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  • Retinal Recovery After Iatrogenic Macular Detachment for Gene Therapy

    By Lynda Seminara and selected by Neil M. Bressler, MD, and Deputy Editors

    Journal Highlights

    JAMA Ophthalmology, March 2017

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    Simunovic et al. observed the effects of limited iatrogenic macular detachment on retinal structure and function after delivery of gene therapy to the subret­inal space. They found that structural recovery occurred within 1 week and function generally was restored by 1 month.

    Five men with choroideremia of confirmed genetic etiology participated in this prospective, interocularly con­trolled study. Gene therapy consisted of unilateral subretinal injection of a 0.1-mL solution containing 1 × 1011 particles of AAA.REP1 (an adeno-asso­ciated viral vector encoding Rab Escort Protein 1). Before surgery and at 1 week and 1 month after it, retinal structure was evaluated with optical coherence tomography, and retinal function was assessed by microperimetry, best-cor­rected visual acuity (BCVA), and the Farnsworth-Munsell 100-hue test.

    In all patients, subretinal fluid dissipated within 1 week after surgery. By 1 month postoperatively, the mean change in central foveal thickness was +9.6 μm for treated eyes and +8.8 μm for control (fellow) eyes. Mean BCVA of treated eyes also improved by the 1-month mark (mean change from baseline, +5.4 letters vs. +0.8 letters for control eyes). From baseline to 1 month postsurgery, threshold sensi­tivity increased for 3 treated eyes and decreased for 2.

    Color discrimination was variable. Although most treated eyes functioned at or above baseline, 1 patient had worsening of a preexisting Verriest type III deficiency in color vision at 1 month. This suggests that the optical density of cone photopigments is decreased in the early postoperative period. No patients had a postoperative shift in the preferred locus of retinal fixation, as measured by microperimetry.

    The authors concluded that struc­tural and functional restoration of the retina develops asynchronously after iatrogenic detachment, with structural recovery occurring within 1 week and visual acuity returning within 1 month. The improvements may be accompa­nied by subtle alterations in threshold sensitivity and color discrimination. These recovery kinetics may be ascribed to the combination of functional gains from REP1 expression and functional losses from retinal detachment. (Also see related commentary by Jacque L. Duncan, MD, in the same issue.)

    The original article can be found here.