Purpose: Long-term medical treatment of glaucoma has an effect on the conjunctiva possibly affecting the outcome of subsequent filtering surgery. An animal study using rabbits was performed to assess the tissue changes caused by timolol, latanoprost, and a combination of both substances.
Methods: Rabbits were treated with timolol, latanoprost or a combination of these drugs for eighteen months. Conjunctival specimens were examined by light microscopy, quantitative transmission electron microscopy and immunohistochemistry with antibodies against matrix metalloproteinase-3 and tissue inhibitors of metalloproteinase-2.
Results: By electron microscopy, the area of subepithelial collagen present was significantly greater (p<0.03; Mann-Whitney test) in timolol-treated eyes (71.6%) compared with the controls (52.7%) and latanoprost-treated eyes (57.7%). An increase of amorphous material was present in timolol-treated eyes (25.6% vs. 7.6% in the controls) as well as a smaller area of empty spaces (2.5% vs. 39.4% in controls). Latanoprost-treated eyes had no significant increase of empty spaces, but showed a marked staining for MMP-3 in the conjunctiva. This staining was not present in controls or in timolol-treated eyes. Morphologically, degenerative changes of fibrocytes were seen in timolol-treated eyes only.
Conclusions: A significant increase of subepithelial collagen density was present in timolol-treated eyes, while this finding was not apparent in latanoprost-treated eyes. Latanoprost-treated eyes showed an up-regulation of MMP-3, which may be the reason for reduced extracellular matrix accumulation in such eyes. The morphologic feature of increased subepithelial collagen density and extracellular matrix changes may relate to failure of filtering blebs.