Choroideremia Gene Therapy Phase 2 Clinical Trial: 24-Month Results

Byron L Lam, Janet L Davis, Ninel Gregori, Robert E. MacLaren, Aniz Girach, Jennifer D. Verriotto, Belen Rodriguez, Potyra R. Rosa, Xiaojun Zhang, William J Feuer

Research output: Contribution to journalArticle

21 Scopus citations


Purpose: To report the final results of a phase 2 high-dose gene therapy clinical trial in choroideremia. Methods: Design: Phase 2 clinical trial. Participants: Six men (aged 32-72 years) with genetically-confirmed advanced choroideremia. Patients received subfoveal injection of AAV2-REP1 (1011 genome particles in 0.1 mL) in the worse-sighted eye. Outcome Measures: Primary measure was best-corrected visual acuity (BCVA) change from baseline in the treated eye compared to the untreated eye. Secondary endpoints included change from baseline in microperimetry, fundus autofluorescence, and spectral-domain optical coherence tomography (OCT). Safety evaluations included adverse events, viral shedding in body fluids, and vector antibody responses. Results: Baseline mean ETDRS BCVA was 65.3 ± 8.8 (SD, range 56-77, 20/32-20/80) letters in the treated eyes and 77.0 ± 4.2 (69-81, 20/25-20/40) letters in the untreated eyes. At 2 years, 1 treated eye improved by 10 letters and another by 5 letters, while 1 untreated eye improved by 4 letters. All other eyes were within 2 letters of baseline. Baseline microperimetry sensitivities in the treated eyes were poor (1.2 ± 2.1 (0, 5.1) dB) and showed no significant change. No serious adverse event occurred. Two patients developed an atrophic retinal hole in a nonfunctioning macular area where baseline OCT showed preexisting thinning. Intraoperative microscope-integrated OCT allowed proper subretinal injection with avoidance of excessive foveal stretching and macular hole formation. Conclusions: Sustained improvement or maintenance of BCVA is achievable in choroideremia with high-dose AAV2-REP1, indicating BCVA is a viable primary outcome in advanced choroideremia. Choroideremia gene therapy delivered with intraoperative OCT has a good safety profile.

Original languageEnglish (US)
Pages (from-to)65-73
Number of pages9
JournalAmerican Journal of Ophthalmology
StatePublished - Jan 1 2019


ASJC Scopus subject areas

  • Ophthalmology

Cite this

Lam, B. L., Davis, J. L., Gregori, N., MacLaren, R. E., Girach, A., Verriotto, J. D., Rodriguez, B., Rosa, P. R., Zhang, X., & Feuer, W. J. (2019). Choroideremia Gene Therapy Phase 2 Clinical Trial: 24-Month Results. American Journal of Ophthalmology, 197, 65-73.