Table 2.
Summary of studies related to age-related macular degeneration included.
| First Author | Years | Country | Study-Design | Sample Size | Main Finding | Rate # |
|---|---|---|---|---|---|---|
| Audrey Cougnard-Grégoire [88] | 2018 | South Korea | Case-control study | 32 Early AMD, 30 late AMD, and 34 normal controls | Serum vitamin D deficiency increases the risk of early AMD with borderline significance [odds ratio (OR) = 3.59; 95% confidence interval (95% CI) 0.95–13.58; p = 0.060], while significantly associated with a higher risk of late AMD (OR = 3.61; 95%CI 1.04–12.51; p = 0.043). In 2 subgroups of late AMD, serum vitamin D deficiency only increase the risk of patients with subretinal fibrosis (OR = 7.54; 95% CI 1.34–42.51), but not. However, there was no significant association between serum vitamin D deficiency and late AMD without subretinal fibrosis (OR = 1.89; 95% CI 0.40–8.92). | 4a |
| Shelley Day [89] | 2017 | Europe (Norway, Estonia, UK, France, Italy, Greece, Spain) | Cross-sectional study | 2209 Early AMD, 150 late AMD and 104 nvAMD | No linear association was found with 25(OH)D and early or late AMD or nvAMD. Deficient status was associated with nvAMD (adjusted OR, 1.27; 95% confidence interval, 1.1–1.45; p < 0.0001), but no association between insufficient or deficient status with early or late AMD. | 4b |
| S Golan [91] | 2015 | United States | Cross-sectional study | 913 subjects | For women with vitamin D deficient (<12 ng/mL), there were 6.7-fold increased odds of AMD (95% CI, 1.6–28.2). | 4b |
| Alix Graffe [78] | 2019 | United States | Prospective study | 1225 subjects | High 25(OH)D3 concentrations, approximately >70 nM, may be associated with decreased odds of incident early AMD. | 4b |
| Rezvan Hashemi [79] | 2017 | United States | Cross-sectional study | 9734 subjects | The adjusted OR (95% CIs) for early AMD among those with adequate (=75 nmol/L) compared to deficient (<30 nmol/L) vitamin D status was 0.94 (0.59–1.50), p-trend = 0.86. Vitamin D status was not associated with early AMD in this cohort sample. | 4b |
| Sujit Itty [96] | 2011 | United States | Cross-sectional study | 1313 subjects | Serum 25(OH)D was associated with decreased odds of early AMD in women younger than 75 years and increased odds in women aged 75 years or older (OR for quintile 5 vs. 1, 0.52; 95% CI, 0.29–0.91; p for trend = 0.02 and OR, 1.76; 95% CI, 0.77–4.13; p for trend = 0.05, respectively). High serum 25(OH)D3 concentrations may protect against early AMD in women younger than 75 years. | 4a |
| Emrah Kan [80] | 2011 | United States | Cross-sectional study | 100 subjects (50 pairs of siblings) | Comparing among affected and unaffected siblings, serum 25(OH)D levels were not statistically different (p = 0.22). Although evaluation of serum 25(OH)D3 was higher in unaffected individuals than in their affected siblings, but the finding did not reach statistical significance. | 4a |
| Eun Chul Kim [94] | 2007 | United States | Cross-sectional study | 7752 subjects | Levels of serum vitamin D were inversely associated with early AMD but not advanced AMD. The odds ratio (OR) and 95% confidence interval (CI) for early AMD among participants in the highest vs. lowest quintile of serum vitamin D was 0.64 (95% CI, 0.5–0.8; p trend <0.001). | 4a |
| Kyoung Lae Kim [81] | 2013 | Denmark | Cross-sectional study | 178 subjects | Across different AMD stages by CARMS, the plasema 25(OH)D levels were comparable. In CARMS 5, the presence of subretinal fibrosis was associated with significantly lower concentrations of 25-hydroxyvitamin D as compared to the absence of subretinal fibrosis (47.2 versus 75.6 nmol/L, p < 0.001). Patients in CARMS 5 with subretinal fibrosis were more likely to have insufficient levels of 25-hydroxyvitamin D compared to patients without subretinal fibrosis (p = 0.006) | 4a |
| Gareth J.McKay [95] | 2020 | United States | RCT | 25,871 subjects | Neither vitamin D3 nor marine ω-3 fatty acid supplementation had a significant overall effect on AMD incidence or progression. | 4a |
| Amy E. Millen [92] | 2017 | France | Prospective cohort study | 2146 subjects | Compared with the highest and lowest quintile of dietary vitamin D intake after adjustment for other confounding facters, there was a lower risk of progression to late AMD and NV (for late AMD: hazard ratio [HR]: 0.60; 95% confidence interval [CI]: 0.43–0.83; p trend = 0.0007; for NV: HR: 0.59; 95% CI: 0.39–0.89; p trend = 0.005) but not GA (HR: 0.83; 95% CI: 0.53–1.30; p trend = 0.35). When supplement use was considered, the effect was in the protective direction but was not significant. A diet rich in vitamin D may prevent or delay progression to advanced AMD, especially nvAMD. | 4a |
| Amy E. Millen [87] | 2016 | Japan | Case-control study | 161 Neovascular AMD patients and 369 healthy controls | Logistic regression analysis demonstrated that low intakes of vitamin D was associated with neovascular AMD (Trend p = 0.002 for vitamin D). High dietary intake of vitamin D is associated with a reduced risk of AMD. | 3a |
| Amy E. Millen [90] | 2011 | France | Cross-sectional study | 311 subjects | Low serum 25OHD concentrations were associated with poorer vision acuity. | 4a |
| Amy E. Millen [97,98] | 2021 | Turkey | Retrospective study | 114 ARMD and 102 healthy controls | The age-related macular degeneration group had significantly lower vitamin D levels than the control group (p > 0.001). Significantly decreased levels of 25(OH) vitamin D in advanced-stage age-related macular degeneration suggest a significant correlation existing between vitamin D deficiency and age-related macular degeneration development | 4a |
| Margaux A. Morrison [76] | 2020 | Egypt | Cross-sectional study | 222 Primary osteoarthritis patients (46 with AMD, 176 without AMD) | Less vitamin D intake were significantly associated with AMD occurrence in primary osteoarthritis patients. | 4b |
| Niyati Parekh [93] | 2019 | Italy | RCT | 30 Intermediate AMD | In intermediate AMD, Macuprev® supplementation (contained vitamin D3 800 IU) increases the function of the macular pre-ganglionic elements, with no associated retinal and choroidal ultra-structural changes. | 4a |
| Amardeep Singh [82] | 2011 | United States | Case series | 184 Caucasian male twin pairs | Higher dietary intake of vitamin D was present in the twins with less severe AMD (p = 0.01) and smaller drusen size (p = 0.05) compared with co-twins, adjusted for smoking and age | 4b |
| William G. Christen [99] | 2015 | France | Cross-sectional study | 91 subjects | Patients with vitamin D deficiency (n = 11) had a reduced mean GCC thickness compared to those without vitamin D deficiency (72.1 ± 7.4 μm versus 77.5 ± 7.5 μm, p = 0.028) | 9/9 * (RoB) |
| Bénédicte M. J. Merle [100] | 2022 | Spain | Cross-sectional study | 93 AMD patients and 93 healthy controls | The AMD patients had statistically significant lower 25 (OH)D levels than healthy controls but the median 25(OH)D levels in different stages and subtypes (early, intermediate, advance atrophic and advanced neovascular) were not statistically significant. | 3a |
| Aya Aoki [101] | 2018 | South Korea | Case-control study | 32 Early AMD, 30 late AMD, and 34 normal controls | Serum vitamin D deficiency increase the risk of early AMD with borderline significance [odds ratio (OR) = 3.59; 95% confidence interval (95% CI) 0.95–13.58; p = 0.060], while significantly associated with a higher risk of late AMD (OR = 3.61; 95%CI 1.04–12.51; p = 0.043). In 2 subgroups of late AMD, serum vitamin D deficiency only increase the risk of patients with subretinal fibrosis (OR = 7.54; 95% CI 1.34–42.51), but not. However, there was no significant association between serum vitamin D deficiency and late AMD without subretinal fibrosis (OR = 1.89; 95% CI 0.40–8.92). | 4a |
| Olivier Beauchet [102] | 2017 | Europe (Norway, Estonia, UK, France, Italy, Greece, Spain) | Cross-sectional study | 2209 Early AMD, 150 late AMD and 104 nvAMD | No linear association was found with 25(OH)D and early or late AMD or nvAMD. Deficient status was associated with nvAMD (adjusted OR, 1.27; 95% confidence interval, 1.1–1.45; p < 0.0001), but no association between insufficient or deficient status with early or late AMD. | 3a |
| Naciye Kabataş [83] | 2015 | United States | Cross-sectional study | 913 subjects | For women with vitamin D deficient (<12 ng/mL), there was 6.7-fold increased odds of AMD (95% CI, 1.6–28.2). | 4a |
| Marwa Yahia Mahgoub [86] | 2019 | United States | Prospective study | 1225 subjects | High 25(OH)D3 concentrations, approximately >70 nM, may be associated with decreased odds of incident early AMD. | 4a |
| Mariacristina Parravano [103] | 2017 | United States | Cross-sectional study | 9734 subjects | The adjusted OR (95% CIs) for early AMD among those with adequate (=75 nmol/L) compared to deficient (<30 nmol/L) vitamin D status was 0.94 (0.59–1.50), p-trend = 0.86. Vitamin D status was not associated with early AMD in this cohort sample. | 8/9 * (RoB) |
| Johanna M Seddon [84] | 2011 | United States | Cross-sectional study | 1313 subjects | Serum 25(OH)D was associated with decreased odds of early AMD in women younger than 75 years and increased odds in women aged 75 years or older (OR for quintile 5 vs. 1, 0.52; 95% CI, 0.29–0.91; p for trend = 0.02 and OR, 1.76; 95% CI, 0.77–4.13; p for trend = 0.05, respectively). High serum 25(OH)D3 concentrations may protect against early AMD in women younger than 75 years. | 4a |
| Mathieu Uro [85] | 2011 | United States | Cross-sectional study | 100 subjects (50 pairs of siblings) | Comparing among affected and unaffected siblings, serum 25(OH)D levels were not statistically different (p = 0.22). Although evaluation of serum 25(OH)D3 was higher in unaffected individuals than in their affected siblings, but the finding did not reach statistical significance. | 3a |
| Perez Serena [104] | 2007 | United States | Cross-sectional study | 7752 subjects | Levels of serum vitamin D were inversely associated with early AMD but not advanced AMD. The odds ratio (OR) and 95% confidence interval (CI) for early AMD among participants in the highest vs. lowest quintile of serum vitamin D was 0.64 (95% CI, 0.5–0.8; p trend <0.001). | 3a |
nvAMD = nonvascular AMD; * The Effective Practice and Organisation of Care (EPOC) RoB Tool for randomized trials; # LEGEND for case-control, cohort, and cross-sectional studies, rating of the studies follow the guidelines from LEGEND.