25‐Hydroxyvitamin D Concentrations and Incidence or Progression of Age‐Related Macular Degeneration: the Atherosclerosis Risk in Communities Study (ARIC)
Authors: Millen Amy E. , Nie Jing , Sahli Michelle W , Mares Julie A , Lutsey Pamela L , Andrews Christopher A , LaMonte Michael J , Klein Barbara EK , Klein Ronald 
Published: November 2023

ObjectiveVitamin D status has been hypothesized to protect against development and progression of age‐related macular degeneration (AMD) via its anti‐inflammatory and anti‐angiogenic properties. We investigated the association between vitamin D status, assessed with 25‐hydroxyvitamin D [25(OH)D] at visit 2 (1990–92), and the incidence or progression of AMD from visit 3 (1993–95) to visit 5 (2011–13) in the population‐based ARIC study.MethodsSerum 25(OH)D concentrations were assessed in 2013 using stored samples from participants drawn at visit 2. Of 12,091 eligible participants attending visit 3, 11,863 had nonmydriatic retinal photographs taken of one randomly chosen eye. At visit 5, retinal photographs were taken of both eyes in a subset of participants (n=1,298). Of these, participants were excluded if they had ungradable photographs at visit 3 or 5 (n=387) or late AMD at visit 3 (n=1), making them ineligible for progression. Eyes from photos taken at both visits were graded using the Wisconsin Age‐Related Maculopathy Grading System, masked to grading results from earlier visits. Then a side‐by‐side grading was conducted on those eyes that had change across visits (either progression or regression) to confirm the incidence or progression of AMD. Participants were further excluded if they were not Caucasian or African American (n=2), if they were missing 25(OH)D (n=62) or other pertinent covariates (n=5). This left an analytic sample of 841 participants (714 Caucasians, 127 African Americans). Logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for AMD incidence or progression among those with 25(OH)D concentrations ≥50 to 75 and >75 nmol/L versus <50 nmol/L. P for linear trend was estimated using continuous 25(OH)D concentrations. ORs were adjusted for age, race, smoking status, and hypertension status. Further adjustment was made in a second multivariable model (n=804) for waist to hip ratio and physical activity.ResultsThere were 215 (25.6%), 417 (49.6%) and 209 (24.9%) participants with 25(OH)D concentrations <50, ≥50 to 75 and >75 nmol/L, respectively. At visit 3, there were 12 cases of prevalent early AMD. Between visits, 80 participants developed incident, early AMD; 11 participants had no AMD at visit 3 but developed late AMD at visit 5; and 3 participants progressed from early to late AMD. OR (95% CIs) for AMD incidence or progression were 0.78 (0.44–1.37) and 0.79 (0.41–1.51) for participants with 25(OH)D ≥50 to 75 and >75 compared to <50 nmol/L after adjustment for age, race, smoking status and hypertension status. The OR (95% CI) for each 10 nmol/L difference in 25(OH)D was 0.95 (0.85–1.08), p‐trend=0.44. After further adjustment for waist to hip ratio and physical activity the OR (95% CI) for each 10 nmol/L difference was 1.00 (0.89–1.13), p‐trend=0.998.Conclusion25(OH)D concentrations were not statistically significantly associated with the odds of incident or progressed AMD in this biracial subset of ARIC visit 5 participants.Support or Funding InformationThis research is supported by the NIH National Institute on Aging grant number R01 AG041776, NIH National Heart, Lung, and Blood Institute grant number R01 HL103706, and the NIH Office of Dietary Supplements grant number R01 HL103706‐S1. The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). The authors thank the staff and participants of the ARIC study for their important contributions.