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PURPOSE: To assess the safety of a recombinant adeno-associated viral vector expressing REP1 (rAAV2.REP1) in choroideremia subjects. METHODS: Design: Phase I clinical trial. PARTICIPANTS: Six adult male subjects, 30-42 years of age, with genetically confirmed choroideremia (CHM) were enrolled. The eye with the worse vision, for all subjects, received a single subfoveal injection of 0.1 mL rAAV2.REP1 containing 1011 genome particles. Subjects were followed up for 2 years thereafter. OUTCOME MEASURES: The primary outcome measure was safety, determined by the number of ocular and systemic adverse events assessed by ophthalmic examination, spectral-domain optical coherence tomography (SD-OCT), and short-wavelength autofluorescence (FAF). Secondary outcome measures were the change from baseline in best-corrected visual acuity (BCVA) in the treated eye compared to the untreated eye, changes in visual function using microperimetry, and the area of retinal pigment epithelium (RPE) preservation by FAF. RESULTS: One subject had an 8-ETDRS-letter BCVA loss from baseline measured at 24 months, while 1 subject had a ≥15-letter BCVA gain. A similar improvement was noted in the untreated eye of another subject throughout the follow-up period. Microperimetry sensitivity showed no improvement or significant change up to 2 years after vector administration. The area of preserved RPE as measured by FAF was noted to decline at a similar rate between the treated and untreated eyes. One subject experienced a serious adverse event: a localized intraretinal immune response, resulting in marked decline in visual function and loss of SD-OCT outer retinal structures. CONCLUSIONS: One serious adverse event was experienced in 6 subjects treated with a subfoveal injection of AAV2.REP1. The area of remaining functional RPE in the treated eye and untreated eye declined at the same rate over a 2-year period. Fundus autofluorescence area is a remarkably predictive biomarker and objective outcome measure for future studies of ocular gene therapy in CHM subjects.

Original publication




Journal article


Am J Ophthalmol

Publication Date





130 - 142


Adaptor Proteins, Signal Transducing, Adult, Alberta, Choroideremia, Follow-Up Studies, Gene Expression, Genetic Therapy, Genetic Vectors, Humans, Injections, Intraocular, Male, Optical Imaging, Parvovirinae, Prospective Studies, Retinal Pigment Epithelium, Tomography, Optical Coherence, Visual Acuity, Visual Field Tests