Structural and Functional Recovery Following Limited Iatrogenic Macular Detachment for Retinal Gene Therapy.

IMPORTANCE

The early decline and recovery of retinal structure and function following iatrogenic macular detachment for retinal gene therapy is not well characterized in those with relatively preserved central visual function. Here, the recovery of retinal structure and function over the first month following iatrogenic retinal detachment for the delivery of adeno-associated viral vector encoding Rab Escort Protein 1 is described as a part of gene therapy for choroideremia.

OBJECTIVE

To study changes in both retinal structure and function during the first month following iatrogenic macular detachment surgery.

DESIGN, SETTING, AND PARTICIPANTS: This prospective interocularly controlled study was conducted between February 1 and December 31, 2015. Treatment consisted of a subretinal injection of 0.1 mL of a gene therapy solution containing 1 × 1011 viral particles performed unilaterally. The participants were 5 males, aged 23 to 71 years, with a clinical and genetic diagnosis of choroideremia.

MAIN OUTCOMES AND MEASURES

Retinal structure and function were assessed at baseline, 1 week, and 1 month using optical coherence tomography, logMAR visual acuity, microperimetry, the Farnsworth-Munsell (FM) 100-hue test, and the Rayleigh match.

RESULTS

Five white male patients aged 23 to 71 years underwent unilateral subretinal gene therapy for genetically confirmed choroidermeia. Optical coherence tomographic images demonstrated a complete resolution of the resulting iatrogenic retinal detachment by 1 week in all 5 patients. At 1 month, the mean (SE) change in central foveal thickness was +9.6 (7.2) μm in treated eyes and +8.8 (12.6) μm in control eyes. The mean (SE) change in visual acuity was +5.4 (3.3) letters in treated eyes and +0.8 (3.1) letters in control eyes. At 1 month, the mean (SE) threshold sensitivity changes were -1.2 (2.1) dB in treated eyes and -1.0 (1.2) dB in control eyes. Color discrimination at the FM 100-hue changed little at 1 month (mean [SE] change in C-index, -0.2 [0.4] in treated eyes and 0.1 [0.2] in control eyes). Rayleigh matches in 1 patient were consistent with a diagnosis of pseudoprotanomaly, suggesting decreased effective optical density of the cone photopigments.

CONCLUSIONS AND RELEVANCE

Retinal structural recovery-as assessed by optical coherence tomography-occurs soon after iatrogenic detachment. Similarly, visual acuity recovers or improves within 1 month of the procedure and may not be accompanied by improvements in threshold sensitivity or color discrimination. Changes in color matching in 1 patient suggest decreased optical density of the cone photopigments in the early postoperative period.