Corneal damage in rabbit in vivo 8-month post sulfur mustard gas ocular exposure

Abstract

Purpose : People exposed to sulfur mustard gas (SM) show severe corneal toxicity and vision loss many months after initial SM exposure. Presently, no systematic in vivo experimental data showing SM-induced long-term corneal injury exists which limits understanding of mechanisms and development of medical countermeasures. This study investigated corneal damage and clinical manifestations in rabbits in vivo 8-month post SM exposure.

Methods : Eyes of New Zealand White rabbits (n=36) exposed to SM were subjected to clinical microscopic (slit-lamp, confocal, spectralis, & specular) examinations, corneal haze scoring, fluorescein eye test, Schirmer’s tear tests (STT), pachymetry, applanation tonometry, and optical coherence tomography. Rabbits were humanely euthanized 8-month post SM, and corneas were collected for histological, molecular, and cellular analyses.

Results : Clinical eye examinations in live rabbits revealed a significant corneal haze (Fante’s scores 2-4), increased central corneal thickness (480.0 ± 22.7), enhanced tear flow (14.1± 2.3), disturbed stromal organization, reduced endothelial density, and ingrowth of neovessels in clear cornea in SM-exposed corneas compared to naïve corneas post-SM. About 40% rabbit corneas showed ulcers, recurrent epithelial defects, and morbid peri-limbal plexus regions 8-month post-SM. Up to 18% SM-exposed rabbit eyes showed keratocoele, ruptured cornea with plugged iris, keratectectsia, perforated corneal ulcer, central corneal thinning, and frequent epithelial-erosion. H&E supported clinical eye exam findings. Additional histopathological and molecular studies are underway.

Conclusions : A single SM exposure caused acute corneal toxicity in all exposed rabbit eyes and long-term corneal morbidity in about 40% rabbit eyes in vivo. Additional analysis is warranted.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.