Ex vivo evaluation of corneal permeation and irritation potential associated with proparacaine hydrochloride misuse.

INTRODUCTION

Proparacaine hydrochloride is a topical ocular anesthetic widely used in diagnostic procedures. Although generally safe when properly administered, repeated or unsupervised use has been associated with clinically relevant corneal injury. In contexts where access to topical anesthetics is insufficiently controlled, misuse may result in cumulative epithelial damage and vision-threatening complications. Despite clinical reports and experimental evidence of corneal toxicity, quantitative data linking exposure conditions to structural corneal damage under controlled ex vivo settings remain limited, particularly regarding dose-injury relationships at the tissue level.

METHODS

Porcine corneas were mounted in Franz diffusion cells to quantify permeation by UV-Vis spectrophotometry and evaluate corneal histopathological changes. Both pure proparacaine and the commercial 0.5% proparacaine hydrochloride ophthalmic solution (Alcaine®, Alcon) were assessed under therapeutic (2.25 mg/mL), abuse (4.5 mg/mL), and infinite-dose (53.152 mg/mL) conditions. Negative (phosphate-buffered saline) and positive (99.5% ethanol) controls were included for histopathological assessment. ANOVA was applied to permeation data, and histopathological scores were analyzed using non-parametric tests.

RESULTS

Proparacaine showed low permeability (9.33 × 10-7 cm/s), with only a small fraction of the applied dose permeating across the cornea during the experimental period. Permeation increased in a concentration- and time-dependent manner. High-dose and infinite-dose exposure conditions resulted in marked epithelial damage, including spongiosis, chromatin condensation, and desquamation, with severity comparable to that induced by ethanol used as a positive control. Differences between formulations were primarily driven by concentration rather than formulation composition, and a correlation was observed between cumulative permeation and the extent of epithelial injury.

CONCLUSION

Proparacaine demonstrates dose-dependent permeation and histopathological changes, emphasizing the risks associated with misuse. The ex vivo model provides relevant and ethically aligned evidence to support ocular hazard assessment through the characterizing of histopathological changes.