Phase I NT-501 Ciliary Neurotrophic Factor Implant Trial for Primary Open-Angle Glaucoma

Jeffrey L. Goldberg, MD, PhD; Gala Beykin, MD; Kellie R. Satterfield, MD; Mariana Nuñez, MD; Byron L. Lam, MD; Thomas A. Albini, MD

Ophthalmology Science (Sep 2023)

Phase I NT-501 Ciliary Neurotrophic Factor Implant Trial for Primary Open-Angle Glaucoma

Jeffrey L. Goldberg, MD, PhD,
Gala Beykin, MD,
Kellie R. Satterfield, MD,
Mariana Nuñez, MD,
Byron L. Lam, MD,
Thomas A. Albini, MD

Affiliations

Jeffrey L. Goldberg, MD, PhD: Spencer Center for Vision Research, Byers Eye Institute, Stanford University, Stanford, California; Shiley Eye Center, University of California San Diego, School of Medicine, San Diego, California; Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida; Correspondence: Jeffrey L. Goldberg, MD, PhD, Byers Eye Institute at Stanford, 2452 Watson Ct, Palo Alto, CA 94303.
Gala Beykin, MD: Spencer Center for Vision Research, Byers Eye Institute, Stanford University, Stanford, California
Kellie R. Satterfield, MD: Shiley Eye Center, University of California San Diego, School of Medicine, San Diego, California
Mariana Nuñez, MD: Spencer Center for Vision Research, Byers Eye Institute, Stanford University, Stanford, California; Shiley Eye Center, University of California San Diego, School of Medicine, San Diego, California; Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida
Byron L. Lam, MD: Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida
Thomas A. Albini, MD: Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida

Journal volume & issue: Vol. 3, no. 3
p. 100298

Abstract

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Purpose: To assess the safety and efficacy of a ciliary neurotrophic factor (CNTF) intraocular implant on neuroprotection and neuroenhancement in glaucoma. Design: Open-label, prospective, phase I clinical trial. Participants: A total of 11 participants were diagnosed with primary open-angle glaucoma (POAG). One eye of each patient was assigned as the study (implant) eye. Methods: The study eye was implanted with a high-dose CNTF-secreting NT-501 implant, whereas the other eye served as a control. All patients were followed up for 18 months. Analysis was limited to descriptive statistics. Main Outcome Measures: Primary outcome was safety through 18 months after implantation assessed by serial eye examinations, structural and functional testing, and adverse events (AEs) recording. Parameters measured included visual acuity (VA), Humphrey visual field (HVF), pattern electroretinogram, scanning laser polarimetry with variable corneal compensation (GDx VCC), and OCT. These parameters were also used for secondary analysis of efficacy outcome. Results: All NT-501 implants were well tolerated with no serious AEs associated with the implant. The majority of AEs were related to the implant placement procedure and were resolved by 12 weeks after surgery. Foreign-body sensation was the most commonly reported AE and was self-limited to the postoperative period. The most common implant-related AE was pupil miosis; no patients underwent explant. Visual acuity and contrast sensitivity decreased more in fellow eyes than in study eyes (VA, −5.82 vs. −0.82 letters; and contrast sensitivity, −1.82 vs. −0.37 letters, for fellow vs. study eyes, respectively). The median HVF visual field index and mean deviation measurements worsened (decreased) in fellow eyes (−13.0%, −3.9 dB) and improved (increased) in study eyes (2.7%, 1.2 dB). Implanted eyes showed an increase in retinal nerve fiber layer thickness measured by OCT and by GDx VCC (OCT, 2.66 μm vs. 10.16 μm; and GDx VCC, 1.58 μm vs. 8.36 μm in fellow vs. study eyes, respectively). Conclusions: The NT-501 CNTF implant was safe and well tolerated in eyes with POAG. Eyes with the implant demonstrated both structural and functional improvements suggesting biological activity, supporting the premise for a randomized phase II clinical trial of single and dual NT-501 CNTF implants in patients with POAG, which is now underway. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Published in Ophthalmology Science

ISSN: 2666-9145 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Ophthalmology
Website: https://www.journals.elsevier.com/ophthalmology-science/

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