Efficacy Outcome Measures for Clinical Trials of USH2A Caused by the Common c.2299delG Mutation

G Calzetti, RA Levy, AV Cideciyan, AV Garafalo, AJ Roman, A Sumaroka, Jason Charng, Elise Héon, SG Jacobson

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

PURPOSE:
To determine the change in vision and retinal structure in patients with the common c.2299delG mutation in the USH2A gene in anticipation of clinical trials of therapy.

DESIGN:
Retrospective observational case series.

METHODS:
Eighteen patients, homozygotes or compound heterozygotes with the c.2299delG mutation in USH2A, were studied with regard to visual acuity, kinetic perimetry, dark- and light-adapted static perimetry, optical coherence tomography (OCT), and autofluorescence (AF) imaging. Serial data were available for at least half of the patients, depending on the parameter analyzed.

RESULTS:
The kinetics of disease progression in this specific molecular form of USH2A differed between the measured parameters. Visual acuity could remain normal for decades. Kinetic and light-adapted static perimetry across the entire visual field had similar rates of decline that were slower than those of rod-based perimetry. Horizontal OCT scans through the macula showed that inner segment/outer segment line width had a similar rate of constriction as co-localized AF imaging and cone-based light-adapted sensitivity extent. The rate of constriction of rod-based sensitivity extent across this same region was twice as rapid as that of cones.

CONCLUSIONS:
In patients with the c.2299delG mutation in USH2A, rod photoreceptors are the cells that express disease early and more aggressively than cones. Rod-based vision measurements in central or extracentral-peripheral retinal regions warrant monitoring in order to complete a clinical trial in a timely manner.
Original languageEnglish
Pages (from-to)114-129
JournalAmerican Journal of Ophthalmology
DOIs
Publication statusPublished - Sep 2018
Externally publishedYes

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