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ASSOCIATION BETWEEN ORAL IRON SUPPLEMENTATION AND RETINAL OR SUBRETINAL HEMORRHAGE IN THE COMPARISON OF AGE-RELATED MACULAR DEGENERATION TREATMENT TRIALS.

ABSTRACT: PURPOSE:Because patients often take iron supplements without medical indication, and iron can accumulate in vascular endothelial cells, the authors evaluated the association of oral iron supplementation with retinal/subretinal hemorrhage in patients with neovascular age-related macular degeneration. METHODS:A post hoc secondary data analysis of comparison of age-related macular degeneration treatments trials was performed. Participants were interviewed for use of oral iron supplements. Trained readers evaluated retinal/subretinal hemorrhage in baseline fundus photographs. Adjusted odds ratios from multivariate logistic regression models assessed the association between iron use and baseline hemorrhage adjusted by age, sex, smoking, hypertension, anemia, and use of antiplatelet/anticoagulant drugs. RESULTS:Among 1,165 participants, baseline retinal/subretinal hemorrhage was present in the study eye in 71% of 181 iron users and in 61% of 984 participants without iron use (adjusted odds ratio = 1.47, P = 0.04), and the association was dose dependent (adjusted linear trend P = 0.048). Iron use was associated with hemorrhage in participants with hypertension (adjusted odds ratio = 1.87, P = 0.006) but not without hypertension. The association of iron use with hemorrhage remained significant among hypertensive participants without anemia (adjusted odds ratio = 1.85, P = 0.02). CONCLUSION:Among participants of comparison of age-related macular degeneration treatments trials, the use of oral iron supplements was associated with retinal/subretinal hemorrhage in a dose-response manner. Unindicated iron supplementation may be detrimental in patients with wet age-related macular degeneration.

SUBMITTER: Song D

PROVIDER: S-EPMC6395574 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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ASSOCIATION BETWEEN ORAL IRON SUPPLEMENTATION AND RETINAL OR SUBRETINAL HEMORRHAGE IN THE COMPARISON OF AGE-RELATED MACULAR DEGENERATION TREATMENT TRIALS.

Song Delu D Ying Gui-Shuang GS Dunaief Joshua L JL Bhuyan Rupak R Li Yafeng Y Maguire Maureen G MG Grunwald Juan E JE Daniel Ebenezer E Hagstrom Stephanie S Martin Daniel F DF

Retina (Philadelphia, Pa.) 20191001 10

<h4>Purpose</h4>Because patients often take iron supplements without medical indication, and iron can accumulate in vascular endothelial cells, the authors evaluated the association of oral iron supplementation with retinal/subretinal hemorrhage in patients with neovascular age-related macular degeneration.<h4>Methods</h4>A post hoc secondary data analysis of comparison of age-related macular degeneration treatments trials was performed. Participants were interviewed for use of oral iron supplem ...[more]

PMID: 30157115

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Project description:PURPOSE:To evaluate the association between use of antiplatelet or anticoagulant drugs and retinal or subretinal hemorrhage in participants with neovascular age-related macular degeneration (AMD) in the Comparison of AMD Treatments Trials (CATT). DESIGN:Cohort study within CATT. PARTICIPANTS:Participants in CATT with untreated active neovascular AMD (n = 1185). METHODS:Participants were interviewed for use of antiplatelet or anticoagulant drugs. Trained readers evaluated photographs for the presence and size of retinal or subretinal hemorrhage at baseline and years 1 and 2. Associations between use of antiplatelet or anticoagulant drugs and hemorrhage were evaluated among all participants and by baseline hypertension status using multivariate logistic regression models. MAIN OUTCOME MEASURES:Odds ratio for association with antiplatelet or anticoagulant use. RESULTS:Among 1165 participants with gradable photographs, 724 (62.1%) had retinal or subretinal hemorrhage at baseline; 84.4% of hemorrhages were 1 disc area (DA) or less, 8.1% were 1 to 2 DA, and 7.5% were more than 2 DA. At baseline, 608 participants (52.2%) used antiplatelet or anticoagulant drugs, including 514 participants (44.1%) using antiplatelets only, 77 (6.6%) using anticoagulants only, and 17 (1.5%) using both. Hemorrhage was present in 64.5% of antiplatelet or anticoagulant users and in 59.6% of nonusers (P = 0.09; adjusted odds ratio [OR], 1.18; 95% confidence interval, 0.91-1.51; P = 0.21). Neither presence nor size of baseline hemorrhage was associated with the type, dose, or duration of antiplatelet or anticoagulant use. Forty-four of 1078 participants (4.08%) had retinal or subretinal hemorrhage detected on 1- or 2-year photographs; these hemorrhages were not associated with antiplatelet or anticoagulant use at baseline (P = 0.28) or during follow-up (P = 0.64). Among participants with hypertension (n = 807), antiplatelet or anticoagulant use was associated with a higher rate of hemorrhage at baseline (66.8% vs. 56.4%; adjusted OR, 1.48; P = 0.01), but not size of retinal or subretinal hemorrhage (P = 0.41). CONCLUSIONS:Most retinal or subretinal hemorrhages in eyes enrolled in CATT were less than 1 DA. Among all CATT participants, antiplatelet or anticoagulant use was not associated significantly with hemorrhage, but it was associated significantly with hemorrhage in participants with hypertension.

Project description:PurposeTo evaluate the association of subretinal hyperreflective material (SHRM) with visual acuity (VA), geographic atrophy (GA), and scar in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).DesignProspective cohort study within a randomized clinical trial.ParticipantsThe 1185 CATT participants.MethodsMasked readers graded scar and GA on fundus photography and fluorescein angiography and graded SHRM on time-domain and spectral-domain (SD) optical coherence tomography (OCT) throughout 104 weeks. Measurements of SHRM height and width in the fovea, within the center 1 mm(2), or outside the center 1mm(2) were obtained on SD OCT images at 56 (n = 76) and 104 (n = 66) weeks.Main outcome measuresPresence of SHRM, as well as location and size, and associations with VA, scar, and GA.ResultsAmong CATT participants, the percentage with SHRM at enrollment was 77%, decreasing to 68% at 4 weeks after treatment and to 54% at 104 weeks. At 104 weeks, scar was present more often in eyes with persistent SHRM than in eyes with SHRM that resolved (64% vs. 31%; P < 0.0001). Among eyes with detailed evaluation of SHRM at weeks 56 (n = 76) and 104 (n = 66), mean VA letter score was 73.5 (standard error [SE], 2.8), 73.1 (SE, 3.4), 65.3 (SE, 3.5), and 63.9 (SE, 3.7) when SHRM was absent, present outside the central 1 mm(2), present within the central 1 mm(2) but not the foveal center, or present at the foveal center (P = 0.02), respectively. When SHRM was present, the median maximum height under the fovea, within the central 1 mm(2) including the fovea and anywhere within the scan, was 86 μm, 120 μm, and 122 μm, respectively. Visual acuity was decreased with greater SHRM height and width (P < 0.05).ConclusionsIn eyes with neovascular age-related macular degeneration (AMD), SHRM is common and often persists after anti-vascular endothelial growth factor treatment. At 2 years, eyes with scar were more likely to have SHRM than other eyes. Greater SHRM dimensions were associated with worse VA. In eyes with neovascular AMD, SHRM is an important morphologic biomarker.

Project description:Contrary to Alzheimer's disease (AD), the APOE2 allele increases and the APOE4 allele reduces the risk to develop age-related macular degeneration (AMD) compared with the most common APOE3 allele. The underlying mechanism for this association with AMD and the reason for the puzzling difference with AD are unknown. We previously demonstrated that pathogenic subretinal mononuclear phagocytes (MPs) accumulate in Cx3cr1-deficient mice due to the overexpression of APOE, interleukin-6, and CC chemokine ligand 2 (CCL2). We here show using targeted replacement mice expressing the human APOE isoforms (TRE2, TRE3, and TRE4) that MPs of TRE2 mice express increased levels of APOE, interleukin-6, and CCL2 and develop subretinal MP accumulation, photoreceptor degeneration, and exaggerated choroidal neovascularization similar to AMD. Pharmacological inhibition of the cytokine induction inhibited the pathogenic subretinal inflammation. In the context of APOE-dependent subretinal inflammation in Cx3cr1(GFP/GFP) mice, the APOE4 allele led to diminished APOE and CCL2 levels and protected Cx3cr1(GFP/GFP) mice against harmful subretinal MP accumulation observed in Cx3cr1(GFP/GFP)TRE3 mice. Our study shows that pathogenic subretinal inflammation is APOE isoform-dependent and provides the rationale for the previously unexplained implication of the APOE2 isoform as a risk factor and the APOE4 isoform as a protective factor in AMD pathogenesis.Significance statementThe understanding of how genetic predisposing factors, which play a major role in age-related macular degeneration (AMD), participate in its pathogenesis is an important clue to decipher the pathomechanism and develop efficient therapies. In this study, we used transgenic, targeted replacement mice that carry the three human APOE isoform-defining sequences at the mouse APOE chromosomal location and express the human APOE isoforms. Our study is the first to show how APOE2 provokes and APOE4 inhibits the cardinal AMD features, inflammation, degeneration, and exaggerated neovascularization. Our findings reflect the clinical association of the genetic predisposition that was recently confirmed in a major pooled analysis. They emphasize the role of APOE in inflammation and inflammation in AMD.

Dataset Information

ASSOCIATION BETWEEN ORAL IRON SUPPLEMENTATION AND RETINAL OR SUBRETINAL HEMORRHAGE IN THE COMPARISON OF AGE-RELATED MACULAR DEGENERATION TREATMENT TRIALS.

Publications

ASSOCIATION BETWEEN ORAL IRON SUPPLEMENTATION AND RETINAL OR SUBRETINAL HEMORRHAGE IN THE COMPARISON OF AGE-RELATED MACULAR DEGENERATION TREATMENT TRIALS.

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