Photo Credit: JensHN

Researchers link early cone dysfunction in RPGR-related retinal dystrophy to high myopia, with timing of degeneration influencing severity and outcomes.

Cone photoreceptor dysfunction in early childhood is associated with high myopia in patients with retinitis pigmentosa GTPase regulator (RPGR)-related retinal dystrophy, according to findings published in the Journal of Ophthalmology.

“Mutations in RPGR cause over 90% of X-linked retinitis pigmentosa (XLRP) cases, which is characterized by childhood onset, centripetal photoreceptor degeneration, and rapid progression to blindness by the fourth decade when cones are affected later in the disease,” Jasmina Cehajic Kapetanovic, PhD, and colleagues wrote.

Patients with RPGR-related retinal dystrophy present with a varied clinical phenotype with either cone-dominated or rod-dominated degeneration. RPGR-related retinal dystrophy is categorized as rod-cone, encompassing XLRP, cone-rod, or cone dystrophy phenotype.

The case series investigated the clinical characteristics of 24 male patients with molecularly confirmed RPGR-related retinal dystrophy to identify associations with refractive error in the cohort. Patients ranged in age from 7 to 57 years. Among them, eight had a cone-rod phenotype, 1 had a cone-only phenotype, and 15 had a rod-cone phenotype.

The median best-corrected visual acuity was 60 letters in the cone-rod and cone-only phenotypes and 65 letters in the rod-cone phenotype, according to the researchers.

Impact of Cone Degeneration on Myopia

High axial myopia was prevalent in patients with cone-dominated degenerations. After adjusting for age and genetic mutation, the estimated mean refractive error was −7.92DS in the cone-rod phenotype and −3.52DS in the rod-cone phenotype. The researchers noted that the difference between the phenotypes was significant.

There was no significant correlation between nucleotide position and refractive error.

“Evaluation of disease progression found that all patients with a fast-progressing, rod-cone phenotype had high myopia,” the researchers wrote. “Conversely, one patient who presented with a slow-progressing, cone-rod phenotype did not have high myopia.”

Retractive trends in the patient cohort suggest that the time of cone photoreceptor degeneration onset (early childhood as opposed to later) is key in the development of high myopia. The mechanism by which cone dysfunction leads to high myopia, however, is not yet entirely understood.

“Better understanding into the mechanisms of myopia development via further controlled studies can prompt earlier intervention strategies to mitigate disease in affected patients and minimize risks of retinal gene therapy surgery for patients enrolling in clinical trials,” Dr. Cehajic Kapetanovic and colleagues wrote.