In vivo confocal microscopy of conjunctiva in preservative‐free timolol 0.1% gel formulation therapy for glaucoma

Abstract

ABSTRACT.Purpose: To evaluate the effects at 1 year of preservative-free timolol gel and preserved timolol eye drops on conjunctiva and tear parameters. Methods: Forty patients with primary open-angle glaucoma or ocular hypertension were randomized to the two treatment groups and compared with 20 healthy age-matched controls. Clinical tests (IOP, Schirmer I test, and lacrimal film break-up time BUT) and in vivo conjunctival confocal microscopy (IVCM) were performed in all patients at baseline and after 12 months. IVCM (HRT II Rostock Cornea Module; Heidelberg Engineering GmbH, Heidelberg, Germany) was performed after topical anaesthesia in the four cardinal locations and at the corresponding limbus to analyse conjunctiva cells. The main IVCM outcomes were goblet cell density and epithelial regularity. Results: IVCM and clinical parameters were similar in the three groups at baseline. After 12 months, intra-epithelial goblet cell density was significantly lower in the preserved (48.25 AE 7.70) than in the preservative-free beta-blocker group (86.83 AE 22.17, p < 0.001) and controls (88.9 AE 18.33, p < 0.001). The epithelial layer was significantly more regular in the preserved beta-blocker medication group than in the preservative-free beta-blocker group (p < 0.001) and the control group (p < 0.001). A significant reduction in both Schirmer I and BUT was found in the group of preserved timolol (respectively, 11.3 AE 2.97 and 8.12 AE 0.99) compared with preservative-free timolol (16.8 AE 1.83 and 11.27 AE 1.27, p < 0.001) and controls (17.8 AE 1.87 and 12.10 AE 1.28, p < 0.001). Conclusions: Based on our IVCM data, preservative-free beta-blocker gel induces less changes at ocular surface than preserved beta-blockers, a fact that should be considered to obtain less adverse effects and maximal adherence to treatment in a chronic condition such as glaucoma.

Conjunctival matrix metalloproteinases and their inhibitors in glaucoma patients

“…This toxicity may be the reason for increased expressions of MMPs and TIMPs in the epithelium of glaucoma patients. Further, switching antiglaucoma medication to eye drops that contain a different preservative (Aihara et al 2013) or to preservative-free solutions (Mastropasqua et al 2013;Frezzotti et al 2014) might be beneficial for the maintenance of tissue integrity and health in the superficial parts of the eye. Thus, in addition to long-term treatment with multiple different eye drops, the preservative BAK itself may contribute to our results.…”

In vivo confocal microscopy: qualitative investigation of the conjunctival and corneal surface in open angle glaucomatous patients undergoing the XEN-Gel implant, trabeculectomy or medical therapy

“…Other common modifications involve nerve plexus alterations and collagen deposition inducing fibrosis [11]. All these chronic inflammatory alterations may negatively influence the surgical outcome thus increasing the possibility of surgical failure by altering the aqueous humor (AH) flow through the bleb wall [12].…”

The Utility of an Artificial Substitute to Improve Corneal Sensitivity in Glaucomatous Patients on Chronic Therapy with Prostaglandin Analogs

“…11 Different authors have shown that the lack of BAK in the drops can improve the ocular surface of glaucomatous patients. 15,24,25 Our results suggest that a single-dose tear supplement may reduce the damaging effects of the preservative BAK on conjunctival cells, on the tear film, and on sensory nerve fibers with alteration of the threshold of excitability, which follows a reduced sensitivity. Since corneal sensitivity and the number of nerve fibers in the cornea and BUT improved, a tear film supplement might be associated to a better corneal function.…”