Histopathological effects of topical ophthalmic preservatives on rat corneoconjunctival surface

被引:124
作者
Becquet, F
Goldschild, M
Moldovan, MS
Ettaiche, M
Gastaud, P
Baudouin, C
机构
[1] Univ Paris 05, Dept Ophthalmol, ERCA INSERM, Hop Ambroise Pare, F-92104 Boulogne, France
[2] Univ Nice, Pharmacol Lab, Nice, France
[3] Univ Nice, Dept Ophthalmol, Nice, France
关键词
conjunctiva; cornea; immunostaining; preservatives; rat;
D O I
10.1080/02713689808951223
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
Purpose. Long term use of topical drugs has clearly been shown to induce toxic immunopathological changes in the ocular surface. However, little is known concerning the respective roles of active compounds and preservatives. Benzalkonium chloride (BAG) is the most used preservative and its cytotoxicity is well known, but other preservatives have not yet been clearly evaluated. We thus performed a comparative study to investigate toxic side effects induced in the rat ocular surface by applications of various preservatives, with special attention to inflammatory infiltrates. Methods. A total of 35 brown Norway rats were divided into seven groups of five each. They received, for one month, in both eyes, either 0.01% cetrimonium chloride, 0.01% benzalkonium chloride, 0.01% benzododecinium bromide, 0.004% thiomersal, 0.05% methyl parahydroxybenzoate or phosphate-buffered saline (PBS), the last group remaining untreated. Then, animals were sacrificed and eyes were processed for histological and immunological procedures with monoclonal antibodies to rat immunocompetent cells. Results. When compared to controls, all preservative-treated eyes consistently showed corneal and conjunctival damage, including epithelial alterations, various degrees of keratinization and inflammatory infiltrates at the limbus and within the conjunctival stroma and epithelium. No difference was found between the five tested drugs. Conclusions. This study confirms that most preservatives used in ophthalmic eyedrops may similarly induce strong histopathological and inflammatory changes in the ocular surface after short term use. Although obtained in animal model, these results confirm strong toxic side effects in patients with preexisting ocular surface disorders and/or receiving topical drugs for long periods.
引用
收藏
页码:419 / 425
页数:7
相关论文
共 33 条
[1]  
ANSEL HC, 1990, PHARM DOSAGE FORMS D, P108
[2]  
BAINES MG, 1991, INVEST OPHTH VIS SCI, V32, P2259
[3]  
Baudouin C, 1996, Curr Opin Ophthalmol, V7, P80, DOI 10.1097/00055735-199604000-00014
[4]  
BAUDOUIN C, 1994, OPHTHALMOLOGY, V101, P454
[5]   QUANTITATIVE-EVALUATION OF THE CORNEAL EPITHELIAL BARRIER - EFFECT OF ARTIFICIAL TEARS AND PRESERVATIVES [J].
BERNAL, DL ;
UBELS, JL .
CURRENT EYE RESEARCH, 1991, 10 (07) :645-656
[6]   CONJUNCTIVAL IMPRESSION CYTOLOGY IN PATIENTS WITH GLAUCOMA USING LONG-TERM TOPICAL MEDICATION [J].
BRANDT, JD ;
WITTPENN, JR ;
KATZ, LJ ;
STEINMANN, WN ;
SPAETH, GL .
AMERICAN JOURNAL OF OPHTHALMOLOGY, 1991, 112 (03) :297-301
[7]   ADVERSE-EFFECTS OF TOPICAL ANTIGLAUCOMA MEDICATION .2. THE OUTCOME OF FILTRATION SURGERY [J].
BROADWAY, DC ;
GRIERSON, I ;
OBRIEN, C ;
HITCHINGS, RA .
ARCHIVES OF OPHTHALMOLOGY, 1994, 112 (11) :1446-1454
[8]   ADVERSE-EFFECTS OF TOPICAL ANTIGLAUCOMA MEDICATION .1. THE CONJUNCTIVAL CELL PROFILE [J].
BROADWAY, DC ;
GRIERSON, I ;
OBRIEN, C ;
HITCHINGS, RA .
ARCHIVES OF OPHTHALMOLOGY, 1994, 112 (11) :1437-1445
[9]   CORNEAL CYTO-TOXICITY OF TOPICALLY APPLIED DRUGS, VEHICLES AND PRESERVATIVES [J].
BURSTEIN, NL .
SURVEY OF OPHTHALMOLOGY, 1980, 25 (01) :15-30
[10]  
BURSTEIN NL, 1977, INVEST OPHTH VIS SCI, V16, P899