Abstract
Purpose :
Corneal epithelial toxicity and effect on healing process have been already attributed to preservatives or some excipients. The goal of this study was to evaluate the corneal toxicity in high-frequency-application of 4 different latanoprost eyedrops formulated with or without preservatives, and containing more or less excipients with known effects as Macrogolglycerol hydroxystearate 40 (MGHS 40).
Methods :
4 different Latanoprost 0.005% formulations were tested: A. preservative free (PF); B. preserved with benzalkonium chloride (BAC) 0.02%; C. PF with MGHS 40 at 2.5% and D. PF with MGHS 40 at 5%. As references, negative control (-) PF Hyaluronic acid 0.18% eyedrops and positive control (+) BAC 0.02% were used. Eyedrops were applied over three days, six times daily on rabbit corneas cultured on an artificial anterior chamber the Ex Vivo Eye Irritation Test (EVEIT) system. Initially, four corneal abrasions (2.1–3.8 mm2) were induced. All defects were monitored by fluorescein stains and photographs. Corneal integrity (fluorescein permeability) and vitality (lactate and glucose quantification) were controlled during experiments.
Results :
Total epithelial healing was observed for test products A, C and (-) at day 3. For test product D, a delayed healing of the initial lesions, not completed on day 3, was noted. As expected, B and (+) show increased and equally pronounced epithelial damage over the observation period. Additionally, the corneal barrier function was significantly affected for B and (+); Also, a higher permeability value of fluorescein was reported for D compared to A, C and (-). Daily quantification of the metabolic activity of each cornea showed an increase in lactate metabolism for B, D and (+). Glucose levels remained in physiological range for all tested items.
Conclusions :
Delayed healing process and metabolic stress symptoms were highlighted for test products B and D containing notably BAC 0.02% and MGHS 40 at 5% respectively. BAC is already well known as toxic for ocular surface, and these results confirm EVEIT as an accurate and reproductible ex vivo model. Besides, MGHS 40, excipient with known effects, seems also to induce a concentration dependent corneal toxicity. Therefore, the use of this preservative and this excipient at high concentration in patients with epithelial defects should be a concern for corneal surface.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.