Association Between Oral Iron Supplementation and Retinal or Subretinal Hemorrhage in the Comparison of Age-Related Macular Degeneration Treatment Trials

Song, Delu; Ying, Gui‐Shuang; Dunaief, Joshua L.; Bhuyan, Rupak; Li, Yafeng; Maguire, Maureen G.; Grunwald, Juan E.; Daniel, Ebenezer; Hagstrom, Stephanie A.; Martín, Daniel

doi:10.1097/iae.0000000000002295

Cited by 3 publications

(2 citation statements)

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“…16 Our previous analysis of CATT data showed that iron use (medication or supplement) was associated with a dose-dependent risk of retinal and subretinal hemorrhage in patients with neovascular AMD. 27 In this study with a low number of patients taking iron medications (n = 15), we found iron medication at a daily dose of 50 mg or more (n = 10) was associated with approximately a doubling of risk of GA in both study eyes ( P = 0.22, Table 2) in multivariate analysis adjusted by the AREDS simple severity scale. Of note, anemia could confound the association between iron medication and GA because temporal macula atrophy due to anemia has been reported in patients with sickle cell disease.…”

Section: Discussionmentioning

confidence: 59%

Systemic Medication Use and the Incidence and Growth of Geographic Atrophy in the Comparison of Age-Related Macular Degeneration Treatments Trials

Song

Hua

VanderBeek

et al. 2021

Retina

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To determine associations of systemic medications with the incidence and growth of geographic atrophy (GA) in participants of the comparison of age-related macular degeneration treatments trials.Methods: Participants of comparison of age-related macular degeneration treatments trials with new untreated choroidal neovascularization in the study eye (one study eye per participant) were randomized to receive treatment with bevacizumab or ranibizumab. Participants were released from clinical trial treatment at 2 years and examined at approximately 5 years. Color fundus photographs and fluorescein angiograms taken at baseline, Years 1, 2, and 5 were assessed for the presence and size of GA by two masked graders. Participants were interviewed about systemic medication use at baseline. Systemic medications previously reported to be associated with age-related macular degeneration were evaluated for associations with GA incidence in study eye using univariable and multivariable Cox models and for association with the GA growth using linear mixed effects models.Results: In multivariable analysis of 1,011 study eyes without baseline GA, systemic medications, including cholinesterase inhibitors, angiotensin-converting enzyme inhibitors, calcium channel blockers, beta-blockers, diuretics, aspirin, steroids, statins, hormone replacement therapy, antacids, and drugs targeting G protein-coupled receptors, were not associated with GA incidence in the study eye (all adjusted hazard ratios #1.86, P $ 0.18). In multivariable analysis of 214 study eyes with longitudinal GA size measurements, calcium channel blockers were associated with a higher GA growth rate (0.40 vs. 0.30 mm/year, P = 0.02).Conclusion: None of the systemic medications analyzed were associated with GA incidence. However, calcium channel blockers were associated with a higher growth rate of GA in the study eye.

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Section: Discussionmentioning

confidence: 59%

Systemic Medication Use and the Incidence and Growth of Geographic Atrophy in the Comparison of Age-Related Macular Degeneration Treatments Trials

Song

Hua

VanderBeek

et al. 2021

Retina

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“…Cd has been found to be significantly higher in blood samples of smokers compared to non-smokers ( Li et al, 2019 ), and is associated with a higher incidence of nAMD ( Kim et al, 2016 ; Park et al, 2015 ). Furthermore, a secondary analysis of the Comparisons of AMD Treatments Trials showed that the use of iron supplements was associated with nAMD in a dose-response manner ( Song et al, 2018 ). Other metal ions such as chromium (Cr), copper (Cu), magnesium (Mg), manganese (Mn), selenium (Se) and zinc (Zn) are known to be involved in cellular antioxidant defense mechanisms ( Lee et al, 2019 ; Salmonowicz et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Association of plasma trace element levels with neovascular age-related macular degeneration

Heesterbeek

Rouhi-Parkouhi

Church

et al. 2020

Experimental Eye Research

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Nanoprotection Against Retinal Pigment Epithelium Degeneration via Ferroptosis Inhibition

Tang

Huo

et al. 2021

Small Methods

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various biological roles, including transepithelial transporting fluids and nutrients, constituting the outer blood-retinal barrier, phagocytosing photoreceptor outer segment tips, and recycling bleached visual pigments. [1] Therefore, RPE dysfunction could contribute to various ocular disorders accompanied by visual impairment and even blindness, most notably age-related macular degeneration (AMD). [2] Currently, the global prevalence of AMD in individuals aged 45 years and older is ≈8.7%. [3] Regarding AMD therapeutic options, the current anti-vascular therapeutic is limited for patients with neovascular AMD, whereas nearly no satisfactory strategies were available for non-neovascular AMD, which drives an urgent requirement to improve treatments among AMD patients. [4] The explicit etiology during the progression of AMD is not thoroughly understood. However, it has been generally accepted that detrimental oxidative stress in metabolically active RPE exerts a causative, primary impact on increased RPE vulnerability and subsequent photoreceptor cell degeneration, ultimately causing impairment of central vision or blindness. [5] Ferrous ions, as a typical source of oxidative stress, have been widely implicated in the progression of AMD. [6] In contrast to the age-matched healthy macula, higher levels of total iron in RPE cells in addition to in Bruch's membrane have been measured in the AMD-affected maculae, [7] and a more than twofold increase in iron concentration was detected in the aqueous humor of dry AMD. [8] Additionally, the excessive iron released from intraocular hemorrhage induces retinal inflammation and peroxidation of unsaturated phospholipids. [9] These studies have shown that iron toxicity and oxidative stress are closely associated with RPE death during AMD progression, suggesting that highly effective ferrous reduction provides a better platform to manage these diseases. Deferoxamine (DFO) is a typical type of iron chelator, yet it can be readily eliminated, with a plasma t 1/2 of ≈5-10 min, after intravenous injection in human subjects. [10] In addition, DFO mainly accumulates in lysosomes, [11] and protects against cells merely by chelating lysosomal iron. [12] However, iron accumulation in the RPE also involves a disruption of mitochondrial iron homeostasis, [13] implicating the limited effects of DFO on alleviating iron overload and oxidative stress-induced RPE damage. Inspiringly, it has been demonstrated that the potent Ca 2+ -substituted iron-binding Prussian blue analogue KCa[Fe III (CN) 6 ] (CaPB) can enter bacterial cells and selectively deplete intracellular iron by a simplistic Lethal oxidative stress and ferrous ion accumulation-mediated degeneration/ death in retinal pigment epithelium (RPE) exert an indispensable impact on retinal degenerative diseases with irreversible visual impairment, especially in age-related macular degeneration (AMD), but corresponding pathogenesisoriented medical intervention remains controversial. In this study, the potent iron-binding nanoscale Prussia...

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Association Between Oral Iron Supplementation and Retinal or Subretinal Hemorrhage in the Comparison of Age-Related Macular Degeneration Treatment Trials

Cited by 3 publications

References 26 publications

Systemic Medication Use and the Incidence and Growth of Geographic Atrophy in the Comparison of Age-Related Macular Degeneration Treatments Trials

Systemic Medication Use and the Incidence and Growth of Geographic Atrophy in the Comparison of Age-Related Macular Degeneration Treatments Trials

Association of plasma trace element levels with neovascular age-related macular degeneration

Nanoprotection Against Retinal Pigment Epithelium Degeneration via Ferroptosis Inhibition

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