Dataset Information

Genetics and Age-Related Eye Disease Study Formulation Interaction in Neovascular Age-Related Macular Degeneration.

ABSTRACT:

Purpose

This work aims to determine whether previously defined genotype risk groups interact with Age-Related Eye Disease Study formulation (AREDS-F) use in progression to neovascular age-related macular degeneration (nvAMD).

Methods

We conducted a case-only study of 265 nvAMD patients. Patients were anonymously genotyped at the complement factor H and age-related maculopathy susceptibility 2 loci and segregated into genotype groups (GTGs) defined by specific combinations of risk alleles. Physicians, who were blind to patients' GTGs, obtained patients' AREDS-F use history. The facility performing genetic analysis was blind to the AREDS-F use history. We used logistic analysis to estimate the interaction coefficient between AREDS-F use and GTG 2 vs GTG 3 in a general-population model.

Results

The odds ratio of numbers of patients reporting prior AREDS-F use to nonuse for GTG 2 vs GTG 3 was 4.18 (P = .001). Logistic regression, correcting for nongenetic risk factors, gave an estimate of the β for interaction of AREDS-F with genotype of 1.57 (P = .001). This estimates a corrected odds ratio associated with the effect of interaction of 4.81 between those in GTG 2 compared with those in GTG 3.

Conclusions

Our data indicate an interaction between GTGs and AREDS-F use that is consistent in size and direction with previously published reports, which had found that using AREDS-F supplements significantly increases the risk of nvAMD for some users and significantly protects other users.

SUBMITTER: Kaufman SR

PROVIDER: S-EPMC9976046 | biostudies-literature | 2021 Jan-Feb

REPOSITORIES: biostudies-literature

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Publications

Genetics and Age-Related Eye Disease Study Formulation Interaction in Neovascular Age-Related Macular Degeneration.

Kaufman Stephen R SR Yoganathan Pradeepa P Small Kent W KW Rusia Deepam D Pachydaki Sophia I SI Conti Stephen M SM Wenz Robert E RE Gersman Mark A MA Shaya Fadi S FS Kustra Rafal R

Journal of vitreoretinal diseases 20200819 1

<h4>Purpose</h4>This work aims to determine whether previously defined genotype risk groups interact with Age-Related Eye Disease Study formulation (AREDS-F) use in progression to neovascular age-related macular degeneration (nvAMD).<h4>Methods</h4>We conducted a case-only study of 265 nvAMD patients. Patients were anonymously genotyped at the complement factor H and age-related maculopathy susceptibility 2 loci and segregated into genotype groups (GTGs) defined by specific combinations of risk ...[more]

PMID: 37009583

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Project description:PurposeTo report the natural history of untreated neovascular age-related macular degeneration (nAMD) regarding subsequent macular atrophy.DesignProspective cohort within a randomized, controlled trial of oral micronutrient supplements.ParticipantsAge-Related Eye Disease Study (AREDS) participants (55-80 years) who demonstrated nAMD during follow-up (1992-2005), prior to anti-vascular endothelial growth factor (VEGF) therapy.MethodsColor fundus photographs were collected at annual study visits and graded centrally for late age-related macular degeneration (AMD). Incident macular atrophy after nAMD was examined by Kaplan-Meier analysis and proportional hazards regression.Main outcome measuresIncident macular atrophy after nAMD.ResultsOf the 4757 AREDS participants, 708 eyes (627 participants) demonstrated nAMD during follow-up and were eligible. The cumulative risks of incident macular atrophy after untreated nAMD were 9.6% (standard error, 1.2%), 31.4% (standard error, 2.2%), 43.1% (standard error, 2.6%), and 61.5% (standard error, 4.3%) at 2, 5, 7, and 10 years, respectively. This corresponded to a linear risk of 6.5% per year. The cumulative risk of central involvement was 30.4% (standard error, 3.2%), 43.4% (standard error, 3.8%), and 57.0% (standard error, 4.8%) at first appearance of atrophy, 2 years, and 5 years, respectively. Geographic atrophy (GA) in the fellow eye was associated with increased risk of macular atrophy (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.17-2.49; P = 0.006). However, higher 52-single nucleotide polymorphism AMD genetic risk score was not associated with increased risk of macular atrophy (HR, 1.03; 95% CI, 0.90-1.17; P = 0.67). Similarly, no significant differences were observed according to SNPs at CFH, ARMS2, or C3.ConclusionsThe rate of incident macular atrophy after untreated nAMD is relatively high, increasing linearly over time and affecting half of eyes by 8 years. Hence, factors other than anti-VEGF therapy are involved in atrophy development, including natural progression to GA. Comparison with studies of treated nAMD suggests it may not be necessary to invoke a large effect of anti-VEGF therapy on inciting macular atrophy, although a contribution remains possible. Central involvement is present in one third of eyes at the outset (similar to pure GA) and increases linearly to half at 3 years.

Project description:Purpose:To identify the development and progression of macular retinal pigment epithelial atrophy in eyes with neovascular (CNV) age-related macular degeneration (AMD) and to correlate with visual acuity (VA). Design:Cohort study. Participants:Age-Related Eye Disease Study 2 (AREDS2) participants with intermediate AMD enrolled in a randomized controlled clinical trial of oral supplements. Analyses were conducted in the subset of AREDS2 participants who were also enrolled in the fundus autofluorescence ancillary (FAF) ancillary study. Methods:Color photographs and FAF images were evaluated in eyes that developed CNV. Presence of geographic atrophy (GA) prior to the incidence of CNV and the development of macular atrophy following incident CNV were assessed. Areas of hypoautofluorescence representing atrophy were measured for area and macular involvement. Enlargement rate of atrophy and change in visual acuity over time were analyzed. Main Outcome Measures:incidence and enlargement rate of atrophy and VA changes in eyes with incident CNV. Results:Incident CNV developed in 334 (9.2%) of eyes evaluated in the AREDS2 FAF substudy. Of these, 40% had macular atrophy at incidence of CNV with half of these attributable to pre-existing GA. Atrophy developed in 14.7 % of eyes over 4 years of follow-up. Mean area of atrophy was largest in eyes with pre-existing GA and CNV (5.17 mm2, p<0.001), and atrophy involved the center of the macula in > 65% of eyes. Mean VA letter score at the annual visit in which CNV was documented was similar in the three groups with atrophy; eyes with CNV and pre-existing GA, incident atrophy at the first visit with CNV, and atrophy during follow up (60 letters). Enlargement rate of atrophy was also similar in eyes in the three groups (1.23 - 1.86 mm2, p = 0.47). Eyes with macular atrophy lost more visual acuity compared to eyes without atrophy, particularly after 2 years of follow-up (-10.9 vs. - 3.6 letters, p = 0.07). Conclusion:Atrophy is commonly seen in neovascular AMD and often can be attributed to pre-existing GA. Macular atrophy and GA appear to be a continuum of the same disease process and are both associated with poor vision.

Project description:PurposeTo analyze the principal cause for poor vision in eyes with best-corrected visual acuity (BCVA) of 20/200 or worse 2 years after neovascular age-related macular degeneration (nAMD).DesignProspective cohort study of participants enrolled in a clinical trial of oral supplements.ParticipantsAge-Related Eye Disease Study 2 (AREDS2) participants whose eyes began anti-vascular endothelial growth factor (VEGF) therapy for incident nAMD and had data available at 2 years.MethodsParticipants underwent refracted BCVA testing, ophthalmoscopic examination, and fundus photography at baseline and annual visits. Self-reports of anti-VEGF injections were collected.Main outcome measuresPrincipal cause of BCVA of 20/200 or worse at 2 years, detected on fundus photography grading.ResultsOf the 594 eligible eyes, the number with BCVA of 20/200 or worse at 2 years was 56 (9.4%). Mean BCVA was 14.9 letters (standard deviation [SD], 12.3 letters; Snellen equivalent, 20/500), versus 70.1 letters (SD, 12.8 letters; Snellen equivalent, 20/40) in the other group. Of the 55 eyes with fundus photography available at 2 years, 33 (60.0%) had central macular atrophy and 22 (40.0%) had central subretinal fibrosis assessed as the principal cause for poor vision. The group with poor BCVA had a higher proportion of non-White participants (8.9% vs. 1.7%; P = 0.006), lower BCVA 2 years earlier (mean, 38.0 letters [SD, 26.7 letters; Snellen equivalent, 20/160] vs. 71.8 letters (SD, 11.9 letters; Snellen equivalent, 20/40]; P < 0.0001), higher proportion with macular atrophy 2 years earlier (26.8% vs. 12.3%; P = 0.003), higher proportion with macular hemorrhage (25.5% vs. 13.2%; P = 0.014), and fewer anti-VEGF injections (7.6 vs. 10.2; P = 0.001).ConclusionsVisual acuity data and fundus photography were obtained in a clinical trial environment, but were related to anti-VEGF therapy given in routine clinical practice. At 2 years after starting anti-VEGF therapy, almost 1 in 10 eyes showed BCVA at the level of legal blindness. From fundus photography grading, the cause of poor vision appeared to be macular atrophy in 60% and subretinal fibrosis in 40%. These data may be useful in understanding the long-term limits to good vision in nAMD.

Dataset Information

Genetics and Age-Related Eye Disease Study Formulation Interaction in Neovascular Age-Related Macular Degeneration.

Purpose

Methods

Results

Conclusions

Publications

Genetics and Age-Related Eye Disease Study Formulation Interaction in Neovascular Age-Related Macular Degeneration.

Similar Datasets

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