Page 171 - DUOKOPT BIBLIOBOOK

EFFICACY

J Kwon, et al. Cytotoxic Effects of Dorzolamide/timolol

cells, as well as numerous dead cells as determined by a thelial cells can proliferate and rabbit corneas can recover
live/dead cell assay. SEM analysis showed that corneal en- their normal clarity after endothelial injury on a time scale
dothelial cells also exhibited a partial loss of microvilli on of several days to weeks [27,28]. To overcome this limita-
the surface as well as extensive destruction of intercellular tion, we evaluated the toxic effects of anti-glaucoma eye-
junctions. However, corneal edema was mild in the eyes drops only 24 hours after injection. Therefore, we could
injected with the preservative-free formulation Cosopt-S, demonstrate distinct differences between endothelial dam-
and damage to the corneal endothelium was minimal. age caused by preservative-containing and preserva-
Based on the results of this study, we concluded that the tive-free eyedrops.
main cause of endothelial toxicity was the preservative, In conclusion, we demonstrated that the main cause of
and not the active ingredients of the anti-glaucomatous endothelial toxicity upon treatment with a dorzol-
agents. Therefore, anti-glaucoma eyedrops containing pre- amide-containing solution was due to the preservative, and
servative may have the potential to cause damage to the not the active ingredient of this anti-glaucoma medication.
corneal endothelium as well as to the ocular surface, espe- Thus, it may be safer to use preservative-free anti-glauco-
cially during the early postoperative period or in cases of ma eyedrops during the early postoperative period or in
an epithelial defect. In these conditions, it seem be safer to cases where enhanced corneal penetration is a concern.
use preservative-free anti-glaucoma eyedrops, as several
studies have already demonstrated that there is no differ-
ence in intraocular pressure reduction between preserva- Conflict of Interest
tive-containing and preservative-free formulations [20-25].
Moreover, benzalkonium chloride expression has been de- No potential conflict of interest relevant to this article
tected in the trabecular meshwork, corneal endothelium, was reported.
lens, and retina after topical drop installation, which may
contribute to toxicity in these tissues [26].
Our study had a few limitations. In order to evaluate Acknowledgements
toxicity, we injected the anti-glaucoma eyedrops directly
into the anterior chamber. Although the eyedrops were di- This research was supported by Basic Science Research
luted, the concentration of anti-glaucoma components and Program through the National Research Foundation of Ko-
preservative was most likely greater than the concentra- rea (NRF) funded by the Ministry of Education, Science
tions that could be obtained following topical administra- and Technology (2012R1A1A2042054). This study was
tion. However, it is difficult to predict the true amount of supported in part by Alumni of Department of Ophthal-
eyedrops that enters through clear corneal wounds during mology, Korea University College of Medicine in 2014.
the early postoperative period. While it is unusual in clini-
cal practice that a high concentration of eyedrops could di-
rectly enter the anterior chamber directly, we reasoned that References
direct injection of dorzolamide eyedrops into the anterior
chamber could represent a case whereby the corneal endo- 1. Lapalus P, Ettaiche M, Fredj-Reygrobellet D, et al. Cyto-
thelium is affected, leading to corneal edema. Thus, long- toxicity studies in ophthalmology. Lens Eye Toxic Res
term use of topical anti-glaucoma eyedrops may affect the 1990;7:231-42.
function of the corneal endothelium and eventually can 2. Guzman-Aranguez A, Calvo P, Ropero I, Pintor J. In vitro
cause corneal edema. Therefore, our study design may effects of preserved and unpreserved anti-allergic drugs on
provide information on the maximal toxic effects of an- human corneal epithelial cells. J Ocul Pharmacol Ther
ti-glaucoma eyedrops on the corneal endothelium in the 2014;30:790-8.
presence or absence of preservative. Another limitation of 3. Mantelli F, Tranchina L, Lambiase A, Bonini S. Ocular
this study was the use of rabbits, whose corneal endotheli- surface damage by ophthalmic compounds. Curr Opin Al-
al cells are different from human corneal endothelial cells lergy Clin Immunol 2011;11:464-70.
in terms of cell proliferation. Indeed, rabbit corneal endo- 4. Baudouin C, Labbe A, Liang H, et al. Preservatives in eye-

349

171