A series of experiments are conducted in vivo using Yucatan mini-pigs (Sus scrofa domestica) to determine thermal damage thresholds to the skin from 1940-nm continuous-wave thulium fiber laser irradiation. Experiments employ exposure durations from 10 ms to 10 s and beam diameters of approximately 4.8 to 18 mm. Thermal imagery data provide a time-dependent surface temperature response from the laser. A damage endpoint of minimally visible effect is employed to determine threshold for damage at 1 and 24 h postexposure. Predicted thermal response and damage thresholds are compared with a numerical model of optical-thermal interaction. Results are compared with current exposure limits for laser safety. It is concluded that exposure limits should be based on data representative of large-beam exposures, where effects of radial diffusion are minimized for longer-duration damage thresholds.
In this paper we report on our combined measurements of the visible lesion thresholds for porcine skin for wavelengths in the infrared from 810 nm at 44 fs to 1318 nm at pulse durations of 50 ns and 350&mgr;s to 1540 nm including pulse durations of 31 ns and 600 &mgr;s. We also measure thresholds for various spot sizes from less than 1 mm to 5 mm in diameter. All three wavelengths and five pulse durations are used extensively in research and the military. We compare these minimum visible lesion thresholds with ANSI standards set for maximum permissible exposures in the infrared wavelengths. We have measured non-linear effects at the laser-tissue interface for pulse durations below 1&mgr;s and determined that damage at these short pulse durations are usually not thermal effects. Damage at the skin surface may include acoustical effects, laser ablation and/or low-density plasma effects, depending on the wavelength and pulse duration. Also the damage effects may be short-lived and disappear within a few days or may last for much longer time periods including permanent discolorations. For femtosecond pulses at 810 nm, damage was almost instant and at 1 hour had an ED50 of 8.2 mJ of pulse energy. After 24 hours, most of the lesions disappeared and the ED50 increased by almost a factor of 3 to 21.3 mJ. There was a similar trend for the 1.318 &mgr; laser for spot sizes of 2 mm and 5 mm where the ED50 was larger after 24 hours. However, for the 1.54 &mgr; laser with a spot size of 5 mm, the ED50 actually decreased by a small amount; from 6.3 Jcm-2 to 6.1 Jcm-2 after 24 hours. Thresholds also decreased for the 1314 nm laser at 350 &mgr;s for spot sizes of 0.7 mm and 1.3 mm diameter after 24 hours. Different results were obtained for the 1540 nm laser at 600 &mgr;s pulse durations where the ED50 decreased for spot sizes 1 mm and below, but increased slightly for the 5 mm diameter spot size from 6.4 Jcm-2 to 7.4 Jcm-2
An assessment of skin damage caused by near-IR laser exposures is reported. The damage from two distinct laser-tissue temporal regimes is compared at two wavelengths (1.3 &mgr;m and 1.5 &mgr;m). Skin damage caused by thermal effects from single laser pulses is compared to damage caused by LIB (laser induced breakdown) using histological examinations. Modeling applications are explored to determine crossover points between thermal and photomechanical damage thresholds.
With the advent of such systems as the airborne laser and advanced tactical laser, high-energy lasers that use 1315-nm wavelengths in the near-infrared band will soon present a new laser safety challenge to armed forces and civilian populations. Experiments in nonhuman primates using this wavelength have demonstrated a range of ocular injuries, including corneal, lenticular, and retinal lesions as a function of pulse duration. American National Standards Institute (ANSI) laser safety standards have traditionally been based on experimental data, and there is scant data for this wavelength. We are reporting minimum visible lesion (MVL) threshold measurements using a porcine skin model for two different pulse durations and spot sizes for this wavelength. We also compare our measurements to results from our model based on the heat transfer equation and rate process equation, together with actual temperature measurements on the skin surface using a high-speed infrared camera. Our MVL-ED50 thresholds for long pulses (350 µs) at 24-h postexposure are measured to be 99 and 83 Jcm–2 for spot sizes of 0.7 and 1.3 mm diam, respectively. Q-switched laser pulses of 50 ns have a lower threshold of 11 Jcm–2 for a 5-mm-diam top-hat laser pulse.
Er:glass lasers have been in operation with both long pulses (hundreds of microseconds) and Q-switched pulses (50 to 100 ns) for more than 35 yr. The ocular hazards of this laser were reported early, and it was determined that damage to the eye from the 1.54-µm wavelength occurred mainly in the cornea where light from this wavelength is highly absorbed. Research on skin hazards has been reported only in the past few years because of limited pulse energies from these lasers. Currently, however, with pulse energies in the hundreds of joules, these lasers may be hazardous to the skin in addition to being eye hazards. We report our minimum visible lesion (MVL) threshold measurements for two different pulse durations and three different spot sizes for the 1.54-µm wavelength using porcine skin as an in vivo model. We also compare our measurements to results from our model, based on the heat transfer equation and the rate process equation. Our MVL-ED50 thresholds for the long pulse (600 µs) at 24 h postexposure were measured to be 20, 8.1, and 7.4 J cm–2 for spot diameters of 0.7, 1.0, and 5 mm, respectively. Q-switched laser pulses of 31 ns had lower ED50 (estimated dose for a 50% probability of laser-induced damage) thresholds of 6.1 J cm–2 for a 5-mm-diam, top-hat spatial profile laser pulse.
Skin damage thresholds were measured and compared with theoretical predictions using a skin thermal model for near-IR laser pulses at 1318 nm and 1540 nm. For the 1318-nm data, a Q-switched, 50-ns pulse
with a spot size of 5 mm was applied to porcine skin and the damage thresholds were determined at 1 hour and 24 hours postexposure using Probit analysis. The same analysis was conducted for a Q-switched, 30-ns pulse at 1540 nm with a spot size of 5 mm. The Yucatan mini-pig was used as the skin model for human skin due to its similarity to pigmented human skin. The ED50 for these skin exposures at 24 hours postexposure was 10.5 J/cm2 for the 1318-nm exposures, and 6.1 J/cm2 for the 1540-nm exposures. These results were compared to thermal model predictions. We show that the thermal model fails to account for the ED50 values observed. A brief discussion of the possible causes of this discrepancy is presented. These thresholds are also compared with previously published skin minimum visible lesion (MVL) thresholds and with the ANSI Standard's MPE for 1318-nm lasers at 50 ns and 1540-nm lasers at 30 ns.
The use of lasers by both the military and civilian community is rapidly expanding. Thus, the potential for and severity of laser eye injury and retinal damage is increasing. Sensitive and accurate methods to evaluate and follow laser retinal damage are needed. The multifocal electroretinogram (mfERG) has the potential to meet these criteria. In this study, the mfERG was used to evaluate changes to retinal function following laser exposure. Landolt C contrast acuity was also measured in the six behaviorally trained Rhesus monkeys. The monkeys then received Nd:YAG laser lesions (1064 nm, 9 ns pulse width) in each eye. One eye received a single foveal lesion of approximately 0.13 mJ total intraocular exposure (TIE) and the other received six parafoveal lesions which varied in TIE from 0.13 to 4 mJ. mfERGs and behavioral data were collected both pre- and post-exposure. mfERGs were recorded using stimuli that contained 103, 241, and 509 hexagons. Landolt C contrast acuity was measured with five sizes of Landolt C (0.33 to 11.15 cycles/degree) of varying contrast. mfERG response densities were sensitive to the functional retinal changes caused by the laser insult. In general, larger lesions showed greater mfERG abnormalities than smaller laser lesions. Deficits in contrast acuity were found to be more severe in the eyes with foveal injuries. Although the mfERG and contrast acuity assess different areas of the visual system, both are sensitive to laser-induced retinal damage and may be complementary tests for laser eye injury triage.
The evaluation of the safety of high-power light sources requires a broad understanding of both thermal and photochemical damage mechanisms in retinal tissue. A comprehensive model which can support complex spectral, temporal and spatial dependency of these effects is essential to evaluation of existing safe exposure limits across a broad parameter space. We present an initial implementation of a thermal damage model along with validating experiments. The model is capable of examining a wide parameter space and is highly extensible to the examination of a variety of damage mechanisms. Also presented is a recent study which examines the effects of a filtered Xenon arc lamp for an exposure duration of ten seconds. This data is examined in relation to the model and a number of historical data points. We also examine exposure limits from the American Council of Government Industrial Hygienists as they apply to these sources.
We report on our measurements of the Minimum Visible Lesion (MVL) thresholds for porcine skin [Yucatan mini-pig (Sus scrofa domestica)] for laser exposures at 810 nm and sub-50 femtosecond (fs) laser pulses. In this study we measured the ED50 skin thresholds from laser pulses that produced multiple self-focusing filaments while propagating from the laser to the skin. These high-powered (1-2 terawatt) filaments were focused on the flank of mini-pig and three trained readers determined the number of lesions becoming visible at 1-hour and 24-hour post-exposure. The observed damage patterns on the skin surface indicated the number of filaments in the laser pulse and these were photographed for future reference. Histological sections were obtained after both readings and the results will be reported later for sub-surface damage. The threshold using preliminary data at 1-hour was 9 mJ of energy and increased to 25 mJ after 24 hours. This increase in threshold indicated that many of the laser pulses produced only superficial damage (erthemia) that disappeared in 24 hours and that nearly 3 times the pulse energy was required to cause subsurface or cellular damage.
To assess the retinal hazards related to simultaneous exposure from two lasers of separate wavelengths, the retinal effects of 5-second laser irradiation from 532 nm and 647 nm were determined in non-human primates. A total of six eyes were exposed using equal amounts of power to determine the damage levels. The results were combined with those of previous, two-wavelength studies done by our group and compared to damage models developed in our lab. The data were also compared to the calculations resulting from use of the currently accepted method of predicting hazards from simultaneous lasing.
We investigate the relationship between the laser beam at the retina (spot size) and the extent of retinal injury from single ultrashort laser pulses. From previous studies it is believed that the retinal effect of single 3-ps laser pulses should vary in extent and location, depending on the occurrence of laser-induced breakdown (LIB) at the site of laser delivery. Single 3-ps pulses of 580-nm laser energy are delivered over a range of spot sizes to the retina of Macaca mulatta. The retinal response is captured sequentially with optical coherence tomography (OCT). The in vivo OCT images and the extent of pathology on final microscopic sections of the laser site are compared. With delivery of a laser pulse with peak irradiance greater than that required for LIB, OCT and light micrographs demonstrate inner retinal injury with many intraretinal and/or vitreous hemorrhages. In contrast, broad outer retinal injury with minimal to no choriocapillaris effect is seen after delivery of laser pulses to a larger retinal area (60 to 300 µm diam) when peak irradiance is less than that required for LIB. The broader lesions extend into the inner retina when higher energy delivery produces intraretinal injury. Microscopic examination of stained fixed tissues provide better resolution of retinal morphology than OCT. OCT provides less resolution but could be guided over an in vivo, visible retinal lesion for repeated sampling over time during the evolution of the lesion formation. For 3-ps visible wavelength laser pulses, varying the spot size and laser energy directly affects the extent of retinal injury. This again is believed to be partly due to the onset of LIB, as seen in previous studies. Spot-size dependence should be considered when comparing studies of retinal effects or when pursuing a specific retinal effect from ultrashort laser pulses.
A new source-term thermal model was used to determine the skin temperature rise using porcine skin parameters for various wavelengths, pulse durations, and laser spot sizes and is compared to the Takata thermal model. Expanding on this preliminary source-term model using a Gaussian profile to describe the spatial extent of laser pulse interaction in skin, we report on the coupling of temporal consideration to the model. Computer simulation of the new source-term model and the Takata thermal model are presented to highlight the theoretical extent of thermal damage. Laser exposures of 1.54 μm, 0.60 ms in duration and using spot sizes of 0.7 mm and 1.0 mm were applied to the porcine skin. The damage thresholds were determined at 1 hour and 24 hours post-exposures using probit analysis. The ED50 for these skin exposures at 24 hours post-exposure were 20 J/cm2and 8.1 J/cm2respectively. These damage thresholds are compared with our model predictions and another thermal model with the damage integral predicting damage levels. They are also compared with previously published skin thresholds and with the ANSI Standard’s MPE for 1540 nm lasers at 0.60 ms.
KEYWORDS: Skin, Temperature metrology, Infrared cameras, Monte Carlo methods, Scattering, Absorption, Pulsed laser operation, Light scattering, Data modeling, Cameras
We have measured the Minimum Visible Lesion (MVL) thresholds for porcine skin and determined the ED50 for exposures at 1314 nm and 0.35 ms laser pulses. An in-vivo pigmented animal model, Yucatan mini-pig (Sus scrofa domestica), was used in this study. We also have measured the thermal response using a high-speed Infrared camera for single pulse temperature recordings for Gaussian beams of 1 mm diameter. Several 2-D measurements of temperature as a function of time were made with an IR array detector thermal camera using a sampling rate of 100 frames per second. In Vitro samples of the same pig skin were used for measurements of the optical properties (absorption coefficient, μa, and reduced scattering coefficient μs) as a function of wavelength around 1315 nm wavelength. A measured surface temperature distribution for one IR laser pulse of 0.37J at a spot size of 1.2 mm diameter gave approximately a 43° C rise at a hot spot. Temperature distributions as a function of time and space will be presented and compared with the measured thresholds.
To properly assess the retinal hazards from several lasers using multiple wavelengths, the retinal effects of 10-second laser irradiation from 532 and 860 nm were determined in non-human primates for several different power combinations of these wavelengths. A total of 12 eyes were exposed using four different ratios of power levels to determine the contribution to the damage levels from each wavelength. The data are compared to the calculations resulting from use of the currently accepted method of predicting hazards from simultaneous laser. The ANSI-Z136 - 2000 standard was used to calculate the combined maximum permissible exposure (MPE) and for comparison with the measured visible lesion thresholds, i.e., ED50s.
A thermal model was used to calculate the skin temperature rise in porcine skin and predict the damage thresholds in terms of laser power for various wavelengths, pulse durations, skin parameters and laser spot sizes. Laser exposures of 1.54 μm, 0.60 ms in duration and using a 0.7 mm spot size were applied to the porcine skin. The damage thresholds were determined at 1-hour and 24-hour post exposures using probit analysis. Only one subject was exposed giving adequate fiducial limits at the 95% confidence level. The ED50 for these 72 exposures was determined to be 58 mJ, giving a radiant exposure of 15 Jcm-2. The damage threshold is compared with model predictions, with work previously published in the literature and with the ANSI Standard’s MPE for 1540 nm lasers at 0.60 ms.
The use of lasers in the infrared region between 1200-1400 nm has steadily increased in various industrial and commercial applications. However, there are few studies documenting damage thresholds for the skin in this region, and current laser safety standards are based on limited data. This study has determined preliminary skin damage thresholds for the Effective Dose for 50% probability (ED50) of a Minimum Visible Lesion (MVL) with laser exposure at 1314nm and 0.35 ms pulse width. An in-vivo pigmented animal model, Yucatan mini-pig (Sus scrofa domestica), was used in this study. The type and extent of tissue damage in the porcine skin was determined through histopathologic examination, and the findings are discussed. Finally, the results of this study were compared to other literature as well as to the existing ANSI Z136.1 (2000) standard for safe use of lasers.
With the advent of future weapons systems that employ high energy lasers, the 1315 nm wavelength will present a new laser safety hazard to the armed forces. Experiments in non-human primates using this wavelength have demonstrated a range of ocular injuries, including corneal, lenticular and retinal lesions, as a function of pulse duration and spot size at the cornea. To improve our understanding of this phenomena, there is a need for a mathematical model that properly
predicts these injuries and their dependence on appropriate exposure parameters. This paper describes the use of a finite difference model of laser thermal injury in the cornea and retina. The model was originally developed for use with shorter wavelength laser irradiation, and as such, requires estimation of several key parameters used in the computations. The predictions from the model are compared to the experimental data, and conclusions are drawn
regarding the ability of the model to properly follow the published observations at this wavelength.
The current laser safety standard for skin exposures, ANSI Z136.1, was based on a limited number of data points for various beam sizes at a few specific wavelengths. To help refine this standard, we explore the existence of a relationship between beam spot size and the ED50 lesion threshold values. In the first phase of this study we analyzed the spot size dependence of the skin lesion thresholds from previously documented experiments. We utilized the thermal skin model to predict damage thresholds and compared these with those presented in this paper. We report the results of this analysis , which we used to design an experiment to determine the true spot-size dependency of skin laser damage thresholds. The data collected in this first phase is discussed and compared to the existing ANSI Z136.1 (2000) laser safety standard.
We have measured the laser-induced breakdown (LIB) thresholds in water using an artificial eye for chirped and non-chirped laser pulses at 44 fs and 810 nm. We compare these measured thresholds to calculated values for a range of pulse widths from 20 fs to 120 fs and for various focal point diameters. The LIB threshold using a flat phase pulse, i.e., no chirped compensation for propagation through the water was measured to be 0.285 (0.280 - 0.290) μJ. Using a pre-chirp on the laser pulse, the LIB threshold dropped by one-third to 0.192 (0.191 - 0.194) μJ.
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.
Laser-induced breakdown is believed to be a primary retinal damage mechanism for sub-50 fs laser pulses. Recent studies of ultrashort pulse ocular effects indicate that with frequency chirp compensation, damage thresholds for the retina can be reduced. However, the reductions in threshold do not follow trends predicted by strictly input pulse duration-dependent models. We present a study of the effects of dispersion and the effects of spherical and chromatic aberrations in the propagation of ultrashort laser pulses. We consider optical models of the eye and also common laboratory optical configurations that mimic the eye. Intensity profiles in the focal volume of the optical system are computed for various materials, models, and amounts of aberration. A comparison of relative peak intensities is used to estimate trends in laser-induced breakdown (LIB) thresholds, based upon computation models previously published. These trends in LIB thresholds are compared to experimental data collected in our laboratory.
Damage thresholds using multiple laser pulses to produce minimum visible lesions (MVL) in rhesus monkey eyes are reported for near-infrared (800 nm) at 130 femtoseconds. Previous studies by our research group using single pulses in the near-infrared (1060 nm) have determined damage thresholds and retinal spot size dependence. We report the first multiple pulse damage thresholds using femtosecond pulses. MVL thresholds at 1 hour and 24 hours postexposure were determined for 1, 100 and 1,000 pulses and we compare these with other reported multiple pulse thresholds. These new data will be added to the databank for retinal MVL's as a function of pulse repetition rate for this pulsewidth and a comparison will be made with the ANSI standard for multiple pulse exposures. Our measurements show that the retinal ED50 threshold/pulse in the paramacula decreases for increasing number of pulses. The MVL-ED50 at the threshold/pulse decreased by a factor of 4 (0.55 (mu) J to 0.13 (mu) J/pulse) for an increase from 1 to 100 pulses.
Single pulses in the near-infrared (800 nanometers) were used to measure retinal minimum visible lesion (MVL) thresholds in rhesus monkey eyes at a pulse width of 130 femtoseconds (fs) within both the macula and paramacula regions. We report the MVL thresholds, determined at 1 hour and 24 hours post exposure, which were obtained within the macula and adjacent paramacula. This data will provide a direct comparison of the sensitivities of different retinal areas to laser injury and provide additional insight to laser damage. These new data points will be added to the databank for MVLs for single pulses. The MVL-ED50 threshold for the macula was measured to be 0.35 (mu) J at 24 hours postexposure, which compares with 0.43 (mu) J measured at 580 nm and the 0.17 (mu) J measured at 532 nm in our laboratory. Our measurements show that the retinal ED50 threshold in the paramacula was larger by a factor of 1.6 than in the macula. This factor of 1.6 is in good agreement with the factor of 1.1 to 2.5 reported in previous studies.
We wish to identify the change in extent of retinal tissue injury due to varying the spot size at the retina of ultrashort laser pulses. We compared the effects of delivery of near infrared (1060 nm) single laser pulses to an 800 micron diameter retinal spot to previously reported laser retinal effects. We examined macular lesions 24 hours after delivery of near-infrared (1060 nm wavelength) ultrashort laser to 804 micron spot-size, using fundus examination, fundus photographs and fluorescein angiograms. Using light microscopy, we examined sections of these lesions obtained 24 hours after laser delivery. The degree of retinal damage was compared to our data published previously by using a modified version of our previous grading scale. The 150 fs near infrared, large spot laser lesions were remarkable in their clinical and pathological appearance. The lesions, rather than centering on a single focal spot of pallor as typically seen in pulsed laser lesions of the retina, demonstrated a spotted pattern of multiple focal lesions across the area of laser delivery. There was also choroidal damage in several eyes but the Bruch's membrane remained intact. Although there was choroidal damage in the 150 fs near infrared wavelength small spot laser lesions there was not significant thermal spread. The small spot ultrashort visible wavelength showed no significant thermal spread and no choroidal damage. Larger spot-size demonstrated a broader area of damage than that of the smaller spot-size and different choroidal effect when compared to smaller sized lesions.
KEYWORDS: Tissues, Transmission electron microscopy, 3D image processing, Confocal microscopy, Microscopy, 3D modeling, Laser tissue interaction, Electron microscopy, Microscopes, 3D image reconstruction
In predicting and measuring laser effect on retinal tissue for most of the visible to near infrared spectrum, one is concerned with the melanosome as the major absorber of incident energy. Differences in the location and density of melanosomes in the retinal pigment epithelium may have an impact on the effect of laser energy delivered to those tissues. Current models use estimates of numbers of melanosomes usually in an even distribution across a 5 - 8 micrometer deep volume. The goal of our study is to identify the three-dimensional distribution of melanosomes within the retinal pigment epithelium (RPE) for the use of those modeling laser tissue effects. We examined normal retinal pigment epithelium using three-dimensional (3-D) reconstruction from images obtained by transmission electron microscopy (TEM), light microscopy (LM) and confocal microscopy. Images were captured on a digital camera system attached to the microscope for both the transmission electron and light microscopy. Three-dimensional reconstruction was performed after digital deconvolution of microscopic images (Vaytek, Inc.). Three- dimensional images were then utilized for analysis of distribution of melanosomes and organelles within the pigment epithelial block. The distribution of melanosomes will be useful for accurate mathematical modeling of laser impact on the retina.
For the past several years the US Air Force has led a research effort to investigate the thresholds and mechanisms for retinal damage from ultrashort laser pulses [i.e. nanosecond (10-9 sec) to femtosecond (10-15 sec) pulse widths]. The goal was to expand the biological database into the ultrashort pulse regime and thus to allow establishment of maximum permissible exposure limits for these lasers. We review the progress made in determining trends in retial damage by ultrashort laser pulses in the visible and near infrared, including variations in spot size and number of pulses. We also discuss the most likely damage mechanisms operative in this pulse width regime and discuss relevance to laser safety.
We review the progress made in determining the trends in retinal damage from laser pulse from one nanosecond to one hundred femtoseconds in the visible and near-infrared wavelength regimes. These trends have suggested a maximum permissible exposure limit for laser pulses in the retinal hazard regime between one nanosecond and one hundred femtoseconds. We discuss the likely mechanisms for retinal damage and the implications to using ultrashort laser systems safely. We will summarize the challenges in appropriately addressing safety when using ultrashort laser systems in advanced applications.
Extensive research of ultrashort ocular damage mechanisms has shown that less energy is required for retinal damage for pulses shorter than one nanosecond. Laser minimum visible lesion thresholds for retinal damage from ultrashort (i.e. < 1 ns) laser pulses occur at lower energies than in the nanosecond to microsecond laser pulse regime. WE review the progress made in determining the trends in retinal damage from laser pulses of one nanosecond to one hundred femtoseconds in the visible and near-infrared wavelength regimes. We discuss the most likely damage mechanism(s) operative in this pulse width regime and discuss implications on laser safety standards.
Single pulses in the near-infrared (1060 nanometers) were used to measure retinal spot size dependence of minimum visible lesion (MVL) thresholds in rhesus monkey eyes at a pulsewidth of 150 femtoseconds. We report the MVL thresholds determined at 1 hour and 24 hours post exposure which were obtained with 2 different lenses placed in front of the eye to vary the retinal spot size. Also we report the fluorescein angiography thresholds (FAVL) for the above measurements. These new data points will be added to the databank for Retinal Maximum Permissible Exposure (MPE) as a function of spot size for this pulsewidth and a comparison will be made with previous spot size dependency studies. Our measurements show that the retinal ED50 threshold fluence decreases for increasing retinal spot sizes. The fluence at the MVL threshold decreased by a factor of 3 for an increase in retinal image diameter by a factor of 4.5 times from the smallest to largest spot size.
Ultrashort pulsed laser retinal effects vary widely depending on the configuration of the laser energy as it reaches the retina and surrounding structures. Tissue response is determined by: wavelength, pulsewidth, energy per pulse, peak irradiance, linear optics of the beam path, and non linear optics of the ultrashort beam. In vivo, we have reported a range of lesions from visible and from near infrared ultrashort laser pulses. New data from additional infrared studies in vivo is combined with our previous data to present an overview of retinal effects and how these might be selected for retinal surgical use.
Single pulses in the near-infrared (1060 and 1064 nanometers) were used to measure ophthalmoscopically minimum visible lesion (MVL) thresholds in the rhesus monkey eyes for pulsewidths of 7 nanoseconds (ns), 20 picoseconds (ps), and 150 femtoseconds (fs). MVL thresholds for 1 hour reading and 24 hour reading are reported as the 50% probability for damage (ED50) together with their fiducial limits. These measured thresholds are compared with previously reported thresholds for near-IR and visible wavelengths for the complete range of pulsewidths (ns, ps, and fs). Threshold doses were lower at the 24 hour reading than at the 1 hour reading and both ED50 for the fs pulsewidths were less than 25% of those for ns pulsewidths. MVL thresholds ranged from 19 (mu) J at 7 ns down to 1 (mu) J at 150 fs. Thresholds measured for the nanosecond and picosecond pulsewidths using infrared laser pulses were an order of magnitude larger than for the visible wavelengths at similar pulsewidths while the 150 fs threshold was only about double the value for the 580 nm visible wavelength at 90 fs.
Self-focusing is a phenomena that is induced in certain materials when high irradiance laser light interacts with the material. High irradiances are most readily achieved with focused ultrashort laser pulses. Past theoretical calculations using the nonlinear wave equation have calculated the critical power for self-focusing by tightly focused beams in water at 580 nm to be 1 MW. The recent pulse propagation model by Feng et al. has been used to find the pulse duration where the self-focusing threshold can be most easily found. In addition, a first-order model of laser-induced breakdown developed by Kennedy has predicted that the threshold for breakdown at each pulse duration is independent of spot size. Thus self-focusing can be seen from a precise measurement of spot size and breakdown threshold. With several optical setups with different predicted spot sizes, we measured the spot size by knife- edge technique at energies far below the breakdown or self- focusing thresholds for a pulse duration of 2.4 ps, 800 fs, and 126 fs. We also measured the laser-induced breakdown threshold for each of these optical setups. The laser- induced breakdown irradiance threshold was constant for those spot sizes that were below the self-focusing threshold, as predicted by Kennedy's model. The measurements of self-focusing for ultrashort laser pulses in water and its implications on retinal damage will be discussed in this paper.
Minimum visible lesions (MVL) are reported for picosecond and nanosecond laser pulses at near-IR wavelengths in the primate eye, Macaca Mulatta. The 50 percent probability for damage (ED50) dosages are reported for the 24 hour for both MVL and fluorescein angiography visible lesion thresholds at the 95 percent confidence level. The thresholds decreased by as much as 48 percent between the 1- hour reading and were lower in all cases at 24 hours. MVL- (ED50) threshold doses were 19.1 uJ at 7 ns and 4.2 uJ and 4.6 uJ at 80 ps and 20 ps respectively. Our thresholds measured for the near-IR laser pulses were lower by a factor of 4 to 8 lower than previously reported values but almost an order in magnitude higher than visible MVL thresholds for similar pulsewidth in the visible wavelengths.
Purpose: to assess the early in vivo evolution of tissue response and wound healing from ultrashort pulsed laser retinal lesions by correlating the cross sectional morphology from sequential optical coherence tomography with histopathologic sectioning. Methods: single ultrashort laser pulses were placed in the Macacca mulatta retina and evaluated by cross-section optical coherence tomography (OCT). These images were compared at selected time-points with corresponding histological sections. Results: OCT was able to detect the acute tissue injury from laser delivery and the evolution of the healing response over 8 days after laser delivery. These OCT images correlated well with histopathologic findings. Conclusion: analysis of the extent of initial laser lesions and the type of healing response can be performed in serial sequence with OCT providing new insight into the healing response form laser injury. This information correlates well with microscopic data.
We have made an indirect in-vivo determination of spot size focusing in the rhesus monkey model. Measurement of the laser induced breakdown threshold both in-vitro and in-vivo allow correlation and assignment of a spot size after focusing through the living eye. We discuss and analyze the results and show how trends in minimum visible lesion data should be assessed in light of chromatic aberration. National laser safety standards are based on minimal visual lesion (MVL) threshold studies in different animal models. The energy required for a retinal lesion depends upon may parameters including wavelength and retinal spot size. We attempt to explain trends in reported MVL threshold studies using a model of the eye which allows calculation of changes in retinal spot size due to chromatic aberration.
Researchers at the USAF Academy and the University of Texas are developing a computer-assisted retinal photocoagulation system for the treatment of retinal disorders (i.e. diabetic retinopathy, retinal tears). Currently, ophthalmologists manually place therapeutic retinal lesions, an acquired technique that is tiring for both the patient and physician. The computer-assisted system under development can rapidly and safely place multiple therapeutic lesions at desired locations on the retina in a matter of seconds. Separate prototype subsystems have been developed to control lesion depth during irradiation and lesion placement to compensate for retinal movement. Both subsystems have been successfully demonstrated in vivo on pigmented rabbits using an argon continuous wave laser. Two different design approaches are being pursued to combine the capabilities of both subsystems: a digital imaging-based system and a hybrid analog-digital system. This paper will focus on progress with the digital imaging-based prototype system. A separate paper on the hybrid analog-digital system, `Hybrid Retinal Photocoagulation System', is also presented in this session.
Recent studies of retinal damage due to ultrashort laser pulses have shown that less energy is required for retinal damage for pulses shorter than one nanosecond. Laser minimum visible lesion thresholds for retinal damage from ultrashort laser pulses are produced at lower energies than in the nanosecond to microsecond laser pulse regime. We review the progress made in determining the trends in retinal damage from laser pulses of one nanosecond to one hundred femtoseconds in the visible and near-infrared wavelength regimes. We have determined the most likely damage mechanism operative in this pulse width regime and discuss implications on laser safety standards.
An artificial eye has been designed and assembled that mimics the focusing geometry of the living eye. The artificial eye’s focusing characteristics are measured and compared with those of the in vivo system. The artificial eye is used to measure several nonlinear optical phenomena that may have an impact on the laser damage thresholds of the retina produced by ultrashort laser pulses. We chose a focal length of 17 mm to simulate the rhesus monkey eye, with a visual cone angle of 8.4 deg for a 2.5-mm diameter laser beam input. The measured focal point image diameter was 5.661 mm, which was 1.5 times the calculated diffractionlimited image diameter. This focusing system had the best M2 of all the systems evaluated. We used the artificial eye to measure the threshold for laser-induced breakdown, stimulated Brillouin scattering, supercontinuum generation, and pulse temporal broadening due to group velocity dispersion.
Successful retinal tracking subsystem testing results in vivo on rhesus monkeys using an argon continuous wave laser and an ultra-short pulse laser are presented. Progress on developing an integrated robotic retinal laser surgery system is also presented. Several interesting areas of study have developed: (1) 'doughnut' shaped lesions that occur under certain combinations of laser power, spot size, and irradiation time complicating measurements of central lesion reflectance, (2) the optimal retinal field of view to achieve simultaneous tracking and lesion parameter control, and (3) a fully digital versus a hybrid analog/digital tracker using confocal reflectometry integrated system implementation. These areas are investigated in detail in this paper. The hybrid system warrants a separate presentation and appears in another paper at this conference.
Lacking established national laser safety standards for sub-nanosecond, single pulse laser systems operating in the visible to near infrared spectral regions has resulted in research efforts designed to define the risks associated with human ocular exposure. The bulk of this work has been focused on visible wavelength laser pulses and resulting retinal threshold damage. We report threshold measurements for Minimum Visible Lesions (MVL) at the retina for picosecond (ps) laser pulses in Macaca Mulatta eyes using near infrared wavelengths (80 ps and 1064 nm). The 50% probability for damage (ED50) dosages are calculated for 1 hour and 24 hour post exposures using the SAS probit analysis. The MVL ED50 threshold and the fiducial limits at the 95% confidence level were found to be 4.16 (3.00 - 5.77) microjoules ((mu) J). Fluorescein angiography (FA) was accomplished at both 1 hour and 24 hour post exposure, however the analysis for FA is currently underway and results will not be reported here.
Threshold measurements for laser-induced breakdown (LIB) and bubble generation for femtosecond laser pulsewidths have been made in vivo for rhesus monkey eyes. These LIB thresholds are compared with model-predicted thresholds for water and minimum visible lesion thresholds in Dutch Belted rabbit and rhesus monkey eyes. LIB thresholds in biological materials including vitreous, normal saline, tap water, and ultrapure water have been measured and reported using an artificial eye. We have recorded on video the first LIB causing bubble formation in any eye in vivo using albino rabbit eyes, pigmented rabbit eyes, and rhesus monkey eyes. External optics were used to focus the image within the vitreous and the bubbles generated were clearly formed anterior to the retina within the vitreous humor. The length of time that the bubbles are visible depends on the pulse energy delivered and may last for several seconds. However, for pulse energies near thresholds, the bubbles have a very short lifetime and may be seen on the video for only one frame. The plasma formation at the breakdown site acts as a limiting mechanism for energy transmission and may explain why high-energy femtosecond pulses at energies up to 100 microjoules sometimes do not cause severe damage to the retina. This fact may also explain why it is so difficult to product hemmorrhagic lesions in either the rabbit or primate eye with 100-femtosecond laser pulses.
Recent studies of retinal damage due to ultrashort laser pulses have shown interesting behavior. Laser induced retinal damage for ultrashort (i.e. less than 1 ns) laser pulses is produced at lower energies than in the nanosecond to microsecond laser pulse regime and the energy required for hemorrhagic lesions is much greater times greater for the nanosecond regime. We investigated the tissue effects exhibited in histopathology of retinal tissues exposed to ultrashort laser pulses.
Optical Coherence Tomography (OCT) is a new, non-invasive diagnostic technique for high resolution optical 3D imaging, which was developed and applied to several different biological materials during the lasi; five years [1, 2, 3]. A unique application ofthis technique is the microscopical cross-sectional imaging ofpostenor structures ofthe eye which are not accessable with other high resolution techniques in-vivo neither with x-ray-imaging nor with high frequency ultrasound scanning. The superior spatial resolution on the order ofabout lOtm laterally and axially, the high signal-to-noise ratio ofmore than 100 db and the fast acquisition-time of one second for a two dimensional scan provides a technique for cross-sectional in-vivo-momtoring ofintraocular structures and therefore the possibility to study the time course of anatomical and pathological developments in the eye. The acute morphological changes of ocular structures and their biological healing response after shortterm impacts such as high-intensity laser exposures are ofparticular interest for the understanding of the mechanisms responsible for therapeutic laser-application in ophthal-mology as well as for laser injury to the eye. A correlation between cross-sectional OCT-images and structural findings using classical histopathological techniques facilitates a better interpretation ofthe characteristic patterns seen in OCTimages and defines the sensitivity ofthe OCT-technique to image morphological details. On the other hand preparational artefacts not avoidable in all histological procedures can be identified and analyzed by comparing histological micrographs with OCT-images of exactly the same structure. First results of an experimental study where retinal effects were produced in monkey eyes using laser pulses from 200 ms to 130 fs in duration are presented in this article. The applied energies from 5tJ to 50 mJ were able to induce the whole spectrum of biological effects possible in the eye, ranging from intraretinal microruptures to extensive thermal denaturation and massive preretinal hemorrhages [4, 5, 6].
Threshold measurements for femtosecond laser pulsewidths have been made for retinal minimum visible lesions (MVLs) in Dutch Belted rabbit and rhesus monkey eyes. Laser-induced breakdown (LIB) thresholds in biological materials including vitreous, normal saline, tap water, and ultrapure water have been measured and reported using an artificial eye. We have recorded on video the first LIB causing bubble formation in any eye in vivo using albino rabbit eyes (New Zealand white) with 120- femtosecond (fs) pulses and pulse energies as low as 5 microjoules ((mu) J). These bubbles were clearly formed anterior to the retina within the vitreous humor and, with 60 (mu) J of energy, they lasted for several seconds before disappearing and leaving no apparent damage to the retina. We believe this to be true LIB because of the lack of pigmentation or melanin granules within the albino rabbit eye (thus no absorptive elements) and because of the extremely high peak powers within the 5-(mu) J, 120-fs laser pulse. These high peak powers produce self-focusing of the pulse within the vitreous. The bubble formation at the breakdown site acts as a limiting mechanism for energy transmission and may explain why high-energy femotsecond pulses at energies up to 100 (mu) J sometimes do not cause severe damage in the pigmented rabbit eye. This fact may also explain why it is so difficult to produce hemorrhagic lesions in either the rabbit or primate eye with 100-fs laser pulses.
Threshold measurements for Minimum Visible Lesions (MVL) at the retina are reported for 60 picoseconds (ps) and 4 nanoseconds (ns), single laser pulses in rhesus monkey eyes using a visible wavelength of 532 nanometers (nm) from a doubled Nd:YAG laser. The 50% probability for damage (ED50) dosages are calculated for 1 hour and 24 hour post exposures using 95% fiducial limits. For both pulsewidths, the threshold values calculated by probit analysis decrease between the 1 hour and 24 hour ophthalmoscopic evaluations. The ED50 value determined for the 60 ps pulsewidth was less than half the value at 4 ns (0.43 (mu) J/60 ps vs. 0.90 (mu) J/4 ns at 24 hours) for both readings. Of the 136 exposures for pulse energies ranging from 0.03 to 5.0 (mu) J no hemorrhagic lesions were produced for either pulsewidth studied. However, at 6.6 (mu) J one intraretinal hemorrhagic lesion was observed for 60 ps. The slope of the probit curve was higher for 60 ps when compared with the 4 ns value (3.03 at 60 ps vs. 2.68 at 4 ns). MVL threshold doses calculated are comparable with those reported in the literature. However, the 4 ns MVL values is less than one order of magnitude (a factor 4.7) above the Maximum Permissible Exposure (MPE) level as defined by the 'American National Standard For The Safe Use Of Lasers', ANSI Z136.1-19932. We present the current MVL data as it compares with previous data obtained for picosecond and femtosecond laser pulse thresholds and provide a preliminary assessment of how the ANSI MPE standard might be amended.
Threshold measurements at 90 femtoseconds (fs) and 600 fs have been made for minimum visible lesions (MVLs) using Dutch Belted rabbit and Rhesus monkey eyes. Laser induced breakdown (LIB) thresholds on biological materials including vitreous, normal saline, tap water, and ultrapure water are reported along with irradiance calculations utilizing nonlinear transmission properties including self-focusing. At both pulsewidths the ED50 dose required for the Rhesus monkey eye was less than half the value determined for the Dutch Belted rabbit eye, all thresholds being 1 microjoule ((mu) J) or less. Measurements on the Rhesus eye at 600 fs found the ED50 dose (0.26 (mu) J) to be much lower than the ED50 dose at 90 fs (0.43 (mu) J). But for these two pulsewidths, almost the same energy level was determined for the Dutch Belted rabbit eye (0.94 (mu) J vs. 1.0 (mu) J). LIB threshold measurements at 100 fs and 300 fs using a simulated eye with isolated vitreous found the ED50 dosages to be 3.5 and 6.0 (mu) J respectively. We found in all cases that the ED50 dosages required to produce MVLs in 24 hours for rabbit and monkey eyes were less than the ED50 values measured for LIB in vitreous or saline or any other breakdown values reported. Also observed was the fact that many of the threshold lesions did not appear in the 1-hour postexposure check but clearly showed up at the 24-hour reading which provided for a much lower threshold dose after 24 hours. We discuss the energy levels and peak powers at which nonlinear effects can begin to occur.
We present our clinical evaluation of hemorrhagic and non-hemorrhagic 90 fs single pulses in rabbits and primates. The rabbit and primate eye present unique in vivo models for evaluation of retinal and choroidal laser induced hemorrhages with distinct differences in their retinal anatomy. We found two different hemorrhagic events to occur in the posterior pole with delivery of 90 fs pulses. First, in the Dutch Belted rabbit, we found large amounts of energy per pulse (from 20 to 60 times ED50) were required for formation of subretinal hemorrhages. Second, in the Rhesus monkey, we found significant numbers of small intraretinal hemorrhages from relatively low energy 90 fs pulses. Both the Dutch Belted rabbit and the Rhesus monkey failed to consistently show subretinal hemorrhagic lesions form very high pulse energies. Our findings suggest more energy absorption at the level of the retinal circulation than the choroidal circulation with our pulse parameters. The effects of the laser on the retinal circulation may be due to the use of a wavelength of 580 nm. At this wavelength the oxyhemoglobin to melanin absorption ratio is nearly at its peak (approximately 0.40), perhaps allowing improved absorption in the retinal vasculature. One precaution with this finding, however, are the distinct differences between primate and non-primate ocular systems. Further studies are required to resolve the differences in damage at the level of the RPE and choroid between rabbits and primates.
Threshold measurements for Minimum Visible Lesions (MVL) at the retina are reported for femtosecond (fs) and picosecond (ps) laser pulses in Rhesus monkey eyes using visible wavelengths. The 50% probability for damage (ED50) dosages are calculated for 1 hour and 24 hour post-exposures at the 95% confidence level. The ED50 values are found to decrease with pulsewidth down to 600 fs. At 90 fs the ED50 dosages were noted to increase slightly when compared with the 3 ps and 600 fs values. Fluorescein angiography (FA) was accomplished at both 1 hour and 24 hour post-exposure and did not demonstrate lower threshold for damage, which has been the case for MVL's created with longer pulse durations (>= nanoseconds). At the 90 fs pulse duration, MVLs were not observed below 0.1 (mu) J. At energies greater than 0.1 (mu) J, both MVL and the absence of MVL's were observed up to 1.4 (mu) J. Above 1.4 (mu) J all energies delivered showed MVL development. Out of 138 data points taken at 90 fs, 94 were between 0.1 and 14 (mu) J, and the observed lesions are distributed with approximately 50% probability throughout this energy rate.
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