In vivo examination of cone photoreceptors in patients with Retinitis Pigmentosa implanted over five years ago with encapsulated Ciliary Neurotrophic Factor

Abstract

Purpose: Using high-resolution retinal imaging, Talcott et al. (IOVS. 2011; 52: 2219-2226) showed a short-term (2-3 year) preservation of cone photoreceptors in eyes of 3 patients with retinitis pigmentosa (RP) treated with encapsulated Ciliary Neurotrophic Factor (CNTF). We examined whether differences in cone photoreceptor density existed between CNTF- and fellow sham-treated eyes 5 years following implantation.

Methods: We examined both eyes of 3 patients (23, 31, 36 years) with RP. One eye of each patient was implanted with sustained-release encapsulated CNTF (NT-501, Neurotech Pharmaceuticals) over 5 years ago in a phase 2 clinical trial. Fellow eyes received a sham-treatment. Ocular biometry was performed (LENSTAR) and 30° x 25° macular volume scans were taken with spectral domain optical coherence tomography (SDOCT) [Spectralis HRA+OCT]. Cone photoreceptors were imaged with an adaptive optics scanning laser ophthalmoscope (AOSLO). Cone densities were calculated (while masked to the treatment assignment) from 0.3 mm to 3.0 mm eccentricity (in 0.3 mm increments) in each of four major meridians at as many locations as possible and compared between fellow CNTF- and sham-treated eyes.

Results: Good structural correspondence was observed between AOSLO and SDOCT images in viewing cystoid macular edema and identifying “transition zones” between healthy photoreceptors and retinal pigment epithelial cells. Compared to mean values in normal eyes, cone densities in an RP patient were reduced at all locations < ~1.5 mm eccentricity and were comparable at higher eccentricities. Cone densities were significantly higher in CNTF-treated eyes versus sham-treated eyes at 71% of all locations examined in all eyes. Differences in cone density between CNTF- and fellow sham-treated eyes were less than our measurement repeatability in normal eyes at 21% of locations.

Conclusions: Assuming fellow eyes had similar cone densities before implantation, the present results suggest that chronic CNTF exposure may reduce cone photoreceptor degeneration over long periods of time in human patients. The results are consistent with Talcott et al.’s observations suggesting short-term preservation of cones in CNTF-treated eyes.

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