Introduction Corneal epithelial toxicity and delayed healing process have already been attributed to preservatives or some excipients. We study the effects of galenic components in antiglaucoma drugs such as benzalkonium chloride (BAC) or surfactants like macrogolglycerol hydroxystearate 40 (MGHS 40) on corneal toxicity in an ex vivo system mimicking chronic use. Methods Latanoprost-containing eyedrops are available with and without preservatives on the market. Unpreserved, they are available in different formulations with various excipients like MGHS at different concentrations (0%, 2.5%, and 5%). We studied these in the ex vivo bioreactor (EVEIT) on initially injured rabbit corneas. The drugs were applied six times daily for observation periods of 3 or 5 days. BAC, 5% MGHS 40 solution, and 0.18% hyaluronic acid served as controls. Macroscopic photographic, biochemical methods and corneal integrity quantification were used for evaluation. Toxicity was assessed by measuring wound healing and corneal fluorescein sodium permeability and was confirmed by histology studies. Results The BAC-preserved formulation resulted in high corneal toxicity, which was expected. Interestingly, the preservative-free (PF) formulation containing 5% MGHS 40, carbomer, macrogol 4000, and sorbitol showed the highest corneal toxicity, followed by the control formulation with equal MGHS 40 concentration, which presented significantly less damage. No toxicity was shown by eyedrops containing 2.5% MGHS 40 or salts only. Conclusion Our study demonstrates a significant corneal toxicity of certain formulations of PF antiglaucoma ophthalmic drugs containing 5% MGHS 40 with other excipients compared to other formulations with lower MGHS 40 concentrations (2.5% or 0%), or even compared to the solution containing 5% MGHS alone. This suggests a concentration-dependent toxicity of MGHS 40, especially in interaction with other excipients, which may increase its epithelial toxicity, and that has to be considered in clinical glaucoma therapy. Further single-component formulation trials are needed to support this interpretation. Supplementary Information The online version contains supplementary material available at 10.1007/s40123-023-00769-y.
PurposeThe corneal bioreactor (BR) in our laboratory, with an intraocular pressure (IOP) of 21 mmHg and the renewal of the culture medium, allows to maintain the homeostasis of the 3 layers of the cornea. We showed that an IOP reduced to 10 mmHg allowed to simulate a corneal edema (760 ± 57 µm) with a healthy epithelium.AimTo compare 2 hyperosmolar eye drops in the evolution of corneal deturgescence and epithelial ulcer healing: ODM5 composed mainly of NaCl 5% and hyaluronic acid (Horus Pharma, Saint‐Laurent‐du‐Var, France) and Muro 128 composed mainly of NaCl 5% and various excipients (Bausch+Lomb, Bridgewater, NJ)MethodsBeforehand, 3 pairs of human corneas were preserved for 2 weeks in the BR filled with CorneaMax (Eurobio, France), with a pressure maintained at 10 mmHg. A central epithelial ulcer of 6.64 ± 0.04 mm in diameter was made (D0). Each cornea received a drop of Muro 128 or ODM5 four times a day. Corneal central volume measurement (Casia 1, Tomey) was performed daily at the beginning and end of the day. Ulcer healing was monitored daily by fluorescein labelling and quantified by image analysis (Fiji) taken with a macroscope. At D14, the corneas were removed and fixed for immunostaining of E‐Cad (cell architecture), Zo‐1 (tight junctions), MUC16 (mucins), K3K12 (cell maturity) and for histology (Saffron Eosin Hemathein).ResultsMean daily volume loss was comparable: 2.43 ± 1.55 mm3 with ODM5 vs. 2.18 ± 1.71 mm3 with Muro 128 (p = 0.698 3). Corneal ulcers in all 3 pairs healed at D4, D5, D5 with ODM5 vs. D5, D13, and 1 cornea never healed with Muro 128. In IHC and histology, the epithelium was of better quality with ODM5.ConclusionsThe efficacy of the 2 eye drops is comparable. Epithelial preservation is partly better with ODM5, possibly related to the presence of hyaluronic acid.
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