Inherited retinal degenerations including retinitis pigmentosa (RP) and Usher Syndrome Types 2 and 3 are orphan diseases. Retinal degenerations cause progressive death of rod and cone photoreceptors with relentless vision loss and ultimate blindness. There are no cures, and effective treatments are extremely limited. Neurotrophic factors such as ciliary neurotrophic factor (CNTF) have shown promise in slowing retinal degeneration in animal models and patients. A Phase 1 study and two Phase 2 studies of sustained-release CNTF delivered by an encapsulated cell technology (NT-501) intravitreal implant in patients with inherited retinal degeneration showed CNTF may be safe and well-tolerated. However, no significant change in vision was observed in either the CNTF or contralateral sham-treated eyes over study periods up to 24 months. Standard clinical imaging techniques cannot visualize individual photoreceptors due to optical imperfections in living eyes. However, adaptive optics scanning laser ophthalmoscopy (AOSLO) can produce images of individual cone photoreceptors in eyes with retinal degeneration. Preliminary studies using AOSLO to image cones in a small number of patients with inherited retinal degenerations showed reduced rates of cone loss in eyes treated with CNTF compared to contralateral eyes that received sham treatment. However, CNTF-treated eyes showed no improvement in visual acuity or visual field sensitivity, perhaps because standard measures of visual function are of lower resolution than the images of individual cones obtained using AOSLO. Higher resolution measures of retinal structure and visual function are necessary to determine whether CNTF is effective in slowing photoreceptor loss and preserving visual function. The objective of this prospective, Phase 2, double-masked, sham-controlled study is to evaluate the safety and efficacy of CNTF delivered by the NT-501 device to slow cone photoreceptor loss in patients with RP and Usher syndrome types 2 and 3 over 24 months. Twenty patients will be randomized to receive the NT-501 device in one eye and sham surgery in the contralateral eye. Patients will be studied twice at baseline, then at 6, 12, 18, 24 and 30 months after implantation of the CNTF-releasing NT-501 device. The primary outcome measure is demonstration of improvement in cone photoreceptor survival in CNTF-treated eyes compared to sham-treated eyes at 24 months using AOSLO. The study will test the hypothesis that CNTF is safe and effective in preventing vision cell death and blindness in patients with inherited retinal degenerations.

Public Health Relevance

CNTF slows photoreceptor death in many models of retinal degeneration caused by different genetic backgrounds, suggesting it may preserve vision in patients with different forms of retinal degeneration. This double-masked, sham-controlled Phase 2 clinical trial will use high-resolution images of photoreceptors in the CNTF and contralateral sham-treated eyes to provide a sensitive measure of disease progression and response to CNTF treatment. If CNTF slows photoreceptor loss in patients with inherited retinal degenerations, the results of this study may lead to the commercialization of a novel, safe and effective treatment that could prevent blindness in approximately 100,000 people with inherited retinal degenerations in the United States annually.

National Institute of Health (NIH)
Food and Drug Administration (FDA)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZFD1-OPD-N (S1))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Francisco
Schools of Medicine
San Francisco
United States
Zip Code