Effect of Ciliary Neurotrophic Factor on Retinal Neurodegeneration in Patients with Macular Telangiectasia Type 2: A Randomized Clinical Trial

Macular Telangiectasia Type 2-Phase 2 CNTF Research Group

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish (US)
JournalOphthalmology
DOIs
StateAccepted/In press - Jan 1 2018

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Ciliary Neurotrophic Factor
Telangiectasis
Randomized Controlled Trials
Single-Blind Method
Retinal Degeneration
Neuroprotective Agents
Neurodegenerative Diseases
Reading
Placebos
Outcome Assessment (Health Care)
Safety
Therapeutics
Research

ASJC Scopus subject areas

  • Ophthalmology

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Effect of Ciliary Neurotrophic Factor on Retinal Neurodegeneration in Patients with Macular Telangiectasia Type 2 : A Randomized Clinical Trial. / Macular Telangiectasia Type 2-Phase 2 CNTF Research Group.

In: Ophthalmology, 01.01.2018.

Research output: Contribution to journalArticle

@article{a2e1b7db2793415dab5f97ce039758d0,
title = "Effect of Ciliary Neurotrophic Factor on Retinal Neurodegeneration in Patients with Macular Telangiectasia Type 2: A Randomized Clinical Trial",
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.",
author = "{Macular Telangiectasia Type 2-Phase 2 CNTF Research Group} and Chew, {Emily Y.} and Clemons, {Traci E.} and Jaffe, {Glenn J.} and Johnson, {Charles A.} and Sina Farsiu and Lad, {Eleonora M.} and Robyn Guymer and Rosenfeld, {Philip J} and Hubschman, {Jean Pierre} and Ian Constable and Henry Wiley and Singerman, {Lawrence J.} and Mark Gillies and Grant Comer and Barbara Blodi and Dean Eliott and Jiong Yan and Alan Bird and Martin Friedlander",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.ophtha.2018.09.041",
language = "English (US)",
journal = "Ophthalmology",
issn = "0161-6420",
publisher = "Elsevier Inc.",

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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 J

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 - 2018/1/1

Y1 - 2018/1/1

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 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.

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 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.

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