No CFH or ARMS2 Interaction with Omega-3 Fatty Acids, Low versus High Zinc, or β-Carotene versus Lutein and Zeaxanthin on Progression of Age-Related Macular Degeneration in the Age-Related Eye Disease Study 2: Age-Related Eye Disease Study 2 Report No. 18

Freekje van Asten, Chi Yang Chiu, Elvira Agrón, Traci E. Clemons, Rinki Ratnapriya, Anand Swaroop, Michael Klein, Ruzong Fan, Emily Y. Chew

Research output: Contribution to journalArticle

Abstract

Purpose: To assess whether genotypes at 2 major loci associated with age-related macular degeneration (AMD), complement factor H (CFH), or age-related maculopathy susceptibility 2 (ARMS2), modify the response to oral nutrients for the treatment of AMD in the Age-Related Eye Disease Study 2 (AREDS2). Design: Post hoc analysis of a randomized trial. Participants: White AREDS2 participants. Methods: AREDS2 participants (n = 4203) with bilateral large drusen or late AMD in 1 eye were assigned randomly to lutein and zeaxanthin, omega-3 fatty acids, both, or placebo, and most also received the AREDS supplements. A secondary randomization assessed modified AREDS supplements in 4 treatment arms: lower zinc dosage, omission of β-carotene, both, or no modification. To evaluate the progression to late AMD, fundus photographs were obtained at baseline and annual study visits, and history of treatment for late AMD was obtained at study visits and 6-month interim telephone calls. Participants were genotyped for the single-nucleotide polymorphisms rs1061170 in CFH and rs10490924 in ARMS2. Bivariate frailty models using both eyes were conducted, including a gene–supplement interaction term and adjusting for age, gender, level of education, and smoking status. The main treatment effects, as well as the direct comparison between lutein plus zeaxanthin and β-carotene, were assessed for genotype interaction. Main Outcome Measures: The interaction between genotype and the response to AREDS2 supplements regarding progression to late AMD, any geographic atrophy (GA), and neovascular AMD. Results: Complete data were available for 2775 eyes without baseline late AMD (1684 participants). The participants (mean age ± standard deviation, 72.1±7.7 years; 58.5% female) were followed up for a median of 5 years. The ARMS2 risk allele was associated significantly with progression to late AMD and neovascular AMD (P = 2.40 × 10–5 and P = 0.002, respectively), but not any GA (P = 0.097). The CFH risk allele was not associated with AMD progression. Genotype did not modify significantly the response to any of the AREDS2 supplements. Conclusions: CFH and ARMS2 risk alleles do not modify the response to the AREDS2 nutrient supplements with respect to the progression to late AMD (GA and neovascular AMD).

Original languageEnglish (US)
JournalOphthalmology
DOIs
StatePublished - Jan 1 2019

Fingerprint

Complement Factor H
Lutein
Eye Diseases
Omega-3 Fatty Acids
Macular Degeneration
Carotenoids
Zinc
Geographic Atrophy
Genotype
Alleles
Zeaxanthins
Macular Degeneration, Age-Related, 2
Food
Therapeutics
Random Allocation
Telephone
Single Nucleotide Polymorphism
Arm

ASJC Scopus subject areas

  • Ophthalmology

Cite this

No CFH or ARMS2 Interaction with Omega-3 Fatty Acids, Low versus High Zinc, or β-Carotene versus Lutein and Zeaxanthin on Progression of Age-Related Macular Degeneration in the Age-Related Eye Disease Study 2 : Age-Related Eye Disease Study 2 Report No. 18. / van Asten, Freekje; Chiu, Chi Yang; Agrón, Elvira; Clemons, Traci E.; Ratnapriya, Rinki; Swaroop, Anand; Klein, Michael; Fan, Ruzong; Chew, Emily Y.

In: Ophthalmology, 01.01.2019.

Research output: Contribution to journalArticle

@article{0545389cff2641429e9e41f845ba21f6,
title = "No CFH or ARMS2 Interaction with Omega-3 Fatty Acids, Low versus High Zinc, or β-Carotene versus Lutein and Zeaxanthin on Progression of Age-Related Macular Degeneration in the Age-Related Eye Disease Study 2: Age-Related Eye Disease Study 2 Report No. 18",
abstract = "Purpose: To assess whether genotypes at 2 major loci associated with age-related macular degeneration (AMD), complement factor H (CFH), or age-related maculopathy susceptibility 2 (ARMS2), modify the response to oral nutrients for the treatment of AMD in the Age-Related Eye Disease Study 2 (AREDS2). Design: Post hoc analysis of a randomized trial. Participants: White AREDS2 participants. Methods: AREDS2 participants (n = 4203) with bilateral large drusen or late AMD in 1 eye were assigned randomly to lutein and zeaxanthin, omega-3 fatty acids, both, or placebo, and most also received the AREDS supplements. A secondary randomization assessed modified AREDS supplements in 4 treatment arms: lower zinc dosage, omission of β-carotene, both, or no modification. To evaluate the progression to late AMD, fundus photographs were obtained at baseline and annual study visits, and history of treatment for late AMD was obtained at study visits and 6-month interim telephone calls. Participants were genotyped for the single-nucleotide polymorphisms rs1061170 in CFH and rs10490924 in ARMS2. Bivariate frailty models using both eyes were conducted, including a gene–supplement interaction term and adjusting for age, gender, level of education, and smoking status. The main treatment effects, as well as the direct comparison between lutein plus zeaxanthin and β-carotene, were assessed for genotype interaction. Main Outcome Measures: The interaction between genotype and the response to AREDS2 supplements regarding progression to late AMD, any geographic atrophy (GA), and neovascular AMD. Results: Complete data were available for 2775 eyes without baseline late AMD (1684 participants). The participants (mean age ± standard deviation, 72.1±7.7 years; 58.5{\%} female) were followed up for a median of 5 years. The ARMS2 risk allele was associated significantly with progression to late AMD and neovascular AMD (P = 2.40 × 10–5 and P = 0.002, respectively), but not any GA (P = 0.097). The CFH risk allele was not associated with AMD progression. Genotype did not modify significantly the response to any of the AREDS2 supplements. Conclusions: CFH and ARMS2 risk alleles do not modify the response to the AREDS2 nutrient supplements with respect to the progression to late AMD (GA and neovascular AMD).",
author = "{van Asten}, Freekje and Chiu, {Chi Yang} and Elvira Agr{\'o}n and Clemons, {Traci E.} and Rinki Ratnapriya and Anand Swaroop and Michael Klein and Ruzong Fan and Chew, {Emily Y.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.ophtha.2019.06.004",
language = "English (US)",
journal = "Ophthalmology",
issn = "0161-6420",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - No CFH or ARMS2 Interaction with Omega-3 Fatty Acids, Low versus High Zinc, or β-Carotene versus Lutein and Zeaxanthin on Progression of Age-Related Macular Degeneration in the Age-Related Eye Disease Study 2

T2 - Age-Related Eye Disease Study 2 Report No. 18

AU - van Asten, Freekje

AU - Chiu, Chi Yang

AU - Agrón, Elvira

AU - Clemons, Traci E.

AU - Ratnapriya, Rinki

AU - Swaroop, Anand

AU - Klein, Michael

AU - Fan, Ruzong

AU - Chew, Emily Y.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Purpose: To assess whether genotypes at 2 major loci associated with age-related macular degeneration (AMD), complement factor H (CFH), or age-related maculopathy susceptibility 2 (ARMS2), modify the response to oral nutrients for the treatment of AMD in the Age-Related Eye Disease Study 2 (AREDS2). Design: Post hoc analysis of a randomized trial. Participants: White AREDS2 participants. Methods: AREDS2 participants (n = 4203) with bilateral large drusen or late AMD in 1 eye were assigned randomly to lutein and zeaxanthin, omega-3 fatty acids, both, or placebo, and most also received the AREDS supplements. A secondary randomization assessed modified AREDS supplements in 4 treatment arms: lower zinc dosage, omission of β-carotene, both, or no modification. To evaluate the progression to late AMD, fundus photographs were obtained at baseline and annual study visits, and history of treatment for late AMD was obtained at study visits and 6-month interim telephone calls. Participants were genotyped for the single-nucleotide polymorphisms rs1061170 in CFH and rs10490924 in ARMS2. Bivariate frailty models using both eyes were conducted, including a gene–supplement interaction term and adjusting for age, gender, level of education, and smoking status. The main treatment effects, as well as the direct comparison between lutein plus zeaxanthin and β-carotene, were assessed for genotype interaction. Main Outcome Measures: The interaction between genotype and the response to AREDS2 supplements regarding progression to late AMD, any geographic atrophy (GA), and neovascular AMD. Results: Complete data were available for 2775 eyes without baseline late AMD (1684 participants). The participants (mean age ± standard deviation, 72.1±7.7 years; 58.5% female) were followed up for a median of 5 years. The ARMS2 risk allele was associated significantly with progression to late AMD and neovascular AMD (P = 2.40 × 10–5 and P = 0.002, respectively), but not any GA (P = 0.097). The CFH risk allele was not associated with AMD progression. Genotype did not modify significantly the response to any of the AREDS2 supplements. Conclusions: CFH and ARMS2 risk alleles do not modify the response to the AREDS2 nutrient supplements with respect to the progression to late AMD (GA and neovascular AMD).

AB - Purpose: To assess whether genotypes at 2 major loci associated with age-related macular degeneration (AMD), complement factor H (CFH), or age-related maculopathy susceptibility 2 (ARMS2), modify the response to oral nutrients for the treatment of AMD in the Age-Related Eye Disease Study 2 (AREDS2). Design: Post hoc analysis of a randomized trial. Participants: White AREDS2 participants. Methods: AREDS2 participants (n = 4203) with bilateral large drusen or late AMD in 1 eye were assigned randomly to lutein and zeaxanthin, omega-3 fatty acids, both, or placebo, and most also received the AREDS supplements. A secondary randomization assessed modified AREDS supplements in 4 treatment arms: lower zinc dosage, omission of β-carotene, both, or no modification. To evaluate the progression to late AMD, fundus photographs were obtained at baseline and annual study visits, and history of treatment for late AMD was obtained at study visits and 6-month interim telephone calls. Participants were genotyped for the single-nucleotide polymorphisms rs1061170 in CFH and rs10490924 in ARMS2. Bivariate frailty models using both eyes were conducted, including a gene–supplement interaction term and adjusting for age, gender, level of education, and smoking status. The main treatment effects, as well as the direct comparison between lutein plus zeaxanthin and β-carotene, were assessed for genotype interaction. Main Outcome Measures: The interaction between genotype and the response to AREDS2 supplements regarding progression to late AMD, any geographic atrophy (GA), and neovascular AMD. Results: Complete data were available for 2775 eyes without baseline late AMD (1684 participants). The participants (mean age ± standard deviation, 72.1±7.7 years; 58.5% female) were followed up for a median of 5 years. The ARMS2 risk allele was associated significantly with progression to late AMD and neovascular AMD (P = 2.40 × 10–5 and P = 0.002, respectively), but not any GA (P = 0.097). The CFH risk allele was not associated with AMD progression. Genotype did not modify significantly the response to any of the AREDS2 supplements. Conclusions: CFH and ARMS2 risk alleles do not modify the response to the AREDS2 nutrient supplements with respect to the progression to late AMD (GA and neovascular AMD).

UR - http://www.scopus.com/inward/record.url?scp=85069706172&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85069706172&partnerID=8YFLogxK

U2 - 10.1016/j.ophtha.2019.06.004

DO - 10.1016/j.ophtha.2019.06.004

M3 - Article

AN - SCOPUS:85069706172

JO - Ophthalmology

JF - Ophthalmology

SN - 0161-6420

ER -