Randomized trial of ciliary neurotrophic factor delivered by encapsulated cell intraocular implants for retinitis pigmentosa

Abstract

Purpose: To evaluate the safety and effect on visual function of ciliary neurotrophic factor delivered via an intraocular encapsulated cell implant for the treatment of retinitis pigmentosa (RP).

Design: Ciliary neurotrophic factor for late-stage retinitis pigmentosa study 3 (CNTF3; n = 65) and ciliary neurotrophic factor for early-stage retinitis pigmentosa study 4 (CNTF4; n = 68) were multicenter, sham-controlled dose-ranging studies.

Methods: Patients were randomly assigned to receive a high- or low-dose implant in 1 eye and sham surgery in the fellow eye. The primary endpoints were change in best-corrected visual acuity (BCVA) at 12 months for CNTF3 and change in visual field sensitivity at 12 months for CNTF4. Patients had the choice of retaining or removing the implant at 12 months for CNTF3 and 24 months for CNTF4.

Results: There were no serious adverse events related to either the encapsulated cell implant or the surgical procedure. In CNTF3, there was no change in acuity in either ciliary neurotrophic factor- or sham-treated eyes at 1 year. In CNTF4, eyes treated with the high-dose implant showed a significant decrease in sensitivity while no change was seen in sham- and low dose-treated eyes at 12 months. The decrease in sensitivity was reversible upon implant removal. In both studies, ciliary neurotrophic factor treatment resulted in a dose-dependent increase in retinal thickness.

Conclusions: Long-term intraocular delivery of ciliary neurotrophic factor is achieved by the encapsulated cell implant. Neither study showed therapeutic benefit in the primary outcome variable.

Trial registration: ClinicalTrials.gov NCT00447980 NCT00447993.

Conflict of interest statement

ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST. David Birch and Glenn Jaffe received consulting fees from Neurotech USA, Inc., Lincoln, Rhode Island; Weng Tao is an employee of Neurotech USA, Inc., Lincoln, Rhode Island. Neurotech USA, Inc., Lincoln, Rhode Island, provided financial support for these studies. Contributions of authors: design of the study (D.G.B., W.T., R.G.W.); data analysis (D.G.B., W.T., G.J.J.); manuscript preparation (D.G.B., W.T., J.L.D.); all authors were involved with the conduct of the studies and had full access to the data, contributed to the data interpretation, and provided revisions to the manuscript.

Copyright © 2013 Elsevier Inc. All rights reserved.

Figures

FIGURE 1

Mean decrease in total Humphrey visual field sensitivity over time in a subset of patients with retinitis pigmentosa participating in the registry study (up to 54 months follow-up). All patients received the high-dose ciliary neurotrophic factor implant in 1 eye. Six patients chose to have the implant removed at 24 months (explant); 10 patients chose to retain the implant (no explant).

FIGURE 2

Representative Spectralis spectral-domain optical coherence tomography scans (Heidelberg Engineering, Heidelberg, Germany) from the horizontal midline of a 30-year-old patient with retinitis pigmentosa at 12 months post implant. (Top) Ciliary neurotrophic factor–treated left eye. (Bottom) Sham-treated right eye. Colored lines are borders obtained with Igor segmentation program. Light green: Bruch membrane/choroid border; yellow: ellipsoid zone (inner/outer segment border); blue: inner nuclear layer/outer plexiform layer border.