Longitudinal Changes of Fixation Location and Stability Within 12 Months in Stargardt Disease: ProgStar Report No. 12

Abstract

Purpose: To investigate the natural history of Stargardt disease (STGD1) using fixation location and fixation stability.

Design: Multicenter, international, prospective cohort study.

Methods: Fixation testing was performed using the Nidek MP-1 microperimeter as part of the prospective, multicenter, natural history study on the Progression of Stargardt disease (ProgStar). A total of 238 patients with ABCA4-related STGD1 were enrolled at baseline (bilateral enrollment in 86.6%) and underwent repeat testing at months 6 and 12.

Results: Outcome measures included the distance of the preferred retinal locus from the fovea (PRL) and the bivariate contour ellipse area (BCEA). After 12 months of follow-up, the change in the eccentricity of the PRL from the anatomic fovea was -0.0014 degrees (95% confidence interval [CI], -0.27 degrees, 0.27 degrees; P = .99). The deterioration in the stability of fixation as expressed by a larger BCEA encompassing 1 standard deviation of all fixation points was 1.21 degrees squared (deg²) (95% CI, -1.23 deg², 3.65 deg²; P = .33). Eyes with increases and decreases in PRL eccentricity and/or BCEA values were observed.

Conclusions: Our observations point to the complexity of fixation parameters. The association of increasingly eccentric and unstable fixation with longer disease duration that is typically found in cross-sectional studies may be countered within individual patients by poorly understood processes like neuronal adaptation. Nevertheless, fixation parameters may serve as useful secondary outcome parameters in selected cases and for counseling patients to explain changes to their visual functionality.

FIGURE 1.

Grading of the bivariate contour ellipse area (BCEA), the preferred retinal locus, and analysis of fixation on fundus autofluorescence images in the example of the right eye of an 18-year-old woman who had been diagnosed with Stargardt disease 5 years before. (Left) The BCEA is the smallest ellipse that encompasses 1, 2, or 3 standard deviations of all fixation events. The MP-1 microperimeter can fully automatically draw this ellipse around the recorded fixation points and calculate the area as shown in the image. A smaller BCEA corresponds to more stable fixation. (Center) A grid was automatically placed on the center of gravity of all fixation events in blue color. The distance between the center of the grid and the fovea could then be determined. (Right) The recorded fixation events can be overlaid on a fundus autofluorescence image, which allows for clearer identification of atrophic macula and analysis of fixation in relation to atrophy.

FIGURE 2.

Correlation of the change in eccentricity of the preferred retinal locus (PRL) with the change in 1 SD-BCEA (bivariate contour ellipse area using 1 standard deviation). Each degree of additional PRL eccentricity was associated with a 1 SD-BCEA, which is 0.089 deg² larger (P = .14; n = 276).

FIGURE 3.

Example of a left eye of a 45-year-old man 14 years after diagnosis that first developed more central, then more eccentric fixation over the course of 12 months. In this example, fixation becomes more stable on each follow-up visit. This case demonstrates the complex nature of the course of fixation parameters over time and how they may provide useful additional information on top of structural or other functional parameters.