Laser hazards on the modern battlefield include numerous applications with the potential for eye damage
from both pulsed and high luminance continuous energy laser devices. The multitude of laser devices
deployed both by friendly and threat forces represent a significant hazard to vision, and consequently duty
performance. Increased application of high luminance devices for tactical use may result in accidental
exposure and temporary or persistent symptoms. These symptoms may be confounded by ongoing ocular
retinal disorders. The management of these patients requires additional laser training to prevent injury as
well as more experience and training for first responders in order to triage individuals with vision
disturbances thought secondary to ocular laser exposure.
The emergence of high resolution optical coherence tomography (OCT) along with evidence showing
beneficial effects of anti-inflammatory drugs for retinal edema and neovascularization suggests a rational
plan for the diagnosis and management of patients with acute laser eye injury. We review the results of
recent experiments we conducted to evaluate treatment of laser lesions followed by reports of two cases of
acute laser eye injury with foveal involvement. The initial presentation of these cases was notable for the
lack of significant abnormalities on fluorescein angiography whereas OCT readily disclosed the size and
extent of retinal involvement from exposure to laser energy. Prompt referral of these cases resulted in rapid
initiation of medical therapy which included a 10-14 day combined course of steroid and non-steroidal anti-inflammatory
medication. An initial decrease in Snellen visual acuity of approximately two lines (20/25- to
20/30) was noted on presentation. In both cases, a measurable improvement of visual acuity was noted by
two weeks post injury. The use of anti-inflammatory medication may enhance the initial recovery of vision
and reduce the likelihood of longer term retinal complications from scarring and neovascularization.
The past several years has seen a severe shortage of pathogen-free Indian origin rhesus macaques due to the increased requirement for this model in retroviral research. With greater than 30 years of research data accumulated using the Rhesus macaque as the model for laser eye injury there exists a need to bridge to a more readily available nonhuman primate model. Much of the data previously collected from the Rhesus monkey (Macaca mulatta) provided the basis for the American National Standards Institute (ANSI) standards for laser safety. Currently a Tri-service effort is underway to utilize the Cynomolgus monkey (Macaca fasicularis) as a replacement for the Rhesus macaque. Preliminary functional and morphological baseline data collected from multifocal electroretinography (mfERG), optical coherence tomography (OCT) and retinal cell counts were compared from a small group of monkeys and tissues to determine if significant differences existed between the species. Initial functional findings rom mfERG yielded only one difference for the n2 amplitude value which was greater in the Cynomolgus monkey. No significant differences were seen in retinal and foveal thickness, as determined by OCT scans and no significant differences were seen in ganglion cell and inner nuclear cell nuclei counts. A highly significant difference was seen in the numbers of photoreceptor nuclei with greater numbers in the Rhesus macaque. This indicates more studies should be performed to determine the impact that a model change would have on the laser bioeffects community and their ability to continue to provide minimal visible lesion data for laser safety standards. The continued goal of this project will be to provide that necessary baseline information for a seamless transition to a more readily available animal model.
Due to the increasing number of optic systems that military personnel are exposed, the development of countermeasures for laser eye injury is of significant concern. Recent reports in the literature suggest some benefit form the use of Light Emitting Diode (LED) therapy on the retina that received a toxic insult. The purpose of this study was to compare retinal cell survival and multifocal electroretinography (mfERG) in a laser retinal injury model following treatment with LED photoillumination. Control and LED array (670 nm) illuminated cynomolgus monkeys received macular Argon laser lesions (514 nm, 130 mW, 100 ms). LED array exposure was accomplished for 4 days for a total dose of 4 J/cm2 per day. Baseline and post-laser exposure mfERGs were performed on most of the subjects. Ocular tissues were collected from four animals at Day 4 poast laser exposure and from two animals at 4 months post laser exposure. The tissues were processed for plastic embedding. Retinal cell counts were performed on the lesion sections. Analysis of Variance (ANOVA) results yielded no significant difference in the sparing of photoreceptors, inner nuclear and ganglion cells between the control and LED illuminated subjects. Although pathology showed no significant support for diode therapy, our early mfERG observations previously reported suggested a more rapid functional recovery. Since there is still no uniform therapy for laser retinal injury, research is continuing to determine novel therapies that may provide retinal cell sparing and functional retinal return.
The small eye model of the snake permits the imaging of the photoreceptor layer as well as the retinal vasculature and individual blood cells when imaged with a confocal scanning laser ophthalmoscope (CSLO). Snake photoreceptors can be imaged down to their internal mode structure, providing comparison between normal and laser damaged photoreceptor internal mode structure. Moving the CSLO into anterior retina provides imaging of the retinal vasculature and individual blood cell response to acute laser photoreceptor injury. Alteration in individual blood cell activity is readily apparent within seconds post laser exposure, as blood cells cumulate and show charactistic "sticky cell" leukocyte behavior. At energy levels near thermal threshold damage levels, damage down to a single photoreceptor is detectable within 24 hours post exposure with near IR laser imaging sources (780 nm), and visualization of internal mode structure disruption mediated at the outer segment of the photoreceptor. Utilization of in vivo biochemical tags for oxidative stress demonstrates that thermal/mechanical and non-thermal mechanisms of photoreceptor damage can reside in adjacent photoceptors. Preliminary studies with actin based biochemical markers indicate the presence of actin in both the photoreceptor and retinal nerve fiber layer, suggesting the possibility of both active recovery and support processes.
The diagnosis of a laser-induced eye injury occurring in occupational or military environments is often complicated by confounding symptoms, the possibility of pre-existing pathology, and/or a lack of visual deficits that can be clearly associated with a specific incident. Two recent cases are described that illustrate the importance of a thorough differential diagnosis when coexisting retinal pathologies are present with potentially different (e.g. laser or disease) etiologies. Indocyanine green angiography (ICG) and ocular coherence tomography (OCT) used in combination with standard ophthalmic imaging can provide helpful insights as to the etiology of these lesions. Vascular choroidal abnormalities such as hemangiomas or occult histoplasmosis infection can produce findings that can mimic the leakage that may be evident from neovascular membranes associated with laser injury. Further evaluation with OCT and conventional fluorescein angiography (FA) is helpful to look for the classic signature of retinal disruption and retinal pigment layer changes that are often present in association with laser injury. Furthermore, a careful situational assessment of a potential laser exposure is important to confirm the diagnosis of laser-induced eye injury.
Retinal tissue is subject to ischemia from diabetic retinopathy and other conditions that affect the retinal vasculature such as lupus erythematosus and temporal arteritis. There is evidence in animal models of reversible ischemia that a therapeutic window exists during early recovery when agents that reduce glutamate activity at its receptor sites can rescue neurons from injury. To model ischemia, we used sodium cyanide (NaCN), to inhibit oxidative metabolism, and 2-deoxyglucose (2-DG) to inhibit glycolysis. Dissociated rabbit retina cells were studied to evaluate the potential neuroprotective effects of N-acetyl-aspartyl-glutamate (MAAG), which competes with glutamate as a low-potency agonist at the NMDA receptor complex. N-acetylated α-linked acidic dipeptidase (NAALADase; the NAAG-hydrolyzing enzyme) is responsible for the hydrolysis of NAAG into glutamate, a neurotransmitter and potent excitotoxin, and N-acetylaspartate. 2-Phosphonyl-methyl pentanedioic acid (PMPA) and β-linked NAAG (β-NAAG), inhibitors of NAALADase, were also tested, since inhibition of NAALADase could reduce synaptic glutamate and increase the concentration of NAAG. We found that metabolic inhibition with NaCN/2-DG for 1 hour caused 50% toxicity as assessed with the MTT assay. Co-treatment with NAAG resulted in dose-dependent protection of up to 55% (p<0.005). When the non-hydrolyzable, NAALADase inhibitor β-NAAG was employed dose-dependent protection of up to 37% was observed (p<0.001). PMPA also showed 48% protection (p<.05-.001) against these insults. These data suggest that NAAG may antagonize the effect of glutamate at the NMDA receptor complex in retina. Inhibition of NAALADase by PMPA and β-NAAG may increase the activity of endogenous NAAG.
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