Informing endpoints for clinical trials of geographic atrophy

Eleonora M Lad; Monika Fleckenstein; Frank G Holz; Liangbo Shen; Lucian V Del Priore; Rufino Silva; Giovanni Staurenghi; Nadia Waheed; Usha Chakravarthy

doi:10.1146/annurev-vision-101922-045110

Informing endpoints for clinical trials of geographic atrophy

Eleonora M Lad, Monika Fleckenstein, Frank G Holz, Liangbo Shen, Lucian V Del Priore, Rufino Silva, Giovanni Staurenghi, Nadia Waheed, Usha Chakravarthy

Research output: Contribution to journal › Review article › peer-review

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Abstract

Geographic atrophy (GA), the non-neovascular advanced form of age-related macular degeneration, remains an important disease area in which treatment needs are currently unmet. Recent clinical trials using drugs that target the complement pathway have shown modest yet consistent reductions in GA expansion but without commensurate changes in measures of visual function. In this review, we summarize information from the wide range of studies describing the characteristics of GA morphology and enumerate the factors influencing the growth rates of lesions and the directionality of expansion. In addition, we review the relationship between GA growth and the various measures of vision that reflect changes in function. We consider the reasons for the discordance between the anatomical and functional endpoints in current use and discuss methods to align these key outcomes.

Original language	English
Pages (from-to)	455-476
Number of pages	22
Journal	Annual Review of Vision Science
Volume	10
Issue number	1
DOIs	https://doi.org/10.1146/annurev-vision-101922-045110
Publication status	Published - 01 Sept 2024

Keywords

Humans
Geographic Atrophy/drug therapy
Clinical Trials as Topic
Visual Acuity/physiology
Disease Progression
Endpoint Determination

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10.1146/annurev-vision-101922-045110Licence: CC BY

Informing endpoints for clinical trials of geographic atrophy
Copyright 2024 the authors. This is an accepted manuscript distributed under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 2.02 MBLicence: CC BY

Cite this

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title = "Informing endpoints for clinical trials of geographic atrophy",

abstract = "Geographic atrophy (GA), the non-neovascular advanced form of age-related macular degeneration, remains an important disease area in which treatment needs are currently unmet. Recent clinical trials using drugs that target the complement pathway have shown modest yet consistent reductions in GA expansion but without commensurate changes in measures of visual function. In this review, we summarize information from the wide range of studies describing the characteristics of GA morphology and enumerate the factors influencing the growth rates of lesions and the directionality of expansion. In addition, we review the relationship between GA growth and the various measures of vision that reflect changes in function. We consider the reasons for the discordance between the anatomical and functional endpoints in current use and discuss methods to align these key outcomes.",

keywords = "Humans, Geographic Atrophy/drug therapy, Clinical Trials as Topic, Visual Acuity/physiology, Disease Progression, Endpoint Determination",

author = "Lad, {Eleonora M} and Monika Fleckenstein and Holz, {Frank G} and Liangbo Shen and Priore, {Lucian V Del} and Rufino Silva and Giovanni Staurenghi and Nadia Waheed and Usha Chakravarthy",

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T1 - Informing endpoints for clinical trials of geographic atrophy

AU - Lad, Eleonora M

AU - Fleckenstein, Monika

AU - Holz, Frank G

AU - Shen, Liangbo

AU - Priore, Lucian V Del

AU - Silva, Rufino

AU - Staurenghi, Giovanni

AU - Waheed, Nadia

AU - Chakravarthy, Usha

PY - 2024/9/1

Y1 - 2024/9/1

N2 - Geographic atrophy (GA), the non-neovascular advanced form of age-related macular degeneration, remains an important disease area in which treatment needs are currently unmet. Recent clinical trials using drugs that target the complement pathway have shown modest yet consistent reductions in GA expansion but without commensurate changes in measures of visual function. In this review, we summarize information from the wide range of studies describing the characteristics of GA morphology and enumerate the factors influencing the growth rates of lesions and the directionality of expansion. In addition, we review the relationship between GA growth and the various measures of vision that reflect changes in function. We consider the reasons for the discordance between the anatomical and functional endpoints in current use and discuss methods to align these key outcomes.

AB - Geographic atrophy (GA), the non-neovascular advanced form of age-related macular degeneration, remains an important disease area in which treatment needs are currently unmet. Recent clinical trials using drugs that target the complement pathway have shown modest yet consistent reductions in GA expansion but without commensurate changes in measures of visual function. In this review, we summarize information from the wide range of studies describing the characteristics of GA morphology and enumerate the factors influencing the growth rates of lesions and the directionality of expansion. In addition, we review the relationship between GA growth and the various measures of vision that reflect changes in function. We consider the reasons for the discordance between the anatomical and functional endpoints in current use and discuss methods to align these key outcomes.

KW - Humans

KW - Geographic Atrophy/drug therapy

KW - Clinical Trials as Topic

KW - Visual Acuity/physiology

KW - Disease Progression

KW - Endpoint Determination

U2 - 10.1146/annurev-vision-101922-045110

DO - 10.1146/annurev-vision-101922-045110

M3 - Review article

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SN - 2374-4642

VL - 10

SP - 455

EP - 476

JO - Annual Review of Vision Science

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Informing endpoints for clinical trials of geographic atrophy

Abstract

Keywords

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