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

Song, Delu, MD, PhD*; Ying, Gui-Shuang, PhD*; Dunaief, Joshua L., MD, PhD*; Bhuyan, Rupak, MD*; Li, Yafeng, MD, PhD*; Maguire, Maureen G., PhD*; Grunwald, Juan E., MD*; Daniel, Ebenezer, MBSS, MPH, PhD*; Hagstrom, Stephanie, PhD; Martin, Daniel F., MD the Comparison of Age-Related Macular Degeneration Treatment Trial Research Group

doi: 10.1097/IAE.0000000000002295
Original Study: PDF Only

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.

Because patients often take oral iron supplements without medical indication, and no study has investigated the potential side effects of oral iron supplement use to the retina, the authors performed this post hoc secondary analysis of comparison of age-related macular degeneration treatments trials data. Our analysis shows for the first time that oral iron supplement use is associated with higher risk of retinal/subretinal hemorrhage in eyes with neovascular age-related macular degeneration, and the association was dose dependent, particularly among those with hypertension.

*Department of Ophthalmology, Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; and

Cleveland Clinic, Cole Eye Institute, Cleveland, Ohio.

Reprint requests: Gui-Shuang Ying, PhD, Perelman School of Medicine, University of Pennsylvania, 3535 Market Street, Suite 700, Philadelphia, PA 19104; e-mail: gsying@pennmedicine.upenn.edu

Supported by the National Center for Advancing Translational Sciences of the NIH (KL2TR001879), NEI/NIH, Bethesda, Maryland (cooperative agreement nos: U10 EY017823, U10 EY017825, U10 EY017826, U10 EY017828, and R21EY023689), Research to Prevent Blindness, the F.M. Kirby Foundation, and the Paul and Evanina Bell Mackall Foundation Trust.

None of the authors has any financial/conflicting interests to disclose.

A listing of the Comparison of Age-Related Macular Degeneration Treatments Trials Research Group is available at www.aaojournal.org.

© 2018 by Ophthalmic Communications Society, Inc.