Risk of geographic atrophy in the comparison of age-related macular degeneration treatments trials

Juan E. Grunwald, Ebenezer Daniel, Jiayan Huang, Gui Shuang Ying, Maureen G. Maguire, Cynthia A. Toth, Glenn J. Jaffe, Stuart L. Fine, Barbara Blodi, Michael Klein, Alison A. Martin, Stephanie A. Hagstrom, Daniel F. Martin

Research output: Contribution to journalArticle

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Abstract

Purpose To describe risk factors for geographic atrophy (GA) in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT). Design Cohort within a randomized clinical trial. Participants We analyzed 1024 CATT patients with no GA visible on color fundus photographs (CFPs) and/or fluorescein angiograms (FAs) at enrollment. Methods Eyes were assigned to ranibizumab (0.5 mg) or bevacizumab (1.25 mg) treatment and to a 2-year monthly or pro re nata (PRN) injection regimen, or monthly injections for 1 year and PRN for 1 year. Demographic, genetic, and baseline ocular characteristics and lesion features of CFP/FA and optical coherence tomography (OCT) were evaluated as risk factors for GA through 2 years of follow-up. Time-dependent Cox proportional hazard models were used to estimate adjusted hazard ratios (aHRs). Main Outcome Measures Development of GA. Results By 2 years, GA developed in 187 of 1024 patients (18.3%). Baseline risk factors for GA development included baseline visual acuity (VA) ≤20/200 (aHR, 2.65; 95% confidence interval [CI], 1.43-4.93), retinal angiomatous proliferation (RAP; aHR, 1.69; 95% CI, 1.16-2.47), GA in the fellow eye (aHR, 2.07; 95% CI, 1.40-3.08), and intraretinal fluid at the foveal center (aHR, 2.10; 95% CI, 1.34-3.31). Baseline factors associated with lower risk for GA development included blocked fluorescence (aHR, 0.49; 95% CI, 0.29-0.82), OCT measurements of subretinal fluid thickness of >25 μ (aHR, 0.52; 95% CI, 0.35-0.78), subretinal tissue complex thickness of >275 compared with ≤75 μ (aHR, 0.31; 95% CI, 0.19-0.50), and vitreomacular attachment (aHR, 0.55; 95% CI, 0.31-0.97). Ranibizumab compared with bevacizumab had a higher risk (aHR, 1.43; 95% CI, 1.06-1.93), and monthly dosing had a higher risk (aHR, 1.59; 95% CI, 1.17-2.16) than PRN dosing. There were no strong associations between development of GA and the presence of risk alleles for CFH, ARMS 2, HTRA1, C3, or TLR3. Conclusions Approximately one fifth of CATT patients developed GA within 2 years of treatment. Independent baseline risk factors included poor VA, RAP, foveal intraretinal fluid, monthly dosing, and treatment with ranibizumab. Anti-vascular endothelial growth factor therapy may have a role in the development of GA.

Original languageEnglish (US)
Pages (from-to)150-161
Number of pages12
JournalOphthalmology
Volume121
Issue number1
DOIs
StatePublished - Jan 2014

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Geographic Atrophy
Macular Degeneration
Confidence Intervals
Therapeutics
Optical Coherence Tomography
Fluorescein
Visual Acuity
Angiography
Color
Subretinal Fluid
Injections
Proportional Hazards Models
Vascular Endothelial Growth Factor A

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Grunwald, J. E., Daniel, E., Huang, J., Ying, G. S., Maguire, M. G., Toth, C. A., ... Martin, D. F. (2014). Risk of geographic atrophy in the comparison of age-related macular degeneration treatments trials. Ophthalmology, 121(1), 150-161. https://doi.org/10.1016/j.ophtha.2013.08.015

Risk of geographic atrophy in the comparison of age-related macular degeneration treatments trials. / Grunwald, Juan E.; Daniel, Ebenezer; Huang, Jiayan; Ying, Gui Shuang; Maguire, Maureen G.; Toth, Cynthia A.; Jaffe, Glenn J.; Fine, Stuart L.; Blodi, Barbara; Klein, Michael; Martin, Alison A.; Hagstrom, Stephanie A.; Martin, Daniel F.

In: Ophthalmology, Vol. 121, No. 1, 01.2014, p. 150-161.

Research output: Contribution to journalArticle

Grunwald, JE, Daniel, E, Huang, J, Ying, GS, Maguire, MG, Toth, CA, Jaffe, GJ, Fine, SL, Blodi, B, Klein, M, Martin, AA, Hagstrom, SA & Martin, DF 2014, 'Risk of geographic atrophy in the comparison of age-related macular degeneration treatments trials', Ophthalmology, vol. 121, no. 1, pp. 150-161. https://doi.org/10.1016/j.ophtha.2013.08.015
Grunwald, Juan E. ; Daniel, Ebenezer ; Huang, Jiayan ; Ying, Gui Shuang ; Maguire, Maureen G. ; Toth, Cynthia A. ; Jaffe, Glenn J. ; Fine, Stuart L. ; Blodi, Barbara ; Klein, Michael ; Martin, Alison A. ; Hagstrom, Stephanie A. ; Martin, Daniel F. / Risk of geographic atrophy in the comparison of age-related macular degeneration treatments trials. In: Ophthalmology. 2014 ; Vol. 121, No. 1. pp. 150-161.
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abstract = "Purpose To describe risk factors for geographic atrophy (GA) in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT). Design Cohort within a randomized clinical trial. Participants We analyzed 1024 CATT patients with no GA visible on color fundus photographs (CFPs) and/or fluorescein angiograms (FAs) at enrollment. Methods Eyes were assigned to ranibizumab (0.5 mg) or bevacizumab (1.25 mg) treatment and to a 2-year monthly or pro re nata (PRN) injection regimen, or monthly injections for 1 year and PRN for 1 year. Demographic, genetic, and baseline ocular characteristics and lesion features of CFP/FA and optical coherence tomography (OCT) were evaluated as risk factors for GA through 2 years of follow-up. Time-dependent Cox proportional hazard models were used to estimate adjusted hazard ratios (aHRs). Main Outcome Measures Development of GA. Results By 2 years, GA developed in 187 of 1024 patients (18.3{\%}). Baseline risk factors for GA development included baseline visual acuity (VA) ≤20/200 (aHR, 2.65; 95{\%} confidence interval [CI], 1.43-4.93), retinal angiomatous proliferation (RAP; aHR, 1.69; 95{\%} CI, 1.16-2.47), GA in the fellow eye (aHR, 2.07; 95{\%} CI, 1.40-3.08), and intraretinal fluid at the foveal center (aHR, 2.10; 95{\%} CI, 1.34-3.31). Baseline factors associated with lower risk for GA development included blocked fluorescence (aHR, 0.49; 95{\%} CI, 0.29-0.82), OCT measurements of subretinal fluid thickness of >25 μ (aHR, 0.52; 95{\%} CI, 0.35-0.78), subretinal tissue complex thickness of >275 compared with ≤75 μ (aHR, 0.31; 95{\%} CI, 0.19-0.50), and vitreomacular attachment (aHR, 0.55; 95{\%} CI, 0.31-0.97). Ranibizumab compared with bevacizumab had a higher risk (aHR, 1.43; 95{\%} CI, 1.06-1.93), and monthly dosing had a higher risk (aHR, 1.59; 95{\%} CI, 1.17-2.16) than PRN dosing. There were no strong associations between development of GA and the presence of risk alleles for CFH, ARMS 2, HTRA1, C3, or TLR3. Conclusions Approximately one fifth of CATT patients developed GA within 2 years of treatment. Independent baseline risk factors included poor VA, RAP, foveal intraretinal fluid, monthly dosing, and treatment with ranibizumab. Anti-vascular endothelial growth factor therapy may have a role in the development of GA.",
author = "Grunwald, {Juan E.} and Ebenezer Daniel and Jiayan Huang and Ying, {Gui Shuang} and Maguire, {Maureen G.} and Toth, {Cynthia A.} and Jaffe, {Glenn J.} and Fine, {Stuart L.} and Barbara Blodi and Michael Klein and Martin, {Alison A.} and Hagstrom, {Stephanie A.} and Martin, {Daniel F.}",
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T1 - Risk of geographic atrophy in the comparison of age-related macular degeneration treatments trials

AU - Grunwald, Juan E.

AU - Daniel, Ebenezer

AU - Huang, Jiayan

AU - Ying, Gui Shuang

AU - Maguire, Maureen G.

AU - Toth, Cynthia A.

AU - Jaffe, Glenn J.

AU - Fine, Stuart L.

AU - Blodi, Barbara

AU - Klein, Michael

AU - Martin, Alison A.

AU - Hagstrom, Stephanie A.

AU - Martin, Daniel F.

PY - 2014/1

Y1 - 2014/1

N2 - Purpose To describe risk factors for geographic atrophy (GA) in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT). Design Cohort within a randomized clinical trial. Participants We analyzed 1024 CATT patients with no GA visible on color fundus photographs (CFPs) and/or fluorescein angiograms (FAs) at enrollment. Methods Eyes were assigned to ranibizumab (0.5 mg) or bevacizumab (1.25 mg) treatment and to a 2-year monthly or pro re nata (PRN) injection regimen, or monthly injections for 1 year and PRN for 1 year. Demographic, genetic, and baseline ocular characteristics and lesion features of CFP/FA and optical coherence tomography (OCT) were evaluated as risk factors for GA through 2 years of follow-up. Time-dependent Cox proportional hazard models were used to estimate adjusted hazard ratios (aHRs). Main Outcome Measures Development of GA. Results By 2 years, GA developed in 187 of 1024 patients (18.3%). Baseline risk factors for GA development included baseline visual acuity (VA) ≤20/200 (aHR, 2.65; 95% confidence interval [CI], 1.43-4.93), retinal angiomatous proliferation (RAP; aHR, 1.69; 95% CI, 1.16-2.47), GA in the fellow eye (aHR, 2.07; 95% CI, 1.40-3.08), and intraretinal fluid at the foveal center (aHR, 2.10; 95% CI, 1.34-3.31). Baseline factors associated with lower risk for GA development included blocked fluorescence (aHR, 0.49; 95% CI, 0.29-0.82), OCT measurements of subretinal fluid thickness of >25 μ (aHR, 0.52; 95% CI, 0.35-0.78), subretinal tissue complex thickness of >275 compared with ≤75 μ (aHR, 0.31; 95% CI, 0.19-0.50), and vitreomacular attachment (aHR, 0.55; 95% CI, 0.31-0.97). Ranibizumab compared with bevacizumab had a higher risk (aHR, 1.43; 95% CI, 1.06-1.93), and monthly dosing had a higher risk (aHR, 1.59; 95% CI, 1.17-2.16) than PRN dosing. There were no strong associations between development of GA and the presence of risk alleles for CFH, ARMS 2, HTRA1, C3, or TLR3. Conclusions Approximately one fifth of CATT patients developed GA within 2 years of treatment. Independent baseline risk factors included poor VA, RAP, foveal intraretinal fluid, monthly dosing, and treatment with ranibizumab. Anti-vascular endothelial growth factor therapy may have a role in the development of GA.

AB - Purpose To describe risk factors for geographic atrophy (GA) in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT). Design Cohort within a randomized clinical trial. Participants We analyzed 1024 CATT patients with no GA visible on color fundus photographs (CFPs) and/or fluorescein angiograms (FAs) at enrollment. Methods Eyes were assigned to ranibizumab (0.5 mg) or bevacizumab (1.25 mg) treatment and to a 2-year monthly or pro re nata (PRN) injection regimen, or monthly injections for 1 year and PRN for 1 year. Demographic, genetic, and baseline ocular characteristics and lesion features of CFP/FA and optical coherence tomography (OCT) were evaluated as risk factors for GA through 2 years of follow-up. Time-dependent Cox proportional hazard models were used to estimate adjusted hazard ratios (aHRs). Main Outcome Measures Development of GA. Results By 2 years, GA developed in 187 of 1024 patients (18.3%). Baseline risk factors for GA development included baseline visual acuity (VA) ≤20/200 (aHR, 2.65; 95% confidence interval [CI], 1.43-4.93), retinal angiomatous proliferation (RAP; aHR, 1.69; 95% CI, 1.16-2.47), GA in the fellow eye (aHR, 2.07; 95% CI, 1.40-3.08), and intraretinal fluid at the foveal center (aHR, 2.10; 95% CI, 1.34-3.31). Baseline factors associated with lower risk for GA development included blocked fluorescence (aHR, 0.49; 95% CI, 0.29-0.82), OCT measurements of subretinal fluid thickness of >25 μ (aHR, 0.52; 95% CI, 0.35-0.78), subretinal tissue complex thickness of >275 compared with ≤75 μ (aHR, 0.31; 95% CI, 0.19-0.50), and vitreomacular attachment (aHR, 0.55; 95% CI, 0.31-0.97). Ranibizumab compared with bevacizumab had a higher risk (aHR, 1.43; 95% CI, 1.06-1.93), and monthly dosing had a higher risk (aHR, 1.59; 95% CI, 1.17-2.16) than PRN dosing. There were no strong associations between development of GA and the presence of risk alleles for CFH, ARMS 2, HTRA1, C3, or TLR3. Conclusions Approximately one fifth of CATT patients developed GA within 2 years of treatment. Independent baseline risk factors included poor VA, RAP, foveal intraretinal fluid, monthly dosing, and treatment with ranibizumab. Anti-vascular endothelial growth factor therapy may have a role in the development of GA.

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