Conjunctival Changes Induced by Prostaglandin Analogues and Timolol Maleate: A Histomorphometric Study

Abstract

Purpose: : To compare histological changes induced by antiglaucoma medications in the rabbit conjunctiva.

Methods: : 50 New Zealand female rabbits with similar age and weight were divided in 5 groups of 10 animals. The left eyes were treated with one daily drop of bimatoprost 0,03%, travoprost 0,004%, latanoprost 0,005%, timolol maleate 0,5% and artificial tears containing benzalkonium chloride (BAK) for 30 days. The right eyes served as controls. Limbal superior conjunctival biopsies (5 mm x 5 mm) were performed at the 8^th and 30^th day in 5 rabbits of each group each time. The conjunctiva was immediately fixed with 10% formaldehyde for 24 hours, followed by HE and PAS staining and optical qualitative microscopy evaluation. Morphohistometric quantitative analyses were made using the Image Pro–Plus 4.5 software. The parameters evaluated were: inflammatory infiltrate, epithelial thickness, number of goblet cells and total area and number of blood vessels. One–way ANOVA with a significance level of 5% followed by Tukey–Kramer post hoc tests were used to analyze numerical variables.

Results: : A baseline low level infiltration, consisting of localized clusters of lymphocytes and rare neutrophils, was observed in the subepithelial connective tissue of most of the control eyes and in the BAK group. At the 8^th and 30^th day post treatment, all other groups exhibited a rather diffuse inflammatory infiltrate, composed by lymphocytes and neutrophils, which was more dense in the timolol group than in the prostaglandin–analogues groups. The timolol group also showed an increased subepithelial collagen density and a significant increase in epithelial thickness (P=0.0035) at the 30^th, which was not present in the other groups. A significant increase (P=0.0015) in number of blood vessels was observed in all treated groups minus BAK. The goblet cell density significantly increased (P=0.0006) with travoprost at 8th day and at 30th day with bimatoprost (P=0.0021) and latanoprost (P=0.009) respectively treated groups.

Conclusions: : An initial increase in goblet cell numbers was initially seen with the use of all prostaglandin analogues. This study suggests that these drugs, however, induce less conjunctival changes than timolol in the rabbit conjunctiva.

Keywords: drug toxicity/drug effects • conjunctiva • pathology: experimental