Impact of dorzolamide, benzalkonium-preserved dorzolamide and benzalkonium-preserved brinzolamide on selected biomarkers of oxidative stress in the tear film

Abstract

Background Long-term use of topical, especially benzalkonium chloride (BAC)-preserved, antiglaucoma medications can cause a negative impact on the ocular surface. The aim of the study was to assess the effect of topical carbonic anhydrase inhibitors (CAIs) on selected oxidative stress biomarkers in the tear film. Methods The patients were divided into four sex-matched groups: group C (n = 25) – control group – subjects who did not use topical antiglaucoma medications, group DL (n = 14) – patients using preservative-free dorzolamide, group DL + BAC (n = 16) – patients using topical BAC-preserved dorzolamide, group BL + BAC (n = 17) – patients using BAC-preserved brinzolamide. Subjects in all the study groups have been using the eye drops two times daily for 6–12 months. The oxidative stress biomarkers in the tear film samples were measured: total protein (TP) concentration, advanced oxidation protein products (AOPP) content, total sulfhydryl (-SH) groups content, the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as Total Oxidant Status (TOS), Total Antioxidant Response (TAR), and Oxidative Stress Index (OSI). Results The advanced oxidation protein products content, Total Oxidant Status as well as superoxide dismutase and catalase activities in the group DL + BAC and BL + BAC were higher in comparison with the group C. The total sulfhydryl groups content was lower in the group DL + BAC and BL + BAC when compared to group C. Oxidative Stress Index was higher in the groups DL + BAC and BL + BAC in comparison with the groups DL and C. Conclusions Use of topical benzalkonium chloride-preserved carbonic anhydrase inhibitors increases oxidative stress in the tear film.

Sleep deprivation induces corneal epithelial progenitor cell over-expansion through disruption of redox homeostasis in the tear film

“…However, the aqueous layer of the TF, secreted by the lacrimal gland, contains various antioxidants, including ascorbic acid, lactoferrin, uric acid, and cysteine, which work in concert to protect the ocular surface against free radical injury ( Álvarez-Barrios et al., 2021 ). Additionally, lacrimal gland-secreted proteins, such as antioxidant enzymes including superoxide dismutase and GPX, make a contribution as antioxidants ( Sedlak et al., 2021 ). This machinery helps maintain the tear redox homeostasis.…”

Clinical Tear Fluid Proteomics—A Novel Tool in Glaucoma Research

“…In addition to the active ingredients of the eye drops, preservatives used in eye drops, especially benzalkonium chloride (BAK), are shown to be a major cause of adverse reactions, and often a switch to preservative-free medication alleviates these symptoms [ 67 , 68 , 69 , 70 ]. Previous studies have highlighted that the prolonged use of these preservatives not only causes ocular surface inflammation but also induces oxidative stress in the tear film [ 71 , 72 ], further tipping off the balance of the ocular surface functions and increasing the risks of OSD development.…”

Effects of topical ketorolac tromethamine on tear parameters, meibography, goblet cell density, and conjunctival oxidative stress in healthy dogs

“…5 Additionally, clinical studies conducted in humans have shown that the long-term use of solutions preserved with BAC is associated with abnormalities of tear film such as hyperosmolarity, instability, and increased oxidative stress. 5,6 An in vitro study conducted in canine corneal epithelial cells showed that BAC caused severe changes and inhibited migration of these cells at all concentrations tested. 7 The most common local adverse events associated with ocular NSAIDs are conjunctival stinging, burning, hyperemia, and corneal anesthesia, whereas corneal melting occurs in rare cases.…”

“…24 Several studies have reported abnormal oxidative stress status in various corneoconjunctival diseases in rabbits, mice, humans, cats, and dogs. 6,[24][25][26][27][28] The role of NSAIDs in oxidative status is controversial. [29][30][31] Additionally, no published studies have demonstrated the effects of ophthalmic NSAIDs on the oxidative stress status of the ocular surface in dogs.…”

“…Experimental studies developed in mice and rabbits report that the chronic use of solutions preserved with BAC may cause meibomian gland dysfunction, decreased density of conjunctival goblet cells, apoptosis of corneal and conjunctival epithelial cells, corneal nerve damage, inflammation of ocular tissues, and fibrotic reactions 5 . Additionally, clinical studies conducted in humans have shown that the long‐term use of solutions preserved with BAC is associated with abnormalities of tear film such as hyperosmolarity, instability, and increased oxidative stress 5,6 . An in vitro study conducted in canine corneal epithelial cells showed that BAC caused severe changes and inhibited migration of these cells at all concentrations tested 7 …”