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  • High-Dose Gene Therapy and BCVA in Choroideremia

    By Lynda Seminara
    Selected By: Richard K. Parrish II, MD
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    Journal Highlights

    American Journal of Ophthalmology, January 2019

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    In a two-year clinical trial, Lam et al. looked at the safety and efficacy of high-dose gene therapy in patients with choroideremia. Their findings demon­strated that the treatment is safe and potentially effective and that best-corrected visual acuity (BCVA) may be an appropriate outcome measure for monitoring the progression of choroi­deremia.

    The authors reported 24-month findings of their phase 2 clinical trial. Six men (32-72 years of age) with advanced choroideremia underwent subfoveal injection of adeno-associated virus 2 capsids that harbored a tran­script encoding Rab escort protein 1 (i.e., AAV2-REP1; 1011 genome particles in 0.1 mL). The eye with worse visual acuity was treated, and the untreated fellow eye served as the control. Injec­tion of vector was performed slowly, guided by microscope-integrated opti­cal coherence tomography.

    The primary outcome measure was change in BCVA from baseline. Secondary endpoints included changes in central visual field (by microperim­etry), color vision, contrast sensitivity, and fundus autofluorescence. To assess safety, adverse events and immunologic parameters were recorded, including viral shedding and vector antibody responses.

    The baseline mean BCVA was 65.3 ± 8.8 letters in treated eyes and 77.0 ± 4.2 letters in untreated eyes. Two years after therapy, the changes from baseline ranged from −1 to +10 letters in treated eyes and −2 to +4 letters in untreated eyes. No eye had a substantial change in microperimetry findings, color vision, or contrast sensitivity; all eyes (treated and control) had progressive shrinkage in areas of fundus autofluorescence. No serious adverse events were noted, and the immunologic profiles were favor­able. In two patients, an atrophic retinal hole developed in a nonfunctioning macular area.

    This slow-injection technique of high-dose gene therapy appears to be safe and may permit maintenance, or even improvement, of BCVA in patients with choroideremia. The fact that no untreated study eye had significant improvement in BCVA suggests that BCVA is a suitable primary outcome measure for future choroideremia trials. The authors acknowledged that larger studies are needed to confirm the promising results. (Also see “Favorable Vision Effects of Retinal Gene Therapy for Choroideremia.”)

    The original article can be found here.