Irradiation of the ocular lens of numerous species by near-UV or short-visible wavelengths induces a blue-green fluorescence, which can be a source of intraocular veiling glare. Wavelengths longer than the ~365-nm lens absorption peak induce progressively weaker but also progressively more red-shifted fluorescence emission. The more red-shifted emission has a higher luminous efficiency and, in fact, earlier studies in this laboratory have demonstrated that the lens fluorescence in the nonhuman primate yields an approximately constant luminous efficiency when excited by equal radiant exposures over the wavelength range from 350 to 430 nm. Now, with the recent development and projected widespread use of "blue" diode lasers, a further study extending the measurements of the induced fluorescence efficiency and of the consequent veiling glare to the human lens seemed timely. The current study quantifies the fluorescence intensity induced in the human lens, both in terms of radiance and luminance, as a function of exciting light intensity, excitation wavelength, and subject age. The spatial distribution of the emitted fluorescence is also examined. These data are shown to imply that exposure to near-UV/blue wavelength sources at "safe" exposure levels (according to existing laser safety standards) can induce a veiling glare intense enough to degrade visual performance, and that the fluorescence intensity and consequent glare disruption show little dependence on subject age.
Irradiation of the ocular lens of numerous species by near-UV or short-visible wavelengths induces a blue-green fluorescence, which can be a source of intraocular veiling glare. Wavelengths longer than the ~365-nm lens absorption peak induce progressively weaker but also progressively more red-shifted fluorescence emission. The more red-shifted emission has a higher luminous efficiency and, in fact, earlier studies in this laboratory have demonstrated that the lens fluorescence in the non-human primate yields an approximately constant luminous efficiency when excited by equal radiant exposures over the wavelength range from 350 to 430 nm. Now, with the recent development and projected widespread use of "blue" and near-UV diode lasers, a further study extending the measurements of the induced fluorescence efficiency and of the consequent veiling glare to the human lens seemed timely. The current study quantifies the fluorescence intensity induced in the human lens, both in terms of radiance and luminance, as a function of exciting light intensity, excitation wavelength and subject age. The spatial distribution of the emitted fluorescence is also examined. These data are shown to imply that exposure to near-UV/blue wavelength sources at "safe" exposure levels (reference existing laser safety standards) can induce a veiling glare intense enough to degrade visual performance, and that the fluorescence intensity and consequent glare disruption show little dependence on subject age.
KEYWORDS: Laser damage threshold, Retina, Laser induced damage, Eye, Data modeling, Medical research, In vivo imaging, Thermal modeling, Optical testing, Imaging systems
The dependence of retinal damage thresholds on laser spot size, for annular retinal beam profiles, was measured in vivo for 3 μs, 590 nm pulses from a flashlamp-pumped dye laser. Minimum Visible Lesion (MVL)ED50 thresholds in rhesus were measured for annular retinal beam profiles covering 5, 10, and 20 mrad of visual field; which correspond to outer beam diameters of roughly 70, 160, and 300 μm, respectively, on the primate retina. Annular beam profiles at the retinal plane were achieved using a telescopic imaging system, with the focal properties of the eye represented as an equivalent thin lens, and all annular beam profiles had a 37% central obscuration. As a check on experimental data, theoretical MVL-ED50 thresholds for annular beam exposures were calculated using the Thompson-Gerstman granular model of laser-induced thermal damage to the retina. Threshold calculations were performed for the three experimental beam diameters and for an intermediate case with an outer beam diameter of 230 μm. Results indicate that the threshold vs. spot size trends, for annular beams, are similar to the trends for top hat beams determined in a previous study; i.e., the threshold dose varies with the retinal image area for larger image sizes. The model correctly predicts the threshold vs. spot size trends seen in the biological data, for both annular and top hat retinal beam profiles.
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.
Though allowable (safe) energy doses of pulsed laser radiation have been determined in the central retina, the sensitivity of the peripheral retina to damage must also be assessed. We used results from ray-tracing in an eye model to estimate laser spot size at the retina and recent thermal model computations of damage thresholds to predict off-axis retinal injury from laser irradiation. The predictions were made for threshold exposures with a 532-nm, 10-ns, Nd:YAG laser beam that filled the dilated pupil (7-mm diameter). Results were compared to previously published measured energy doses at the cornea needed to produce a minimally visible lesion (MVL) in the peripheral retina of rhesus subjects. We predicted the threshold for injury at the macula, and at selected portions of peripheral retina out to 60 degree(s) from the fovea. Both predictions and measured data were normalized to their respective macula values. Normalized predicted thresholds in the peripheral retina increased as a function of angular distance from the macula. This varied from the measured data which, on the other hand, were relatively insensitive to angular position in the peripheral retina. The difference is likely due to improvements in methods of assessing retinal injury that have been incorporated into the model.
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.
The dependence of retinal damage threshold on laser spot size was examined for two pulsewidth regimes; nanosecond- duration Q-switched pluses from a doubled Nd:YAG laser and microsecond-duration pulses from a flashlamp-pumped dye laser. Threshold determination were conducted for nominal retinal image sizes ranging form 1.5 mrad to 100 mrad of visual field, corresponding to image diameters of approximately 22 micrometers to 1.4 mm on the primate retina. Together, this set of retinal damage threshold reveals the functional dependence of threshold on spot size. The threshold dose was found to vary with the area of the image for larger image sizes. The experimental results were compared to the predictions of the Thompson-Gerstman granular model of laser-induced retinal damage. The experimental and theoretical trends of threshold variation with retinal spot size were essentially the same, with both data sets showing threshold dose proportional to image area for spot sizes >= 150 micrometers . The absolute values predicted by the model, however, were significantly higher than experimental values, possibly because of uncertainty in various biological input parameters, such as the melanosome absorption coefficient and the number of melanosomes per RPE cell.
Mechanisms of photic injury to the eye can be categorized as photochemical, photothermal or photodistruptive. Exposure wavelength, exposure duration, ocular tissue characteristics and response criteria are key factors in the delineation of the ocular injury mechanisms. Depending on the exposure condition, one or all of the laser-tissue interaction mechanisms can be involved. Although photic injury to the eye was initially assumed to involve thermal mechanisms, more recent research has demonstrated that ocular effects can be produced by light exposure without a significant retinal temperature rise. Photochemical mechanisms are also implicated in UV photic injury to the cornea and lens. Exposure of the retina to short visible wavelengths for prolonged durations results in photochemical retinal damage with negligible localized retinal temperature elevation. For exposure conditions where photochemical mechanisms are dominate, the reciprocity of irradiance and exposure duration is apparent. The latency until observation of a photochemical lesion is often 24-48 hours whereas a thermal lesion is observed immediately or within a few hours after the exposure. Action spectra for photochemical injury to the eye are discussed in the context of ocular injury thresholds and current permissible exposure limits.
The dependence of retinal damage threshold on laser spot size was examined for two pulsewidth regimes; nanosecond- duration Q-switched pulses from a doubled Nd:YAG laser and microsecond-duration pulses from a flashlamp-pumped dye laser. Threshold determinations were conducted for nominal retinal image sizes ranging from 1.5 mrad to 100 mrad of visual field, corresponding to image diameters of approximately 22 μm to 1.4 mm on the primate retina. In addition, baseline collimated-beam damage thresholds were determined for comparison to the extended source data. Together, this set of retinal damage thresholds reveals the functional dependence of threshold on spot size. The threshold dose was found to vary with the area of the image for larger image sizes. The results are compared to previously published extended source damage thresholds and to the ANSI Z136.1 laser safety standard maximum permissible exposure levels for diffuse reflections.
An earlier report documented exposure parameters for inducing corneal, lens, and retinal damage with a laser emitting in the `eye-safe' wavelength range (Nd:YAG laser radiation at 1.318 micrometers and 1.356 micrometers ). Ocular damage thresholds are much higher for these wavelengths than for visible wavelength lasers. However, it was also noted that an exposure in the `eye-safe' wavelength range may result in multiple damage sites throughout the ocular medium and retina/choroid; that seemingly unaffected exposure sites, when monitored over time, may reveal slowly developing (days or longer) tissue degeneration; and, that the tissue degradation may ultimately involve regions greater in area than those directly irradiated by the laser. In order to elucidate the nature of tissue degeneration following IR laser exposure, the comparative pathology of retinal tissues exposed to argon and IR laser radiation is reported. Further, periodic post-exposure exams were conducted using scanning laser ophthalmoscopy to monitor the in vivo progress of the ocular tissue response following IR exposures. These observations are also contrasted to the results of corresponding examinations following visible wavelength laser exposures.
We have evaluated the acute effects of Argon laser injury to the retinal nerve fiber layer (NFL) in the non-human primate. Single Argon laser exposures of 150 millijoules were employed to induce retinal NFL injury. Retinal NFL injury is not acute; unlike its parallel in retinal disease it has two components that emanate from the acute retinal injury site. The ascending component is more visible, primarily because it is ascending toward the disk, representing ganglion cell axons cut off from their nutrient base, the ganglion cell body; the descending component may require up to 3 weeks to develop. Its characterization depends on the distribution of retinal NFL and the slower degeneration of the ganglion cell bodies. Fluorescein angiography suggest a retinal capillary loss that occurs in the capillary bed of the retinal NFL defect. It may reflect a reduced capillary vascular requirement of the NFL as well as a possible reduction of activity in the axonal transport mechanisms in the ascending NFL defect.
We have evaluated secondary laser induced retinal effects in non-human primates with a Rodenstock confocal scanning laser ophthalmoscope. A small eye animal model, the Garter snake, was employed to evaluate confocal numerical aperture effects in imaging laser retinal damage in small eyes vs. large eyes. Results demonstrate that the confocal image resolution in the Rhesus monkey eye is sufficient to differentiate deep retinal scar formation from retinal nerve fiber layer (NFL) damage and to estimate the depth of the NFL damage. The best comparison with histological depth was obtained for the snake retina, yielding a ratio close to 1:1 compared to 2:1 for the Rhesus. Resolution in the Garter snake allows imaging the photoreceptor matrix and therefore, evaluation of the interrelationship between the primary damage site (posterior retina), the photoreceptor matrix, and secondary sites in the anterior retina such as the NFL and the epiretinal vascular system. Alterations in both the retinal NFL and epiretinal blood flow rate were observed within several minutes post Argon laser exposure. Unique aspects of the snake eye such as high tissue transparency and inherently high contrast cellular structures, contribute to the confocal image quality. Such factors may be nearly comparable in primate eyes suggesting that depth of resolution can be improved by smaller confocal apertures and more sensitive signal processing techniques.
Repeated extended source Q-switched exposure centered on the macula has been shown to produce a Bullseye maculopathy. This paper provides a confocal scanning laser ophthalmoscopic evaluation with regard to the retinal nerve fiber layer (NFL) and deeper choroidal vascular network. Confocal imaging revealed that the punctate annular appearance of this lesion in the deeper retinal layers is associated with retinal nerve fiber bundle disruptions and small gaps in the retinal NFL. No choroidal dysfunction was noticed with Indocyanine green angiography. It is hypothesized that retinal NFL damage occurs either through disruption of retinal pigment epithelial cell layer support to the NFL or through direct exposure to high spatial peak powers within the extended source beam profile, causing direct microthermal injury to the NFL. The apparent sparring of the fovea reflects central retinal morphology rather than a lack of retinal damage to the fovea.
This study is concerned with ocular effects of laser radiation in the wavelength range from approximately equals 1.1 micrometers to 2.0 micrometers which includes the so-called 'eye-safe' range where retinal and corneal damage thresholds are significantly higher than the corresponding thresholds for more common visible and far-IR lasers. Across this wavelength range, ocular safe exposure limits vary rapidly with wavelength and are up to approximately equals 6 orders of magnitude greater than exposure limits for visible wavelengths. However, recent developments in laser technology have yielded a variety of powerful near-IR laser sources. Such lasers are not 'eye safe' but, rather, may emit peak powers orders of magnitude above tissue-damaging levels. This report focuses on the unique aspects of laser-tissue interactions for 'eye-safe' wavelengths. In contrast to past experience where the laser energy is absorbed primarily in a thin layer (either at the corneal or skin surface for longer IR wavelengths or at the retinal pigment epithelium for visible wavelengths), 'eye- safe' wavelengths are attenuated gradually through a volume of tissue and may affect any one or several sites within the cornea, lens, and retina. The reaction of the irradiated organism to the volumetric heating associated with such penetrating laser wavelengths does not conform with expectations of an immediate or relatively early observable lesion. Rather, the observable consequences of the laser exposure may take days to become apparent and may involve degeneration across a wider expanse of tissue than that directly irradiated by the laser. For these reason, IR laser exposures bear close scrutiny to redefine both the usual tissue damage criteria and then the appropriate safe exposure limits.
Retinal nerve fiber layer (NFL) damage can be induced by retinal laser photocoagulation. This type of thermal injury involves degeneration in both descending and ascending directions from the photic injury site. We have repeated early studies in evaluation of the acute phases of the injury process. Our findings indicate that the ascending or Wallerian portion of the NFL degeneration requires less time than the descending portion; an early neural debris channel occurs in close proximity to retinal vessels and appears to enter the optic disc in close proximity to the retinal vasculature. Angiography of the ascending debris sheath suggests possible capillary pattern modulation associated with this neural debris sheath. Retinal traction evident in with other acute injuries appears at 2 weeks and disappears after 8 weeks suggesting secondary control factors other than retinal hemorrhage in the development of retinal traction bands.
We have evaluated acute laser retinal exposure in non-human primates using a Rodenstock scanning laser ophthalmoscope (SLO) equipped with spectral imaging laser sources at 488, 514, 633, and 780 nm. Confocal spectral imaging at each laser wavelength allowed evaluation of the image plane from deep within the retinal vascular layer to the more superficial nerve fiber layer in the presence and absence of the short wavelength absorption of the macular pigment. SLO angiography included both fluorescein and indocyanine green procedures to assess the extent of damage to the sensory retina, the retinal pigment epithelium (RPE), and the choroidal vasculature. All laser exposures in this experiment were from a Q-switched Neodymium laser source at an exposure level sufficient to produce vitreous hemorrhage. Confocal imaging of the nerve fiber layer revealed discrete optic nerve sector defects between the lesion site and the macula (retrograde degeneration) as well as between the lesion site and the optic disk (Wallerian degeneration). In multiple hemorrhagic exposures, lesions placed progressively distant from the macula or overlapping the macula formed bridging scars visible at deep retinal levels. Angiography revealed blood flow disturbance at the retina as well as at the choroidal vascular level. These data suggest that acute parafoveal laser retinal injury can involve both direct full thickness damage to the sensory and non-sensory retina and remote nerve fiber degeneration. Such injury has serious functional implications for both central and peripheral visual function.
`Optical aging' of the lens of the eye results from the cumulative photochemical effects of ambient light exposures and may be exacerbated by any number of disease processes and exogenous agents including acute or chronic exposure to above- ambient levels of ultraviolet and/or blue light. This `optical aging' of the lens is manifested by increased scattering of visible light, increased absorption of short-visible wavelengths, and increased fluorescence emitted at short- to mid-visible wavelengths when irradiated with UV or blue light. With age and with or without exacerbating factors, the initially clear lens takes on an increasingly yellowish and ultimately brunescent coloration associated with cortical cataract. We conducted in vivo measurements of the lens fluorescence induced by UV and blue wavelengths. The fluorescence intensity was quantitated as a function of intensity of exciting light and excitation wavelength. It was shown that other `safe' blue laser exposures induced enough of a fluorescent veiling glare to imply interference with visual function. The visual deficit was objectively demonstrated by monitoring visual evoked potential amplitudes while subjects were irradiated with blue laser light. A related study demonstrated the utility of a prototype optical biopsy instrument as a diagnostic tool for assessing the optical properties of the lens. Optical signatures of individual lenses were characterized by compiling the backscatter and fluorescence spectra elicited by each of several exciting wavelengths. By examining the optical signatures of a population of approximately 100 human lenses, several metrics were chosen for gauging the optical quality of a given lens relative to the norm for the subject's chronological age. These metrics may serve to identify cases of accelerated `optical aging' and provide early evidence of cataract or other disease processes.
Ultraviolet radiation in the ambient environment or from artificial sources may pose both acute and chronic hazards to the skin and the ocular tissues. In general terrestrial conditions have evolved such that there are only narrow safety margins between ambient UV levels and exposure levels harmful to the human. Obvious examples of acute consequences ofUV overexposure are sunburn and snowblindness as well as analogous conditions induced by artificial sources such as the welder''s arc mercury vapor lamps and UV-emitting lasers. Further chronic UV exposure is strongly implicated as a causative agent in certain types of cataract and skin cancer. This presentation will summarize a number of specific cases where UV radiation affected the primate cornea. Data presented will include the action spectra for far- and near-UV induced ocular damage the pulsewidth and total energy dependencies of ocular thresholds studies of cumulative effects of repeated UV exposures and quantitative determinations of tissue repair or recovery rates. Depending on the exposure parameters utilized photochemical thermal or photoablative damage mechanisms may prevail. 1.
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