Toxicity of antiglaucoma drugs with and without benzalkonium chloride to cultured human corneal endothelial cells

Figures & data

Table 1 Antiglaucoma eye drops evaluated in the present study

Active component	Trade name and manufacturer	Preservative	CVS50a	CVS40/80a
Timolol maleate (0.5%) 0.5%	Timoptol (Banyu Pharmaceutical, Tokyo, Japan)	0.005% BAK	5	2 (4–2)
Preservative-free timolol maleate (0.5%)	No trade name and prepared for investigational use only. Provided by Merck and Co, Whitehouse Station, NJ, USA	none	9	7 (7–0)
Dorzolamide (1%)	1% Trusopt (Banyu Pharmaceutical)	0.005% BAK	6	2 (5–3)
Preservative-free dorzolamide (1%)	No trade name and prepared for investigational use only. Provided by Merck and Co	none	9	6 (6–0)
Travoprost (0.004%)	Travatan (Alcon Laboratories, Fort Worth, TX, USA)	0.015% BAK	4	0 (3–3)
Travoprost (0.004%)	Travatan Z (Alcon Laboratories)	SofZia system	9	9 (9–0)
Latanoprost (0.005%)	Xalatan (Pfizer, New York, NY, USA)	0.02% BAK	3	−4 (2–6)

a Note: The CVS was calculated after 10, 30, or 60 minutes’ exposure of each drug as follows: CVS40/80 = (number of viability values >80%) − (number of viability values <40%); CVS50 = number of viability value ≥50%.

Abbreviations: CVS, cell viability score; BAK, benzalkonium chloride; SofZia, an ionic buffering preservative system containing borate, sorbitol, propylene glycol, and zinc.^11,34

Figure 1 Viability of cultured human corneal endothelial cells after exposure to antiglaucoma eye drops for 10, 30, or 60 minutes, or 48 hours. Exposure to drugs containing the preservative benzalkonium chloride led to markedly lower cell viability, especially at higher concentrations and following longer exposure. Data are expressed as the mean ± standard deviation. Drugs without benzalkonium chloride are represented by open symbols and solid lines.

Note: *P < 0.01 (Student’s t test) or NS for comparisons of *^1,NS1Timoptol vs preservative-free timolol maleate; *^2,NS2Trusopt vs preservative-free dorzolamide, and *^3,NS3Travatan vs Travatan Z in each concentration and exposure time.
Abbreviation: NS, nonsignificant.

Figure 2 Effect of antiglaucoma eye drops and BAK on the viability of cultured human corneal endothelial cells after 30 minutes’ exposure. BAK was used at concentrations of 0.01% and 0.005%. Note that cell viabilities were lower for 0.5% Timoptol and 1% Trusopt than for 0.005% BAK. In comparison, higher cell viabilities were seen with Xalatan (used at a 2-fold dilution, containing 0.01% BAK) and Travatan (used at a 2-fold dilution, containing 0.0075% BAK) than for 0.01% BAK alone.

Note: Data are expressed as the mean ± standard deviation. *P < 0.01 (Student’s t test).
Abbreviation: BAK, benzalkonium chloride.

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