David J. Stolarski

Spectrally resolved white-light interferometry for measurement of ocular dispersion

Spectrally resolved white-light interferometry was used to measure the wavelength dependence of refractive index (i.e., dispersion) for various ocular components. Verification of the techniques efficacy was substantiated by accurate measurement of the dispersive properties of water and fused silica, which have both been well-characterized in the past by single-wavelength measurement of the refractive index. The dispersion of bovine and rabbit aqueous and vitreous humors was measured from 400 to 1100 nm. In addition, the dispersion was measured from 400 to 700 nm for aqueous and vitreous humors extracted from goat and rhesus monkey eyes. An unsuccessful attempt was also made to use the technique for dispersion measurement of bovine cornea and lens. The principles of white-light interferometry, including image analysis, measurement accuracy, and limitations of the technique, are discussed. In addition, alternate techniques and previous measurements of ocular dispersion are reviewed.

Retinal damage and laser-induced breakdown produced by ultrashort-pulse lasers

Abstract• Background: In vivo retinal injury studies using ultrashort-pulse lasers at visible wavelengths for both rabbit and primate eyes have shown that the degree of injury to the retina is not proportional to the pulse energy, especially at suprathreshold levels. In this paper we present results of calculations and measurements for laser-induced breakdown (LIB), bubble generation, and self-focusing within the eye. • Methods: We recorded on video and measured the first in vivo LIB and bubble generation thresholds within the vitreous in rabbit and primate eyes, using external optics and femtosecond pulses. These thresholds were then compared with calculations from our LIB model, and calculations were made for self-focusing effects within the vitreous for the high peak power pulses. • Results: Results of our nonlinear modeling and calculations for self-focusing and LIB within the eye were compared with experimental results. The LIB ED50 bubble threshold for the monkey eye was measured and found to be 0.56 μJ at 120 fs, compared with the minimum visible lesion (MVL) threshold of 0.43 μJ at 90 fs. Self-focusing effects were found to be possible for pulsewidths below 1 ps and are probably a contributing factor in femtosecond-pulse LIB in the eye. • Conclusions: Based on our measurements for the MVL thresholds and LIB bubble generation thresholds in the monkey eye, we conclude that in the femtosecond pulsewidth regime for visible laser pulses, LIB and self-focusing are contributing factors in the lesion thresholds measured. Our results may also explain why it is so difficult to produce hemorrhagic lesions in either the rabbit or primate eye with visible 100-fs laser pulses even at 100 μJ of energy.

Ultrashort laser pulse bioeffects and safety

Recent studies of retinal damage due to ultrashort laser pulses have shown that less energy is required for retinal damage for pulses shorter than 1 ns than that for longer pulses. It has also been shown that more energy is required for near-infrared (NIR) wavelengths than in the visible because the light focuses behind the retina, requiring more energy to produce a damaging fluence on the retina. We review the progress made in determining the trends in retinal damage from laser pulses of 1 ns to 100 fs in the visible and NIR wavelength regimes. We have determined the most likely damage mechanism(s) operative in this pulse width regime.

Integrated light spectroscopy of laser-induced breakdown in aqueous media

In the scientific literature there is little information that describes the fundamental physical processes of laser induced breakdown (LIB) in transparent liquids. Our goal is to characterize these fundamental properties, which are critical to the understanding of retinal and other ophthalmic damage produced by ultrashort laser pulses. Laser pulses of 5.0 nanoseconds (ns) at less than 5.0 milli-Joules (mJ) per pulse and pulses of 80 picoseconds (ps) at 0.5 to 1.5 mJ per pulse from a Nd:YAG regenerative amplifier were used to produce LIB in a variety of aqueous media. These include physiological saline solution, triple-distilled water, and tap water. The resulting luminescent plasmas were analyzed using integrated light spectroscopy from a Chromex 0.25 meter (m) spectrograph. Plasmas were recorded in the wavelength region from 300 to 900 nm. Each spectrum obtained was analyzed using a Planck distribution for blackbody emission. The surface temperatures of the plasmas for the two pulse durations were computed to be in the 5000 K to 10,000 K range, depending on the pulse duration and energy. Also, the spectrographs from the saline solution included distinct spectral lines of emission over the broad band spectra, such as the 589 nm atomic emission line of sodium. We will discuss the time-integrated spectroscopy of LIB in various solution, and how LIB might mediate retinal damage induced by ultrashort laser pulses.

Porcine skin visible lesion thresholds for near-infrared lasers including modeling at two pulse durations and spot sizes

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 micros) at 24-h postexposure are measured to be 99 and 83 J cm(-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 J cm(-2) for a 5-mm-diam top-hat laser pulse.

Infrared skin damage thresholds from 1940-nm continuous-wave laser exposures

Abstract. A series of experiments were conducted in vivo using Yucatan miniature pigs (Sus scrofa domestica) to determine thermal damage thresholds to the skin from 1319-nm continuous-wave Nd:YAG laser irradiation. Experiments employed exposure durations of 0.25, 1.0, 2.5, and 10 s and beam diameters of ∼0.6 and 1 cm. Thermal imagery data provided a time-dependent surface temperature response from the laser. A damage endpoint of fifty percent probability of a minimally visible effect was used 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. Resultant trends with respect to exposure duration and beam diameter are compared with current standardized exposure limits for laser safety. Mathematical modeling agreed well with experimental data, predicting that though laser safety standards are sufficient for exposures <10  s, they may become less safe for very long exposures.

Precision Targeting with a Tracking Adaptive Optics Scanning Laser Ophthalmoscope

Precise targeting of retinal structures including retinal pigment epithelial cells, feeder vessels, ganglion cells, photoreceptors, and other cells important for light transduction may enable earlier disease intervention with laser therapies and advanced methods for vision studies. A novel imaging system based upon scanning laser ophthalmoscopy (SLO) with adaptive optics (AO) and active image stabilization was designed, developed, and tested in humans and animals. An additional port allows delivery of aberration-corrected therapeutic/stimulus laser sources. The system design includes simultaneous presentation of non-AO, wide-field (~40 deg) and AO, high-magnification (1-2 deg) retinal scans easily positioned anywhere on the retina in a drag-and-drop manner. The AO optical design achieves an error of <0.45 waves (at 800 nm) over ±6 deg on the retina. A MEMS-based deformable mirror (Boston Micromachines Inc.) is used for wave-front correction. The third generation retinal tracking system achieves a bandwidth of greater than 1 kHz allowing acquisition of stabilized AO images with an accuracy of ~10 μm. Normal adult human volunteers and animals with previously-placed lesions (cynomolgus monkeys) were tested to optimize the tracking instrumentation and to characterize AO imaging performance. Ultrafast laser pulses were delivered to monkeys to characterize the ability to precisely place lesions and stimulus beams. Other advanced features such as real-time image averaging, automatic highresolution mosaic generation, and automatic blink detection and tracking re-lock were also tested. The system has the potential to become an important tool to clinicians and researchers for early detection and treatment of retinal diseases.

Thresholds for retinal injury from multiple near-infrared ultrashort laser pulses

Multiple-pulse lasers are routinely used in the laboratory for research, manufacturing, medical procedures, and in military applications. In order to provide a safe work environment for personnel using these lasers, safety standards have been established and have been in use for many years. These safety standards have addressed laser pulses of nanosecond duration and longer. Recently, safety standards have been updated to address laser pulses as short as 100 femtoseconds in duration. In order to tie these “ultrashort” laser pulses to hazard trends in currently established standards for multiple-pulse exposures with repetition rates less than several kilohertz, this experiment was conducted. Reported herein are minimum visible lesion thresholds in the paramacula of the primate retina using an 800-nm wavelength laser with 1,000 pulses per second, at 130 femtoseconds (fs) pulse duration. The minimum visible lesion (MVL) thresholds were determined at 1 h and 24 h post exposure for 1, 10, 100, 1,000, and 10,000 pulses and are compared with thresholds reported by other researchers. These new data are evaluated relative to the current safety standards for retinal exposure limits as a function of the number of pulses for femtosecond-pulse duration. Data from this study show that the retinal ED50 thresholds/pulse in the paramacula decrease by almost a factor of four as the number of pulses goes from one to ten and then decrease very little for an increase of three decades more in the number of pulses. The MVL-ED50 at the threshold decreased from 0.55 &mgr;J for a single pulse to 0.15 &mgr;J/pulse for 10 pulses and then only to 0.11 &mgr;J/pulse for 10,000 pulses.

Infrared laser damage thresholds for skin at wavelengths from 0.810 to 1.54 microns for femtosecond to microsecond pulse durations

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

Simultaneous Exposure Using 532 and 860 nm lasers for visible lesion thresholds in the rhesus retina.

The growth of commercially available, simultaneous multi-wavelength laser systems has increased the likelihood of possible ocular hazard. For example, many systems utilize frequency multiplying methods to produce combinations of visible, near-infrared, and ultraviolet wavelengths. Unfortunately, very little data exists to substantiate the current methods for estimating hazards from simultaneous lasing. To properly assess the retinal hazards from these wavelengths, the retinal effects of 10-s laser irradiation from 532 and 860 nm were determined in non-human primates for four different relative dosage combinations of these wavelengths. This pair of wavelengths represents the typical problem of a visible-wavelength laser combined with an in-band, infrared wavelength that is not as well focused at the retina—a situation difficult to address. To add confidence to the experimental results obtained, a theoretical thermodynamic model was developed to predict the minimal damage threshold for simultaneous wavelengths at 1 h post exposure. The new model calculations and the data obtained are compared with results from one currently accepted method of predicting relative exposure limits from multi-wavelength systems. In addition, the current ANSI-Z136-2000 standard was used to compute the combined MPEs for comparison with measured visible lesion thresholds. A total of 12 eyes were exposed using four different ratios of power levels (532/860 power rations) to determine the contribution to the damage levels from each wavelength. The experimental data were analyzed using probit analysis at both 1-h and 24-h post exposure to determine the minimum-visible-lesion (MVL) thresholds at ED50 values, and these thresholds at 24 h varied from 5.6 mW to 17 mW total intraocular power.