Table 2.
Comparing different studies on the role of antioxidants in thyroid eye disease
| Writer/year | Study design | Population | Mean age (year) | TED grade | Thyroid status | Type of antioxidant treatment | Follow-up | Result | Side effects | ||
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Chang et al., 199328 | Experimental, orbital fibroblast cell culture | Case: 2 Normal: 2 (2 PTM) |
32 | Moderately severe, activity is not specified/with OD | Not mentioned | PTX | NA | Inhibition of GAG release and fibroblast proliferation | NA | |
| 2 | Balazs et al., 199722 | Quasi-experimental, pilot study | Case: 10 | 45.2 | Moderately severe, activity is not specified/with OD | Euthyroid | PTX | 12 weeks | ↓Serum GAG and TNFα, ↓Soft tissue involvement | Moderate and persistent nausea at the begging | |
| 3 | Burch et al., 199729 | Experimental, orbital fibroblast cell culture | Case: 2 Normal: 2 |
Not available | Moderately severe, activity is not specified/with OD | Not mentioned | Allopurinol nicotinamide | NA | ↓Cell proliferation | NA | |
| 4 | Hiromatsu et al., 199830 | Experimental, orbital fibroblast cell culture | Case: 4 Normal: 3 |
Not available | Activity and severity are not specified/with OD | Not mentioned | Nicotinamide | NA | ↓ICAM-1 and HLA-DR expression and | ↓Cell proliferation | NA |
| 5 | Bouzas et al., 200023 | Prospective nonrandomized comparative study | Case: 11 Normal: 11 |
Case: 36.7 Control: 34.8 |
Mild and moderately severe, active | Euthyroid | Allopurinol nicotinamide | 3 months | ↑Total eye score (NOSPECS) ↑Patient satisfaction |
None | |
| 6 | Finamor et al., 200420 | Prospective randomized trial | Case: 9 Normal: 9 |
Case: 41.5 Control: 40 |
All 3 severity stages but inactive | Euthyroid | PTX | 6 months | ↓Proptosis and questionnaire scores | Nausea, abdominal pain | |
| 7 | Marcocci et al. 201121 | Prospective randomized double-blind, placebo-controlled trial | Total: 159 Se: 55 PTX: 52 Placebo: 52 |
Se: 43 PTX: 43.7 Placebo: 44.6 |
Mild GO, active and inactive | Not mentioned | Se, PTX | 12 months | ↑QoL ↓CAS |
Se (none) gastrointestinal with PTX | |
| 8 | Lisi et al., 201131 | Experimental, orbital fibroblast cell culture | Case: 5 Normal: 5 |
Case: 47.4 Control: NA |
Moderately severe, inactive/with OD | Euthyroid | Quercetin | NA | ↓Cell proliferation and HA release | NA | |
| 9 | Yoon et al., 201232 | Experimental, orbital fibroblast cell culture | Case: 13 Normal: 3 |
Case: 46 Control: 56 |
Moderately severe, inactive/with OD | Euthyroid | Quercetin | NA | ↓MMP-2 and MMP-9, fibrotic markers and suppressive effects | NA | |
| 10 | Tsai et al., 201333 | Experimental, orbital fibroblast cell culture | Case: 7 Normal: 5 |
Case: 37.6 Control: 35.2 |
Severity is not specified inactive/with OD | Euthyroid | Vitamin C N-acetyl-l-cysteine |
NA | ↓Cell proliferation and superoxide anion | NA | |
| 11 | Kim et al., 201534 | Experimental, orbital fibroblast cell culture | Case: 6 Normal: 4 |
Not available | Moderately severe, (CAS <4)/with OD | Euthyroid | Resveratrol | NA | ↓Oxidative stress and ROS | NA | |
| 12 | Dehina et al., 201624 | Case-control, serum elements study | Total: 84 Mild: 31 Severe: 53 Active: 62 Inactive: 22 |
Not available (median: 46) | Used NOSPECS (mild, moderately severe, and sight threatening), active and inactive | Hyper: 51 Hypo: 10 Eu: 23 |
Serum Se, SePP | NA | No significant associations and changes | NA | |
| 13 | Dottore et al. 201735 | Experimental, Orbital fibroblast Cell culture | Case: 6 Normal: 6 |
Case: 60.1 Control: 66.1 |
Moderately severe, inactive/with OD | Not mentioned | Se | NA | ↓Oxidative stress and cell proliferation | NA | |
| 14 | Dottore et al., 201736 | Experimental, orbital fibroblast cell culture | Case: 6 Normal: 6 |
Case: 60.1 Control: 66.1 |
Severity is not specified inactive/with OD | Not mentioned | Se | NA | ↓Apoptosis, LDH (necrosis), inhibition of oxidative stress (↓GSSG) | NA | |
| 15 | Federige et al., 201725 | Case-control, serum elements study | GD without GO: 19 GD with GO: 21 HT: 14 HT+LT4: 19 Control: 21 |
Case: 52.5 Control: 51 |
GO defined as having proptosis and CAS >1, severity is not specified | Euthyroid | Serum Se, SePP | NA | ↓SePP serum level in GO and HT patients | NA | |
| 16 | Dottore et al., 201837 | Experimental, orbital fibroblast cell culture | Case: 6 Normal: 6 |
Case: 49.1 Control: 62.6a |
Moderately severe, inactive/with OD | Not mentioned | Retinol, β-carotene, Vitamin E | NA | ↓H2O2-dependent oxidative stress, antiproliferative action | NA | |
| 17 | Dottore et al., 201838 | Experimental, orbital fibroblast cell culture | Case: 6 Normal: 6 |
Case: 49.1 Control: 62.6 |
Moderately severe, inactive/with OD | Not mentioned | Vitamin C >N-acetyl-l-cysteine, Melatonin |
NA | ↓H2O2-dependent oxidative stress | NA | |
| 18 | Liu et al., 201826 | Case-control, serum elements study | Newly diagnosed GD: 66 Euthyroid GD: 55 Euthyroid GO: 57 Control: 66 |
Case: 38.06 Control: 42.3 |
Mild-to-moderate GO according to EUGOGO classification, severity is not specified | Euthyroid/subclinical hyper | Serum Se | NA | ↓Se serum level in all cases than control group | NA | |
| 19 | Olesik et al., 202027 | Case-control, serum elements study | TAO: 56 Control: 20 |
Case: Hyper: 53 Eu: 48 Control: Not available |
Active (CAS >3), moderate-to-severe according to EUGOGO classification | Hyper: 34 Eu: 22 |
Serum Vitamin C, Uric acid | NA | Lower Vitamin C, higher uric acid levels in active TAOs than controls | NA | |
| 20 | Kim et al., 202139 | Experimental, orbital fibroblast cell culture | Case: 7 Normal: 5 |
Case: 41.1 Control: Not available |
Inactive (CAS <3), severity is not specified | Euthyroid | Se | NA | Suppression of hyaluronan production, IL1α, and TNFα (all in dose-dependent manner) nInhibition of ROS generation and IL8 |
NA |
TED: Thyroid eye disease, PTX: Pentoxifylline, GD: Graves’ disease, GO: Graves’ orbitopathy, HT: Hashimoto’s thyroiditis, TAO: Thyroid-associated orbitopathy, Se: Selenium, NOSPECS: No sign or symptoms, only signs, soft tissue involvement with symptoms and signs, proptosis, extraocular muscle involvement, corneal involvement, sight loss, CAS: Clinical activity score, EUGOGO: European Group on Graves’ Orbitopathy, SePP: Selenoprotein P , GAG: Glycoseaminoglycan, TNFα: Tumor necrosis factor-α, ICAM-1: Intercellular adhesion molecule 1, HLA: Human leukocyte antigen, QoL: Quality of life, MMP-2: Matrix metalloproteinase-2, ROS: Reactive oxygen species, LDH: Lactate dehydrogenase, GSSG: Glutathione disulfide, IL: Interleukin, NA: Not applicable, H2O2: Hydrogen peroxide, PTM: Pretibial myxedema, LT4: Levothyroxine, OD: Orbital decompression, HA: Hyaluronic acid, HLA-DR: Human leukocyte antigen-DR isotype, Eu: Euthyroid, ↓: Decreased, ↑: Increased