Clinical phenotypes and prognostic full-field electroretinographic findings in Stargardt disease

Abstract

Purpose: To investigate the relationships between clinical and full-field electroretinographic (ERG) findings and progressive loss of visual function in Stargardt disease.

Design: Retrospective cohort study.

Methods: We performed a retrospective review of data from 198 patients with Stargardt disease. Measures of visual function over time, including visual acuity, quantified Goldmann visual fields, and full-field ERG data were recorded. Data were analyzed using SAS statistical software. Subgroup analyses were performed on 148 patients with ERG phenotypic data, 46 patients with longitudinal visual field data, and 92 patients with identified ABCA4 mutations (46 with 1 mutation, and 47 with 2 or more mutations).

Results: Of 46 patients with longitudinal visual field data, 8 patients with faster central scotoma progression rates had significantly worse scotopic B-wave amplitudes at their initial assessment than 20 patients with stable scotomata (P = .014) and were more likely to have atrophy beyond the arcades (P = .047). Overall, 47.3% of patients exhibited abnormal ERG results, with rod-cone dysfunction in 14.2% of patients, cone-rod dysfunction in 17.6% of patients, and isolated cone dysfunction in 15.5% of patients. Abnormal values in certain ERG parameters were associated significantly with (maximum-stimulation A- and B-wave amplitudes) or tended toward (photopic and scotopic B-wave amplitudes) a higher mean rate of central scotoma progression compared with those patients with normal ERG values. Scotoma size and ERG parameters differed significantly between those with a single mutation versus those with multiple mutations.

Conclusions: Full-field ERG examination provides clinically relevant information regarding the severity of Stargardt disease, likelihood of central scotoma expansion, and visual acuity deterioration. Patients also may exhibit an isolated cone dystrophy on ERG examination.

FIGURE 1

Graph showing scotoma progression rate in patients with Stargardt disease. Patients with at least 3 visits had scotoma sizes quantitated with planimetry. Scotomata progression of more than 2.0 cm²/year is depicted as dark grey diamonds, and patients with progression of less than 1.0 cm²/year are shown as light grey squares. Quickly progressing patients had an average progression rate of 4.04 cm²/year compared with the slowly progressing patients, who exhibited an average progression rate of 0.29 cm²/year.

FIGURE 2

Bar graph showing full-field electroretinography (ERG) phenotypes in patients with Stargardt disease from all available ERG data: 47.3% all Stargardt patients exhibited abnormal full-field ERG results.

FIGURE 3

Bar graph showing the percent of abnormal results by full-field electroretinography (ERG) parameter in patients with Stargardt disease. Percentage of patients with abnormal full-field ERG parameters are shown. All values less than 2 standard deviations from the mean were considered abnormal for amplitude measures, and all values more than 2 standard deviations from the mean were considered abnormal for latency measures.

FIGURE 4

Bar graph showing full-field electroretinography (ERG) parameter versus scotoma progression rates in Stargardt disease. Patients with abnormal full-field ERG parameters tended toward exhibiting larger average scotoma progression rates, with abnormal photopic and scotopic B-wave amplitudes nearing statistical significance. Abnormal maximum stimulation A-wave and B-wave amplitudes were associated significantly with larger average scotoma progression rates.

FIGURE 5

Bar graph showing the percent of patients with abnormal electroretinography (ERG) parameters by disease stage in Stargardt disease. P values correspond to the comparison of the distribution of disease stages with abnormal versus normal values of each full-field ERG parameter using an extended Fisher exact test. Abnormal full-field ERG parameters, in particular photopic and scotopic B-wave amplitudes and latencies, maximum stimulation A-wave amplitude and latency, and maximum stimulation B-wave latency, were statistically significantly associated with higher disease stages.