This clinical trial is a single-site, 30 patient study for participants who have early stage retinitis pigmentosa, or Usher syndrome (type 2 or 3). Funding Source - FDA OOPD and Foundation Fighting Blindness.

This clinical trial is a prospective, randomized, double-masked, sham-controlled trial of 30 study participants who have early-stage retinitis pigmentosa, or Usher syndrome (type 2 or 3). The trial will be conducted at the University of California, San Francisco. Individuals with these diseases experience gradually worsening vision that ultimately may lead to blindness due to a genetic condition in which specialized cells in the eye's retina called photoreceptor cells cease functioning and/or die. The study is intended to use a relatively new, non-invasive technology called AOSLO (adaptive optics scanning laser ophthalmoscopy) in combination with a routine standard of care measurement called sdOCT (Spectral Domain Optical Coherence Tomography) to demonstrate that when a device that secretes an investigational drug called CNTF (Ciliary Neurotrophic Factor) is surgically placed in the patient's eye, one type of photoreceptor called "cone photoreceptors" is preserved such that the gradual loss of vision is halted.

Inclusion Criteria:

1. Participant must be between 18 and 55 years of age.
2. Participant must have a diagnosis of retinitis pigmentosa or Usher Syndrome type 2 or 3 (without profound deafness or cochlear implants).
3. Participant must understand and sign the protocol informed consent. If the participant's vision is impaired to the point where he/she cannot read the informed consent document, the document will be read to the participant in its entirety.
4. Best-corrected visual acuity must be no worse than 20/63 (at least 59 letters).
5. Participants must have clear natural lenses.
6. Participants must have less than 6 diopters myopia.
7. Participants must be medically able to undergo ophthalmic surgery for the NT-501 device insertion and able to undergo all assessments and tests associated with the protocol.
8. Females of childbearing potential (women with last menses <1 year prior to screening) must agree to use an effective form of birth control from study onset until they complete the study.
9. Participants must have reproducible baseline AOSLO image at 2 baseline imaging sessions with quality suitable to identify a minimum of 7 regions of interest (ROIs) at which reliable cone spacing and/or density measures can be made over the central 5.7 degrees.
10. Participants must have interocular symmetry of disease severity as measured by cone spacing, with a difference of less than 2 standard deviations in average cone spacing z-scores at the selected ROIs between the 2 eyes.
11. Participant's clinical diagnosis must be consistent with retinal degeneration in the set of retinitis pigmentosa (RP) dystrophies.

Exclusion Criteria:

1. Participant is medically unable to comply with study procedures or follow-up visits.
2. Participant who has any of the following lens opacities: cortical opacity > standard 3, posterior subcapsular opacity > standard 3, or a nuclear opacity > standard 3 as measured on the AREDS clinical lens grading system; or participant is pseudophakic or aphakic.
3. Participant has history of corneal opacification or lack of optical clarity.
4. Participant has undergone LASIK surgery or other refractive surgery for either eye.
5. Participant has nystagmus.
6. Participant has greater than 6 diopters myopia.
7. Participant has cystoid macular edema with cysts present within 4 degrees of the foveal center that prevent acquisition of at least 7 regions of interest with clear images of cone photoreceptors.
8. Participant has fewer than 7 regions of interest (ROIs) present on 2 baseline AOSLO image montages.
9. Participant has retinal vascular disease such as diabetic retinopathy or prior retinal vascular occlusive disease.
10. Participant has chronic requirement (e.g., ≥4 weeks at a time) for ocular medications or has disease(s) that in the judgment of the examining physician are vision threatening, toxic to the lens, retina, or optic nerve or may affect the primary outcome.
11. Participant has a requirement of acyclovir and/or related products during study duration. To be eligible for this study, the participant must discontinue use of these products prior to enrollment and must not continue with the products until after they have completed the study.
12. Participant is receiving systemic steroids or other immunosuppressive medications.
13. Participant is currently participating in or has participated in any other clinical trial of a drug by ocular or systemic administration within the last 6 months.
14. Participant has previous exposure to an intra-ocular device or implant into the eye (excluding intra-ocular lens).
15. Participant has uveitis or other retinal inflammatory disease.
16. Participant has a history of myocardial infarction within the last 12 months.
17. Participant is pregnant or lactating.
18. Participant is considered immunodeficient or has a known history of HIV. A laboratory test for HIV will be performed, and a positive result is also an exclusion criterion.
19. Participant with a history of ocular herpes zoster.
20. Participant is on chemotherapy.
21. Participant has a history of malignancy, except study participant with cancer treated successfully ≥5 years prior to inclusion in the trial.
22. Participant with severe hearing disabilities in both ears.
23. Participant who has been diagnosed and treated for amblyopia as an infant.
24. Participant who, in the opinion of the study doctor, will not be a good study subject.

44 eyes of 22 patients were randomized to receive either NT-501 implant or sham surgery.

Serious and Other (Not Including Serious) Adverse Events were collected only for randomized participants through study completion, an average of 36 months. However, mortality is noted for one participant who passed away due to unrelated issues before being randomized.

Non-ocular, Non-serious adverse events were not required to be collected per protocol. All-Cause Mortality and Non-Ocular Serious Adverse Events are reported at the participant level. Ocular Serious and Other (Not Including Serious) Adverse Events are presented with total number of eyes monitored/assessed as the at Risk population.