Low risk of IOP elevations found with drug combination

June 1, 2008

In a multi-center, randomized, double-masked study of 306 healthy volunteers, the anti-inflammatory combination of loteprednol/tobramycin was found to produce lower levels of steroid-induced IOP rise than the combination of dexamethasone/tobramycin.

Key Points

Cincinnati-The combination of loteprednol etabonate/tobramycin (Zylet, Bausch & Lomb) produces a lower level of steroid-induced IOP rise than the combination of dexamethasone/tobramycin (TobraDex, Alcon Pharmaceuticals), according to Edward J. Holland, MD.

"As clinicians, we know there are clearly indications for the use of steroids," Dr. Holland told Ophthalmology Times. "But because of the risk of IOP rise, many clinicians are hesitant to use steroids in cases where they're indicated, or else they're hesitant to use them for long periods.

"So we evaluated the effects of loteprednol/tobramycin and dexamethasone/tobramycin and found that the loteprednol/tobramycin combination was significantly less likely to produce an elevation in IOP," Dr. Holland said.

In a multi-center, randomized, double-masked, parallel-group study, 156 volunteers received the loteprednol/tobramycin combination, and 150 volunteers received the dexamethasone/tobramycin combination. Dosing for both groups was four times daily, at 4-hour intervals, for 28 days.

Ocular health measures, such as IOP and visual acuity, were assessed five times at regular intervals throughout the study, and again after the study on day 29. Direct ophthalmoscopy (undilated) was performed on all volunteers prior to the study and again on day 29. IOP for all volunteers was measured by Goldmann applanation tonometry.

Three subjects (1.95%) from the loteprednol/tobramycin group (1.95%) experienced IOP increases of >10 mm Hg from their baseline IOPs at any study visit, compared with 11 subjects (7.48%) from the dexamethasone/tobramycin group (p = 0.0280).

Mean changes from baseline IOP ranged from –0.01 to 0.35 mm Hg in the loteprednol/tobramycin group, and from 0.78 to 1.71 mm Hg in the dexamethasone/tobramycin group. In addition, mean IOP changes over the course of treatment were not statistically significant at any visit in the loteprednol/tobramycin group.

Other than the differences in IOP increases, there were no other significant differences between the two groups, on either visual acuity measures or adverse ocular effects. Both therapies were well tolerated.

Dr. Holland and his colleagues theorize that a difference in how the drugs are metabolized may be the reason for the differences in their effect on IOP. Dexamethasone and most other steroids available for ocular use are known as ketone steroids. Because these types of steroids are not metabolized by esterases, they may have a longer half-life and thus remain the anterior chamber of the eye longer than loteprednol, which is the only ester steroid available for ophthalmic use.

Dr. Holland and his colleagues did not compare central corneal thickness (CCT) of the two groups in this study. They add, however, that the study was designed to examine the change in IOP within the groups, so baseline CCT should not be a factor. In addition, there is no evidence that steroid use affects CCT, they said.

While this study used healthy volunteers, Dr Holland said the findings are sufficient to warrant further study, and also are compelling enough to affect ophthalmologists' considerations when prescribing topical ophthalmic corticosteroid therapy.

"This study looked at healthy volunteers, but I have used steroids in many patients who have chronic corneal inflammation as well as external eye disease," Dr. Holland said. "Loteprednol is an excellent steroid choice because of its efficacy equal to prednisolone as a very good anti-inflammatory medication, combined with its excellent safety parameters, which this study helps demonstrate."