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Original Investigation
February 2, 2017

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

Author Affiliations
  • 1Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
  • 2Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
  • 3Retinal Unit, Sydney Eye Hospital, Sydney, New South Wales, Australia
  • 4Save Sight Institute, Discipline of Ophthalmology, University of Sydney, Sydney, New South Wales, Australia
  • 5Moorfields Eye Hospital, London, United Kingdom
JAMA Ophthalmol. Published online February 2, 2017. doi:10.1001/jamaophthalmol.2016.5630
Key Points

Question  Does limited iatrogenic detachment of the macula have a detrimental short-term effect on retinal structure and function?

Findings  In this prospective interocularly controlled study of 5 patients who underwent gene therapy for choroideremia, structural recovery occurred within 1 week of iatrogenic retinal detachment, while functional recovery occurred within 1 month. However, subtle functional changes to color matching—consistent with reduced cone photopigment optical density—persisted at 1 month in 1 patient.

Meaning  Retinal structure and function appears to recover rapidly following iatrogenic macular detachment.


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.