Cone Photoreceptor Structure in Patients with Inherited Retinal Degeneration at 12 months in a Randomized Trial of Sustained-Release Ciliary Neurotrophic Factor

Abstract

Purpose: To characterize longitudinal changes in outer retinal structure at 12 months in patients with retinitis pigmentosa (RP) participating in a randomized trial of sustained-release ciliary neurotrophic factor (CNTF).

Methods: 9 patients with RP or Usher syndrome type III were randomized to receive a high-dose, open-membrane CNTF implant in one eye and sham surgery in the fellow eye. Patients were participants in a 24-month longitudinal study of CNTF. In this per protocol analysis of 8 patients who completed 12 months of implantation, measures of visual function included visual acuity (VA), foveal sensitivity, kinetic and static perimetry area, and photopic full-field electroretinography (ERG) amplitudes and timing. Spectral-domain optical coherence tomography (SD-OCT) images were segmented using custom software and were used to calculate photoreceptor inner/outer segment junction, or ellipsoid zone (EZ), band width. The 4 patients with the highest quality adaptive optics scanning laser ophthalmoscopy (AOSLO) images of macular cones (as assessed by masked raters) were selected for analysis at 0, 6, and 12 months. All analyses were masked to treatment assignment.

Results: After 12 months, visual acuity improved slightly (2.25-3.25 letters) in all eyes (P = 0.01). Kinetic visual field area to Goldmann V4e and I4e targets was significantly lower in all eyes at 12 months compared to baseline (P <0.001). ERG amplitudes and SD-OCT measures (including EZ width) in all eyes were comparable to baseline. Analyzing CNTF- and sham-treated eyes together yielded evidence of a modest increase in AOSLO-derived cone spacing measures in these 4 patients over 12 months.

Conclusions: In this masked assessment of current data for the first prospective study to evaluate AOSLO cone spacing measures in an intervention trial for RP, modest evidence of a change in cone spacing was observed after 12 months. Cone spacing may serve as a sensitive outcome measure in clinical trials for retinal degenerations.

Keywords: 696 retinal degenerations: hereditary • 550 imaging/image analysis: clinical • 648 photoreceptors