Thirty-seven New Zealand Red rabbits were either dosed with methyiprednisolone sodium succinate (MP, n18) about 20 nun before laser irradiafion, or they were left untreated (n=19). Dosing with MP was tapered at 30, 30, 20, 20, and 10 mg/kg/day for five consecutive days. Retinas were irradiated with a multi-lime argon laser to produce retinal injuries (grid of 16 lesions/eye) near hemorrhaging levels (285 mW/lOmsec, 290 ?m retinal spot size). A variety of funduscopic and histologic assessments were made for hemorrhagic and non-hemorrhagic lesions from 10 miii to 6 mo after injury. Fluorescein angiography showed that non-hemorrhagic control lesions stopped leaking at 3d post injury, but MPtreated lesions leaked for 2-4 days longer. After MP treatment, funduscopic lesion areas were similar to controls during the first 24 h then became smaller by 1 mo. After 1 mo, MP-treated lesions increased in area while controls became reduced. Histologic analysis showed no effect on reduction of neutrophils (PMN) in MP-treated lesions over controls at 3 hr. At 24 hi, retinal PMN values in hemorrhagic lesions ofthe MP group were elevated (p<0.05) while monocyte/macrophage counts were reduced (p<0.05) compared to control. At 4d, MP impeded replacement oflost retinal tissue, and contributed to retinal hole development at 1 mo followed by extensive enhancement of chorio-retinal scarring at 6 mo. In severe laser-induced retinal trauma, the immunosuppressive effects of high dose MP therapy contributed to a variety of untoward wound healing outcomes, thereby suggesting caution in its use to treat similar injuries in humans.

The increasing number oflaser applications in military and industrial settings has resulted in a rising number of laser eye injuries. Laser-induced macular holes are one type of injury, usually caused by accidental exposure to radiation from a Q-switched Nd:YAG laser operating at 1 064 nm. Laser-induced macular holes share many features with idiopathic macular holes. Optical coherence tomography was employed in the evaluation oftwo patients with laserinduced macular holes. Tomographic features were compared with those found in patients with idiopathic macular holes. An animal model of laser-induced macular hole was also evaluated in order to elucidate the histologic correlation ofthe OCT findings.

The rising number ofapplications ofultrashort laser systems presents new challenges in laser safety. Retinal damage studies have demonstrated that less energy is required to create a retinal burn for pulses shorter than one nanosecond than for pulses longer than one nanosecond. 1-3 Furthermore, as laser systems become more complex, the potential for accidental injury increases. In this paper we report the accidental injury from a Ti:Sapphire amplifier system delivering 100 picosecond pulses. The circumstances leading to the binocular injury included the use of inadequate eye protection, a defective amplifier crystal and the very dim appearance of 800 nm light. Ophthalmologists evaluating patients with laser eye injury should be prepared to discuss the physiology ofthe injury and prognosis with their patients.

Ocular motility generated by various fixation strategies show a lower propensity to visit laser damaged retinal areas as compared to non-laser damaged sites. This selectivity provides a non-invasive methodology for characterizing retinal pathology by mapping eye movement visitation under various visual function fixation strategies. Ocular motor techniques for imaging eye movement maps of normal and damaged retinal regions are demonstrated with reference to retinal target location at the retina. Eye movement data digitized from a contrast sensitivity task provided video data of eye movement fixation patterns simultaneously with retmal location oftarget placement dunng periods of visual fixation required in a Landolt ring contrast sensitivity task. These data were digitized with specialized algorithms that linked target location with retmal morphology and pathology In one patient with central macular retmal damage, retmal based maps demonstrated strong consistency with measurements made with nonretina1 higher resolution Purkinje eye movement apparatus. Such eye movement maps differed primarily eye movement density within a given area but were generally comparable with respect focal areas mapped in retinal space. These data suggest that lower resolution video based imaging can provide a non-invasive assessment oflaser induced retinal damage.

The threshold for laser-induced retinal damage in the rhesus eye was determined for 14 wavelengths from 410 nm to 580 nm. The laser source was a tunable Optical Parametric Oscillator (OPO) pumped by the 3rd harmonic of a Nd:YAG laser. The laser pulse duration was 3.5 ns. The wavelength dependence of the injuiy threshold was consistent with the prediction of a model based on the transmission of the preretinal ocular media, absorption in the retinal pigment epithelium, and variation of h-radiance diameter resulting from chromatic aberration of the eye optics. The threshold for 24hour observation was only slightly lower than the threshold for 1-hour observation. The laser-induced retinal hemorrhage threshold was less than a factor of two greater than the minimum visible lesion (MVL) threshold for wavelengths from 442 nm to 410 nm. This results from the presence ofa dense capillary network in the inner retina and a large hemoglobin absorption peak.

In order to provide a direct comparison of the damage thresholds for mode-locked systems to those with continuous-wave (CW) or non-pulsed output, we have performed an experiment with lasers possessing otherwise identical output characteristics. Our work presents an in-vivo minimal visible lesion (MVL) study. Titanium:Sapphire lasers produced 800-nm output for either mode-locked (76 MHz repetition rate, 120 femtosecond) or continuous-wave exposures. Alternating laser exposures were delivered to the paramacular retinal region of rhesus subjects. Laser exposure duration was set to one-quarter second for both types of exposures. Through ophthalmoscopic examination of the fundus, an MVL threshold for damage is established with probit analysis. Approximately 75 data points for each type of exposure were collected. The laser dosage thresholds and confidence intervals for minimal visible damage at twenty-four hours postexposure are reported for mode-locked and CW exposures. Results are compared with published studies conducted at similar pulse duration and similar CW wavelengths.

In previous investigations of q-switched laser retinal exposure in awake task oriented non-human primates (NHPs), the threshold for retinal damage occurred well below that of the threshold for permanent visual function loss. Visual function measures used in these studies involved measures of visual acuity and contrast sensitivity. In the present study, we examine the same relationship for q-switched laser exposure using a visual performance task, where task dependency involves more parafoveal than foveal retina. NHPs were trained on a visual pursuit motor tracking performance task that required maintaining a small HeNe laser spot (0.3 degrees) centered in a slowly moving (0.5deg/sec) annulus. When NHPs reliably produced visual target tracking efficiencies > 80%, single q-switched laser exposures (7 nsec) were made coaxially with the line of sight of the moving target. An infrared camera imaged the pupil during exposure to obtain the pupillary response to the laser flash. Retinal images were obtained with a scanning laser ophthalmoscope 3 days post exposure under ketamine and nembutol anesthesia. Q-switched visible laser exposures at twice the damage threshold produced small (about 50?m) retinal lesions temporal to the fovea; deficits in NHP visual pursuit tracking were transient, demonstrating full recovery to baseline within a single tracking session. Post exposure analysis of the pupillary response demonstrated that the exposure flash entered the pupil, followed by 90 msec refractory period and than a 12 % pupillary contraction within 1.5 sec from the onset of laser exposure. At 6 times the morphological threshold damage level for 532 nm q-switched exposure, longer term losses in NHP pursuit tracking performance were observed. In summary, q-switched laser exposure appears to have a higher threshold for permanent visual performance loss than the corresponding threshold to produce retinal threshold injury. Mechanisms of neural plasticity within the retina and at higher visual brain centers may mediate the stability of visual function and performance metrics. Long term repeated exposure to the retina, however, may eventually dampen the ability of higher visual brain centers to detect declining retinal neural output from cumulative retinal damage. Individuals chronically exposed to such laser sources should have more frequent ophthalmic retinal surveillance.

Introduction: For an accidental laser exposure, the duration of the incident radiation on a specific retinal site depends on the initial fixation, the kinetics of the aversion (blink reflex) and the orienting response (eye movement) toward or away from the light image. Pupilary constriction during the exposure will attenuate the retinal irradiance. Methods: In this study, tracking performance was measured in eight volunteers exposed to O1, LO, and 10 second laser flashes while tracking a dynamic target (O28 degs) through a monocular telescope equipped with a miniature video camera to monitor eye response. The collimated 514 nm argon laser beam produced corneal radiant exposures of 0. 16, 0.33, and LO mJ/cm2 for the 0. 1, LO, and 3O second conditions respectively. Total time off target and maximum absolute error scores were measured for bright (430 nits) and dim (43 nits) ambient luminance conditions. Eye response (blink and pupilary response) was assessed by evaluation of the video from the eye camera. Volunteer reports of the visual experience were recorded. Results: Total time off target (> 0.5 mrad) was maximal for the 3 second exposure condition and minimal for the 0. 1 second conditions. Analysis of the data indicated that there was no photic induced blink reflex for the 0. 1 second condition under the bright light condition. For some volunteers, blinks did occur during the longer duration exposures but were not classic reflex blinks. Pupil responses following the laser presentation showed pupil diameters decreased from initial values of approximately 6 mm to 23 mm which reduced the total energy into the eye at that point by a factor of 10. Volunteers reported smeared and multiple afterimages for the 3 second condition, however, only a single, focal, afterimage was reported for the 0. 1 second condition. This information reflects a history of eye movements during the exposure; Summary: For durations of 100 msec or less, physiological mechanisms that would limit the retinal radiant exposure are not operative for the conditions investigated in this study. For the a 1 second exposure condition, fracking performance was not affected for the bright light vials and only minimally affected foe the dim light trials.

This manuscript details recent studies ofocular effects ofpulsed and cw laser radiation at wavelengths of I .3 15 and 1.3 1 8 ?m, and compares corneal, lens and retinal damage thresholds. The results indicate that for the exposure conditions studied, relatively minor changes in pulsewidth and/or wavelength can substantially alter threshold levels and change the tissue site(s) exhibiting the lowest damage threshold. The discussion suggests that these data may be applied to re-assess laser safety standards in the near-IR to far-IR transition-region. Also discussed are unique aspects ofthe laser-tissue interaction for these penefrating wavelengths where the incident laser radiation is relatively evenly absorbed throughout the ocular medium and the retina. In such cases of "volurnefric" absorption obsewable manifestations of laser insult may be delayed (hours to days) and may ultimately involve inflammatory responses or other disruption oftissue not directly irradiated by the laser.

Dutch Belted rabbit corneas and corneal equivalent (CE) tissue were exposed to 0.8 millisecond pulses of 1540 nm laser light. We report the single pulse ED50 for Dutch belted rabbits and for in-vitro corneal equivalent tissues. A histological comparison between the two tissues is presented. Remarkable similarities between the two models in both location and extent of damage are noted. We postulate which cellular energy absorption mechanisms are significant at 1540 nm and how this relates to the histopathology presented.

Corneal epithelial damage thresholds were determined for exposures to sequences of pulses from a Tm:YAG laser (wavelength 2.02 ?m). Pulse repetition frequencies were 1, 10, 20, and 100 Hz and individual pulse durations were 0.300 sec at 1 Hz, 0.025 sec at 10 and 20 Hz, and 0.005 sec at 100 Hz. Threshold damage is correlated by an empirical power lawof the form '1th= CN?, in which '1th is the threshold irradiance and N is the number of pulses. The constant C differs depending on the pulse repetition frequency and individual pulse duration. The exponent a varies between 0.22 and 0.29. For some exposure conditions the empirical power law underestimates the damage threshold for small numbers of pulses.

Concepts in dosimetry pertinent to hazard evaluation of optical radiation and specifically laser radiation are discussed. The basic units of power, energy, irradiance, exposure and radiance will be reviewed, as well as the relation of retinal exposures and experimental data given as intra-ocular energy to exposure limits specified in exposure at the cornea or time integrated radiance. Averaging apertures and field of views are specified with the exposure limits to be used when exposure values are measured or calculated which in turn are compared to exposure limits for laser radiation or broadband optical radiation. The size of the averaging aperture for irradiance measurements or the size of the averaging field of view for radiance measurements is closely linked to biophysical effects and dimensions such as the diameter of the pupil of the eye or the angular extent of eye movements. In some cases, the specified size of the averaging aperture and FOV result in measured irradiance and radiance values, which are much smaller than the real physical values. In the latest revision of the international laser safety standard, IEC 60825-1, and in the revised ICNIRP laser limits, blue light limits are split from the thermal limits and are given in irradiance, specifying corresponding measurement criteria for the measurement FOV. The derivation of the irradiance limit from the basic radiance limit as it is specified for the broadband blue light hazard (for instance by ACGIH and ICNIRP) can be understood on the basis of the specification for the measurement FOV.

For more than 10 years there has been a doubt regarding experimental results repoited by the USAMRD-WRAIR. The USAMRD-WRMR report reveals an unexplainable significant variation of the ED50 with small changes in wavelength Reanalyzing the data of the USAMRD-WRAlR with several different analysis methods reveals a large correlafion between inconsistent ED50 estimations to wavelength with larger ED50 values, which can be related to the large ED50 variations

An indication of the level of uncertainty in laser injury studies relates to the slope of the transformed dose-response curve, or the "probit plot" of the data. The most cited threshold in a laser injury experiment is the point on the probit plot that represents a 50 % probability of injury: the ED-50. This value is frequently referred to as the "threshold," even though some experimental damage points exist below this "threshold." An analysis of any number of example data sets reveals that the slope in most experiments could not be explained by biological variation alone. The optical, thermophysical and biological factors influencing the probit plot are critically analyzed. By theoretically modelling an experiment, small errors in focus are shown to produce a substantial change in the ED-50 and the slope of the probit plot. The implications of plotting spot-size dependence with ED-50 values are shown to be significant, and can lead to erroneous conclusions regarding the apparent spot-size dependence.

The most common method of analysis for 'sin vivo laser tissue experiments" is the probit regression. The data gathered at these experiments are specific in that there are very few repetitions of the exact stimulus exposure; thus the response frequencies for most stimulus are either '0' or '1'. Though such type of data is acceptable in probit, it seems that such data might not produce robust estimates of the ED50 and the slope. The accuracy of the probit's estimation was investigated by the use of Monte-Carlo simulation. Preliminary results suggest that the accuracy of the probifs estimations is conditional and might be biased in a way that raise doubts about the validity ofthe conclusions based on probit's estimations.

In laser safety, dose-response curves describe the probability for ocular injury as a function of ocular energy, and are often used to quantify the risk for ocular injury given a certain level of exposure to laser radiation. In principal, a dose-response curve describes the biological variation of the individual thresholds in a population. In laser safety, a log-normal cumulative distribution is generally assumed for the dose-response curve, for instance when Probit analysis is performed. The lognormal distribution is defined by two parameters, the median, called ED50, and the slope. When animal experiments are performed to obtain dose-response curves for laser induced injury, experimental uncertainty such as focussing errors as well as variability within the group of experimental animals, such as inter-individual variability of absorption of the ocular media, can influence the shape of the dose-response curve. We present simulations of uncertainties and variabilities that show that the log-normal dose-response curve as obtained in a animal experiments can grossly overestimate the probability for ocular damage for small doses. It is argued that the intrinsic slope for an individual’s dose-response curve is rather steep, even for retinal injury, however, the dose-response curve for a group or population can be broader when there is inter-individual variability of parameters which influence the threshold. The quantitative results of the simulation of the grouping of individual dose-response curves can serve as basis to correct potentially biased dose-response curves as well as to characterize the uncertainty associated with the ED50 and the slope of the dose-response curve. A probabilistic risk analysis model, which accounts for these uncertainties by using Monte-Carlo simulation, was developed for retinal laser injuries from pulsed lasers with wavelengths from 200 nm to 20 µm, and the interpretation of the results are discussed on the basis of example calculations.

While the major technological goal of laser eye protection (LEP) is to attenuate any laser radiation that passes through it, consideration of the physical format in which it is realized must not be overlooked. The best protective material can be rendered essentially useless if it does not cover the appropriate field of regard for the wearer To map the visual field of regard (FOR) coverage provided by LEP devices, the field ofview evaluation apparatus (FOVEA) was used The FOVEA is a onemeter radius arc perimeter contaming computer-controlled light emitting diodes at one-degree mtervals Three different mapppings of the visual field can be obtained with this facility (a) the monocular baseline FOR, (b) the accessibility the LEP demonstrates agamst the direct threat (i e , a laser source entering the eye beyond frame edge), and (c) the accessibility to indirect hazard (i e , laser energy reflected from the lens backside entenng the eye) Comparison of the direct and indirect fields of regard demonstrates the wide coverage variation generated by alternate frame styles and differing head shapes. These results need to be intereted with respect to FOVEA limitations. First, the full FOR is mapped without regard for the relative importance of the periphery versus the fovea. Second, the coverage from a particular frame style must be measured and specified with an appropriate range of anthropometric face forms to ensure coverage consistency.

During long-term viewing of a continuous light source, head and eye movements affect the distribution of energy deposited in the retina. Previous studies by this group of eye movements during a fixation task were used in revising the safety limits for long term viewing ofsuch sources. These studies have been continued to determine the effect of source brightness on the nature of fixational eye movements VoIuntees fixated for up to 50 seconds on a HeNe laser (? 632 8 nm) masked by a 25 xm diameter aperture to produce a small source subtending OO3 mrad in the visual field. The source was attenuated to yield cornea! irradiance values m the range 0 6 pW/cm2 to 6 tW/cm2 Eye movements were recorded using a Dual Purkmje Image Eye Tracker The hypothesis was that eye movements become more erratic as source intensity is increased toward levels that induce an aversion response This would add a safety maigin when viewing a bright source, as the energy deposited in the retina would be spread over a larger area However, the data do not exhibit any change in the tightness of fixation with increasing source intensity. The area covered by the eye movements during successive 250 ms time slices exhibits a relatively flat trend during the course ofthe 50 second fixation task for all source intensities considered in this study, suggesting that there was no loss of ability to fixate nor drive to an aversion response during the course ofthe trials.

A deterministic approach to laser hazard assessment is used in most laser safety standards. Personnel are protected from hazardous laser radiation is by defining a space withm which the direct, reflected, or scattered radiation during laser operation exceeds the safe Maximum Permissible Exposure level. Controlling access to this space insures safety. Although this approach has satisfied the commercial and industrial laser communities for many years, it may not be applicable to the highpower (up to megawatt) laser systems currently being developed by the US military. These systems will have extremely long laser hazard distances, and controlling access to this space will be unrealistic, especially when the likelihood of hazardous human exposure is low. For these situations, an alternative analytical approach that estimates both the level of risk and the degree of risk reduction achievable by controlling key contributors can be applied. Analytic risk assessment tools are finding increasing application in a wide variety of hazard assessments, m both industrial and commercial situations. These tools use scientific data, assumptions, and mathematical models to estimate the likelihood, frequency, and severity of harm to people exposed to the hazard. This paper will discusses application of such tools to laser safety and considers the uncertainties associated with probability density functions applied to key factors such as atmospheric scmtillation, reflected radiation, population distribution and ocular injury.

Single pulse, 1540 nm laser light with a pulse width of 1 microsecond altered the morphologic appearance of explant rabbit and pig corneas following ex vivo exposure. Using digital images of the post-exposure corneas projected onto a measuring grid, we could accurately locate the relative position of the circular laser lesion in the embedded tissue. This allowed us to section through the lesion with micrometer precision and accurately resolve the inside edge, middle and outside edge of the laser lesion. All tissue sections used for morphometric analysis were taken through the middle of the lesion. Several features of the response to laser exposure may reflect species-specific tissue differences. The rabbit corneal epithelium showed a homogeneous coagulative necrosis with a distinct demarcation between necrotic and normal epithelium. The pig epithelium also showed a distinct demarcation between necrotic and normal epithelium, however, there were several remarkable differences in the tissue response between the two species including coagulative necrosis pattern and nuclear morphology. These changes suggested a different and less severe response of the pig epithelium to the laser light when compared to the rabbit epithelium.