Gatifloxacin vs. Moxifloxacin:
Their Ocular Surface Effects
Study shows a nonpreserved formulation is less tolerable than a preserved anti-infective.
By Henry D. Perry, M.D., Rockville Centre, N.Y.
One of the main requirements of an ideal antibiotic -- aside from a broad spectrum of effectiveness -- is that it be nontoxic and noninflammatory. Anecdotal reports have noted that unpreserved moxifloxacin (Vigamox) caused ocular redness and irritation. Elsewhere, we've heard that preserved gatifloxacin (Zymar) may be more toxic than moxifloxacin because it contains the preservative benzalkonium chloride (BAK). These claims motivated my colleagues and me to evaluate the effect of these fourth-generation fluoroquinolones on the ocular surface in 30 subjects with no ocular pathology.
Baseline evaluation
We evaluated the eyes at baseline for conjunctival erythema, conjunctival vascularity, pupil size and anterior chamber (AC) cell and flare. We measured the pupils with a Colvard pupillometer under scotopic conditions. We measured conjunctival erythema, vascularity and AC reactions on a scale of 0 to 3.
We used commercially available gatifloxacin 0.3% preserved with BAK 0.005% and moxifloxacin 0.5% solutions in masked bottles. One drop from each bottle was placed in either the right or left eye two times at 1-minute intervals.
The pupil size, conjunctival erythema, vascularity and AC cell and flare were measured by a masked observer who did not administer the drops. The subjects graded pain, light sensitivity and irritation in each eye on a scale of 1 to 10.
Gatifloxacin produced fewer clinical signs of inflammation to the ocular surface compared with moxifloxacin in a double-blind, head-to-head study of these fourth-generation fluoroquinolones. Subjects complained of significantly less ocular irritation and pain with gatifloxacin than with moxifloxacin.
Findings favor preserved solution
Evaluation of conjunctival erythema showed that there was almost four times more erythema in the moxifloxacin eyes than in the gatifloxacin eyes.
Next, we looked at conjunctival vascularity. Vascularity with moxifloxacin increased significantly (2.5 times baseline), whereas gatifloxacin increased by 0.33 as much. This means the increase in vascularity in the moxifloxacin eyes was seven times greater than that in the gatifloxacin eyes.
The difference in pupillary size before and after administration of drops proved noteworthy as well. At baseline, a 5.6-mm pupil decreased to about 5 mm with moxifloxacin, a 12% decrease. We saw no statistically significant change in pupil size in the gatifloxacin eyes; there was actually a slight increase in pupil size, but it was not statistically significant.
Evaluation of pain following instillation of the drops also resulted in some interesting findings. Patients reported a three-fold difference in the level of post-drop pain, with the moxifloxacin subjects experiencing greater pain. The moxifloxacin subjects had six times more irritation than their counterparts.
Statistically significant outcomes
Our results showed that moxifloxacin was associated with statistically significant conjunctival erythema and statistically significant vascularity compared with baseline, 5 minutes after instillation of the drops.
We observed no difference in conjunctival erythema or vascularity with gatifloxacin, and the irritation and pain were significantly less severe with gatifloxacin compared with moxifloxacin.
We also noted a significant reduction in pupil size in eyes receiving moxifloxacin, and no change in pupil size with gatifloxacin. Nor was there any change in the gatifloxacin subjects with respect to AC cell, flare or light sensitivity. Subjects with light-colored irides were most likely to experience erythema and irritation.
How to explain the difference?
We concluded that gatifloxacin produced fewer clinical signs of ocular surface inflammation compared with moxifloxacin. In theory, the pupillary constriction, pain, redness and irritation induced by moxifloxacin may be caused by release of endogenous prostaglandins. A follow-up study is planned to further evaluate this theory.
Dr. Perry is a senior founding partner of Ophthalmic Consultants of Long Island. He is also an associate professor of ophthalmology at Cornell School of Medicine, and Chief of Cornea Service at North Shore University Hospital and Nassau County Medical Center.
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Ocular Topical Redux: Preservatives Rule |
Preserved and nonpreserved have become catchy terms for categorizing ocular topical drugs. A look at the history of their use in ophthalmology practice shows, however, that preserved solutions remain the rule, nonpreserved the exception. Traditionally, most topical ocular drugs have contained preservatives. Preservative-free artificial tears are the exception. The rationale is that people with dry eyes who needed frequent doses of tears will accumulate the preservatives on their eyes. And because the ocular surface is already compromised from the dry eye, the preservative buildup could lead to toxicity. Over the years, however, most topical ocular medications continued to contain preservatives. For cortico-steroids and glaucoma medications, the reason is obvious: Preservatives addressed the concern that infectious agents would contaminate the medications. Although there was less worry about contamination of antibiotics, including preservatives was still considered beneficial to stabilize the solution during extremes of temperature. Also, their effect on the corneal and conjunctival epithelium may have allowed better penetration of the antibiotic; and perhaps most important, they prevented contamination from other infectious agents such as fungi and parasitic organisms. Ofloxacin (Ocuflox), the antibiotic used most commonly in ophthalmology during the past decade, includes the preservative benzalkonium chloride (BAK). This preservative at 0.005% has had an excellent track record. In my referral practice, where I've used ofloxacin to treat countless patients, I don't recollect a single case of toxicity due to this preservative. This is because antibiotics are rarely used for more than 7 to 10 days, unlike other agents, such as glaucoma drops, which are used long-term.
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References
Burstein NL. Corneal cytotoxicity of topically applied drugs, vehicles and preservatives. Surv Ophthalmol. 1980;25:15-30.
Baudouin C. Side effects of antiglaucomatous drugs on the ocular surface. Curr Opin Ophthalmol. 1996;7:80-86.
Baudouin C, Pisella PJ, Fillacier K et al. Ocular surface inflammatory changes induced by topical antiglaucoma drugs: human and animal studies. Ophthalmology.. 1999;106:556-563.
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