Dataset Information

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

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 η² 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 (η² of 0.73 [0.53, 0.83]; -1.79 dB/y [-2.2, -1.37]) and mean sensitivity (η² 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 η² of 0.54 [0.34, 0.68]; -0.02 log₁₀(µV)/y [-0.02, -0.01]). The genotype explained a large fraction of variability in the ERG-based age of disease initiation (adjusted R² 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.

SUBMITTER: Pfau M

PROVIDER: S-EPMC10524499 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

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

Pfau Maximilian M Huryn Laryssa A LA Boyle Marisa P MP Cukras Catherine A CA Zein Wadih M WM Turriff Amy A Ullah Ehsan E Hufnagel Robert B RB Jeffrey Brett G BG Brooks Brian P BP

American journal of ophthalmology 20230520

<h4>Purpose</h4>To systematically assess the ability to detect change and retest reliability for a panel of visual function assessments in ABCA4 retinopathy.<h4>Design</h4>Prospective natural history study (NCT01736293).<h4>Methods</h4>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 func ...[more]

PMID: 37211138

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Project description:PurposeTo review and describe in detail the clinical course, functional and anatomic characteristics of RP2-associated retinal degeneration.DesignRetrospective case series.ParticipantsMale participants with disease-causing variants in the RP2 gene.MethodsReview of all case notes and results of molecular genetic testing, retinal imaging (fundus autofluorescence [FAF] imaging, OCT), and electrophysiology assessment.Main outcome measuresMolecular genetic testing, clinical findings including best-corrected visual acuity (BCVA), qualitative and quantitative retinal imaging analysis, and electrophysiology parameters.ResultsFifty-four molecularly confirmed patients were identified from 38 pedigrees. Twenty-eight disease-causing variants were identified, with 20 not previously clinically characterized. Fifty-three patients (98.1%) presented with retinitis pigmentosa. The mean age of onset (range ± standard deviation [SD]) was 9.6 years (1-57 ± 9.2 years). Forty-four patients (91.7%) had childhood-onset disease, with mean age of onset of 7.6 years. The most common first symptom was night blindness (68.8%). Mean BCVA (range ± SD) was 0.91 logarithm of the minimum angle of resolution (logMAR) (0-2.7 ± 0.80) and 0.94 logMAR (0-2.7 ± 0.78) for right and left eyes, respectively. On the basis of the World Health Organization visual impairment criteria, 18 patients (34%) had low vision. The majority (17/22) showed electroretinogram (ERG) evidence of a rod-cone dystrophy. Pattern ERG P50 was undetectable in all but 2 patients. A range of FAF findings was observed, from normal to advanced atrophy. There were no statistically significant differences between right and left eyes for ellipsoid zone width (EZW) and outer nuclear layer (ONL) thickness. The mean annual rate of EZW loss was 219 μm/year, and the mean annual decrease in ONL thickness was 4.93 μm/year. No patient with childhood-onset disease had an identifiable ellipsoid zone (EZ) after the age of 26 years at baseline or follow-up. Four patients had adulthood-onset disease and a less severe phenotype.ConclusionsThis study details the clinical phenotype of RP2 retinopathy in a large cohort. The majority presented with early-onset severe retinal degeneration, with early macular involvement and complete loss of the foveal photoreceptor layer by the third decade of life. Full-field ERGs revealed rod-cone dystrophy in the vast majority, but with generalized (peripheral) cone system involvement of widely varying severity in the first 2 decades of life.Financial disclosure(s)Proprietary or commercial disclosure may be found after the references.

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Dataset Information

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

Purpose

Design

Methods

Results

Publications

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

Similar Datasets

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