TY - JOUR
T1 - Effect of Ciliary Neurotrophic Factor on retinal neurodegeneration in patients with Macular Telangiectasia Type 2
T2 - a randomized clinical trial
AU - Macular Telangiectasia Type 2-Phase 2 CNTF Research Group
AU - Chew, Emily Y.
AU - Clemons, Traci E.
AU - Jaffe, Glenn J.
AU - Johnson, Charles A.
AU - Farsiu, Sina
AU - Lad, Eleonora M.
AU - Guymer, Robyn
AU - Rosenfeld, Philip
AU - Hubschman, Jean Pierre
AU - Constable, Ian
AU - Wiley, Henry
AU - Singerman, Lawrence J.
AU - Gillies, Mark
AU - Comer, Grant
AU - Blodi, Barbara
AU - Eliott, Dean
AU - Yan, Jiong
AU - Bird, Alan
AU - Friedlander, Martin
PY - 2019/4/1
Y1 - 2019/4/1
N2 - 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: Ninety-nine study eyes of 67 eligible participants were enrolled. Methods: Single-masked randomized clinical trial of 24 months’ duration conducted from May 2014 through April 2017 in 11 clinical centers of retinal specialists in the United States and Australia. Participants were randomized 1:1 to surgical implantation of intravitreal sustained delivery of human CNTF versus a 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 (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 women [61%]; 58 white persons [86%]), 65 (97%) completed the study. Two participants (3 study eyes) died and 3 participants (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 2 (P = 0.04) at 24 months. Retinal sensitivity changes, measured using microperimetry, were correlated highly 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 that of the treated group (decrease, 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 group (P = 0.02). Serious adverse ocular effects were found in 2 of 51 persons (4%) in the sham group and 2 of 48 persons (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.
AB - 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: Ninety-nine study eyes of 67 eligible participants were enrolled. Methods: Single-masked randomized clinical trial of 24 months’ duration conducted from May 2014 through April 2017 in 11 clinical centers of retinal specialists in the United States and Australia. Participants were randomized 1:1 to surgical implantation of intravitreal sustained delivery of human CNTF versus a 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 (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 women [61%]; 58 white persons [86%]), 65 (97%) completed the study. Two participants (3 study eyes) died and 3 participants (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 2 (P = 0.04) at 24 months. Retinal sensitivity changes, measured using microperimetry, were correlated highly 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 that of the treated group (decrease, 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 group (P = 0.02). Serious adverse ocular effects were found in 2 of 51 persons (4%) in the sham group and 2 of 48 persons (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.
UR - http://www.scopus.com/inward/record.url?scp=85057488581&partnerID=8YFLogxK
U2 - 10.1016/j.ophtha.2018.09.041
DO - 10.1016/j.ophtha.2018.09.041
M3 - Article
C2 - 30292541
AN - SCOPUS:85057488581
SN - 0161-6420
VL - 126
SP - 540
EP - 549
JO - Ophthalmology
JF - Ophthalmology
IS - 4
ER -
