Effects of Glaucoma Medications on Corneal Endothelium, Keratocytes, and Subbasal Nerves Among Participants in the Ocular Hypertension Treatment Study

Abstract

Purpose: To compare subbasal corneal nerve and keratocyte density and endothelial characteristics of ocular hypertensive patients treated with medications or observation. Methods: Participants in the Ocular Hypertensive Treatment Study(OHTS) randomized at Mayo Clinic to medication or observation were evaluated with specular microscopy annually for 6 years. Confocal microscopy was performed 78 to 108 months after enrollment. Subbasal nerve density was calculated by manual tracing and digital image analysis. Keratocyte density was determined by manual counting methods. Data were compared using a t test and a rank sum test.Results: After 6 years, corneal endothelial cell density, percent hexagonal cells, and coefficient of variation of cell area for the observation (n = 21) and medication groups (n = 26) were similar (2415 6 300 vs. 2331 6 239 cells/mm 2 ; 63% 6 11% vs. 65% 6 10%; and 0.32 6 0.07 vs. 0.30 6 0.06, respectively). Of 38 participants undergoing confocal examination, the medication group (n = 19) had fewer nerves (3.8 6 2.1 vs. 5.9 6 2.0 nerves/frame; P = 0.02) and a lower nerve density (5643 6 2861 vs. 9314 6 3743 mm/mm 2 ; P = 0.007) than the observation patients (n = 10). An additional 9 patients in the observation group, who began medication before confocal scanning, had intermediate nerve densities. Fullthickness keratocyte density was similar, with 22,257 6 2419 and 23,430 6 3285 cell/mm 3 in the observation and medication groups, respectively.Conclusions: Chronic administration of glaucoma medications causes a decrease in the number and density of corneal subbasal nerve fiber bundles but does not affect keratocyte density or corneal endothelial characteristics.

Corneal sensitivity and morphology of the corneal subbasal nerve plexus in primary congenital glaucoma

“…It has been reported that chronic topical treatment with timolol and latanoprost may induce toxic effects on ocular surface, leading to reduction of the corneal subbasal nerve density, thereby affecting corneal sensitivity. 33 Moreover, Baratz et al 34 have documented that chronic administration of glaucoma medication in patients with ocular hypertension causes a decrease in the corneal subbasal nerve density without affecting keratocyte density or corneal endothelial characteristics. However, it has been suggested that ocular surface changes induced by timolol and latanoprost are mainly attributed to the preservatives, 33 whereas Baratz et al 34 evaluated a small sample size (n ¼ 27) with 10 different glaucoma medications, which did not allow any subgroup analysis, thereby preventing the authors from implicating specific medications or preservatives, as also indicated by the authors themselves.…”

“…However, it has been suggested that ocular surface changes induced by timolol and latanoprost are mainly attributed to the preservatives, 33 whereas Baratz et al 34 evaluated a small sample size (n ¼ 27) with 10 different glaucoma medications, which did not allow any subgroup analysis, thereby preventing the authors from implicating specific medications or preservatives, as also indicated by the authors themselves. 34 Nevertheless, although there is no definitive proof that carboanhydrase inhibitors or brimonidine eye drops affect the corneal subbasal nerve density, one could not exclude such an effect.…”

Topical cyclosporine to control ocular surface disease in patients with chronic glaucoma after long-term usage of topical ocular hypotensive medications

“…The described confocal microscopy changes include significant decrease in density of superficial epithelial cells, higher density of basal epithelial cells, activated stromal keratocytes, higher beading of the nerves, lower number of sub-basal nerves and higher SBNFL tortuosity in those with ocular hypotensive medications with preservatives. 14,26 Cyclosporine 0.05% is a topical immunomodulatory compound with anti-inflammatory properties that have been demonstrated to have a benefit in the treatment of dry eye. Topical hypotensive therapy with fixed combinations (prostaglandin analog and beta blocker eye drops) has been observed to increase the expression of the inflammatory markers HLA-DR and interleukin-6 with resultant deterioration in the ocular surface after three months of therapy.…”

“…5 The role of in vivo confocal microscopy in ocular surface analysis of dry eye and glaucomatous patients has been elucidated. 5,[7][8][9][10][11][12][13][14] Topical cyclosporine has been proven to have a beneficial effect in cases of dry eye disease (DED). 15 In a recent study in rabbit eyes beneficial effects of topical cyclosporine has been demonstrated on adverse ocular surface changes produced by long-term antiglaucoma medications.…”

Comparative Evaluation of Antihypertensive Drug’s Efficacy in Patients With Primary Glaucoma at Early and Advanced Stages

“…Надо отметить что, несмотря на отсутствие консерванта в препарате Тафлу-прост, при его применении наблюдалась гиперемия конъ-юнктивы [14,15,16,17,18]. Можно предположить, что ги-перемия связана с активным действием простагландинов, как медиаторов воспаления и аллергических реакций, независимо от наличия или отсутствия консервантов в составе препарата [19,20,21,22,23,24].…”