A Need to Revise Human Exposure Limits for Ultraviolet UV-C Radiation†.

The COVID-19 pandemic has greatly heightened interest in ultraviolet germicidal irradiation (UVGI) as an important intervention strategy to disinfect air in medical treatment facilities and public indoor spaces. However, a major drawback of UVGI is the challenge posed by assuring safe installation of potentially hazardous short-wavelength (UV-C) ultraviolet lamps. Questions have arisen regarding what appear to be unusually conservative exposure limit values in the UV-C spectral band between 180 and 280 nm. We review the bases for the current limits and proposes some adjustments that would provide separate limits for the eye and the skin at wavelengths less than 300 nm and to increase both skin and eye limits in the UV-C below 250 nm.

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.

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).

Assessment of alleged retinal laser injuries.

Accidental retinal laser injuries are easily diagnosed when there are known laser sources, typical macular injuries, and visual deficits consistent with retinal findings. Decisions are more difficult when retinal findings are subtle or absent, despite reported visual problems and somatic complaints. Inaccurate diagnosis of an ocular laser injury can precipitate a costly, lengthy sequence of medical and legal problems. Analysis of laser-tissue interactions and the characteristics of unambiguous retinal laser injuries provide 6 key questions to facilitate difficult diagnoses. Case reports demonstrate the usefulness of answering these questions before making diagnostic decisions. Retinal laser lesions that cause serious visual problems are readily apparent ophthalmoscopically and angiographically. Accidental, intentional, or clinical retinal laser lesions do not cause chronic eye, face, or head pains. Diagnosis of a retinal laser injury should be evidence based, not a matter of conjecture or speculation.

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.

Laser eye injuries in military occupations.

INTRODUCTION: Lasers (light amplification by stimulated emission of radiation) play an important role in our world and their use is increasing. They are powerful tools for good, but can also cause tragedy, especially in an aviation environment. Information about injuries associated with lasers is limited. This study highlights several laser eye injuries in the U.S. military and discusses issues pertaining to them. METHODS: We gathered data from the U.S. Army Safety Center, the U.S. Army Center for Health Promotion and Preventive Medicine, and the Walter Reed Army Institute of Research. This paper describes ten representative cases of laser eye injury that occurred in the U.S. military between 1984 and 2000. RESULTS: Patients suffered retinal damage, though no corneal injury occurred. Most were caused by accidental exposure to a Q-switched, Neodynium:YAG (Nd:YAG) laser at 1064 nm wavelength. The incidents occurred both on and off duty, indoors and outdoors, and from close and long ranges. None of the victims were wearing eye protection. Inadequate training and poor equipment design were major factors in at least six of the nine unintentional cases. The tenth occurred during military operations in the Persian Gulf. All of the victims needed several months medical care and follow up. Two received medical discharges as a result of their injuries. DISCUSSION: As illustrated by these cases, human and societal costs from unintentional laser eye injuries can be reduced by improving operator training, safety procedure compliance, and equipment design. In addition, intentional laser eye injuries are a growing concern and further research is needed to design appropriate protection, treatment and countermeasures.

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.

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.

Transplantation of quantum dot-labelled bone marrow-derived stem cells into the vitreous of mice with laser-induced retinal injury: survival, integration and differentiation.

Accidental laser exposure to the eyes may result in serious visual impairment due to retina degeneration. Currently limited treatment is available for laser eye injury. In the current study, we investigated the therapeutic potential of bone marrow-derived stem cells (BMSCs) for laser-induced retinal trauma. Lineage negative bone marrow cells (Lin(-) BMCs) were labelled with quantum dots (Qdots) to track the cells in vivo. Lin(-) BMCs survived well after intravitreal injection. In vivo bromodeoxyuridine (BrdU) labelling showed these cells continued to proliferate and integrate into injured retinas. Furthermore, they expressed markers that distinguished retinal pigment epithelium (RPE), endothelium, pericytes and photoreceptors. Our results suggest that BMSCs participate in the repair of retinal lesions by differentiating into retinal cells. Intravitreal transplantation of BMSCs is a potential treatment for laser-induced retinal trauma.

Oxygen enhances lethal effect of high-intensity, ultrashort electrical pulses.

The study explored the effect of ambient oxygen on mammalian cell survival after exposure to 10 ns duration, high voltage electrical pulses (nsEP, 80-90 or 120-130 kV/cm; 200-400 pulses per exposure). Cell samples were equilibrated with pure nitrogen, atmospheric air, or pure oxygen prior to the nsEP treatment and were returned to the incubator (air + 5% CO2) shortly after the exposure. The experiments established that survival of hypoxic Jurkat and U937 cells exceeded that of air-equilibrated controls about twofold (P < .01). Conversely, saturation of the medium with oxygen prior to exposure decreased Jurkat cell survival about 1.5 times, P < .01. Attenuation of the cytotoxic effect under hypoxic conditions resembled a well-known effect of oxygen on cell killing by sparsely ionizing radiations and may be indicative of the similarity of underlying cell damage mechanisms.

Adjustment of guidelines for exposure of the eye to optical radiation from ocular instruments: statement from a task group of the International Commission on Non-Ionizing Radiation Protection (ICNIRP).

A variety of optical and electro-optical instruments are used for both diagnostic and therapeutic applications to the human eye. These generally expose ocular structures to either coherent or incoherent optical radiation (ultraviolet, visible, or infrared radiation) under unique conditions. We convert both laser and incoherent exposure guidelines derived for normal exposure conditions to the application of ophthalmic sources.

Comparison of dose dependences for bioeffects of continuous-wave and high-peak power microwave emissions using gel-suspended cell cultures.

The study compared bioeffects of continuous wave (CW) microwaves and short, extremely high power pulses (EHPP) at the same carrier frequency (9.3 GHz) and average power (1.25 W). The peak transmitted power for EHPP was 250 kW (0.5-micro s pulse width, 10 p.p.s.), producing the E field of 1.57 MV/m in the waveguide. A biological endpoint was the density of yeast cells, achieved after a 6 h growth period in a solid nutrient medium (agarose gel) during EHPP or CW exposure. Owing to power losses in the medium, the specific absorption rate (SAR) ranged from 3.2 kW/kg at the exposed surface of the sample to 0.6 mW/kg at 24 mm depth. Absorption and penetration of EHPP was identical to CW, producing peak SAR values 200 000 times higher than the average SAR, as high as 650 MW/kg at the surface. CW and EHPP exposures produced highly nonuniform but identical heating patterns in exposed samples. Following the exposure, the samples were sliced in a plane perpendicular to the wave propagation, in order to separate cell masses exposed at different SAR levels. Cell density in the slices was determined by nephelometry and compared to unexposed parallel control samples. Cell density was strongly affected by irradiation, and the changes correlated well with the local temperature rise. However, the data revealed no statistically significant difference between CW and EHPP samples across the entire studied range of SAR levels (over six orders of magnitude). A trend (P<0.1) for such a difference was observed in slices that were exposed at a time average SAR of 100 W/kg and higher, which corresponded to peak SAR above 20 MW/kg for the EHPP condition. These numbers could be indicative of a threshold for a specific (not merely thermal) exposure effect if the trend is confirmed by future studies.

Effects of high power microwave pulses on synaptic transmission and long term potentiation in hippocampus.

Effects of short, extremely high power microwave pulses (EHPP) on neuronal network function were explored by electrophysiological techniques in the isolated rat hippocampal slice model. Population spikes (PS) in the CA1 area were evoked by repeated stimulation (1 per 30 s) of the Schaffer collateral pathway. A brief tetanus (2 s at 50 Hz) was used to induce long term potentiation (LTP) of synaptic transmission. In three different series of experiments with a total of 160 brain slices, the EHPP irradiation was performed before, during, or after the tetanus. The EHPP carrier frequency was 9.3 GHz, the pulse width and repetition rate were from 0.5 to 2 micros and from 0.5 to 10 Hz, respectively, and the peak specific absorption rate (SAR) in brain slices reached up to 500 MW/kg. Microwave heating of the preparation ranged from 0.5 degrees C (at 0.3 kW/kg time average SAR) to 6 degrees C (at 3.6 kW/kg). The experiments established that the only effect caused by EHPP exposure within the studied range of parameters was a transient and fully reversible decrease in the PS amplitude. Recovery took no more than a few minutes after the cessation of exposure and return to the initial temperature. This effect's features were characteristic of an ordinary thermal response: it was proportional to the temperature rise but not to any specific parameter of EHPP, and it could also be induced by a continuous wave (CW) irradiation or conventional heating. Irradiation did not affect the ability of neurons to develop LTP in response to tetanus or to retain the potentiated state that was induced before irradiation. No lasting or delayed effects of EHPP were observed. The results are consistent with the thermal mechanism of EHPP action and thus far provided no indication of EHPP-specific effects on neuronal function.

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.