title: In vitro and in vivo corneal effects of latanoprost combined with brimonidine, timolol, dorzolamide, or brinzolamide.
abstract: To examine the relevance of concentration of benzalkonium chloride (BAK) on the cornea, we investigated the effects of latanoprost containing BAK alone and in combination with other antiglaucoma drug classes on corneal epithelium in vitro in a cultured rabbit corneal cell line (SIRC) and in vivo, using a corneal resistance device (CRD). [In vitro] staten's seruminstitut rabbit corneal cells were exposed to 0.005% latanoprost for 30s, followed by either phosphate buffered saline (control), 0.1% brimonidine, 0.5% timolol, 1% dorzolamide, or 1% brinzolamide. The number of viable cells was counted at 8, 15, and 30min. [In vivo] Albino rabbits were administered one drop of 0.005% latanoprost, followed 5min later by one drop of an agent from the in vitro trial. This was repeated every 15min for a total of three times. The change in corneal barrier function was assessed by measuring the corneal resistance at 2 and 30min after the final administration. [In vitro] At 8min, the viable cell count in the latanoprost+dorzolamide group was significantly lower than in the control group. At 15 and 30min, all treatment groups, except the latanoprost+brimonidine group, demonstrated significantly lower viable cell counts than the control group. [In vivo] At 2min after the final eye drop, the latanoprost+timolol group and the latanoprost+brinzolamide group demonstrated significantly lower corneal resistance than did the latanoprost+brimonidine group. No significant difference was observed between the agents at 30min. In conclusion, when combining latanoprost containing benzalkonium chloride with other classes of antiglaucoma drugs, brimonidine may cause the least corneal damage, and the number of drug administrations may be an important factor.
authors.affiliation: Department of Ophthalmology, Kanazawa Medical University, Uchinada, Japan. Electronic address: fukuda@kanazawa-med.ac.jp.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Fukuda
authors.affiliation: Department of Ophthalmology, Visual Science, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Takeda
authors.affiliation: Department of Ophthalmology, Kanazawa Medical University, Uchinada, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Shibata
authors.affiliation: Department of Ophthalmology, Kanazawa Medical University, Uchinada, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Shibata
authors.affiliation: Department of Ophthalmology, Kanazawa Medical University, Uchinada, Japan.
authors.forename: Teppei
authors.initials: T
authors.lastname: Shibata
authors.affiliation: Department of Ophthalmology, Visual Science, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Sugiyama
authors.affiliation: Department of Ophthalmology, Kanazawa Medical University, Uchinada, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D000068438:Brimonidine Tartrate / Q000009:adverse effects; D002470:Cell Survival / Q000187:drug effects; D017097:Electric Impedance; D019573:Epithelium, Corneal / Q000166:cytology / Q000187:drug effects; D007429:Intraocular Pressure / Q000187:drug effects; D000077338:Latanoprost; D008297:Male; D009883:Ophthalmic Solutions / Q000009:adverse effects*; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology*; D011817:Rabbits; D012449:Safety; D013449:Sulfonamides / Q000009:adverse effects; D013843:Thiazines / Q000009:adverse effects; D013876:Thiophenes / Q000009:adverse effects; D013999:Timolol / Q000009:adverse effects
chemical_list: D009883:Ophthalmic Solutions; D011461:Prostaglandins F, Synthetic; D013449:Sulfonamides; D013843:Thiazines; D013876:Thiophenes; D000068438:Brimonidine Tartrate; D000077338:Latanoprost; D013999:Timolol; C111827:brinzolamide; C062765:dorzolamide
keywords: Albino rabbit; Antiglaucoma drugs; Benzalkonium chloride (BAK); CR ratio (%); Staten's seruminstitut rabbit corneal (SIRC) cells