Treatment strategies for ocular toxicity from chloropicrin

This research is focused examination of ocular injury from chloropicrin (CP), synthesizing recent findings on exposure routes, toxic outcomes, mechanistic hypotheses, and possible therapeutic approaches. The review underscores the disproportionate vulnerability of the eye, particularly the corneal epithelium, to CP, a volatile chemical threat agent increasingly used as a pesticide and fumigant and possessing the potential for intentional or accidental release. CP exposure produces immediate ocular, respiratory and dermal effects, and ocular symptoms can appear as early as 24 hours post-exposure. Reported ocular manifestations include inflammation, corneal edema, gross tissue damage, and potential loss of vision. The authors emphasize that despite the prevalence of ocular effects even at low concentrations, the toxic pathophysiology of CP in ocular tissues and the identity and roles of its reactive breakdown products remain insufficiently characterized, limiting development of effective treatments.

The review situates CP ocular toxicity within the broader context of vesicating chemical warfare agents (CWAs), drawing parallels to better-studied agents such as sulfur mustard, nitrogen mustard, and lewisite. Tewari-Singh et al. argue that mechanistic insights and therapeutic strategies developed for these agents can inform CP research because of overlapping patterns of ocular injury and shared mechanistic hallmarks. They note that CP's breakdown products, such as chlorine, phosgene, nitric oxides and ammonia, are pulmonary toxicants that can also damage ocular tissues, and that the tear film may act as a reservoir on the corneal surface, exacerbating injury. The review calls attention to the limited but growing set of models developed to study CP ocular toxicity, including in vitro, ex vivo, and in vivo systems. These models provide early evidence of CP-related toxic effects and begin to identify potential biomarkers, but the authors highlight the need for targeted mechanistic studies and efficacy testing of candidate countermeasures in relevant in vivo ocular injury models.

The authors review available and proposed medical countermeasures, stressing the current absence of broadly effective, evidence-based treatment strategies for CP-induced ocular injury. They discuss how comparison with ocular studies of NM, SM and lewisite, where more extensive mechanistic and therapeutic research exists, can guide the identification of conserved injury pathways and candidate interventions. The review also surveys technologies, methods, and biomarkers that can support discovery and validation of treatments, and it outlines challenges inherent to ocular injury research from chemical threat agents, such as replicating exposure scenarios, identifying reliable biomarkers of injury and recovery, and translating preclinical efficacy to clinically relevant outcomes.

The authors conclude by proposing future directions: expanding mechanistic investigations in validated ocular models, leveraging knowledge from other vesicant agents to nominate broad-spectrum therapies, applying relevant toxicity biomarkers during efficacy testing, and integrating emerging technologies to accelerate identification of effective medical countermeasures. Their synthesis aims to catalyze targeted research that will ultimately yield validated treatments to prevent and mitigate the severe corneal and ocular injuries caused by chloropicrin exposure.