Original article
Long-term Follow-up of Patients With Retinitis Pigmentosa Receiving Intraocular Ciliary Neurotrophic Factor Implants

https://doi.org/10.1016/j.ajo.2016.07.013Get rights and content

Purpose

To evaluate the long-term efficacy of ciliary neurotrophic factor delivered via an intraocular encapsulated cell implant for the treatment of retinitis pigmentosa.

Design

Long-term follow-up of a multicenter, sham-controlled study.

Methods

Thirty-six patients at 3 CNTF4 sites were randomly assigned to receive a high- or low-dose implant in 1 eye and sham surgery in the fellow eye. The primary endpoint (change in visual field sensitivity at 12 months) had been reported previously. Here we measure long-term visual acuity, visual field, and optical coherence tomography (OCT) outcomes in 24 patients either retaining or explanting the device at 24 months relative to sham-treated eyes.

Results

Eyes retaining the implant showed significantly greater visual field loss from baseline than either explanted eyes or sham eyes through 42 months. By 60 months and continuing through 96 months, visual field loss was comparable among sham-treated eyes, eyes retaining the implant, and explanted eyes, as was visual acuity and OCT macular volume.

Conclusions

Over the short term, ciliary neurotrophic factor released continuously from an intravitreal implant led to loss of total visual field sensitivity that was greater than the natural progression in the sham-treated eye. This additional loss of sensitivity related to the active implant was reversible when the implant was removed. Over the long term (60–96 months), there was no evidence of efficacy for visual acuity, visual field sensitivity, or OCT measures of retinal structure.

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)

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