Intervisit variability of visual parameters in Leber congenital amaurosis caused by RPE65 mutations

Abstract

Purpose: To determine the intervisit variability of kinetic visual fields and visual acuity in patients with Leber congenital amaurosis (LCA) caused by mutations in the RPE65 (Retinal Pigment Epithelium-specific protein 65kDa) gene.

Methods: RPE65-LCA patients (n = 20; ages 11-40 years) were studied on at least two visits separated by fewer than 120 days using Goldmann visual field (GVF) and ETDRS visual acuity (VA) in a retrospective review. GVFs were quantified by computing the spherical coordinates of their vertices and calculating the solid angle subtended, and reported in normalized solid-angle units (nsu) as a percentage of average normal field extent. Repeatability coefficients were calculated using 95% confidence intervals on log(10)-converted variables.

Results: Visual field extents in RPE65-LCA spanned a wide range from 4 to 95 nsu. The repeatability coefficient was 0.248 (log(10)nsu), suggesting cutoffs for significant change (in nsu) of +77% for improvement and -44% for worsening. VA in RPE65-LCA ranged from logMAR = 0.14 to 1.96 (20/40 to 20/1250). The repeatability coefficient was 0.170 (logMAR) (±8.5 ETDRS letters). Comparisons with published studies of ungenotyped retinitis pigmentosa showed that the RPE65-LCA patients had higher variability in kinetic field extent. VA variability in RPE65-LCA fell within reported results for retinitis pigmentosa.

Conclusions: Variability data for GVF and VA are provided to permit interpretation of the significance of increases and decreases of these functional outcomes in ongoing and planned clinical trials of therapy for LCA caused by RPE65 mutations.

Figure 1

Intervisit variability of kinetic visual fields in RPE65-LCA. (A) Visual field extent in one eye of patients with RPE65 mutations, measured by the same examiner and perimeter in two or three visits within a 120-day interval. Ordinate is in nsu; mean normal extent corresponds to 100 nsu. Bottom: Examples of Goldmann perimeter charts (shown as left eyes) recorded on different visits for four representative patients. (B) Variability shown as intervisit differences (referenced to median or first visit when n = 2) against mean visual field extent. Differences do not depend strongly on mean level of extent. Dashed lines depict 95% confidence limits for determining significant change between a pair of visits.

Figure 2

Intervisit variability of best-corrected VAs in patients with RPE65-LCA. (A) Multiple visits in different days within an interval of fewer than 85 days are shown ranked by mean VA across visits. Right: Scale indicates equivalent Snellen fractions. (B) Fluctuation around the mean for individual VA data (subtraction of visit data minus mean of all visits for each patient) illustrating the range of variation. (C) Variability shown as intervisit differences (referenced to median or first visit when n = 2) against mean acuity, showing no strong dependence of differences with acuity level. Dashed lines depict 95% confidence limits for determining significant change between two visits. Right: Scale is a correspondence to letters read on an ETDRS chart.