Visual Function Decline Resulting from Geographic Atrophy: Results from the Chroma and Spectri Phase 3 Trials
Visual Function Decline Resulting from Geographic Atrophy: Results from the Chroma and Spectri Phase 3 Trials
Purpose
To assess visual function outcomes to 48 weeks in patients with bilateral geographic atrophy (GA) secondary to age-related macular degeneration included in 2 interventional clinical trials: relationship to baseline lesion size, outcomes by baseline lesion characteristic subgroups, and correlation of visual function outcomes with GA area.
Design
The Chroma and Spectri studies (ClinicalTrials.gov identifiers, NCT02247479 and NCT02247531, respectively) were identically designed phase 3, double-masked, multicenter, randomized, sham injection-controlled clinical trials that evaluated intravitreal lampalizumab in GA.
Participants
Eligible patients were 50 years of age or older with well-demarcated bilateral GA (lesion size, 1–7 disc areas) without evidence of or previous treatment for choroidal neovascularization in either eye and best-corrected visual acuity (BCVA) letter score of 49 letters or more (≥1 GA lesion within 250 μm of foveal center if BCVA ≥79 letters).
Methods
Patients (pooled n = 1881) were randomized 2:1:2:1 to lampalizumab every 4 weeks, sham every 4 weeks, lampalizumab every 6 weeks, or sham every 6 weeks. Sham arms were pooled for analysis.
Main Outcome Measures
Functional end points included change in BCVA from baseline to week 48, low-luminance visual acuity, mesopic microperimetry (number of absolute scotomatous points, mean macular sensitivity), binocular and monocular maximum reading speed, and 2 validated patient-reported outcome measures: Functional Reading Independence Index and 25-item National Eye Institute Visual Function Questionnaire.
Results
Enlargement of GA area, approximately 2 mm2/year on average across all treatment groups in each study, was accompanied by overall deterioration in all functional end points. No statistically significant differences were found between lampalizumab or sham arms for changes from baseline in functional assessment scores. Of visual function tests, only microperimetry outcomes were correlated moderately with GA lesion area when assessed cross-sectionally at baseline and week 48.
Conclusions
Chroma and Spectri provide a unique data set of functional end points in GA that are relevant for future clinical trials. Patients with bilateral GA experienced a consistent decline in visual function over 48 weeks, but measures of visual function were not correlated strongly with GA lesion area. It is not possible to predict visual function outcomes from GA lesion size.
673-688
Heier, Jeffery
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Pieramici, Dante
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Chakravarthy, Usha
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Patel, Sunil
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Gupta, Sunil
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Lotery, Andrew
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Lad, Eleonora M.
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Silverman, David
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Henry, Erin C.
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Anderesi, Majid
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Tschosik, Elizabeth
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Gray, Sarah
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Ferrara, Daniela
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Guymer, Robyn H.
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July 2020
Heier, Jeffery
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Pieramici, Dante
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Chakravarthy, Usha
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Patel, Sunil
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Gupta, Sunil
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Lotery, Andrew
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Lad, Eleonora M.
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Silverman, David
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Henry, Erin C.
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Anderesi, Majid
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Tschosik, Elizabeth
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Gray, Sarah
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Ferrara, Daniela
acaec3ab-6cff-4fb8-8744-4160d7967dac
Guymer, Robyn H.
ce21dd40-50d0-439a-bb21-b8ad044a721c
Heier, Jeffery, Pieramici, Dante, Chakravarthy, Usha, Patel, Sunil, Gupta, Sunil, Lotery, Andrew, Lad, Eleonora M., Silverman, David, Henry, Erin C., Anderesi, Majid, Tschosik, Elizabeth, Gray, Sarah, Ferrara, Daniela and Guymer, Robyn H.
(2020)
Visual Function Decline Resulting from Geographic Atrophy: Results from the Chroma and Spectri Phase 3 Trials.
Ophthalmology Retina, 4 (7), .
(doi:10.1016/j.oret.2020.01.019).
Abstract
Purpose
To assess visual function outcomes to 48 weeks in patients with bilateral geographic atrophy (GA) secondary to age-related macular degeneration included in 2 interventional clinical trials: relationship to baseline lesion size, outcomes by baseline lesion characteristic subgroups, and correlation of visual function outcomes with GA area.
Design
The Chroma and Spectri studies (ClinicalTrials.gov identifiers, NCT02247479 and NCT02247531, respectively) were identically designed phase 3, double-masked, multicenter, randomized, sham injection-controlled clinical trials that evaluated intravitreal lampalizumab in GA.
Participants
Eligible patients were 50 years of age or older with well-demarcated bilateral GA (lesion size, 1–7 disc areas) without evidence of or previous treatment for choroidal neovascularization in either eye and best-corrected visual acuity (BCVA) letter score of 49 letters or more (≥1 GA lesion within 250 μm of foveal center if BCVA ≥79 letters).
Methods
Patients (pooled n = 1881) were randomized 2:1:2:1 to lampalizumab every 4 weeks, sham every 4 weeks, lampalizumab every 6 weeks, or sham every 6 weeks. Sham arms were pooled for analysis.
Main Outcome Measures
Functional end points included change in BCVA from baseline to week 48, low-luminance visual acuity, mesopic microperimetry (number of absolute scotomatous points, mean macular sensitivity), binocular and monocular maximum reading speed, and 2 validated patient-reported outcome measures: Functional Reading Independence Index and 25-item National Eye Institute Visual Function Questionnaire.
Results
Enlargement of GA area, approximately 2 mm2/year on average across all treatment groups in each study, was accompanied by overall deterioration in all functional end points. No statistically significant differences were found between lampalizumab or sham arms for changes from baseline in functional assessment scores. Of visual function tests, only microperimetry outcomes were correlated moderately with GA lesion area when assessed cross-sectionally at baseline and week 48.
Conclusions
Chroma and Spectri provide a unique data set of functional end points in GA that are relevant for future clinical trials. Patients with bilateral GA experienced a consistent decline in visual function over 48 weeks, but measures of visual function were not correlated strongly with GA lesion area. It is not possible to predict visual function outcomes from GA lesion size.
Text
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In preparation date: 2019
Accepted/In Press date: 21 January 2020
e-pub ahead of print date: 31 January 2020
Published date: July 2020
Additional Information:
Funding Information:
Financial Disclosure(s): The author(s) have made the following disclosure(s): J.S.H.: Consultant ? 4D Molecular Technologies, Adverum, Aerpio, Allegro, Apellis, AsclepiX, Bayer, Beaver-Visitec, Daiichi-Sankyo, Genentech, Inc/Roche, Heidelberg, Hemera, Janssen R&D, Kanghong, Kodiak, Neurotech, Notal Vision, Novartis, Ocular Therapeutix, Ocunexus, Optos, Quark, Regeneron, Regenxbio, Santen, SciFluor, Shire, Stealth Biotherapeutics, ThromboGenics, TLC, Tyrogenex. D.P.: Consultant ? Genentech, Inc/Roche, Kodiak, Novartis, Regeneron, ThromboGenics; Financial support ? Aerpio, Allergan, Genentech, Inc/Roche, Ophthea, Regeneron, Regenxbio, ThromboGenics, Topcon. S.S.P.: Consultant ? Allergan, Genentech, Inc/Roche; Financial support ? Alcon, Allergan, Clearside, Daiichi-Sankyo, Genentech, Inc/Roche, Ophthotech, Regeneron. S.Gu.: Financial support ? Allergan, Astellas, Clearside, Genentech, Inc, Iris, Magellan Rx, Novartis, USR. A.L.: Consultant ? Bayer, Gyroscope, Roche; Financial support - Bayer. E.M.L.: Consultant ? Allegro, Apellis, Galimedix, Gemini Therapeutics, Genentech, Inc/Roche, Novartis, Retrotope; Financial support ? Apellis, LumiThera, Novartis, Roche (through Duke University). Supported by F. Hoffmann-La Roche Ltd., Basel, Switzerland, which was involved in design and conduct of the studies; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Funding was provided by F. Hoffmann-La Roche Ltd. for third-party writing assistance, which was provided by Anne Nunn, PhD, CMPP, of Envision Pharma Group. Obtained funding: N/A
Publisher Copyright:
© 2020 American Academy of Ophthalmology
Identifiers
Local EPrints ID: 444953
URI: http://eprints.soton.ac.uk/id/eprint/444953
ISSN: 2468-6530
PURE UUID: 2862f87a-ac26-438b-ae1a-42006518b909
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Date deposited: 12 Nov 2020 17:33
Last modified: 16 Mar 2024 03:32
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Contributors
Author:
Jeffery Heier
Author:
Dante Pieramici
Author:
Usha Chakravarthy
Author:
Sunil Patel
Author:
Sunil Gupta
Author:
Eleonora M. Lad
Author:
David Silverman
Author:
Erin C. Henry
Author:
Majid Anderesi
Author:
Elizabeth Tschosik
Author:
Sarah Gray
Author:
Daniela Ferrara
Author:
Robyn H. Guymer
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