Original articleLong-term Follow-up of Patients With Retinitis Pigmentosa Receiving Intraocular Ciliary Neurotrophic Factor Implants
Section snippets
Methods
Patients were followed for 24 months in the CNTF4 trial (registered as NCT00447980 on clinicaltrials.gov). There was an optional registry study in which the patients were followed for an additional 12 months. Three of the CNTF4 study sites continued to follow 24 patients out of the 36 enrolled for durations up to 8 years (mean duration of follow-up = 80 months). These included 8 patients with the low-dose device and 16 patients with the high-dose device. The original trial design approved by
Results
A summary of outcome data on the visit approximately 80 months post implant surgery is shown in the Table. Mean logMAR BCVA in the ciliary neurotrophic factor–treated eye at follow-up was 0.26 (20/32). This was not significantly different (P = .96) from the mean logMAR BCVA in the sham eye of 0.25 (20/32).
Changes in total visual field sensitivity on the final visit were comparable (P = .88) for those receiving the low-dose device and those receiving the high-dose device, so doses were combined
Discussion
CNTF3 and CNTF4 studies showed that long-term exposure to potential therapeutic agents could be safely achieved through encapsulated-cell implants.1 Although the surgical procedure was well tolerated and there were no serious adverse events related to the implantation or to the active study agent, there was no evidence of efficacy in the randomized studies. Indeed, visual field sensitivity declined more in treated eyes than in sham eyes, perhaps owing to documented effects on phototransduction
References (22)
- et al.
Structural determinants of neurotrophin action
J Biol Chem
(1995) - et al.
Long-term protection of retinal structure but not function using RAAV.CNTF in animal models of retinitis pigmentosa
Mol Ther
(2001) - et al.
AAV-mediated delivery of ciliary neurotrophic factor prolongs photoreceptor survival in the rhodopsin knockout mouse
Mol Ther
(2001) - et al.
Effects of adeno-associated virus-vectored ciliary neurotrophic factor on retinal structure and function in mice with a P216L rds/peripherin mutation
Exp Eye Res
(2002) - et al.
A computerized method of visual acuity testing: adaptation of the early treatment of diabetic retinopathy study testing protocol
Am J Ophthalmol
(2003) - et al.
Yearly rates of rod and cone functional loss in retinitis pigmentosa and cone-rod dystrophy
Ophthalmology
(1999) - et al.
Ciliary Neurotrophic Factor Retinitis Pigmentosa Study Group. Randomized trial of ciliary neurotrophic factor delivered by encapsulated cell intraocular implants for retinitis pigmentosa
Am J Ophthalmol
(2013) - et al.
Ciliary neurotrophic factor (CNTF) for human retinal degeneration: phase I trial of CNTF delivered by encapsulated cell intraocular implants
Proc Natl Acad Sci U S A
(2006) - et al.
The tripartite CNTF receptor complex: activation and signaling involves components shared with other cytokines
J Neurobiol
(1994) - et al.
Neurotrophic factors cause activation of intracellular signaling pathways in Müller cells and other cells of the inner retina, but not photoreceptors
Invest Ophthalmol Vis Sci
(2000)
Cloning, mapping, and retinal expression of the canine ciliary neurotrophic factor receptor α (CNTFRα)
Invest Ophthalmol Vis Sci
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