes with respect to myopia (P = 0.098) and high myopia rates (P = 0.037). The comparison of refractive error between retinitis pigmentosa and diseases mainly affecting the central retina showed no difference, and the refraction analyses in diseases of different onset ages yielded no significance. Moreover, there was no difference in the myopia rate between the diseases and general population. Among the genotypes, a higher spherical equivalent was seen in RPGR and PROM1-related patients and emmetropic trends were observed in patients with CRB1 and PRPF31 mutations. Furthermore, significantly poorer visual acuity was found in ABCA4, CRB1 and PROM1-related patients, and more preserved visual acuity was seen in patients with EYS, USH2A, and RDH12 mutations.

Conclusions: No significant differences were observed in visual acuity, refractive state and myopia rate between patients with inherited retinal disease and the general population, and different subtypes of inherited retinal disease shared similar refractive state, except for higher cylindrical dioptres found in patients with Leber's congenital amaurosis. The heterogeneity of disease-causing genes in Asian patients may lead to variable refractive state.

Fig. 1. Refractive error and visual acuity distribution among disease subtypes.

Box plots showing different refractive state parameters for RP, MD + CD/CRD, LCA, and BCD. A Cylindrical distribution of diseases. The patients with LCA had statistically higher cylindrical dioptres than the other three subtypes. B Spherical equivalent distribution among subtypes. No statistical significance was found. C Visual acuity (logMAR) distribution among the subtypes. No statistically significant differences were observed. *P value <0.05; **P value < 0.005.

Fig. 2. Myopia rates and high myopia rates of different age groups among disease subtypes and the general population.

Line charts showing age-stratified myopia and high myopia rates among the four disease subtypes. Proportion tests were performed between the general population and each disease subtype. A–D Myopia rates between the general population and RP, MD + CD/CRD, BCD, and LCA patients of different age groups. E–H High myopia percentages between the general population and RP, MD + CD/CRD, BCD, and LCA patients of different age groups. **P value < 0.01.

Fig. 3. Refractive error distribution of both eyes (N = 420) among the nine major genotypes after age adjustment using the ANCOVA test.

Box plots showing different refractive state parameters among disease-causing genes. A Cylindrical dioptres distribution among genotypes. No statistical significance was found. B Spherical equivalent distributions among genotypes. Higher SE dioptres were observed in PRGR, and PROM1-related patients and less myopic or even more hyperopic trends were observed in patients with CRB1 and PRPF31 mutations. C Distribution of visual acuity among the pathogenic genes. Profoundly impaired vision was observed in patients with ABCA4, CRB1 and PROM1 mutations, and those with EYS, USH2A and RDH12 mutations had better preserved visual acuity. *P value < 0.05; **P value < 0.01; ***P value <0.001.