Development of refractive errors – what can we learn from inherited retinal dystrophies?

PURPOSE: It is unknown which retinal cells are involved in the retina-to-sclera signaling cascade causing myopia. As inherited retinal dystrophies (IRD) are characterized by dysfunction of a single retinal cell type and have a high risk of refractive errors, a study investigating the affected cell type, causal gene and refractive error in IRDs may provide insight herein.

DESIGN: Case-control study.

METHODS: Study population: 302 patients with IRD from two ophthalmogenetic centers in the Netherlands. Reference population: population-based Rotterdam Study-III and ERF Study (N=5,550). Distributions and mean spherical equivalent (SE) were calculated for main affected cell type and causal gene; and risks of myopia and hyperopia were evaluated using logistic regression.

RESULTS: Bipolar cell related dystrophies were associated with the highest risk of SE high myopia 239.7; OR mild hyperopia 263.2, both P<0.0001; SE -6.86 D [SD 6.38]); followed by cone dominated dystrophies (OR high myopia 19.5, P<0.0001; OR high hyperopia 10.7, P=0.033; SE -3.10 D [SD 4.49]); rod dominated dystrophies (OR high myopia 10.1, P<0.0001; OR high hyperopia 9.7, P=0.001; SE -2.27 D [SD 4.65]); and RPE related dystrophies (OR low myopia 2.7; P=0.001; OR high hyperopia 5.8; P=0.025; SE -0.10 D [SD 3.09]). Mutations in RPGR (SE -7.63 D [SD 3.31]) and CACNA1F (SE -5.33 D [SD 3.10]) coincided with the highest degree of myopia; in CABP4 (SE 4.81 D [SD 0.35]) with the highest degree of hyperopia.

CONCLUSIONS: Refractive errors, in particular myopia, are common in IRD. The bipolar synapse, and the inner and outer segments of the photoreceptor may serve as critical sites for myopia development.