Graefe'sArch Clin Exp Ophthalmol (1995) 233:154-162 © Springer-Verlag1995 Raffaele Nuzzi Alessandro Vercelli Claudia Finazzo Cecilia Cracco Conjunctiva and subconjunctival tissue in primary open-angle glaucoma after long-term topical treatment: an immunohistochemical and ultrastructural study Received: 22 December 1993 Revised version received: 20 September 1994 Accepted: 21 September 1994 Presented in an abbreviated form at ECORA/EUPO First Annual Meeting, 4-6 October 1993, Bonn R. Nuzzi ([~) • C. Finazzo Institute of Clinical Ophthalmology, University of Turin, via Juvarra 19, 1-10122 Turin, Italy A. Vercelli • C. Cracco Department of Human Anatomy and Physiology, University of Turin, corso M. D'Azeglio 52, 1-10126 Turin, Italy Abstract • Background: Primary open-angle glaucoma is commonly treated with long-term hypotensive medical therapy. When this ap- proach becomes inadequate, thera- py proceeds with surgery. The present study investigates morpho- logical changes in the conjunctival and subconjunctival tissues in- duced by short- and long-term top- ical medical therapy of primary open-angle glaucoma. • Methods: Comparisons were made between biopsy specimens from glaucoma- tous patients, who received specific eyedrop therapy (timolol and pilo- carpine) for various periods of time, and control patients with no conjunctival pathology or topical treatment. Histological, immuno- histochemical and ultrastructural parameters were investigated. • Results: The morphometric anal- ysis of histological sections and im- munohistochemistry (anti-fi- bronectin antibody) in medium- and long-term therapy patients showed: (a) significant increases in the thickness and number of ep- ithelial cell layers; (b) significant in- creases in the fibroblast density in both subepithelial and deep con- nective tissue; and (c) a more com- pact connective tissue, richer in collagen fibers arranged in whirls, with some inflammatory elements. These findings were confirmed by the ultrastructural analysis. In the same patients, the other immuno- histochemical parameters investi- gated (anti-HLA-DR, anti-CDla, anti-CD4, anti-CD8, anti-IL2 and C3b antibodies) revealed a tenden- cy to chronic inflammation. Fol- lowing specific surgery, this tenden- cy manifested itself in a diffuse im- mune response, especially in those patients who underwent medium- and long-term medical therapy. • Conclusion: According to these results, antiglaucomatous surgery should be rehabilitated and consid- ered as an alternative to long-term medical therapy in the first-in- stance treatment of primary open- angle glaucoma. Introduction In primary open-angle glaucoma (POAG), the current initial therapy - following early diagnosis - is directed at lowering intraocular pressure [18, 25, 31] in order to arrest deterioration of glaucomatous optic neuropathy and preserve the visual field [2, 21, 25, 31]. The prevail- ing means to this end is long-term hypotensive medical treatment [2, 6, 12, 17, 18, 21, 22, 30, 31] with topically administered drugs such as timolol or pilocarpine [3, 5, 13]. When this approach becomes inadequate, therapy proceeds with argon laser trabeculoplasty [4] or surgery [6, 7]. Glaucoma filtration surgery includes trabeculec- tomy, which produces an additional pathway for aqueous humor to leave the eye, through a sclerostomy under the conjunctiva [7, 14, 19, 26]. Unfortunately, such surgical intervention is not uniformly successful [17, 21, 22, 24, 26, 27, 29, 32, 42], probably due to scar-