Emily Y Chew1, Traci E Clemons2, Glenn J Jaffe3, Charles A Johnson4, Sina Farsiu3, Eleonora M Lad3, Robyn Guymer5, Philip Rosenfeld6, Jean-Pierre Hubschman7, Ian Constable8, Henry Wiley9, Lawrence J Singerman10, Mark Gillies11, Grant Comer12, Barbara Blodi13, Dean Eliott14, Jiong Yan15, Alan Bird16, Martin Friedlander17. 1. Division of Epidemiology and Clinical Application, National Eye Institute, National Institutes of Health, Bethesda, Maryland. Electronic address: echew@nei.nih.gov. 2. The Emmes Corporation, Rockville, Maryland. 3. Duke Reading Center, Duke University, Durham, North Carolina. 4. Neurotech Pharmaceutical, Cumberland, Rhode Island. 5. Centre for Eye Research, University of Melbourne, Melbourne, Australia. 6. Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida. 7. Jules Stein Eye Institute, University of California, Los Angeles, California. 8. Lions Eye Institute, University of Western Australia, Perth, Australia. 9. Division of Epidemiology and Clinical Application, National Eye Institute, National Institutes of Health, Bethesda, Maryland. 10. Retina Associates of Cleveland, Cleveland, Ohio. 11. Save Sight Institute, University of Sydney, Sydney, Australia. 12. Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan. 13. Department of Ophthalmology, University of Wisconsin, Madison, Wisconsin. 14. Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts. 15. Department of Ophthalmology, Emory University, Atlanta, Georgia. 16. Department of Inherited Eye Disease, Moorfields Eye Hospital, London, United Kingdom. 17. Department of Molecular Medicine, The Scripps Research Institute; Division of Ophthalmology, Scripps Clinic; and the Lowy Medical Research Institute, La Jolla, California.
Abstract
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 mm2 (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.
RCT Entities:
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 humanCNTF 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 mm2 (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.
Authors: Jun W Kim; Cesar P Marquez; R Andres Parra Sperberg; Jiaxiang Wu; Won G Bae; Po-Ssu Huang; E Alejandro Sweet-Cordero; Jennifer R Cochran Journal: Proc Natl Acad Sci U S A Date: 2020-06-10 Impact factor: 11.205
Authors: Marin L Gantner; Kevin Eade; Martina Wallace; Michal K Handzlik; Regis Fallon; Jennifer Trombley; Roberto Bonelli; Sarah Giles; Sarah Harkins-Perry; Tjebo F C Heeren; Lydia Sauer; Yoichiro Ideguchi; Michelle Baldini; Lea Scheppke; Michael I Dorrell; Maki Kitano; Barbara J Hart; Carolyn Cai; Takayuki Nagasaki; Mehmet G Badur; Mali Okada; Sasha M Woods; Catherine Egan; Mark Gillies; Robyn Guymer; Florian Eichler; Melanie Bahlo; Marcus Fruttiger; Rando Allikmets; Paul S Bernstein; Christian M Metallo; Martin Friedlander Journal: N Engl J Med Date: 2019-09-11 Impact factor: 91.245