Study: Latanoprost, brimonidine have minimal side effects on the conjunctiva

The absence of subjective complaints from patients confirmed the results of objective clinical and morphological testing.

ByMichela Cimberle

FLORENCE – Latanoprost and brimonidine were equally well tolerated and did not produce significant modifications of either the ocular surface or the tear film in a small study here.

“They are both effective in lowering IOP and they have few conjunctival side effects,” said Massimo Susini, MD.

This is important not only for the patient’s comfort and quality of life, but also because a well-preserved conjunctiva can better tolerate surgery in case medical therapy becomes ineffective, he explained. Subclinical chronic inflammation of the conjunctiva, which is a common side effect of other drugs, is often the cause of cystic blebs and encapsulated blebs, due to fibroblast proliferation and collagen deposits in the area of filtration, Dr. Susini said.

Minimal morphological changes

The study evaluated the effects of the two drugs in two groups of 11 patients each with primary open-angle glaucoma over 2 years. One group received Xalatan (latanoprost, Pfizer) in a single daily dose, while another second group received Alphagan (brimonidine tartrate 2%, Allergan) twice a day. Patients were seen once a month after the beginning of treatment until the end of the follow-up.

Morphological testing analyzed the state of the ocular surface by impression cytology and conjunctival biopsy, while clinical tests were performed to evaluate allergic and inflammatory reactions and the presence of subjective ocular discomforts connected with tear deficiency.

Methods of action

Brimonidine
An alpha-agonist with a significantly higher relative selectivity for the alpha-2 receptors. Alpha-agonists lower IOP by reducing aqueous humor production and increasing aqueous humor outflow.
Latanoprost
A prostaglandin analog. It acts predominantly by increasing uveoscleral outflow, which it does by remodeling the surfaces of the cells of the ciliary muscle, increasing the size of the intercellular spaces through which fluid can presumably flow more easily.

Source: M. Sussini, MD

“Impression cytology measured the percentage of the goblet cell:epithelial cell ratio and the degree of metaplasia of the conjunctival epithelial cells. Results were within normal limits, showing only a 1% decrease of goblet cells in both groups, and very moderate signs of metaplasia,” Dr. Susini said.

Conjunctival biopsy showed no histological differences between the two groups.

“At 24 months there were no variations in epithelial thickness, and only a slight decrease in the number of goblet cells. The number of inflammatory cells and fibroblasts had slightly increased, but there was only a weak tendency toward fibrosis in the subepithelial region. No increase of subepithelial collagen tissue was observed,” he said.

Tear testing

Results of the Schirmer test showed a statistically significant variation of tear secretion between 1 year and 2 years of treatment with latanoprost.

“There was a mean difference of 4 mm between the beginning and the end of the study. The end result, which was 16.6 mm at 24 months, was within normal limits, and didn’t produce any subjective discomfort,” Dr. Susini said.

The tear breakup time test showed good stability of the tear film, with no significant changes from baseline. Rose bengal testing showed no significant variations in the presence of dead epithelial cells in both groups.

Allergic reactions were observed in two patients of the brimonidine group. No hypertrichosis, increased iris pigmentation or uveitis were observed in latanoprost patients.

“The effects of both medications on the conjunctiva are comparable,” Dr. Susini concluded. “The results of objective testing were confirmed by the absence of subjective complaints on behalf of patients, like visual discomforts, dry eye, burning or foreign body sensations.”

The role of the preservative benzalkonium chloride (BAK), which is contained in a different concentration in both agents, is still to be investigated. The higher contents of the substance in latanoprost, which could lead to a potentially higher cytotoxicity, might be compensated by the once-a-day dosing of the drug.

It should be noted that this study used the 2% formulation of Alphagan, which contains BAK. This formulation has been discontinued in the United States and replaced with Alphagan P (brimonidine tartrate 1.5%), which contains no BAK.

For Your Information:

Massimo Susini, MD, can be reached at II Clinica Oculistica, Università degli Studi di Firenze, V.le Morgagni 85, 50134 Florence, Italy; +(39) 055-229-9800; fax: +(39) 055-225-600; e-mail: m.susini@libero.it. Dr. Susini has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

Allergan can be reached at 2525 Dupont Drive, Irvine, CA 92612 U.S.A.; +(1) 714-246-4500; fax: +(1) 714-246-5913; Web site: www.allergan.com.
Pfizer Inc. can be reached at 253 East 42nd Street, New York, NY 10017, U.S.A.; +(1) 212-733-2323; Web site: www.pfizer.com.