Laser-induced corneal injury: validation of a computer model to predict thresholds.

The exposure and emission limits of ICNIRP, IEC 60825-1 and ANSI Z136.1 to protect the cornea are based on a limited number of in-vivo studies. To broaden the database, a computer model was developed to predict injury thresholds in the wavelength range from 1050 nm to 10.6 µm and was validated by comparison with all applicable experimental threshold data (ED50) with exposure duration between 1.7 ns and 100 s. The model predictions compare favorably with the in-vivo data with an average ratio of computer prediction to ED50 of 0.94 (standard deviation ± 30%) and a maximum deviation of less than 2. This computer model can be used to improve exposure limits or for a quantitative risk analysis of a given exposure of the cornea.

Laser-induced retinal damage threshold for repetitive-pulse exposure to 100-µs pulses.

The laser-induced retinal injury thresholds for repetitive-pulse exposures to 100-µs-duration pulses at a wavelength of 532 nm have been determined for exposures of up to 1000 pulses in an in vivo model. The ED50 was measured for pulse repetition frequencies of 50 and 1000 Hz. Exposures to collimated beams producing a minimal retinal beam spot and to divergent beams producing a 100-µm-diameter retinal beam spot were considered. The ED50 for a 100-µs exposure was measured to be 12.8 µJ total intraocular energy for a minimal retinal beam spot exposure and 18.1 µJ total intraocular energy for a 100-µm-diameter retinal beam spot. The threshold for exposures to N > 1 pulse was found to be the same for both pulse repetition frequencies. The variation of the ED50 with the number of pulses is described well by the probability summation model, in which each pulse is considered an independent event. This is consistent with a threshold-level damage mechanism of microcavitation for single-pulse 100-µs-duration exposures. The data support the maximum permissible exposure levels for repetitive-pulse exposure promulgated in the most recent laser safety guidelines.

Damage threshold from large retinal spot size repetitive-pulse laser exposures.

The retinal damage thresholds for large spot size, multiple-pulse exposures to a Q-switched, frequency doubled Nd:YAG laser (532 nm wavelength, 7 ns pulses) have been measured for 100 µm and 500 µm retinal irradiance diameters. The ED50, expressed as energy per pulse, varies only weakly with the number of pulses, n, for these extended spot sizes. The previously reported threshold for a multiple-pulse exposure for a 900 µm retinal spot size also shows the same weak dependence on the number of pulses. The multiple-pulse ED50 for an extended spot-size exposure does not follow the n dependence exhibited by small spot size exposures produced by a collimated beam. Curves derived by using probability-summation models provide a better fit to the data.

A new understanding of multiple-pulsed laser-induced retinal injury thresholds.

Laser safety standards committees have struggled for years to formulate adequately a sound method for treating repetitive-pulse laser exposures. Safety standards for lamps and LEDs have ignored this issue because averaged irradiance appeared to treat the issue adequately for large retinal image sizes and skin exposures. Several authors have recently questioned the current approach of three test conditions (i.e., limiting single-pulse exposure, average irradiance, and a single-pulse-reduction factor) as still insufficient to treat pulses of unequal energies or certain pulse groupings. Schulmeister et al. employed thermal modeling to show that a total-on-time pulse (TOTP) rule was conservative. Lund further developed the approach of probability summation proposed by Menendez et al. to explain pulse-additivity, whereby additivity is the result of an increasing probability of detecting injury with multiple pulse exposures. This latter argument relates the increase in detection probability to the slope of the probit curve for the threshold studies. Since the uncertainty in the threshold for producing an ophthalmoscopically detectable minimal visible lesion (MVL) is large for retinal exposure to a collimated laser beam, safety committees traditionally applied large risk reduction factors ("safety factors") of one order of magnitude when deriving intrabeam, "point-source" exposure limits. This reduction factor took into account the probability of visually detecting the low-contrast lesion among other factors. The reduction factor is smaller for large spot sizes where these difficulties are quite reduced. Thus the N⁻°·²5 reduction factor may result from the difficulties in detecting the lesion. Recent studies on repetitive pulse exposures in both animal and in vitro (retinal explant) models support this interpretation of the available data.

Review of thresholds and recommendations for revised exposure limits for laser and optical radiation for thermally induced retinal injury.

Exposure limits (ELs) for laser and optical broadband radiation that are derived to protect the retina from adverse thermally-induced effects vary as a function of wavelength, exposure duration, and retinal irradiance diameter (spot size) expressed as the angular subtense α. A review of ex vivo injury threshold data shows that, in the ns regime, the microcavitation-induced damage mechanism results in retinal injury thresholds below thermal denaturation-induced thresholds. This appears to be the reason that the injury thresholds for retinal spot sizes of about 80 µm (α = 6 mrad) and pulse durations of about 5 ns in the green wavelength range are very close to current ELs, calling for a reduction of the EL in the ns regime. The ELs, expressed in terms of retinal radiant exposure or radiance dose, currently exhibit a 1/α dependence up to a retinal spot size of 100 mrad, referred to as αmax. For α ≥ αmax, the EL is a constant retinal radiant exposure (no α dependence) for any given exposure duration. Recent ex vivo, computer model, and non-human primate in vivo threshold data provide a more complete assessment of the retinal irradiance diameter dependence for a wide range of exposure durations. The transition of the 1/α dependence to a constant retinal radiant exposure (or constant radiance dose) is not a constant αmax but varies as a function of the exposure duration. The value of αmax of 100 mrad reflects the spot size dependence of the injury thresholds only for longer duration exposures. The injury threshold data suggest that αmax could increase as a function of the exposure duration, starting in the range of 5 mrad in the µs regime, which would increase the EL for pulsed exposure and extended sources by up to a factor of 20, while still assuring an appropriate reduction factor between the injury threshold and the exposure limit.

Thermal lensing in ocular media exposed to continuous-wave near-infrared radiation: the 1150-1350-nm region.

Ocular damage threshold data remain sparse in the continuous wave (CW), near-infrared (NIR) radiation region save for the 1300-nm area that has been investigated in the past several decades. The 1300-nm ocular damage data have yielded unusual characteristics where CW retinal damage was observed in rabbit models, but never in nonhuman primate models. This paper reviews the existing 1300-nm ocular damage threshold data in terms of the fundamental criteria of an action spectrum to assist in explaining laser-tissue effects from near-infrared radiation in the eye. Reviewing the action spectrum criteria and existing NIR retinal lesion data lend evidence toward the significant presence of thermal lensing in ocular media affecting damage, a relatively unexplored mechanism of laser-tissue interaction.

Ex vivo and computer model study on retinal thermal laser-induced damage in the visible wavelength range.

Excised bovine eyes are used as models for threshold determination of 532-nm laser-induced thermal damage of the retina in the pulse duration regime of 100 micros to 2 s for varying laser spot size diameters. The thresholds as determined by fluorescence viability staining compare well with the prediction of an extended Thompson-Gerstman computer model. Both models compare well with published Rhesus monkey threshold data. A previously unknown variation of the spot size dependence is seen for different pulse durations, which allows for a more complete understanding of the retinal thermal damage. Current International Commission on Nonionized Radiation Protection (ICNIRP), American National Standards Institute (ANS), and International Electromechanical Commission (IEC) laser and incoherent optical radiation exposure limits can be increased for extended sources for pulsed exposures. We conclude that the damage mechanism at threshold detected at 24 and 1 h for the nonhuman primate model is retinal pigment epithelium (RPE) cell damage and not thermal coagulation of the sensory retina. This work validates the bovine ex vivo and computer models for prediction of thresholds of thermally induced damage in the time domain of 10 micros to 2 s, which provides the basis for safety analysis of more complicated retinal exposure scenarios such as repetitive pulses, nonconstant retinal irradiance profiles, and scanned exposure.

Laser-induced retinal damage threshold measurements with wavefront correction.

An adaptive optics (AO) system was incorporated into a laser retinal exposure setup in order to correct for refractive error and higher-order aberrations of the nonhuman primate (NHP) eye during an in vivo retinal ED(50) measurement. Using this system, the ED(50) for a 100-ms, 532-nm small spot size exposure was measured to be 1.05 mJ total intraocular energy (TIE), a reduction of 22% from the value measured without aberration correction. The ED(50) for a 3.5-ns, 532-nm exposure was measured to be 0.51 microJ TIE, the lowest ED(50) reported for a ns-duration exposure. This is a reduction of 37% from the value measured without aberration correction and is a factor of only 2.6 higher than the maximum permissible exposure (MPE) for a 3.5-ns, visible wavelength small spot size exposure. The trend of in vitro measurements using retinal explants suggests that the in vivo ED(50) for small spot-size exposures could potentially be one order of magnitude smaller than the previously reported in vivo ED(50). Distortion of the incident laser beam by ocular aberrations cannot fully explain the discrepancy between the in vivo measurements with no aberration correction and the in vitro results.

Steroidal and nonsteroidal antiinflammatory medications can improve photoreceptor survival after laser retinal photocoagulation.

OBJECTIVE: To determine whether methylprednisolone or indomethacin can enhance photoreceptor survival after laser retinal injury in an animal model. DESIGN: Experimental study. PARTICIPANTS: Twenty rhesus monkeys. METHODS: Twenty rhesus monkeys (Macaca mulatta) received a grid of argon green (514.5 nm, 10 ms) laser lesions in the macula of the right eye and a grid of neodymium:yttrium-aluminum-garnet (Nd:YAG; 1064 nm, 10 ns) lesions in the macula of the left eye, followed by randomization to 2 weeks of treatment in 1 of 4 treatment groups: high-dose methylprednisolone, moderate-dose methylprednisolone, indomethacin, or control. The lesions were assessed at day 1, day 14, 2 months, and 4 months. The authors were masked to the treatment group. This report discusses the histologic results of ocular tissue harvested at 4 months. MAIN OUTCOME MEASURE: The number of surviving photoreceptor cell nuclei within each lesion was compared with the number of photoreceptor nuclei in surrounding unaffected retina. The proportion of surviving photoreceptor nuclei was compared between each treatment group. RESULTS: Argon retinal lesions in the high-dose steroid treatment group and the indomethacin treatment group demonstrated improved photoreceptor survival compared with the control group (P = 0.004). Hemorrhagic Nd:YAG lesions demonstrated improved survivability with indomethacin treatment compared with controls (P = 0.003). In nonhemorrhagic Nd:YAG laser retinal lesions, the lesions treated with moderate-dose steroids demonstrated improved photoreceptor survival compared with the control group (P = 0.004). CONCLUSIONS: Based on histologic samples of retinal laser lesions 4 months after injury, treatment with indomethacin resulted in improved photoreceptor survival in argon laser lesions and hemorrhagic Nd:YAG laser lesions. Treatment with systemic methylprednisolone demonstrated improved photoreceptor survival in argon retinal lesions and in nonhemorrhagic Nd:YAG lesions.

Variation of laser-induced retinal injury thresholds with retinal irradiated area: 0.1-s duration, 514-nm exposures.

The retinal injury threshold dose for laser exposure varies as a function of the irradiated area on the retina. Zuclich reported thresholds for laser-induced retinal injury from 532 nm, nanosecond-duration laser exposures that varied as the square of the diameter of the irradiated area on the retina. We report data for 0.1-s-duration retinal exposures to 514-nm, argon laser irradiation. Thresholds for macular injury at 24 h are 1.05, 1.40, 1.77, 3.58, 8.60, and 18.6 mJ for retinal exposures at irradiance diameters of 20, 69, 136, 281, 562, and 1081 microm, respectively. These thresholds vary as the diameter of the irradiated retinal area. The relationship between the retinal injury threshold and retinal irradiance diameter is a function of the exposure duration. The 0.1-s-duration data of this experiment and the nanosecond-duration data of Zuclich show that the ED(50) (50% effective dose) for exposure to a highly collimated beam does not decrease relative to the value obtained for a retinal irradiance diameter of 100 microm. These results can form the basis to improve current laser safety guidelines in the nanosecond-duration regime. These results are relevant for ophthalmic devices incorporating both wavefront correction and retinal exposure to a collimated laser.

Wavelength dependence of ocular damage thresholds in the near-ir to far-ir transition region: proposed revisions to MPES.

This report summarizes the results of a series of infrared (IR) laser-induced ocular damage studies conducted over the past decade. The studies examined retinal, lens, and corneal effects of laser exposures in the near-IR to far-IR transition region (wavelengths from 1.3-1.4 mum with exposure durations ranging from Q-switched to continuous wave). The corneal and retinal damage thresholds are tabulated for all pulsewidth regimes, and the wavelength dependence of the IR thresholds is discussed and contrasted to laser safety standard maximum permissible exposure limits. The analysis suggests that the current maximum permissible exposure limits could be beneficially revised to (1) relax the IR limits over wavelength ranges where unusually high safety margins may unintentionally hinder applications of recently developed military and telecommunications laser systems; (2) replace step-function discontinuities in the IR limits by continuously varying analytical functions of wavelength and pulsewidth which more closely follow the trends of the experimental retinal (for point-source laser exposures) and corneal ED50 threshold data; and (3) result in an overall simplification of the permissible exposure limits over the wavelength range from 1.2-2.6 mum. A specific proposal for amending the IR maximum permissible exposure limits over this wavelength range is presented.

Retinal injury thresholds for blue wavelength lasers.

The interaction mechanism leading to laser-induced retinal alteration can be thermal or non-thermal, depending upon the wavelength of the laser radiation and the duration of the exposure. To investigate the effect of exposure duration on the interaction mechanism, retinal injury thresholds in the rhesus monkey were experimentally measured for exposure to laser radiation at wavelengths of 441.6, 457.9, 476.5, and 496.5 nm. Exposure durations were 0.1, 1, 5, 16, and 100 s; and 1/e retinal irradiance diameters were 50, 125, and 327 microm. Tissue response was observed via ophthalmoscope 1 h and 48 h post exposure. Thermal and non-thermal damage thresholds were obtained depending upon the exposure duration. These threshold data are in agreement with data previously reported in the literature for 100-s duration exposures, but differences were noted for shorter exposures. The current study yielded an estimated injury threshold for 1-s duration, 327-microm retinal irradiance diameter exposures at 441.6 nm, which is an order of magnitude higher than that previously reported. This study provides evidence that laser-induced retinal damage is primarily induced via thermal mechanisms for exposures shorter than 5 s in duration. Arguments are presented that support an amendment of the thermal hazard function, R(lambda).

Laser-induced macular holes demonstrate impaired choroidal perfusion.

PURPOSE: To evaluate choroidal perfusion following creation of a laser-induced macular hole in a nonhuman primate model. METHODS: Six rhesus monkeys underwent macular exposures delivered by a Q-switched Nd:YAG laser. The lesions were evaluated with fluorescein angiography and indocyanine green angiography using scanning laser ophthalmoscopy. RESULTS: Each lesion produced vitreous hemorrhage and progressed to a full-thickness macular hole. Indocyanine green angiography revealed no perfusion of the choriocapillaris beneath the lesion centers. Fluorescein angiography demonstrated mild enlargement of the foveal avascular zone due to loss of perifoveal capillaries. Histopathologic evaluation showed replacement of the choriocapillaris with fibroblasts and connective tissue. CONCLUSIONS: Nd:YAG laser-induced macular holes result in long-term impairment of choroidal perfusion at the base of the hole due to choroidal scarring and obliteration of the choriocapillaris. Evaluation of choroidal perfusion may be useful in assessment of laser-injured patients. Impairment in choroidal perfusion may have functional implications for surviving photoreceptors.

Effect of source intensity on ability to fixate: implications for laser safety.

During long-term viewing of a continuous light source, head and eye movements affect the distribution of energy deposited in the retina. Previous studies of eye movements during a fixation task provided data used for revising the safety limits for long-term viewing of such sources. These studies have been continued to determine the effect of source brightness on the nature of fixational eye movements. Volunteers fixated for 50 s on a HeNe laser (lambda = 632.8 nm) masked by a small aperture to produce a target subtending approximately 0.03 mrad in the visual field. The source was attenuated to yield corneal irradiance values in the range 0.6 pW cm(-2) to 6 microW cm(-2). Eye movements were recorded using a Dual Purkinje Image Eyetracker. The data were characterized by fixation ellipses that represent areas of the retina in which the image of the spot was located 68% of the time of each trial. Significant variation across subjects in the tightness of fixation was observed. Over the eight orders of magnitude of source brightness used in this experiment (10(-13) to 10(-6) W cm(-2)), no subject showed more than roughly a factor of two variation in the area of the fixation ellipse. No statistically significant trend in tightness of fixation as a function of source brightness was observed. There was no loss of ability to fixate, nor any drive to aversion, at the higher source intensities.

Human pupil and eyelid response to intense laser light: implications for protection.

Natural ocular protective measures induced by laser glare at 514 nm were evaluated concomitant with the performance of a tracking task. Light-induced eyelid and pupil responses of 5 volunteers, 1 woman and 4 men, ages 23 to 60 years, were recorded as they tracked a target moving at 0.3 degrees/sec. with an optical sight. Frame-by-frame analysis of video images of the eye allowed assessment of the eyelid response (squint and blink) and measurement of the pupil diameter. Three laser exposure durations (0.1, 1.0, and 3.0 sec.) were used during bright and dim ambient light conditions. All laser exposure trials produced a pupillary constriction with a latency, i.e., the time from the onset of the laser exposure until the pupil began to constrict, of approximately 100 msec. In a representative 3-sec. exposure, the total intraocular energy was reduced by 69% as the pupil diameter decreased from 6.0 to 2.5 mm. For the 0.1-sec. exposures at 1.6 mW/cm2, a blink reflex was observed on 2 of 10 trials under the dim ambient conditions and not observed on 9 trials under bright conditions. For 1- and 3-sec. exposures at 0.33 mW/cm2, a blink reflex was observed on four (3 bright and 1 dim) of the 38 trials. For conditions evaluated, pupillary constriction was consistent and provided some protection when the exposure duration exceeded the pupillary latency period; however, a blink reflex was observed on only a limited number of trials, possibly due to the exposure dose, the small retinal irradiance diameter produced by the laser exposure, and the volunteers' attention to the demanding performance task.