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Outcome Measures for Clinical Trials of Leber Congenital Amaurosis Caused by the Intronic Mutation in the CEP290 Gene.

Authors :
Jacobson SG
Cideciyan AV
Sumaroka A
Roman AJ
Charng J
Lu M
Choi W
Sheplock R
Swider M
Kosyk MS
Schwartz SB
Stone EM
Fishman GA
Source :
Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2017 May 01; Vol. 58 (5), pp. 2609-2622.
Publication Year :
2017

Abstract

Purpose: To determine efficacy outcome measures for clinical trials of Leber congenital amaurosis (LCA) associated with a common intronic mutation in the CEP290 gene.<br />Methods: CEP290-LCA patients (ages 5-48) with the intronic mutation (c.2991+1655A>G) were studied as a retrospective observational case series using clinical methods and with full-field sensitivity testing (FST), optical coherence tomography (OCT), autofluorescence imaging (NIR-RAFI), transient pupillary light reflex (TPLR), oculomotor control and instability (OCI), a mobility course, and a questionnaire (NEI-VFQ). Patients were investigated cross-sectionally but a subset was able to be followed longitudinally.<br />Results: With FST, there was no rod function; cone sensitivities had a wide range from not detectable to near normal. OCT analyses indicated retained central photoreceptors with abnormal distal laminae. Based on OCT and FST, most patients had dissociation of structure and function. TPLR was nondetectable in the majority of patients, with responders demonstrating severe losses in light sensitivity. OCI was abnormal in most patients. NEI-VFQ scores had a similar range to those of other severe retinopathies. Mobility scores were consistent with FST sensitivities. In patients examined with FST, OCT, and NIR-RAFI over long-term intervals (7-10 years), there was limited but detectable disease progression.<br />Conclusions: Efficacy would be a quantitative change in foveal cone function and possibly distal laminar structure. FST provides a subjective photoreceptor-based outcome; OCT and NIR-RAFI can assess photoreceptor and RPE structure. TPLR and OCI can provide objective measures of postretinal transmission. Minimal change over a decade indicates that there is no practical value in natural history studies.

Details

Language :
English
ISSN :
1552-5783
Volume :
58
Issue :
5
Database :
MEDLINE
Journal :
Investigative ophthalmology & visual science
Publication Type :
Academic Journal
Accession number :
28510626
Full Text :
https://doi.org/10.1167/iovs.17-21560