In Vivo Microscopic Assessment of Ocular Surface Changes Induced by Antiglaucoma Medications

To investigate the impact of topical antiglaucoma treatment on the development of ocular surface disease (OSD) in glaucomatous eyes using in vivo confocal microscopy (IVCM).

Retrospective clinical cohort study. Data were collected from October 2021 to January 2024.

39 eyes receiving monotherapy of either a prostaglandin analog (28) or beta-blocker (11), 28 eyes receiving polytherapy of three or more unique pharmacologic classes, and 11 healthy eyes without glaucoma or OSD. Exclusion criteria included a prior history of corneal disease, corneal surgery or laser procedure, use of topical anti-inflammatory medication, or intraocular surgery or medication changes within the last six months.

Central corneal images were obtained using IVCM. Image grading was performed by two independent, masked observers. Ocular surface disease index (OSDI) surveys were collected from each patient.

Dendritic cell density (DCD), epithelial wing cell (WCD) and basal cell density (BCD), nerve fiber density (ND), nerve tortuosity and reflectivity, and OSDI scores were compared among the treatment and control groups. Linear regression tests were performed to analyze the effect of type and quantity of pharmacologic classes prescribed, duration of antiglaucoma medication use, and glaucoma severity on the corneal parameters.

Patients on chronic antiglaucoma medications had significantly higher mean OSDI scores as compared to control, indicating worsening OSD. Treated eyes demonstrated significantly increased mean DCD and significantly decreased mean WCD and BCD as compared to control. Beta-blockers induce significantly greater cytotoxic effect on the corneal epithelium and nerve plexus as compared to prostaglandin analogs. Alpha-agonists were significantly associated with higher ND compared to other pharmacologic classes. Rho-associated protein kinase inhibitors demonstrate a significant, positive relationship with OSDI scores. The number of pharmacologic classes prescribed significantly predicts increases in DCD.

Chronic use of topical antiglaucoma medications greatly contributes to the severity of OSD amongst glaucoma patients in a dose-dependent manner. Patients treated with antiglaucoma medications not only have severe OSD symptoms but also microstructural anatomic changes to the central cornea, characterized by inflammation and corneal nerve attenuation. Clinicians should recognize the unintended effects of antiglaucoma medications on the ocular surface.