Intraretinal pigment migration predicts gene location in inherited retinal dystrophies

Abstract

Purpose : Intraretinal pigment migration (IPM), or bone spicule pigmentation, is a common feature seen on fundus examination of inherited retinal dystrophy (IRD) patients. The pigment clumps are composed of retinal pigment epithelial cells that translocate through the retina following photoreceptor cell death. We hypothesized that the function and location of the disease-causing gene will lead to differences in the timing and extent of pigmentary manifestation, whereby mutations in RPE-specific genes result in the absence of pigment migration, and mutations in photoreceptor-specific genes give rise to prominent pigment migration.

Methods : A cohort of 357 patients with IRDs was categorized based on the recognized location and function of the gene implicated in disease: non-ciliary photoreceptor (PR), ciliary and periciliary photoreceptor (CP), and retinal pigment epithelium (RPE). Presence of IPM was evaluated through indirect ophthalmoscopy and confirmed using wide-field color fundus and spectral domain-optical coherence tomography (SD-OCT) imaging. A χ²-test was performed using R statistical software to determine whether the incidence of IPM was independent of the gene category. A Fisher’s exact test was applied to determine the incidence of IPM after stratification by age between the PR and CP groups. The RPE cohort was excluded in age stratification due to limited sample size. A binary logistic regression model using gene category and age category as explanatory variables was fitted to predict the incidence of IPM based on gene and age.

Results : A pooled χ²-test identified a difference in the incidence of IPM among the three gene categories (p=7.206×10^-12). After further stratification by age, the incidence of IPM increased as a function of age (p<0.001) and was significantly different between the CP and RPE (p<0.001), and the PR and RPE (p<0.001) gene categories. Moreover, nearly no IPM was seen in patients with RPE-specific gene mutations.

Conclusions : Our findings suggest that the presence of IPM may be used as a biomarker in patients with photoreceptor gene mutations however is less valuable in the evaluation of RPE-specific retinal disease. These findings can help clinicians focus on candidate gene testing. Our binary logistic regression model may also be used to predict the incidence of pigment migration in patients based on identified genetic etiology and age.

This is a 2020 ARVO Annual Meeting abstract.