Behind the Lab Door

Retinal imaging of subjects implanted with ciliary neurotrophic factor (CNTF)-releasing encapsulated cell implant for early-stage retinitis pigmentosa

Institution: University of California, San Francisco

Author/principal investigator: Jacque L. Duncan, MD

Abstract/statement of the trial’s goals

This clinical trial is a prospective, randomized, double-masked, sham-controlled trial of 10 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, noninvasive technology called adaptive optics scanning laser ophthalmoscopy (AOSLO) in combination with a routine standard of care measurement called spectral domain optical coherence tomography (SD-OCT) to demonstrate that when a device that secretes an investigational drug called ciliary neurotrophic factor (CNTF) 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 and, to a lesser extent, reversed.

ClinicalTrials.gov identifier: NCT01530659

Study population: 10

Inclusion criteria:

Participant must have a diagnosis of retinitis pigmentosa or Usher syndrome type 2 or 3 (without profound deafness or cochlear implants).
Participant must understand and sign the protocol informed consent. If the participant’s vision is impaired to the point where he or she cannot read the informed consent document, the document will be read to the participant in its entirety.
Best corrected visual acuity must be no worse than 20/63 (at least 59 letters).
Participants must have clear natural lenses.
Participants must have less than 6 D of myopia.
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.
Women of childbearing potential (women with last menses less than 1 year prior to screening) must agree to use an effective form of birth control from study onset until they complete the 30-month study.
Participants must have reproducible baseline AOSLO image.
Participants must have interocular symmetry of disease severity.
Participant’s clinical diagnosis must be consistent with retinal degeneration in the set of retinitis pigmentosa dystrophies.

Exclusion criteria:

Participant is medically unable to comply with study procedures or follow-up visits.
Participant who has any of the following lens opacities: cortical opacity greater than standard 3, posterior subcapsular opacity greater than standard 3, or a nuclear opacity greater than standard 3; or participant is pseudophakic or aphakic.
Participant has history of corneal opacification or lack of optical clarity.
Participant has undergone LASIK or other refractive surgery for either eye.
Participant has nystagmus.
Participant has greater than 6 D of myopia.
Participant has cystoid macular edema with cysts present within 4° of the foveal center.
Participant has fewer than seven regions of interest present on baseline AOSLO image montages.
Participant has retinal vascular disease such as diabetic retinopathy or prior retinal vascular occlusive disease.
Participant has chronic requirement (eg, 4 weeks or more 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.
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.
Participant is receiving systemic steroids or other immunosuppressive medications.
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.
Participant has previous exposure to an intraocular device or implant into the eye (excluding IOL).
Participant has uveitis or other retinal inflammatory disease.
Participant has a history of myocardial infarction within the last 12 months.
Participant is pregnant or lactating.
Participant is considered immunodeficient or has a known history of HIV.
Participant has a history of ocular herpes zoster.
Participant is on chemotherapy.
Participant has a history of malignancy, except study participant with cancer treated successfully 5 years or more prior to inclusion in the trial.
Participant with severe hearing disabilities in both ears.
Participant who has been diagnosed and treated for amblyopia as an infant.
Participant who, in the opinion of the study doctor, will not be a good study subject.

Enrollment status: Currently recruiting participants

A note from the institution regarding the value of this trial:

We will study normal subjects and patients with retinal degenerations using measures of cone photoreceptor structure obtained using AOSLO, a technique that permits noninvasive imaging of individual cones in living eyes. We will correlate AOSLO images with SD-OCT images of the retina and with visual acuity, visual field testing and electroretinography. Three independent graders will count cones in each image from each eye at each visit. We will analyze how well the measures from the different graders compare to each other, how much difference exists between the eyes, and how much change happens between visits and between eyes. Finally, we will investigate these measures in patients with retinitis pigmentosa and Usher syndrome who have received CNTF in one eye and compare them to the other eye, which will be randomly assigned to receive a sham surgery as a control.