## 4 Vitamins C and E and Dry Eye Disease  
Vitamin C is a water-soluble vitamin composed of six carbons that has the molecular formula C\({}_{6}\)H\({}_{8}\)O\({}_{6}\)[77]. It has anti-oxidative, anti-inflammatory, and immunomodulatory functions, which can be helpful for the prevention of DED [17]. Human tear film contains high vitamin C levels, which may be helpful for anti-oxidative and anti-inflammatory defense on the ocular surface [78]. Vitamin C has been assumed to have a therapeutic role in the repair of corneal wounds [79]. An experimental study using a rat model recently showed that vitamin C improved corneal edema and alleviated inflammation after corneal injury caused by ultraviolet B exposure [80]. [PERSON] et al. [81] reported that topical vitamin C attenuated corneal inflammatory cell infiltration, promoted limbal stem cell proliferation, and decreased corneal neovascularization after corneal alkali burns in a mouse model.  
Vitamin E comprises a group of fat-soluble compounds composed of a chromatol ring with a side chain at the C2 position [82] that also have anti-oxidative activity, which may also be helpful for antioxidant defense on the ocular surface and in the of DED [19]. An experimental study using a rabbit model recently showed that vitamins C and E demonstrated similar effects on corneal wound healing [20].  
In patients with DM, the oral supplementation of vitamins C (1000 mg/day) and E (400 IU a day) for 10 days resulted in an improvement in TBUT and Schirmer scores, ab increase in conjunctival goblet cell density, and the restoration of conjunctival squamous metaplasia, which might have been caused by a reduction in oxidative damage to the ocular surface [83; 84]. A prospective randomized trial also revealed that oral antioxidant supplementation, including with vitamins A, C, and E, led to an improvement in TBUT, Schirmer scores, corneal fluorescein staining scores, and tear reactive oxygen species level [85].  
[PERSON] et al. [86] reported that topical vitamin E combined with coenzyme Q10 may be effective for the recovery of corneal subbasal nerve flexus and the stability of the ocular surface after cataract surgery [86]. [PERSON] et al. [87] showed that eye drops containing 0.1% cross-linked hyaluronic acid, coenzyme Q10, and vitamin E had a similar efficacy in improving tear film stability and dry eye symptoms compared to a higher dose of carmellose eye drops in menopausal women taking antidepressants, suggesting the possible efficacy of vitamin E [87]. The topical application of vitamin E combined with coenzyme Q10 was also helpful for the restoration of the homeostasis of the ocular surface and tear film stability in pediatric patients and eyes exposed to chlorinated water [88; 89].  
[PERSON] et al. [90] recently demonstrated that the use of a mixture of 3% diquadfosol and vitamin E (tocopherol 0.005% or 0.01%) eye drops was superior to 3% diquadfosol eye dropsfor the improvement of the tear film and lipid layer, the recovery of the corneal epithelium, the amelioration of ocular surface inflammation, and an increase in conjunctival goblet cell density, suggesting that vitamin E alone might have an effect in treating DED [90].  
However, it is difficult to determine the effect of vitamins C or E alone using these data, and further studies are necessary for the evaluation of the effect of each vitamin.