Oxidative and antioxidative stress markers in dry eye disease: A systematic review and meta‐analysis

Abstract

Purpose To conduct a systematic review and meta‐analysis on the levels of oxidative stress markers and antioxidants in dry eye disease (DED) compared with healthy subject. Method The PubMed, Cochrane Library, Embase, Science Direct and Google Scholar databases were searched on 10 January 2021 for studies reporting oxidative and antioxidative stress markers in DED and healthy controls. Main meta‐analysis was stratified by type of biomarkers, type of samples (tears, conjunctival cells or biopsies), Sjögren’s syndrome (SS) (patients with or without SS) and by geographical zones (Asia or Europe). Results We included nine articles, for a total of 333 patients (628 eye samples) with DED and 165 healthy controls (451 eye samples). There is an overall increase in oxidative stress markers in DED compared with healthy controls (standard mean deviation = 2.39, 95% confidence interval 1.85–2.94), with a significant increase in lipid peroxide (1.90, 0.69–3.11), myeloperoxidase (2.17, 1.06–3.28), nitric oxide synthase 3 (2.52, 0.95–4.08), xanthine oxidase/oxidoreductase (2.41, 1.40–5.43), 4‐hydroxy‐2‐nonenal (4HNE) (4.75, 1.67–7.84), malondialdehyde (3.00, 2.55–3.45) and reactive oxygen species (1.31, 0.94–1.68). Oxidative stress markers were higher in tears, conjunctival cells and conjunctival biopsies of DED than controls. Even if small number of studies were included for antioxidants, catalase seemed to be decreased in DED compared with healthy controls (−2.17, −3.00 to −1.34), with an increase of antioxidants in tears of DED patients without SS (1.13, 0.76–1.49). Conclusion Oxidative stress markers, and probably antioxidants, were dysregulated in DED, establishing a local oxidative environment in tears, conjunctival cells and tissues.

Application of regulation of reactive oxygen species and lipid peroxidation to disease treatment

“…(53) Following these reports, several clinical studies on the adminis-Table 1. Diseases involving reactive oxygen species and free radicals Brain/neurological disorders cerebral infarction, (4) diabetic neuropathy, (7) Alzheimer's disease/dementia, (8)(9)(10)(11) Parkinson's disease (12,13) Respiratory diseases pneumonia/infections, (14) smoking, (15) bronchial asthma, (16) chronic obstructive pulmonary disease (17) Cardiovascular diseases myocardial infarction, (18) arteriosclerosis, (19) ischemia-reperfusion injury, (18) heart failure, (20) cardiomyopathy (21) Gastrointestinal disorders gastric ulcer, (22) non-alcoholic steatohepatitis, (3) inflammatory bowel disease/ulcerative colitis (23) Endocrine disorders diabetes, (24) hyperlipidemia (25) Urologic diseases chronic nephritis, diabetic nephropathy, (26) nephrotic syndrome (27) Ophthalmic disorders cataract, (28) glaucoma, (29) age-related macular degeneration, (30) diabetic retinopathy, (24) retinopathy of prematurity, (31) dry eye (32) Other diseases cancer, (33) atopic dermatitis, (34) sunlight dermatitis, (35) chronic granulomatosis, (36) rheumatoid arthritis, (37) systemic lupus erythematosus, (37) chronic fatigue syndrome, (38) aging, (39) stains/wrinkles…”

Lipid, Aqueous and Mucin Tear Film Layer Stability and Permanence within 0.15% Liposome Crosslinked Hyaluronic Acid versus 0.15% Non-Crosslinked Hyaluronic Acid Measured with a Novel Non-Invasive Ocular Surface Analyzer

“…In addition, the incorporation of antioxidant agents in the formulation of artificial tears is recommended, since oxidative stress is one of the factors involved in DED [17]. Crocin is a natural chemical compound of the carotenoid or pigment type found in the stigmas of the Crocus sativus or saffron flower.…”

Regenerative cerium oxide nanozymes alleviate oxidative stress for efficient dry eye disease treatment

“…DED is the most common eye disease in ophthalmic consultation except for refractive errors [ 2 ]. The prevalence of DED is surging dramatically, with and without symptoms, ranging from 5% to 50% in the world [ 3 , 4 ], disrupting seriously visual-life quality and imposing billions of economic burdens on society. In recent years, with the high-frequency use of video display terminals (mainly computers, mobile phones, etc.…”

“…When the ocular surface tissue is subjected to environmental stress (such as ultraviolet rays, high temperature, wind and sand, etc. ), the ROS level will grow sharply, and the balance between ROS and antioxidant enzymes will be disrupted [ 4 , 18 ]. Subsequently, pathological changes will appear in the cornea, conjunctiva and lacrimal gland, followed by tear film hyperosmolarity and decreased stability, inducing the occurrence of DED [ 19 , 20 ].…”