Abstract
Purpose :
Subretinal gene therapy necessitates iatrogenic detachment of the macula; although rhegmatogenous and exudative detachments involving this region are well-studied, little is known about the short-term effects of iatrogenic macula detachment in patients with comparatively well-preserved central vision. We therefore aimed to study the short-term recovery of structure and function following iatrogenic macula detachment performed as part of retinal gene therapy.
Methods :
Five participants aged 23-71 yr, with baseline visual acuities in treated eyes ranging from 39 to 70 ETDRS letters, were recruited from a Phase I/II trial of gene therapy for choroideremia (ClinicalTrials.gov identifier NCT01461213). Subjects underwent unilateral sub-retinal injection of 0.1mL of a solution containing 1011 AAV.REP1 particles. Patients were assessed prior to surgery with follow-up at 1 day, 1 week and 1 month following surgery. Structure was assessed by spectral-domain OCT and function by visual acuity, microperimetry, color discrimination (FM 100Hue) and color matching (Rayleigh match).
Results :
Resolution of sub-retinal fluid occurred by day 1 following the procedure. No evidence of change in central foveal thickness was found (change at 1 month +6.5 ± 5.8 μm vs. +19 ± 13.9 μm in treated and untreated eyes respectively). Visual acuity (change at 1 month +5.4 ± 3.3 letters and +0.8 ± 3.1 letters in treated and untreated eyes respectively) and microperimetry (-0.85 ± 3.9 dB vs. -0.7 ± 2.1 dB in treated and untreated eyes respectively) recovered to baseline by 1 month. In one subject, pseudoprotanomaly was observed at the Rayleigh match (change in log anomalquotient of > -0.2), suggesting decreased cone photopigment optical density. This finding was accompanied by a loss of tritan color discrimination at the FM100 Hue and persisted at 1 month.
Conclusions :
The limited iatrogenic macular detachment performed as part of gene therapy in this study recovers by day 1 and, in contrast to macula-off rhegmatogenous detachment, does not appear to appreciably affect central foveal thickness. Whilst visual acuity and threshold sensitivity appear to recover by 1 month, subtle alterations in color matching – indicative of decreased cone photopigment optical density – may persist.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.