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Natural History of Visual Dysfunction in ABCA4 Retinopathy and Its Genetic Correlates. | LitMetric

AI Article Synopsis

  • - The study aimed to evaluate how well different visual function assessments can measure changes in ABCA4 retinopathy over time and how reliable these assessments are when repeated.
  • - A total of 67 participants with confirmed ABCA4 variants underwent various tests, revealing that microperimetry was the most sensitive measure for detecting changes over a 2-year period, while electroretinography (ERG) showed significant changes over 5 years.
  • - The findings suggest that while microperimetry is effective, it’s only available for a portion of patients, and ERG could allow for broader participation in clinical trials by capturing the progression of ABCA4-related retinal disease.

Article Abstract

Purpose: To systematically assess the ability to detect change and retest reliability for a panel of visual function assessments in ABCA4 retinopathy.

Design: Prospective natural history study (NCT01736293).

Methods: Patients with at least 1 documented pathogenic ABCA4 variant and a clinical phenotype consistent with ABCA4 retinopathy were recruited from a tertiary referral center. Participants underwent longitudinal, multifaceted functional testing, including measures of function at fixation (best-corrected visual acuity, low-vision Cambridge Color Test), macular function (microperimetry), and retina-wide function (full-field electroretinography [ERG]). Two- and 5-year ability to detect change was determined based on the η statistic.

Results: A total of 134 eyes from 67 participants with a mean follow-up of 3.65 years were included. In the 2-year interval, the microperimetry-derived perilesional sensitivity (η of 0.73 [0.53, 0.83]; -1.79 dB/y [-2.2, -1.37]) and mean sensitivity (η of 0.62 [0.38, 0.76]; -1.28 dB/y [-1.67, -0.89]) showed most change over time, but could only be recorded in 71.6% of the participants. In the 5-year interval, the dark-adapted ERG a- and b-wave amplitude showed marked change over time as well (eg, DA 30 a-wave amplitude with an η of 0.54 [0.34, 0.68]; -0.02 log(µV)/y [-0.02, -0.01]). The genotype explained a large fraction of variability in the ERG-based age of disease initiation (adjusted R of 0.73) CONCLUSIONS: Microperimetry-based clinical outcome assessments were most sensitive to change but could only be acquired in a subset of participants. Across a 5-year interval, the ERG DA 30 a-wave amplitude was sensitive to disease progression, potentially allowing for more inclusive clinical trial designs encompassing the whole ABCA4 retinopathy spectrum.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10524499PMC
http://dx.doi.org/10.1016/j.ajo.2023.05.014DOI Listing

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