Altered expression of aquaporin 1 and aquaporin 5 in the cornea after primary blast exposure.

Purpose: Our study aimed to determine whether the altered expression of biomarkers linked to corneal injuries, such as the edema-regulating proteins aquaporin-1 and aquaporin-5 (AQP1 and AQP5), occurred following primary blast exposure. Methods: Adult male Dutch Belted rabbits were anesthetized and exposed to blast waves with peak overpressures of 142.5-164.1 kPa (20.4-23.4 psi). These exposure groups experienced peak blast overpressure-specific impulses (impulse per unit surface area) of 199.6-228.5 kPa-ms. Unexposed rabbits were included as controls. The animals were euthanized at 48 h post-exposure. Corneas obtained from the euthanized blast-exposed and control rabbits were processed for quantitative PCR and western blot to quantify mRNA and the protein expression of AQP1 and AQP5. Immunohistochemical analysis was conducted to determine the cellular localization of AQP1 and AQP5. Results: Corneal thickness increased up to 18% with the peak blast overpressure-specific impulses of 199.6-228.5 kPa-ms at 48 h after blast exposure. mRNA levels of AQP1 and AQP5 increased in the whole cornea lysates of blast-exposed rabbits relative to those of the controls. Western blot analyses of whole cornea lysates revealed that the expression levels of AQP1 and AQP5 were approximately 2- and 1.5-fold higher, respectively, in blast-exposed rabbits compared to controls. The extent of AQP1 immunostaining (AQP1-IS) increased in the epithelial cell layer after blast exposure. The AQP5-IS pattern changed from a mixed membrane and cytoplasmic expression in the controls to predominantly cytoplasmic expression in the basally located cornea epithelial cells of blast-exposed rabbits. Conclusions: Primary blast exposure resulted in edema-related changes in the cornea manifested by the altered expression of the edema-regulating proteins AQP1 and AQP5 with blast overpressure-specific impulses. These findings support potential acute corneal injury mechanisms in which the altered regulation of water permeability is caused by primary blast exposure.

Low-Level Primary Blast Causes Acute Ocular Trauma in Rabbits.

The objective of this study was to determine whether clinically significant ocular trauma can be induced by a survivable isolated primary blast using a live animal model. Both eyes of 18 Dutch Belted rabbits were exposed to various survivable low-level blast overpressures in a large-scale shock tube simulating a primary blast similar to an improvised explosive device. Eyes of the blast-exposed rabbits (as well as five control rabbits) were thoroughly examined before and after blast to detect changes. Clinically significant changes in corneal thickness arose immediately after blast and were sustained through 48 h, suggesting possible disruption of endothelial function. Retinal thickness (RT) increased with increasing specific impulse immediately after exposure. Intraocular pressure (IOP) was inversely correlated with the specific impulse of the blast wave. These findings clearly indicate that survivable primary blast causes ocular injuries with likely visual functional sequelae of clinical and military relevance.

Simulations of Porcine Eye Exposure to Primary Blast Insult.

PURPOSE: A computational model of the porcine eye was developed to simulate primary blast exposure. This model facilitates understanding of blast-induced injury mechanisms. METHODS: A computational model of the porcine eye was used to simulate the effects of primary blast loading for comparison with experimental findings from shock tube experiments. The eye model was exposed to overpressure-time histories measured during physical experiments. Deformations and mechanical stresses within various ocular tissues were then examined for correlation with pathological findings in the experiments. RESULTS: Stresses and strains experienced in the eye during a primary blast event increase as the severity of the blast exposure increases. Peak stresses in the model occurred in locations in which damage was most often observed in the physical experiments. CONCLUSIONS: Blast injuries to the anterior chamber may be due to inertial displacement of the lens and ciliary body while posterior damage may arise due to contrecoup interactions of the vitreous and retina. Correlation of modeling predictions with physical experiments lends confidence that the model accurately represents the conditions found in the physical experiments. TRANSLATIONAL RELEVANCE: This computational model offers insights into the mechanisms of ocular injuries arising due to primary blast and may be used to simulate the effects of new protective eyewear designs.

Anatomical manifestations of primary blast ocular trauma observed in a postmortem porcine model.

PURPOSE: We qualitatively describe the anatomic features of primary blast ocular injury observed using a postmortem porcine eye model. Porcine eyes were exposed to various levels of blast energy to determine the optimal conditions for future testing. METHODS: We studied 53 enucleated porcine eyes: 13 controls and 40 exposed to a range of primary blast energy levels. Eyes were preassessed with B-scan and ultrasound biomicroscopy (UBM) ultrasonography, photographed, mounted in gelatin within acrylic orbits, and monitored with high-speed videography during blast-tube impulse exposure. Postimpact photography, ultrasonography, and histopathology were performed, and ocular damage was assessed. RESULTS: Evidence for primary blast injury was obtained. While some of the same damage was observed in the control eyes, the incidence and severity of this damage in exposed eyes increased with impulse and peak pressure, suggesting that primary blast exacerbated these injuries. Common findings included angle recession, internal scleral delamination, cyclodialysis, peripheral chorioretinal detachments, and radial peripapillary retinal detachments. No full-thickness openings of the eyewall were observed in any of the eyes tested. Scleral damage demonstrated the strongest associative tendency for increasing likelihood of injury with increased overpressure. CONCLUSIONS: These data provide evidence that primary blast alone (in the absence of particle impact) can produce clinically relevant ocular damage in a postmortem model. The blast parameters derived from this study are being used currently in an in vivo model. We also propose a new Cumulative Injury Score indicating the clinical relevance of observed injuries.

Paintball trauma and mechanisms of optic nerve injury: rotational avulsion and rebound evulsion.

PURPOSE: Ballistic impact studies and supercomputer modeling were performed to elicit the mechanisms of optic nerve rupture that may accompany blunt ocular trauma. METHODS: Paintball ocular impact responses were studied with abattoir-fresh porcine eyes. Physics-based numerical code CTH was used to produce robust geometric and constitutive models of the eye and orbit, providing a comparative 3-D finite volume model to help determine the mechanisms underlying empirical ballistic observations. RESULTS: Among 59 porcine eye specimens submitted to paintball impact in the 1- to 13-J range, 10 (17%) disengaged completely from the orbital mount. In each instance the paintball penetrated the orbit adjacent to the globe, producing rotation and eventual globe repulsion, dramatically evident on high-speed film images. Supercomputer modeling yielded similar globe-expulsive results when orbital constraints were in place, but not when these were removed. In these models, tangential (grazing) impact sheared the nerve flush with the globe via a strain rate effect within 260 µs, with minimal posterior displacement and just 5° of globe rotation. Midperipheral impact produced compressive globe distortion and posterior displacement, followed by rebound and tractional nerve avulsion 10 mm behind the lamina after 700 µs and 20° of globe rotation. CONCLUSIONS: Constitutive modeling studies suggest at least two trajectory-dependent mechanisms for optic nerve rupture with paintball impact on the eye. Tangential glancing blows produce strain-rate rotational avulsion, abscising the optic nerve with minimal internal globe disruption, whereas off-center direct impact produces slower rotational-rebound evulsion, traumatizing the globe and breaching the nerve posteriorly. The latter mechanism would be expected to arise more commonly and would most likely be clinically masked by accompanying intraocular injury.

Numerical modeling of paintball impact ocular trauma: identification of progressive injury mechanisms.

PURPOSE: To create a computer-based numerical simulation model for comparison with empiric paintball-ocular ballistic study findings, allowing identification of the dynamic physical mechanisms (stress, strain, pressure) responsible for intraocular traumatic injury accompanying blunt ocular impact. Virtual experiments with numerical models could exploit mathematical "instrumentation" to facilitate internal observation impossible with physical experiments alone. METHODS: Models of human eye structures and orbit were implemented into the finite-volume Eulerian numerical hydrocode CTH. Numerical simulation results were compared with dynamic imaging and postimpact histopathology obtained during previous ballistic impact experiments on fresh porcine eyes impacted with paintballs. Forty numerical simulations and 59 impact experiments were conducted as part of the study. RESULTS: Time-lapse correlations showed the CTH models to be dynamically commensurate with orbital penetration and globe deformation measured from ballistic high-speed videos. CTH also predicted the types and levels of damage observed in detailed postimpact pathologic assessments of porcine specimens. High strain in the ciliary body and zonule corresponded with angle recession and lens displacement pathologically. Globe rupture was attained at the highest paintball impact velocities in both the porcine ballistic studies and CTH models, consistent with predicted dynamic intraocular pressures. The simulations also revealed that phenomena such as macular Berlin's edema, midperipheral retinoschisis, and choroidal and retinal detachment might be explained by focal dynamic pressure-wave reflection from the interior surface of the globe. CONCLUSIONS: Significant insight was gained regarding the physical mechanisms responsible for injury. CTH predictions corresponded closely with previous ballistic experimental results, adding intraocular detail otherwise unattainable.

Blunt eye trauma: empirical histopathologic paintball impact thresholds in fresh mounted porcine eyes.

PURPOSE: Ballistic studies were conducted using gelatin-embedded abattoir-fresh porcine eyes suspended within clear acrylic orbits to discern the energy required to produce specific ocular injuries. Paintball impact provides a robust ballistic model for isolating and quantifying the role of direct blunt force in ocular trauma. METHODS: Fifty-nine porcine orbital preparations received direct blows from 0.68 caliber (16-18 mm diameter/3.8 g) paintballs fired at impact velocities ranging from 26 to 97 meters per second (2-13.5 J). Five additional eyes not subjected to ballistic impact were also evaluated as controls. Impact energies were correlated with histopathologic damage. RESULTS: Minimum impact energies consistently producing damage in experimental eyes unobserved in control specimens were: 2 joules--posterior lens dislocation, zonulysis, capsular rupture, and choroidal detachment; 3.5 joules--moderate angle recession; 4 joules--anterior lens dislocation; 4.8 joules--peripapillary retinal detachment; 7 joules--severe angle recession, iridodialysis, and cyclodialysis; 7.5 joules--corneal stromal distraction; 9.3 joules--choroidal segmentation; and 10 joules--globe rupture. CONCLUSIONS: Impact thresholds correlating traumatic ocular pathology with impact energy followed a positive stepwise progression in severity with impact energies between 2 and 10 joules. Moderate angle recession commensurate with typical clinical traumatic glaucoma was not observed among control eyes, but occurred at relatively low impact energy of 3.5 joules among test eyes. Extensive disruption in and around the angle (iridodialysis/cyclodialysis) consistently occurred at energies >7 joules. Globe rupture required a minimum energy of 10 joules.