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

18 Citations (Scopus)


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.

Retrospective observational case series.

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.

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.

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
Number of pages16
JournalAmerican Journal of Ophthalmology
Publication statusPublished - Sept 2018
Externally publishedYes


Dive into the research topics of 'Efficacy Outcome Measures for Clinical Trials of USH2A Caused by the Common c.2299delG Mutation'. Together they form a unique fingerprint.

Cite this