Impact of the use of anti-glaucoma medications on the risk of herpetic keratitis recurrence.

PURPOSE: Numerous case reports have associated anti-glaucoma medications with recurrence of herpes simplex virus (HSV) and herpes zoster virus (HZV) keratitis. The aim of our study was to determine whether different anti-glaucoma agents are associated with recurrence of herpetic keratitis. METHODS: This was a retrospective cohort study using health databases from a Canadian province from January 2001 to December 2012. A new cohort of users on topical prostaglandins (PGs), beta blockers (BBs), alpha-2 agonists (AAs) and carbonic anhydrase inhibitors (CAIs) was created. The date of the third anti-glaucoma drug dispensation within 90 days was deemed the index date of the case. Herpetic keratitis events, as defined by an ICD-9/10 code for HSV or HZV keratitis, or the dispensation of an anti-viral medication by either an ophthalmologist or an optometrist, were examined prior to and following the index date. Risk ratios (RRs) were computed to compare the risk of HSV/HZV keratitis among the PG, BB, AA, and CAI groups individually and collectively while adjusting for age and sex. RESULTS: Among 19,986 users of glaucoma medications identified, there were 684 cases of HSV/HZV keratitis. There was no increased risk of HSV/HZV keratitis recurrence for any of the four glaucoma medications classes individually or collectively when adjusted for age and sex. There was also no increased risk for redeveloping either HSV keratitis only or HZV keratitis only amongst all anti-glaucoma users. CONCLUSION: There is no association between the use of topical ocular hypotensive therapies and HSV/HZV keratitis recurrence. Further studies are needed to confirm these findings.

Effect of Bevacizumab on the Viability and Metabolism of Human Corneal Epithelial and Endothelial Cells: An In Vitro Study.

Purpose: To examine the cytotoxic effects of bevacizumab on the viability and metabolism of human corneal epithelial cells (HCEpCs) and human corneal endothelial cells (HCEnCs), as well as human retinal pigment epithelial (ARPE-19) cells for comparison. Methods: Immortalized cell lines of HCEpCs, HCEnCs, and ARPE-19 cells were exposed to clinically relevant concentrations of bevacizumab (0.313-5.00 mg/mL). The ApoTox-Glo Triplex Assay was used to assess cell viability, cytotoxicity, and apoptosis, and the Mitochondrial ToxGlo Assay was used to assess cell membrane integrity and adenosine triphosphate (ATP) levels after a 24-hour treatment period. Results: Across all three cell types, we observed similar results of a decrease in cell viability at 5.00 mg/mL (P < 0.05) and an increase in cytotoxicity at 5.00 mg/mL (P < 0.05), whereas apoptotic activity remained unchanged (P > 0.05), which is a profile consistent with cells undergoing primary necrosis at high concentrations. Additionally, cell membrane integrity was compromised at 5.00 mg/mL (P < 0.05), whereas no decrease in ATP levels were observed (P > 0.05). Thus, no interference with mitochondrial oxidative phosphorylation in ATP production was seen, and the cells were able to maintain normal metabolic levels at high concentrations of bevacizumab. Conclusions: HCEpCs, HCEnCs, and ARPE-19 cells experience a decrease in viability and undergo primary necrosis when exposed to bevacizumab at a concentration of 5.00 mg/mL; however, they are able to maintain normal metabolism and mitochondrial function at the high concentrations used for the treatment of corneal neovascularization. Translational Relevance: This study provides safety data on the concentrations of bevacizumab injected intravitreally and complements clinical data showing toxicity of topical bevacizumab on corneal epithelial and endothelial cells.