Table 3.
Results of human studies. CAT = combined antioxidant therapy.
| Oral Antioxidant Studied | Recruited Patients [n] | Outcomes in Treated Patients | Follow-Up | Reference |
|---|---|---|---|---|
| Alpha lipoic acid | 467 | No results preventing clinically significant macular edema in T2DM. No improvement in best-corrected visual acuity. | 2 years | Haritoglou et al., 2011 [107] |
| Antioxidant combination: Alpha lipoic acid or Selenium or Vit. E | 80 | All treated groups showed decreased blood TBARS levels and urinary albumin excretion rates. | 3 months | Khahler et al., 1993 [108] |
| Calcium Dobesilate | 18 | No influence on the capillary resistance of diabetic retinopathy | 8 months | Larsen et al., 1977 [109] |
| Calcium Dobesilate | 42 | No results in non-proliferative diabetic retinopathy | 42 [6 months] 36 [1 year] | Stamper et al., 1978 [110] |
| Calcium Dobesilate | 50 | Treated DM + glaucoma patients showed decrease of capillary fragility, blood viscosity and microvascular hyperpermeability. | 3 months | Vojnikovic et al., 1984 [111] |
| Calcium Dobesilate | 37 | Decrease of whole blood viscosity and capillary fragility. | 3 months | Benarroch et al., 1985 [112] |
| Calcium Dobesilate [Dexium®] or Pycnogenol® | 32 | Both drugs improved exudates, Dexium® only in 1 case. Both drugs, particularly Pycnogenol®, showed improvements on parameter of automated visual field. | 6 months | Leydhecker et al., 1986 [113] |
| Calcium Dobesilate | 79 | Non-insulin dependent diabetics showed reducing of whole blood and plasma viscosity and retinal hemorrhages. | 6 months | Vojnikovic, 1991 [114] |
| Calcium Dobesilate | 137 | In T2DM, better improvement than placebo on microaneurysms, DR level and retinal hemorrhages. | 2 years | Ribeiro et al., 2006 [115] |
| Calcium Dobesilate | 635 | No effects reducing development of clinically significant macular edema in T2DM | 5 years | Haritoglou et al., 2009 [116] |
| Calcium Dobesilate | 40 | NPDR with macular edema received laser +placebo or laser + Ca Dob. This study showed no statistically significant difference in macular thickness between Doxium and placebo. | 6 months | Feghhi et al., 2014 [117] |
| CAT formulation [Vitalux Forte®] | 105 | No effect on visual acuity. T2DM treated group show retardation of progression and maintainance of antioxidant plasma status level and decreased plasmatic MDA. | 5 years | Garcia-Medina et al., 2011 [118] |
| CAT: Alpha lipoic acid +genistein+Vitamins C, E and B. | 32 | Pre-retinopathic diabetics treated group showed increases ERG oscillatory potencial values and plasma antioxidant levels. | 30 days | Nebbioso et al., 2012 [119] |
| CAT: Coenzyme Q10, Pycnogenol®, Vitamin E. | 68 | Treated T2DM: significantly reduced free oxygen radical test levels and CMT. | 6 months | Domanico et al., 2015 [120] |
| CAT: DHA, glutathione, hydroxytyrosol, vitamins E, C, B1, B2, B3, B6, B9, B12, lutein, zeaxanthin, Se, Mn, Zn, Cu. | 208 | Reduced MDA, significant increased TAS in treated T2DM with diabetic retinopathy group. | 18 months | Roig Revert et al., 2015 [121] |
| CAT [DiVFuSS formula] | 67 | Better visual function. No effect on macular thickness. | 6 months | Chous et al., 2016 [122] |
| CAT or Coenzyme Q10 | 60 | Lower ROS expression (LPO, nitrites/nitrates) and augment antioxidant defences. | 6 months | Rodriguez-Carrizalez. 2016 [123] |
| CAT: DHA, EPA, vitamins B, C, E and Zeaxantin | 55 | RD patients with macular edema treated with ranibizumab. Thinner macular in the supplemented group. | 3 years | Lafuente et al., 2018 [124] |
| Crocin | 60 | Patients with refractory DME divided in 3 groups: 5 mg crocin, 15 mg crocin and placebo. 15 mg crocin group showed significant reduction of HbA1c and CMT and increase of BCVA compared with placebo group | 9 months | Sepahi S et al., 2018 [125] |
| Ginkgo biloba extract | 25 | Decrease of MDA and fibrinogen levels. Improved blood parameters (viscosity, viscoelasticity, red blood cell deformability, and retinal blood flow). | 3 months | Huang et al., 2004 [126] |
| Lutein + zeaxanthin | 90 | Treated group showed improvement of visual acuity, contrast sensitivity and reduction of foveal thickness. | 3 months | Hu BJ et al., 2011 [127] |
| Lutein | 31 | Treated NPDR showed improvement at low spatial frequency in contrast sensitivity. | 9 months | Zhang PC et al., 2017, [128] |
| Lutein + zeaxanthin | 72 | T2DM NPDR patients 36 received L and 36 received L+ Z. No significant differences in visual acuity, contrast sensitivity and glare sensitivity. | 4 months | Yongo-bo et al., 2019, [129] |
| Pycnogenol® | 30 | Treated group showed not worsening of retinal retinal function and visual acuity. | 2 months | Spadea et al., 2001 [130] |
| Pycnogenol® | 46 | Improvement of visual acuity, flow at the central retinal artery. Reduction in retinal thickness. In T2DM. | 3 months | Steigerwalt et al. 2009 [131] |
| Resveratrol | 13 | T1DM showed significant decreased levels of MDA and increased total antioxidant capacity between baseline and endpoint. There was no change in the serum levels of TNF- alpha and IL-1beta. | 2 months | Ali Movahed et al. 2020, [132] |
| Vitamin C | 40 | Vitreous levels of vitamin C in PDR patients showed a tenfold decrease, which was associated with degree of macular ischemia. | Park SM et al., 2019, [133] | |
| Vitamin E | 45 | Diabetic patients showed decreased retinal blood flow that improved after treatment similarly to non-diabetic cases. | 8 months | Bursell et al., 1999 [134] |
| Vitamin E | 282 | Decrease of MDA. | 3 months | Chatziralli et al., 2017 [135] |
| Zinc | 18 | Patients with retinopathy showed increasement of plasmatic GSH-px activity. All patients showed decrease of TBAR. | 3 months | Faure et al., 1995 [136] |
| Zinc | 45 | DM patients had a negative correlation between serum VEFG levels and Zinc. Treated group showed no changes in VEGF levels. | 3 months | Kheirouri et al., 2019, [137] |