Study: cornea not adversely affected by latanoprost use

Results showed equivalency to timolol, but suggest need for increased surveillance in cases of existing corneal compromise.

CLEVELAND — Latanoprost did not impact negatively on corneal endothelial cell counts or corneal thickness in a study of 369 patients here. After 1 year of study, researchers reported that the drug compared favorably with timolol.

The year-long study was carried out with 369 participants at 22 clinical sites throughout the United States, and led by Jonathan H. Lass, MD, professor and chairman of ophthalmology at Case Western Reserve University and director of ophthalmology at University Hospitals of Cleveland. Pharmacia Corp. employees assisted in data analysis.

Safe in healthy corneas

“Latanoprost and its combination with timolol can be considered to have good long-term safety in ocular hypertensive and primary open-angle glaucoma subjects,” the study reported. However, the authors also cautioned clinicians to look for any corneal changes “when managing the glaucoma subject with compromised endothelium.”

In an interview with Ocular Surgery News, Dr. Lass noted that “The corneas in some glaucoma patients may not be normal, and I think we need to be more observant with these patients.

“Latanoprost is a prostaglandin analogue, but at such a low concentration with a potent intraocular pressure-lowering effect,” Dr. Lass continued. “You have to respect it as a prostaglandin analogue, but from our study it has no effect on the cornea.”

Study highlights

The study was a parallel, randomized, double-masked, active-controlled, 1-year multicenter trial. Each of the 369 participants had to have a central corneal endothelial cell count greater than or equal to 1500 cells/mm². Participants also had to have a central corneal thickness less than 0.68 mm and a mean intraocular pressure (IOP) of less than 22 mg Hg. All patients agreed to treatment in both eyes. Patients received either timolol 0.5%, latanoprost 0.005% or a fixed combination (FC) of latanoprost 0.005% and timolol 0.5%.

Seventy-three percent of the patients were white with an approximately equal number of men and women, all with similar baseline IOP. Baseline central endothelial cell density and corneal thickness were similar among the three groups under study.

Corneal changes were observed in study subjects in all three groups. Punctate epithelial erosions occurred in 18 subjects, five receiving latanoprost, six receiving FC and seven receiving timolol.

Three-hundred thirty-three patients (90%) completed the 1-year study; 10 were withdrawn because they required additional glaucoma medication.

Within expected range

Endothelial cell losses occurred at a rate consistent with normal aging, the authors indicated. Endothelial cell counts and corneal thickness are indirect measures of corneal health, yet still provide a highly efficient and reproducible means of evaluating change over time, and are “reflective of clinically important direct toxic effects on the endothelium by the determination of any compromise of endothelial function reserve.” The study determined that cells losses among all 3 groups were comparable with essentially no cell loss over the year with a standard deviation of about 2%. This is reflective of the rate of cell loss that would occur annually in a normal population over a 10-year period, according to the study authors.

“The changes in mean central corneal thickness of 1% or less in all three groups … were most reassuring regarding the safety of all three agents,” the study said.

Multiple drops effect

There are conflicting data regarding corneal endothelial cell counts and corneal thickness in glaucoma and ocular hypertensive patients, according to the study. Some research has indicated that there are essentially no differences between the population and age-matched normals, whereas other studies cited in their investigation “found a significantly lower mean endothelial cell density in open-angle glaucoma subjects than age-matched controls. … Those patients receiving three or four medications had lower cell counts than those receiving one or two medications. … Therefore ongoing prospective, double-blind studies are needed comparing new drugs to existing drugs and then comparing these results to age-matched normals and untreated ocular hypertensives in parallel and longitudinal fashion for as long as possible,” the authors reported.

For Your Information:

• Jonathan H Lass, MD, one of several principal investigators involved in this study, can be reached at University Hospitals of Cleveland, 11100 Euclid Ave., Cleveland, OH 44106-5068; (216) 844-8590; fax: (216) 983-0544; e-mail: jh17@po.cwru.edu. Dr. Lass has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.