Table 4.
Summary of studies related to diabetic retinopathy included.
| First Author | Years | Country | Study-Design | Sample Size | Main Finding | Rate # |
|---|---|---|---|---|---|---|
| HülyaAksoy [130] | 2000 | Turkey | Cross-sectional study | 20 DM without DR patients, 15 DM with BDR patients, 14 pre-DM with PDR patients, 17 DM with PDR patients and 20 healthy controls | There was an inverse relationship between the severity of the retinopathy, neovascularization, and serum 1,25(OH)2D3 concentrations, being the lowest in PDR and the highest in diabetic patients without retinopathy patients. Mean 1,25(OH)2D3 concentrations fell with increasing severity of diabetic retinopathy. Only mean 1,25(OH)2D3 concentrations were not significantly different between NDR and BDR, pre-PDR and PDR (p > 0.05). Mean 1,25(OH)2D3 concentrations were significantly different among the other groups (p < 0.05). | 3a |
| Atsushi Suzuki [131] | 2006 | Japan | Descriptive study | 581 T2DM patients and 51 healthy controls | Serum concentration of 25(OH)D3 were associated with HbAlc (p = 0.013). Microvascular complications and insulin treatment in T2DM patients are associated with the co-existence of hypovitaminosis D although serum creatinine levels were below 2.0 mg/dl. | 4a |
| Harleen Kaur [132] | 2011 | Australia | Cross-sectional study | 517 T1DM patients | Vitamin D deficiency is associated with an increased prevalence of retinopathy in young people with T1DM. In logistic regression, retinopathy was associated with VDD (odds ratio 2.12 [95% CI 1.03–4.33]), diabetes duration (1.13, 1.05–1.23), and HbA1c (1.24, 1.02–1.50). | 4a |
| Christel Joergensen [175] | 2011 | Denmark | Prospective observational study | 227 T1DM patients | In patients with type 1 diabetes, severe vitamin D deficiency independently predicts all-cause mortality (unadjusted HR 2.0 [0.9–4.4], p = 0.1 and HR 2.7 [1.1–6.7], p = 0.03, respectively) but not development of microvascular complications in the eye (HR 1.1 [0.7–1.7], p = 0.8) and kidney (unadjusted HR 1.1 [0.5–2.4], p = 0.8 and HR 1.3 [0.3–5.4], p = 0.7, respectively). | 3a |
| Patricia A. Patrick [133] | 2012 | United States | Cross-sectional study | 1790 subjects | There is an association between severity of diabetic retinopathy and prevalence of vitamin D deficiency (β = 1.3, p = 0.01, unadjusted; and β = 1.2, p = 0.01, adjusted for age and obesity status given their clinical significance). However, regression analysis of these data did not demonstrate a statistically significant relationship between the 2 variables (β = −0.04, p = 0.07, unadjusted; and β = −0.03, p = 0.13, adjusted). The findings were inconclusive about the existence of a relationship between retinopathy severity and serum 25(OH)D3 concentration. | 3a |
| John F Payne [176] | 2012 | Georgia | Cross-sectional study | 221 subjects (17 No diabetes or ocular diseases; 51 No diabetes with ocular disease; 41 No BDR; 40 NPDR; 42 PDR) | Patients with diabetes had lower 25(OH)D levels than did those without diabetes (22.9 ng/mL versus 30.3 ng/mL, respectively; p < 0.001). Patients with diabetes, especially those with PDR, have lower 25(OH)D levels than those without diabetes. The mean 25(OH)D levels, stratified by group, were as follows: no diabetes or ocular disease = 31.9 ng/mL; no diabetes with ocular disease = 28.8 ng/mL; no background diabetic retinopathy = 24.3 ng/mL; nonproliferative diabetic retinopathy = 23.6 ng/mL; and PDR = 21.1 ng/mL | 3a |
| Rania NAM Reheem [168] | 2013 | Egypt | Cross-sectional study | 200 DM patients with suspected DR (43 T1DM; 157 T2DM) | Low levels of vitamin D might be a risk marker of development or progression of diabetic retinopathy. Mean serum concentration of 1, 25 dihydroxy vitamin D 3 (1,25(OH)2D3) was significantly lower in diabetic patients with retinopathy than those with no retinopathy (NR) (51.4 ± 16.64 vs. 70.7 ± 15.56 pmol/L, p < 0.001). There was a significant negative correlation between the mean level of 1, 25(OH)2D3 and the degree of severity of retinopathy (p < 0.001). It might be advisable that detailed ophthalmologic examination is needed for diabetics whose serum 1, 25(OH)2D3 concentrations gradually decreased. The measurement of serum 1, 25(OH)2D3 concentrations could become a useful biochemical means to predict the severity of DR in patients with diabetes mellitus | 3a |
| Hala Ahmadieh [134] | 2013 | Lebanon | Cross-sectional study | 136 T2DM and 74 controls | Low serum 25(OH)D3 level was an independent predictor for diabetic neuropathy (OR 4.5 [95% CI 1.6–12]) and diabetic retinopathy (OR 2.8 [95% CI 2.1–8.0]) in patients with T2DM for vitamin D < 20 versus vitamin D ≥ 20 ng/mL after adjustment for HbA1c, age, smoking, BMI and disease duration. | 4a |
| Myra Poon [177] | 2013 | Australia | Cross-sectional study | 481 DM | VDD was associated with a two-fold increased risk of DR. VDD is not associated with changes in retinal vascular geometric measures, suggesting an earlier role in the time course of DR pathogenesis. | 4a |
| Jimmy D. Alele [170] | 2013 | United States | Cross-sectional study | 936 T2DM patients | Vitamin D status had no significant impact on the incidence of vascular events in a cohort of high-risk veterans with diabetes. No differences in the odds associated with retinopathy or renal disease onset or progression in the lowest versus highest vitamin D quartile were observed. | 4b |
| NaokiShimo [135] | 2014 | Japan | Cross-sectional study | 75 T1DM patients (21 with VDD; 54 without VDD) | Vitamin D deficiency was significantly associated with retinopathy in young Japanese T1DM patients. In a multivariate regression analysis, duration of diabetes (adjusted OR; 1.14, 95% CI; 1.02–1.27, p = 0.02) and VDD (adjusted OR; 3.45, 95% CI; 1.11–10.6, p = 0.03) were independent determinants of DR. | 4a |
| R He [136] | 2014 | China | Cross-sectional study | 625 T2DM with no DR patients, 562 T2DM with non-sight-threatening DR patients and 333 T2DM with sight-threatening DR patients | Vitamin D deficiency is an independent risk factor for diabetic retinopathy (OR 1.93) and sight-threatening diabetic retinopathy (OR 2.42) (both p < 0.01). The prevalence of sight-threatening diabetic retinopathy doubles when the serum 25(OH)D3 level is <15.57 ng/mL (odds ratio 2.38, p < 0.01). | 4a |
| Sarita Bajaj [137] | 2014 | India | Observational caase-control study | 158 T2DM patients and 130 healthy controls | Vitamin D deficiency was found to be significantly associated with neuropathy (χ2 = 5.39, df = 1, p = 0.020), retinopathy (χ2 = 6.6, df = 1, p = 0.010), and nephropathy (χ2 = 10. 52, df = 1, p = 0.001). | 2a |
| Donghyun Jee [169] | 2014 | South Korea | Cross-sectional study | 18,363 subjects | There was an inverse relationships of blood 25-hydroxyvitamin D levels with any DR and proliferative DR but only in men. After adjusting for potential confounders, including age, sex, diabetes duration, hemoglobin A1c levels, and hypertension, the odds ratios (OR) for any DR and proliferative DR among men decreased significantly in the highest blood 25-hydroxyvitamin D level quintile relative to the lowest quintile (OR, 0.37; 95% confidence interval [CI], 0.18–0.76; p for trend =0.004 and OR, 0.15; 95% CI, 0.03–0.83; p for trend = 0.043). | 4a |
| Giacomo Zoppini [138] | 2015 | Italy | Cross-sectional study | 715 T2DM patients | There is an inverse and independent relationship between circulating 25(OH)D3 levels and the prevalence of microvascular complications in patients with T2DM. Serum 25(OH)D levels decreased significantly in relation to the severity of either retinopathy or nephropathy or both. In multivariate logistic regression analysis, lower 25(OH)D levels were independently associated with the presence of microvascular complications (considered as a composite end point; OR 0.758; 95% CI 0.607 to 0.947, p = 0.015). | 4a |
| Markus Herrmann [139] | 2015 | Australia, New Zealand, and Finland | Multinational, double-blind, placebo-controlled trial | 9795 T2DM patients | Low blood 25(OH)D3 concentrations are associated with an increased risk of macrovascular and microvascular disease events in T2DM. A 50 nmol/L difference in blood 25OH-D concentration was associated with a 23% (p = 0.007) change in risk of macrovascular complications. | 4a |
| G Bhanuprakash Reddy [167] | 2015 | India | Cross-sectional case-control study | 82 T2DM with DR patients and 99 healthy controls | There is a possible association between vitamin D deficiency and type 2 diabetes, but not specifically with retinopathy. | 3a |
| Celil Alper Usluogullari [140] | 2015 | Turkey | Cross-sectional study | 557 T2DM patients (299 DPN, 223 DN and 235 DR) and 112 healthy controls | Vitamin D deficiency is associated with microvascular complications in DM patients. After adjustment, the 25 (OH) D level was confirmed to be an independent protective factor for DPN (odds ratio [OR]: 0.968, p = 0.004]) and DN (OR: 0.962, p = 0.006). The prevalence of DPN and DN increased significantly as the serum 25 (OH) D levels decreased. | 4a |
| Nuria Alcubierre [154] | 2015 | Spain | Case-Control study | 139 DR patients and 144 NDR patients | Patients with more advanced stages of retinopathy (grades 2–4) had lower concentrations of 25(OH)D and were more frequently vitamin D deficient as compared with patients not carrying this eye complication. The multivariate analyses showed that there was a significant association of retinopathy and 25(OH)D, even when considering other variables associated with this variable which were consistent when analyzing both the concentrations of 25(OH)D and the presence of vitamin D deficiency, as defined by a 25(OH)D <15 ng/mL (values 0.04 and 0.009, respectively.) | 2a |
| Shokoufeh Bonakdaran [174] | 2015 | Iran | Cross-sectional study | 235 T2DM patients (153 NDR, 64 NPDR and 18 PDR) | This study did not find any association between diabetic retinopathy and its severity and vitamin D insufficiency. Vitamin D insufficiency is not related to risk factors of diabetic retinopathy. 25(OH)D level was not significant different between NDR, NPDR and PDR groups. Correlation between 25 (OH) D level and other known risk factors of diabetic retinopathy was not significant. | 3b |
| Lian Engelen [155] | 2015 | 16 European countries | Prospective cohort study | 532 T1DM patients | In individuals with type 1 diabetes, both higher 25(OH)D2 and 25(OH)D3 are associated with a lower prevalence of macroalbuminuria, but not of retinopathy and CVD. | 3b |
| Adem Gungor [156] | 2015 | Turkey | Prospective study | 50 VDD with DR patients and 50 VDD without DR patients | The results indicate that vitamin D functions as a neuroprotective component for optic nerves. Low serum 25(OH)D concentrations contribute to RNLF thinning in early-stage DR patients with VDD. The mean RNFL thickness of group 1 was significantly reduced compared to that of group 2 (p < 0.001). A significant relationship between the mean RNFL thickness and serum 25(OH)D concentrations was observed in group 1 (p < 0.001). | 3a |
| Amy E Millen [178] | 2016 | United States | Population-based prospective study | 1305 DM patients | 25(OH)D3 concentrations ≥75 nmol/L were associated with lower odds of any retinopathy assessed 3 years later. ORs (95 % CIs) for retinopathy, adjusted for race and duration, were 0.77 (0.45–1.32), 0.64 (0.37–1.10), and 0.39 (0.20–0.75), p for trend = 0.001, for participants with 25(OH)D of 30–<50, 50–<75, and ≥75 nmol/L, respectively. Further adjustment for hypertension minimally influenced results (data not show), but adjustment for HBA1c attenuated the OR among those with 25(OH)D ≥75 (0.47 [0.23–0.96], p for trend = 0.030). | 3a |
| Uazman Alam [171] | 2016 | UK | Prospective observational follow-up study | 657 DM patients (257 NDR, 243 BDR, 135 PPDR and 22 PDR) | This study has found no association between serum 25(OH)D and the presence and severity of diabetic retinopathy or maculopathy. There was no correlation of DR with 25(OH)D (OR 1.00 (95% CI 0.98–1.02), = NS), gender, or ethnicity. | 3b |
| Chan-Hee Jung [179] | 2016 | South Korea | Cross-sectional study | 257 T2DM patients (men: 21 deficient, 60 insufficient and 30 sufficient; women: 63 deficient, 72 insufficient and 11 sufficient) | Serum 25(OH)D level < 10 ng/mL is independently associated with increased DPN in male patients and increased DN in female patients with T2DM. For men, the prevalence of DPN was significantly higher in vitamin D deficient patients than those with insufficient or sufficient vitamin D (38%, 11.7%, and 10%, respectively; p = 0.005). The prevalence of DR and DN was not different according to the vitamin status. For women, the prevalence of DN was significantly higher in patients with vitamin D deficiency than in the other 2 vitamin D status (40%, 20.6%, and 0%, for vitamin D-deficient, vitamin D-insufficient, and vitamin D-sufficient groups, respectively; p = 0.007) and the prevalence of DPN and DR was not different among 3 status. | 4a |
| Xianglong Yi [180] | 2016 | China | Case-control study | 22 PDR patients, 29 NPDR patients and 24 healthy controls | There is a potential protective effect of 1,25(OH)2 D3 in DR, whereas supplementation with 1,25(OH)2 D3 might be an effective strategy for preventing the development of DR | 2a |
| M Long [141] | 2017 | United States | Retrospective cross-sectional study | 842 DR patients, 301 mild NPR patients, 195 severe NPR patients and 106 PDR | Vitamin D deficiency associated with severe DR in patients with well controlled glycasemia. After adjusting gender, ethnicity and duration of diabetes, the interaction of HbA1 with vitamin D deficiency significantly affected retinopathy severity (p = 0.029). | 4b |
| Banu Boyuk [157] | 2017 | Turkey | Cross-sectional case-control study | 206 T2DM patients and 34 healthy controls | There is an inverse relationship between the circulating 25(OH) D level and the prevalence of retinopathy and neuropathy in T2DM patients. The level of serum 25-hydroxyvitamin D (25(OH) D) was significantly lower in the T2DM patients (11.16 ± 3.99 ng/mL vs. 15.58 ± 3.16 ng/mL; p < 0.05). Serum 25(OH) D levels weresignificantly lower in the presence of retinopathy and neuropathy (p < 0.05 for both), but no significant association between Vitamin D level and microalbuminuria was found. | 3b |
| Anurag Chaurasia [158] | 2017 | India | Case-control study | 120 DM patients (40 No BDR, 42 mild-mod NPDR and 38 sev–v.serv NPDR and PDR) and 100 NDM patients (58 no DM and ocular diseases and 42 no DM with ocular diseases) | Diabetic subjects, especially those with NPDR (severe and very severe grade) and PDR have lower Vitamin D levels than those without diabetes. Subjects with vitamin D insufficiency are at risk of having retinopathy 9.75 times that of vitamin D sufficient subjects (Odds Ratio 9.75; 95% C.I. 1.96 to 48.46). The mean vitamin D level in Diabetics (20.7 ± 6.91 ng/mL) is significantly less than that in non-diabetics (27.51 ± 5.53 ng/mL) (p < 0.0001). Also, diabetics have significantly higher proportion of subjects with vitamin D insufficiency (91.3%) as compared to Non-Diabetics (68%). | 4a |
| Beteal Ashinne [142] | 2018 | India | Retrospective study | 3054 T2DM patients | Lower serum 25(OH)D3 was associated with increased severity of DR and the presence of vitamin D deficiency was associated with a two-fold increased risk for PDR. A statistically significant difference in the serum vitamin D means of these categorizations: no DR (13.7 ± 2.1 ng/mL), non-sight threatening DR (12.8 ± 2.1 ng/mL), sight threatening DR (11.1 ± 2.2 ng/mL), (p < 0.001). | 4a |
| Abdulbari Bener [143] | 2018 | Turkey | Cross-sectional study | 638 DM patients | Vitamin D deficiency is considered as a risk factor for DR and hearing loss among diabetic patients. | |
| Krishnamoorthy Ezhilarasi [181] | 2018 | India | Case-control study | 200 T2DM patients, 216 T2DM with microvascular complications, 198 T2DM with macrovascular complications and 252 controls with nomal glucose tolerance | VDR (rs1544410) SNP was found to be associated with decreased serum (25[OH]D) levels in both micro-macrovascular complications of T2DM among South Indian Population. | 4a |
| Josef Richter [159] | 2018 | Czech Republic | Clinic Controlled Trial | 52 DR patients (Vitamin D and Beta-glucan supplement, Vitamin D and placebo supplement and vitamin D supplement only) | Significant vitamin D deficits were found in all cases, even after three months of supplementation with vitamin D. | 7/9 * (RoB) |
| Martina Závorková [182] | 2018 | Czech Republic | Clinic Controlled Trial | 54 DR patients (beta-glucan and vitamin D supplement, vitamin D and placebo supplement, vitamin D supplement only, no supplementation | Glucan and vitamin D supplementation strongly influence lipid metabolism and have positive effects on human health. | 7/9 * (RoB) |
| Gauhar Nadri [144] | 2019 | India | Cross-sectional study | 24 DM without DR patients, 24 DM with NPDR patients and 24 DM with PDR patients | Serum vitamin D levels of ≤ 18.6 ng/mL serve as sensitive and specific indicator for proliferative disease, among patients of DR. Univariate ordinal logistic regression analysis found vitamin D as a significant predictor of severity of diabetic retinopathy {OR (95% CI) = 1.11 (1.06–1.16) (p < 0.01 or p < 0.001)}. ROC curve analysis demonstrated vitamin D cut off value of 18.6 ng/mL to be significantly associated with NPDR and PDR | 4a |
| Jing Yuan [145] | 2019 | China | Cross-sectional study | 889 T2DM patients | Vitamin D deficiency is significantly associated with risk of PDR. The odd ratio in VDD individuals was significantly increased (1.84, 95% CI 1.18–2.86) for DR, 1.60 (95% CI 1.06–2.42) for PDR, compared with those in vitamin D sufficient individuals, adjusted by age, sex, blood pressure, kidney function, diabetic duration, and HbA1c. | 4a |
| Heng Wan [146] | 2019 | China | Cross-sectional study | 4767 DM patients | Lower serum 25(OH)D3 concentration is significantly associated with higher prevalence of DR in middle-aged and elderly diabetic adults. Compared with the first 25(OH)D quartile (relatively lower concentraion), participants in the fourth quartile (relatively higher concentration) had a lower prevalence of high ACR (OR 0.77, 95% CI 0.61, 0.96) (p for trend <0.01). For DR, the OR of DR for the fourth 25(OH)D quartile when compared with the first quartile was 0.62 (95% CI: 0.47, 0.82; p for trend <0.01). | 4a |
| Abdulhalim Senyigit [160] | 2019 | Turkey | Cross-sectional study | 163 T2DM patients and 40 controls | Low serum 25-OHD levels were found to be associated with the development of diabetes and complications. Serum 25(OH)D levels in all patients were significantly lower than the control group (p < 0.05). Levels of 25(OH)D for those with complications were lower than that without complications. (p values for nephropahty and retinopathy groups were <0.001 while that for neuropahty was <0.01). Low serum 25-OHD levels may be a consequence of even worse metabolic control of diabetes. | 3a |
| Abdulla Almoosa [161] | 2019 | Bahrain | Prospective observational study | 300 T2DM patients (150 NDR, 99 NPDR and 51 PDR) | VDD was commonly found in type II DM patients. Lower serum 25(OH)D levels were associated with more severe DR. | 3b |
| Mehrdad Afarid [148] | 2020 | Iran | Cross-sectional study | 21 DM with NPR patients, 9 DM with PDR patients and 30 DM with no DR patients | Patients with DR had lower levels of serum vitamin D compared with those without retinopathy, especially those with severe NPDR and PDR | 3a |
| Amy E. Millen [178] | 2020 | Portugal | Retrospective observational study | 182 T1DM patients | Lower levels of vitamin D were associated with an increased prevalence of diabetic retinopathy in patients with T1DM, after adjusting for possible confounders. The lower circulating 25(OH)D levels were significantly associated with greater prevalence of DR after adjusting for confounders (OR = 0.94; 95% CI 0.90–0.99, p = 0.023). | 4a |
| Lina H. M. Ahmed [150] | 2020 | Qatar | Case-control study | 274 T2DM patients and 222 healthy controls | Vitamin D3 was associated with diabetic retinopathy whilst vitamin D2 was not. | 2a |
| Lina H. M. Ahmed [162] | 2021 | Qatar | Cross-sectional study | 460 T2DM patients and 290 healthy controls | Vitamin D3 metabolites were associated with diabetic retinopathy, whereas total vitamin D levels were not, suggesting that endogenous vitamin D(3) metabolites are a better measure of diabetic microvascular complications. The lower 1,25(OH)2D3 levels were associated with diabetic retinopathy (p = 0.006) hypertension and dyslipidemia (both p = 0.01) and CAD (p = 0.012); while no association between either total 1,25(OH)2D or 1,25(OH)2D3 levels with diabetic neuropathy, PAD or CAD. | 3a |
| Alexandra E. Butler [147] | 2020 | Qatar | Cross-sectional study | 460 T2DM patients and 290 healthy controls | Lower 25(OH)D(3) was associated with retinopathy (p < 0.03) and dyslipidemia (p < 0.04), but not neuropathy or vascular complications | 3a |
| Ying Xiao [166] | 2020 | China | Cross-sectional study | 4284 T2DM patients | In unadjusted analyses, DR was associated with VDD status (PR: 1.147; 95% CI: 1.025–1.283), the associate retained after adjusted with age and sex and other demographic and physical measurements. However, the significance diminished after adjusting all confounders (PR: 1.093; 95% CI: 0.983–1.215). | 4a |
| Gauhar Nadri [163] | 2021 | India | Cross-sectional study | 66 T2DM patients (22 No DR, 22 NPDR and 22 PDR) and 22 controls | Low serum vitamin D levels correlate with increased severity of DR. | 4a |
| Li Lu [151] | 2021 | China | Retrospective study | 55 PDR patients, 25 non-diabetic patients with idiopathic macular hole patients and 10 NDR patients | In ROC-curve analyses, both serum and vitreous 25(OH)D showed discriminatory ability in predicting DR (NPDR and PDR) and PDR. In DR prediction, they obtained the same area under curve (AUC) of 0.77. Serum 25 (OH) D has a better predictive value (AUC: 0.77) than serum 25 (OH) D (AUC: 0.66) in PDR prediction. | 4a |
| Wei-Jing Zhao [152] | 2021 | China | Cross-sectional study | 815 T2DM patients | Vitamin D deficiency is independently associated with higher risk of diabetic peripheral neuropathy and DR, but not diabetic retinopathy, in T2DM patients. Univariate analysis showed that the 25 (OH) D was significantly correlated with DPN (odds ratio [OR]: 0.969, 95% confidence interval [CI]: 0.950–0.989, p = 0.003) and DN (OR: 0.950, 95% CI: 0.928–0.973, p < 0.001), but not with DR (OR: 1.014, 95% CI: 0.994–1.034, p = 0.165). Multiple logistic regression analysis after adjustment showed that the 25 (OH) D level was an independent protective factor for DPN and DN. | 4a |
| Xin Zhao [153] | 2021 | China | Retrospective study | 636 T2DM patients (466 NDR, 120 BDR and 50 PDR) | A close association was observed between 25(OH)D3 level and DR in the elderly male patients and postmenopausal women with T2DM. There was a significant difference was observed among the three groups in men and women (men: χ2 = 7:75, p < 0.05; women: χ2 = 7:75, p < 0.05) | 4a |
| Mehmet Balbaba [172] | 2021 | Turkey | Prospective study | 20 T2DM-DR patients, 20 T2DM-NDR patients and 20 healthy controls | Vitamin D levels were similar between diabetic patients with and without DR and healthy control subjects | 3b |
| Saeed Karimi [183] | 2021 | Iran | Prospective comparative case series study | 71 diabetic macular edema patients | In diabetic macular edema patients with vitamin D deficiency, vitamin D supplement therapy had some beneficial effects on central macular thickness reduction following three injections of intravitreal bevacizumab; nevertheless, these effects were not statistically significant | 8/9 * (RoB) |
| Elise Girard [173] | 2021 | French Guiana | Cross-sectional study | 361 DM patients | There was no significant difference between type of diabetes and VD deficiency. There was no significant relation between nephropathy and vitamin D deficiency even after adjustment with confounders. Patients with diabetic retinopathy had significantly greater median vitamin D concentrations than those without retinopathy (respectively, 31 ng/mL (interquartile range (IQR) = 23–34) vs. 26 ng/mL (IQR = 23–32), p = 0.03). | 4a |
| José M. Castillo-Otí [164] | 2021 | Spain | Case-Control study | 385 T2DM patients (30 with DR, 335 without DR) | Levels of 25(OH)D and treatment of diabetes were significantly associated with DR after adjusting for other risk factors. Patients with both 25(OH)D and 1,25(OH)2D less than or equal to 16 ng/mL and 29 pg/mL respectively had a greated risk of DR (OR 5.21, 95% CI: 1.76, 15.42; p = 0.003). | 4a |
| Martina Tomić [165] | 2021 | Croatia | Cross-sectional study | 94 T2DM patients (69 without DR and 25 with NPDR) | Hypovitaminosis D is often in T2DM, especially in those with proliferative DR. | 3b |
Diabetic retinopathy (DR), background diabetic retinopathy (BDR), non-proliferative retinopathy (NPR), preproliferative diabetic retinopathy (pre-PDR), proliferative diabetic retinopathy (PDR), Diabetes mellitus (DM), Type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), diabetic kidney disease (DKD); * 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.