Comparison of retinal development in idiopathic infantile nystagmus and nystagmus associated with albinism, PAX6 mutations and achromatopsia.

Abstract

Purpose : Infantile nystagmus (IN) is a genetically heterogeneous disease which can arise due to mutations in genes expressed within the developing retina. Previous work has focussed on documenting the foveal defects associated with IN. We aimed to characterise the intra-retinal abnormalities (foveal and parafoveal) associated with IN.

Methods : OCTs (Copernicus HR, 3µm axial resolution; protocol: 7x7mm, 743x75: AxB) were obtained from 108 IN patients due to FRMD7 mutations (n=45), PAX6 mutations (n=15), albinism (n=34) and achromatopsia (n=14). OCTs were obtained from controls (n=52). Thickness measurements were obtained from a single foveal B-scan. Custom scripts in ImageJ were used for segmentation and deriving intra-retinal thickness measurements. Nasal and temporal parafoveal thickness measurements represent average measurements between 1mm to 3mm on either side of the fovea.

Results : Foveal hypoplasia was seen in all patients with albinism (grades 1-4) and PAX6 mutations (grades 1-3). Only a proportion of patients (12/45) with FRMD7 mutations had foveal hypoplasia (all grade 1). Parafoveal nerve fibre layer (NFL) was significantly thinner in all groups compared to controls (p<0.0001). PAX6 mutations were associated with the thinnest NFL, however this reduction was confined to the nasal parafovea. FRMD7 and achromatopsia groups had significant reduction to both nasal and temporal NFL. The parafoveal ganglion cell layer and inner plexiform (GCL+IPL) complex and outer plexiform layer (OPL) was significantly reduced in PAX6, albinism and achromatopsia (p<0.01). Patients with achromatopsia had significantly thinner foveal and parafoveal outer nuclear layer (ONL) in comparison to the other groups and controls. No significant differences were noted in parafoveal ONL between PAX6, albinism, FRMD7 and controls.

Conclusions : This study highlights the specific retinal defects in patients with IN. Patients with albinism had more severe grades of foveal hypoplasia compared to the other groups. We report for the first time the significant changes to the intra-retinal layers in PAX6, albinism and achromatopsia. The NFL loss was most severe in patients with PAX6 mutations. Consistent with cone photoreceptor loss, achromatopsia patients had a reduction in the ONL thickness at the fovea and parafovea.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.