Effect of Ciliary Neurotrophic Factor on Retinal Neurodegeneration in Patients with Macular Telangiectasia Type 2: A Randomized Clinical Trial.
PURPOSE: To test the effects of an encapsulated cell-based delivery of a neuroprotective agent, ciliary neurotrophic factor (CNTF) on progression of macular telangiectasia type 2, a neurodegenerative disease with no proven effective therapy.
DESIGN: Randomized sham-controlled clinical trial PARTICIPANTS: 99 study eyes of 67 eligible participants were enrolled.
METHODS: Single-masked randomized clinical trial of 24 months duration conducted May 2014 to April 2017 in eleven clinical centers of retinal specialists in United States and Australia. Participants were randomized 1:1 surgical implant of intravitreal sustained delivery of human ciliary neurotrophic factor (CNTF) vs. sham procedure.
MAIN OUTCOME MEASURES: The primary outcome was the difference in the area of neurodegeneration as measured in the area of the ellipsoid zone disruption (or photoreceptor loss) measured on spectral domain optical coherence tomography (SD-OCT) images at 24 months from baseline between the treated and untreated groups. Secondary outcomes included comparison of visual function changes between treatment groups.
RESULTS: Among the 67 participants who were randomized (mean age, 62 ± 8.9 years, 41 (61%) women, 58 (86%) white), 65 (97%) completed the study. Two participants (3 study eyes) died and 3 (4 eyes) were found ineligible. The eyes receiving sham treatment had 31% greater progression of neurodegeneration than the CNTF-treated eyes, the difference in mean area of photoreceptor loss was 0.05 ± 0.03 mm (p = 0.04) at 24 months. Retinal sensitivity changes, measured using microperimetry, were highly correlated with the changes in the area of photoreceptor loss (r = 0.86, p < 0.0001). The mean retinal sensitivity loss of the sham group was 45% greater than the treated group (decrease of 15.81±8.93 dB [p=0.07]). Reading speed deteriorated in the sham group (-13.9 words per minute) with no loss in the treated eyes (p = 0.02). Serious adverse ocular effects were found in 2/51 (4%) of the sham group and 2/48 (4%) in the treated group.
CONCLUSIONS: In participants with macular telangiectasia type 2, a surgical implant that released CNTF into the vitreous cavity, compared with a sham procedure, slowed the progression of retinal degeneration. Further research is needed to assess longer-term clinical outcomes and safety.