Importance:Previous studies of the role of dietary and supplementary calcium in age-related macular degeneration (AMD) have produced mixed results, suggesting that supplementation and decreased dietary intake are both harmful.Objective:To evaluate the association of baseline dietary and supplementary calcium intake with progression of AMD.Design, Setting, and Participants:This study involved secondary analyses of participants enrolled in the Age-Related Eye Disease Study (AREDS). The AREDS study (1992-2001) enrolled patients from academic and community-based retinal practices in the United States. Men and women with varying severity of AMD were included. Data analysis for this article occurred from September 2015 to December 2018.Exposures:Baseline self-reported dietary or supplementary calcium intake.Main Outcomes and Measures:Development of late AMD, geographic atrophy (central or noncentral), or neovascular AMD detected on centrally graded baseline and annual fundus photographs.Results:A total of 4751 participants were included (mean [SD] age, 69.4 [5.1] years); 4543 (95.6%) were white, and 2655 (55.9%) were female. Compared with those who were in the lowest quintile, the participants in the highest quintile of dietary calcium intake had a lower risk of developing late AMD (hazard ratio [HR], 0.73 [95% CI, 0.59-0.90]), central geographic atrophy (HR, 0.64 [95% CI, 0.48-0.86]), and any geographic atrophy (HR, 0.80 [95% CI, 0.64-1.00]). The participants in the highest tertile of supplementary calcium intake had a lower risk of developing neovascular AMD (HR, 0.70 [95% CI, 0.50-0.97]) compared with those who did not take calcium supplements. When stratified by sex, women in the highest quintile of dietary calcium intake had a lower risk of developing late AMD (HR, 0.73 [95% CI, 0.56-0.97]) compared with those in the lowest quintile. Women in the highest tertile of calcium supplementation had a lower risk of progression to neovascular AMD (HR, 0.67 [95% CI, 0.48-0.94]) compared with those who did not take calcium supplements. Similar findings were found in men for dietary calcium. Too few men took calcium supplements to allow for analyses.Conclusions and Relevance:In this secondary analysis, higher levels of dietary and supplementary calcium intake were associated with lower incidence of progression to late AMD in AREDS participants. The results may be owing to uncontrolled confounding or chance and should be considered hypothesis development requiring additional study.

PURPOSE:To analyze brightness, contrast, and color balance of digital versus film retinal images in a multicenter clinical trial, to propose a model image from exemplars, and to optimize both image types for evaluation of age-related macular degeneration (AMD).METHODS:The Age-Related Eye Disease Study 2 (AREDS2) is enrolling subjects from 90 clinics, with three quarters of them using digital and one quarter using film cameras. Image brightness (B), contrast (C), and color balance (CB) were measured with three-color luminance histograms. First, the exemplars (film and digital) from expert groups were analyzed, and an AMD-oriented model was constructed. Second, the impact of B/C/CB on the appearance of typical AMD abnormalities was analyzed. Third, B/C/CB in AREDS2 images were compared between film (156 eyes) and digital (605 eyes), and against the model. Fourth, suboptimal images were enhanced by adjusting B/C/CB to bring them into accord with model parameters.RESULTS:Exemplar images had similar brightness, contrast, and color balance, supporting an image model. Varying a specimen image through a wide range of B/C/CB revealed greatest contrast of drusen and pigment abnormalities against normal retinal pigment epithelium with the model parameters. AREDS2 digital images were more variable than film, with lower correspondence to our model. Ten percent of digital were too dim and 19% too bright (oversaturated), versus 1% and 4% of film, respectively. On average, digital had lower green channel contrast (giving less retinal detail) than film. Overly red color balance (weaker green) was observed in 23% of digital versus 8% of film. About half of digital (but fewer film) images required enhancement before AMD grading. After optimization of both image types, AREDS2 image quality was judged as good as that in AREDS (all film).CONCLUSIONS:A histogram-based model, derived from exemplars, provides a pragmatic guide for image analysis and enhancement. In AREDS2, the best digital images matched the best film. Overall, however, digital provided lower contrast of retinal detail. Digital images taken with higher G-to-R ratio showed better brightness and contrast management. Optimization of images in the multicenter study helps standardize documentation of AMD (ClinicalTrials.gov NCT00345176).

Objective: To compare gradings of lesions associated with age-related macular degeneration (AMD) from digital and stereoscopic film images.Design: Instrument validation study.Participants: Sixty-two subjects (124 eyes) with varying degrees of AMD, including no AMD.Methods: images of the optic disc and macula were taken using a 45degrees digital camera (6.3 megapixels) through dark-adapted pupils and pharmacologically dilated pupils. In addition, 30degrees stereoscopic retinal film images were taken through pharmacologically dilated pupils of the same eyes. All images were graded for drusen size, type, and area; pigmentary abnormalities; geographic atrophy; and neovascular lesions using the modified Wisconsin Age-Related Maculopathy Grading System. Exact agreement and unweighted kappa scores were calculated for paired gradings resulting from digital and film images.Main Outcome Measure: Agreement between gradings obtained from stereoscopic slide transparencies and digital nonstereoscopic images.Results: Exact agreement between gradings of digital and stereoscopic film images taken through pharmacologically dilated pupils was 91% (kappa=0.85) for the categories of none, early AMD, and late AMD. Exact agreement for gradings of digital images taken through dark-adapted pupils compared with gradings of film images was 80% (kappa=0.69). Exact agreement for gradings of digital images captured through dark-adapted and pharmacologically dilated pupils was 86% (kappa=0.78). In addition, kappa scores for agreement between different approaches for individual lesions were moderate to almost perfect.Conclusions: Gradings resulting from high-resolution digital images, especially when the pupil is pharmacologically dilated, are comparable with those resulting from film-based images. We conclude that digital imaging of the retina is useful for epidemiological studies of AMD.