Clinical and genetic factors associated with progression of geographic atrophy lesions in age-related macular degeneration

Felix Grassmann; Monika Fleckenstein; Emily Y. Chew; Tobias Strunz; Steffen Schmitz-Valckenberg; Arno P. Göbel; Michael L. Klein; Rinki Ratnapriya; Anand Swaroop; Frank G. Holz; Bernhard H.F. Weber

doi:10.1371/journal.pone.0126636

Clinical and genetic factors associated with progression of geographic atrophy lesions in age-related macular degeneration

Felix Grassmann, Monika Fleckenstein, Emily Y. Chew, Tobias Strunz, Steffen Schmitz-Valckenberg, Arno P. Göbel, Michael L. Klein, Rinki Ratnapriya, Anand Swaroop, Frank G. Holz, Bernhard H.F. Weber

Medical Sciences

Research output: Contribution to journal › Article › peer-review

62 Citations (Scopus)

Abstract

Worldwide, age-related macular degeneration (AMD) is a serious threat to vision loss in individuals over 50 years of age with a pooled prevalence of approximately 9%. For 2020, the number of people afflicted with this condition is estimated to reach 200 million. While AMD lesions presenting as geographic atrophy (GA) show high inter-individual variability, only little is known about prognostic factors. Here, we aimed to elucidate the contribution of clinical, demographic and genetic factors on GA progression. Analyzing the currently largest dataset on GA lesion growth (N = 388), our findings suggest a significant and independent contribution of three factors on GA lesion growth including at least two genetic factors (ARMS2-rs10490924 [P < 0.00088] and C3-rs2230199 [P < 0.00015]) as well as one clinical component (presence of GA in the fellow eye [P < 0.00023]). These correlations jointly explain up to 7.2% of the observed inter-individual variance in GA lesion progression and should be considered in strategy planning of interventional clinical trials aimed at evaluating novel treatment options in advanced GA due to AMD.

Original language	English
Article number	e0126636
Journal	PloS ONE
Volume	10
Issue number	5
DOIs	https://doi.org/10.1371/journal.pone.0126636
Publication status	Published - 11 May 2015

Bibliographical note

Acknowledgments
We thank the patients and control individuals for their participation in the study, Kerstin Meier and Jürgen Kaschkötö (Institute of Human Genetics, University of Regensburg) for their technical support, and the FAM-Study Group for providing patients and controls. This study was supported in parts by the Deutsche Forschungsgemeinschaft (WE 1259/19-2 to BHFW), the Alcon Research Institute (to BHFW, EYC and AS), the Intramural Research program of the National Eye Institute (EYC and AS), and by grants from the National Eye Institute, National Institutes of Health, Bethesda, MD (R01-EY021532 to MLK).

Access to Document

10.1371/journal.pone.0126636

Cite this

Grassmann, F., Fleckenstein, M., Chew, E. Y., Strunz, T., Schmitz-Valckenberg, S., Göbel, A. P., Klein, M. L., Ratnapriya, R., Swaroop, A., Holz, F. G., & Weber, B. H. F. (2015). Clinical and genetic factors associated with progression of geographic atrophy lesions in age-related macular degeneration. PloS ONE, 10(5), Article e0126636. https://doi.org/10.1371/journal.pone.0126636

@article{7dd3f6bca5c242daad07d5fed64b4219,

title = "Clinical and genetic factors associated with progression of geographic atrophy lesions in age-related macular degeneration",

abstract = "Worldwide, age-related macular degeneration (AMD) is a serious threat to vision loss in individuals over 50 years of age with a pooled prevalence of approximately 9%. For 2020, the number of people afflicted with this condition is estimated to reach 200 million. While AMD lesions presenting as geographic atrophy (GA) show high inter-individual variability, only little is known about prognostic factors. Here, we aimed to elucidate the contribution of clinical, demographic and genetic factors on GA progression. Analyzing the currently largest dataset on GA lesion growth (N = 388), our findings suggest a significant and independent contribution of three factors on GA lesion growth including at least two genetic factors (ARMS2-rs10490924 [P < 0.00088] and C3-rs2230199 [P < 0.00015]) as well as one clinical component (presence of GA in the fellow eye [P < 0.00023]). These correlations jointly explain up to 7.2% of the observed inter-individual variance in GA lesion progression and should be considered in strategy planning of interventional clinical trials aimed at evaluating novel treatment options in advanced GA due to AMD.",

author = "Felix Grassmann and Monika Fleckenstein and Chew, {Emily Y.} and Tobias Strunz and Steffen Schmitz-Valckenberg and G{\"o}bel, {Arno P.} and Klein, {Michael L.} and Rinki Ratnapriya and Anand Swaroop and Holz, {Frank G.} and Weber, {Bernhard H.F.}",

note = "Acknowledgments We thank the patients and control individuals for their participation in the study, Kerstin Meier and J{\"u}rgen Kaschk{\"o}t{\"o} (Institute of Human Genetics, University of Regensburg) for their technical support, and the FAM-Study Group for providing patients and controls. This study was supported in parts by the Deutsche Forschungsgemeinschaft (WE 1259/19-2 to BHFW), the Alcon Research Institute (to BHFW, EYC and AS), the Intramural Research program of the National Eye Institute (EYC and AS), and by grants from the National Eye Institute, National Institutes of Health, Bethesda, MD (R01-EY021532 to MLK).",

year = "2015",

month = may,

day = "11",

doi = "10.1371/journal.pone.0126636",

language = "English",

volume = "10",

journal = "PloS ONE",

issn = "1932-6203",

publisher = "PUBLIC LIBRARY SCIENCE",

number = "5",

}

TY - JOUR

T1 - Clinical and genetic factors associated with progression of geographic atrophy lesions in age-related macular degeneration

AU - Grassmann, Felix

AU - Fleckenstein, Monika

AU - Chew, Emily Y.

AU - Strunz, Tobias

AU - Schmitz-Valckenberg, Steffen

AU - Göbel, Arno P.

AU - Klein, Michael L.

AU - Ratnapriya, Rinki

AU - Swaroop, Anand

AU - Holz, Frank G.

AU - Weber, Bernhard H.F.

N1 - Acknowledgments We thank the patients and control individuals for their participation in the study, Kerstin Meier and Jürgen Kaschkötö (Institute of Human Genetics, University of Regensburg) for their technical support, and the FAM-Study Group for providing patients and controls. This study was supported in parts by the Deutsche Forschungsgemeinschaft (WE 1259/19-2 to BHFW), the Alcon Research Institute (to BHFW, EYC and AS), the Intramural Research program of the National Eye Institute (EYC and AS), and by grants from the National Eye Institute, National Institutes of Health, Bethesda, MD (R01-EY021532 to MLK).

PY - 2015/5/11

Y1 - 2015/5/11

N2 - Worldwide, age-related macular degeneration (AMD) is a serious threat to vision loss in individuals over 50 years of age with a pooled prevalence of approximately 9%. For 2020, the number of people afflicted with this condition is estimated to reach 200 million. While AMD lesions presenting as geographic atrophy (GA) show high inter-individual variability, only little is known about prognostic factors. Here, we aimed to elucidate the contribution of clinical, demographic and genetic factors on GA progression. Analyzing the currently largest dataset on GA lesion growth (N = 388), our findings suggest a significant and independent contribution of three factors on GA lesion growth including at least two genetic factors (ARMS2-rs10490924 [P < 0.00088] and C3-rs2230199 [P < 0.00015]) as well as one clinical component (presence of GA in the fellow eye [P < 0.00023]). These correlations jointly explain up to 7.2% of the observed inter-individual variance in GA lesion progression and should be considered in strategy planning of interventional clinical trials aimed at evaluating novel treatment options in advanced GA due to AMD.

AB - Worldwide, age-related macular degeneration (AMD) is a serious threat to vision loss in individuals over 50 years of age with a pooled prevalence of approximately 9%. For 2020, the number of people afflicted with this condition is estimated to reach 200 million. While AMD lesions presenting as geographic atrophy (GA) show high inter-individual variability, only little is known about prognostic factors. Here, we aimed to elucidate the contribution of clinical, demographic and genetic factors on GA progression. Analyzing the currently largest dataset on GA lesion growth (N = 388), our findings suggest a significant and independent contribution of three factors on GA lesion growth including at least two genetic factors (ARMS2-rs10490924 [P < 0.00088] and C3-rs2230199 [P < 0.00015]) as well as one clinical component (presence of GA in the fellow eye [P < 0.00023]). These correlations jointly explain up to 7.2% of the observed inter-individual variance in GA lesion progression and should be considered in strategy planning of interventional clinical trials aimed at evaluating novel treatment options in advanced GA due to AMD.

UR - http://www.scopus.com/inward/record.url?scp=84930642724&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0126636

DO - 10.1371/journal.pone.0126636

M3 - Article

C2 - 25962167

AN - SCOPUS:84930642724

SN - 1932-6203

VL - 10

JO - PloS ONE

JF - PloS ONE

IS - 5

M1 - e0126636

ER -

Clinical and genetic factors associated with progression of geographic atrophy lesions in age-related macular degeneration

Abstract

Bibliographical note

Access to Document

Other files and links

Fingerprint

Cite this