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Ciliary neurotrophic factor may benefit patients with macular telangiectasia type 2
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Intravitreal sustained delivery of human ciliary neurotrophic factor showed efficacy in slowing the progression of retinal degeneration in patients with macular telangiectasia type 2, a condition with no known effective therapy.
Ciliary neurotrophic factor (CNTF) is a neuroprotective agent that has reduced photoreceptor cell loss in animal models of retinal degeneration. It is produced by Neurotech Pharmaceuticals as an encapsulated cell-based drug delivery system with the name of Neurotech-501. Genetically modified human retinal pigment epithelium cells, encapsulated in a semipermeable hollow fiber membrane, release CNTF in the vitreous.
A multicenter randomized sham-controlled clinical trial including 11 clinical sites in the U.S. and Australia evaluated the effects of CNTF in 67 patients with macular telangiectasia type 2 randomly assigned to receive either the implant or sham. The implant was inserted into the vitreous cavity through a 2-mm pars plana incision and was secured to the sclera by a suture. Follow-up was at 24 months.
Eyes that received the implant had 31% less neurodegeneration progression than the sham eyes. The mean area of photoreceptor loss measured on spectral-domain OCT increased by 0.22 mm2 in the implant group compared with 0.27 mm2 in the sham group. Mean reading speed was preserved in the implant group, while it decreased by 13.9 words per minute in the sham group.
“This finding is likely clinically meaningful, because one of the major early symptoms reported by patients with macular telangiectasia type 2 is difficulty with reading, despite preserved measure of distance visual acuity. Metamorphopsia (distortion) and the presence of scotomas in both eyes contribute to difficulty with near vision tasks that require scanning,” the authors wrote.
There were no differences in central visual acuity loss between the groups, and the loss was minimal. No safety concerns regarding the use of the implant were seen on electroretinography and visual field testing. – by Michela Cimberle
Disclosures: Chew reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
Perspective
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Judy E. Kim, MD
Using a novel cell-based surgically implanted drug delivery system, this randomized prospective sham-controlled multicenter phase 2 clinical trial evaluated the effects of ciliary neurotrophic factor (CNTF) on the course of macular telangiectasia type 2. Change in the area of ellipsoid zone disruption measured on OCT between baseline and 24 months was used as a marker for photoreceptor loss and the primary outcome measure. The study found that the eyes receiving CNTF had slower progression of retinal degeneration while maintaining reading speed. The treatment group had a higher incidence of delayed dark adaptation and miosis compared with the sham group.
Because these findings are from a phase 2 trial, we cannot yet recommend it clinically. However, currently there is no proven treatment for macular telangiectasia type 2, a disease with progressive central vision loss. Therefore, trials on agents that may have a treatment benefit, such as CNTF, are important and give hope to our patients, families and the physicians. This trial also expands our knowledge of this fascinating condition and suggests that neuroprotection may be a viable treatment option to further investigate. Finally, it suggests that intravitreal implantation of an encapsulated cell-based delivery system, a novel drug delivery method, could be considered for other agents and other conditions.
Because this was a phase 2 trial, the sample size was small and the duration of the study was only 24 months. For this chronic and progressive condition, it will be important to know the durability of this drug delivery system, the longer-term patient outcomes, including clinical and functional benefits and side effects, and the generalizability of this treatment for patients with varying degrees of severity. We eagerly await the results of two phase 3 studies that are ongoing.
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