Abstract
Ocular injury by lewisite (LEW), a potential chemical warfare and terrorist agent, results in edema of eyelids, inflammation, massive corneal necrosis and blindness. To enable screening of effective therapeutics to treat ocular injury from LEW, useful clinically-relevant endpoints are essential. Hence, we designed an efficient exposure system capable of exposing up to six New-Zealand white rabbits at one time, and assessed LEW vapor-induced progression of clinical ocular lesions mainly in the cornea. The right eye of each rabbit was exposed to LEW (0.2 mg/L) vapor for 2.5, 5.0, 7.5 and 10.0 min and clinical progression of injury was observed for 28 days post-exposure (dose–response study), or exposed to same LEW dose for 2.5 and 7.5 min and clinical progression of injury was observed for up to 56 days post-exposure (time–response study); left eye served as an unexposed control. Increasing LEW exposure caused corneal opacity within 6 h post-exposure, which increased up to 3 days, slightly reduced thereafter till 3 weeks, and again increased thereafter. LEW-induced corneal ulceration peaked at 1 day post-exposure and its increase thereafter was observed in phases. LEW exposure induced neovascularization starting at 7 days which peaked at 22–35 days post-exposure, and remained persistent thereafter. In addition, LEW exposure caused corneal thickness, iris redness, and redness and swelling of the conjunctiva. Together, these findings provide clinical sequelae of ocular injury following LEW exposure and for the first time establish clinically-relevant quantitative endpoints, to enable the further identification of histopathological and molecular events involved in LEW-induced ocular injury.
Highlights
Lewisite [dichloro(2-chlorovinyl)arsine; L; LEW], a potential chemical warfare and terrorist agent, is a potent arsenical vesicant that induces rapid inception of severe pain and blistering upon exposure, and immediately causes skin, eye and respiratory tract damages [1,2,3,4]
Literature reports on animal testing for ocular injuries are limited to the 1940's [15,16,17,18], whereby, LEW injuries were characterized by an immediate appearance of edema and blepharospasm, which can be serious with massive necrosis and eventual blindness [15, 18]
Since sequelae of injury following LEW exposure is not well defined, the current study was designed to evaluate the clinical manifestation 6 h to 56 days (8 weeks) post LEW-exposure. Due to their size and similarity to human eye, New Zealand White rabbit eyes were exposed to LEW in a pre-pilot study to first determine its target dose employing the information from a historical literature reference which indicated that conjunctivitis and eyelid swelling would occur within 5.0 min of exposure [17]
Summary
Lewisite [dichloro(2-chlorovinyl)arsine; L; LEW], a potential chemical warfare and terrorist agent, is a potent arsenical vesicant that induces rapid inception of severe pain and blistering upon exposure, and immediately causes skin, eye and respiratory tract damages [1,2,3,4]. LEW was developed as an arsenical vesicant during World War I but was not used; stockpiles are known to exist posing a potential threat of its accidental exposure or use as a warfare/terrorist agent [5, 6]. The main reactive and toxic breakdown product of LEW is arsine oxide; LEW liberates hydrochloric acid, which lowers the pH of the eye and causes superficial opacity [16] These early reports on LEW-induced clinical and pathologic characteristics of corneal tissue give some information and description of injury; ocular injuries from this vesicant are not well defined. Quantitative assessments to establish useful biomarkers for both mechanistic and efficacy studies are not available
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
