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Laser Eye Effects (1968)

Chapter: Retinal Injury From Laser and Light Exposure

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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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Suggested Citation:"Retinal Injury From Laser and Light Exposure." National Research Council. 1968. Laser Eye Effects. Washington, DC: The National Academies Press. doi: 10.17226/18639.
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CHAPTER I I RETINAL INJURY FR0M LASERS AND 0THER LIGHT SOURCES Walter J. Geeraets* The purpose of this report is the review and discussion of some of the findings presented in the literature relating to permanent injury to the eye caused by laser irradiation and light coagulation. Since this study is concerned with our present knowledge of retinal energy doses capable of producing permanent injury, only those studies are summarized and discussed which give data on exposure times, image sizes of the irradiating beam on the retina, and energy levels. A point which must be stressed is the definition of "retinal thres- hold lesions". Since the introduction of the term "retinal threshold lesions" by Ham £t aj_.l a number of misunderstandings regarding this concept have occurred, both in the literature and in the minds of in- vestigators concerned with the problem of retinal injury. The original definition of a threshold lesion as an ophthalmoscopically observable lesion barely visible five minutes after exposure was based on probit analysis of RD-50 datal. A burn of this type may be termed "threshold" or "minimal" only in the sense that it fits this particular definition, but it may not be threshold or minimal by other criteria or examination procedures2. During recent years it has been shown that irreversible damage at lower levels of irradiance can be demonstrated by more refined techniques, such as histochemistry2, electroretinography^, and others'*. In addition, irreversible lesions can appear at lower irradiance when the observation time is extended to several days after exposureS-7. In this report the amount of energy required for the production of minimal ophthalmoscopic visible lesions is given as retinal irradiance (watts/cm2) or retinal dose (j/cm2). Presenting the "threshold" ir- radiances or doses for various wavelengths and exposure times for energy incident on the retina, rather than on the cornea, has the advantage that certain physical considerations such as pupillary diameter, trans- mission co-efficient of the ocular media, and spectral absorption char- acteristics of the retina and choroid are already incorporated into these data. Therefore, in a given situation the energy density on the cornea has to be determined, and from this measurement the retinal ir- radiance can easily be calculated by using the equation: 0r=0cxD2xk= watts/cm2 d2 *Department of 0phthalmology and Biophysics Medical College of Virginia - Richmond, Virginia 20

0 = retinal irradiance (watts/cm2) 0C = corneal irradiance (watts/cm2) D = pupillary diameter k = average transmission coefficient through the ocular media for a given spectral distribution or wavelength. d = diameter of the image on the retina, depending on the divergence of the incident beam of light and the focal length of the eye (for the normal emmetropic human eye approximately 0.3 mm/l° bean divergence). INTR0DUCTI0N Thermal injury to the retina has been known for many centuries. As early as 200-130 A.D., Galen described eclipse blindness^- Galilieo received ocular injury by watching the sun through his telescope-?. In this century, a great number of people received retinal burns during the solar eclipse in 1912. However, the first scientific description of thermal injury to the eye was reported by Verhoeff and Bell These investigators pointed out that eclipse burns were actually thermal lesions, originating in the retinal pigment epithelium by the transfer of light energy to heat. During World War II, numerous foveal lesions were documented among persons using optical instrumentation to "spot" planes attacking from the direction of the sun'2. With the development of nuclear weapons another source capable of producing retinal injury was introduced. In 1953 Buettner and Rose'3 pointed to this potential hazard to the eye and brought attention to the focal properties of the eye which compensates for the "inverse square law" of attenuation out to distances where the spot size of the fireball on the retina is limited by diffraction. The field conditions were simulated in the laboratory by Ham et^ a_K , who used an army search light as the power source, and by the extensive work of a group of in- vestigators of the USAF School of Aerospace Medicine, Brooks AFB, Texas . 0n the basis of the effects of eclipse burns on the human retina, Meyer-Schwi ckerath '5 began experiments with high power light sources to develop "clinical light coagulation" for the treatment of certain ocular pathologies. During this development he first used the sun itself as the light source. This was followed by a carbon arc lamp and finally, in collaboration with Littman, he developed the Xenon high pressure lamp coagulator, which has become well known as the "Zeiss light coagulator". The first clinical light coagulation of a retinal lesion was performed in this country by Guerry in 1958'" using the ex- perimental instrumentation of Ham et. a].l. 21

With the advancement in research and development of lasers, a new source of radiation has become available which presents great potential hazard to the eye if the proper protective mechanisms are not used. After the development of the first successful optical laser in 1 by Gordon, Zeiger, and Townes '7 of Columbia University, Mai man succeeded in the development of the ruby solid state laser in 1959- Since then, enormous progress has been made in the advancement of laser technology. Today, coherent electromagnetic radiation by simulated emission extends spectrally from the ultraviolet to the far infrared utilizing solid state lasers, liquid lasers, and gaseous lasers. The power of these devices ranges from milliwatts to gigawatts (see section l) They may be operated as pulsed lasers, ranging from few nanoseconds to several milliseconds, or they may produce continuous radiation (CW). Their unique properties lie in their directionality, monochromaticity, coherency, and polarization. 0CULAR SPECTRAL CHARACTERISTICS Ocular transmission. The production of thermal lesions in the ocu- lar fundus depends, among other factors, upon the spectral quality of the light incident on the cornea and the spectral characteristics of the eye itself. In previous articles 19~25 the spectral characteristics of the eye have been described. The spectral range over which trans- mission studies had been performed varied with the various investigators but generally included the visible portion. The early work of Ludvigh and McCarthy l9 was hampered by lack of more refined and modern instru- mentation and gives much lower transmission coefficients than those re- ported by Kinsey 20 anc| Geeraets and coworkers 2^+,25 . It is more difficult to account for the discrepancy between the latter results and those given by Prince ^, Wiesinger, et al. have shown that there is little difference between their transmTs"s7on values for rabbit ocular media and that for a 1 cm thickness of physiological saline. To estimate retinal injury by light exposure, absorption data for retina and choroid are best given for energy incident on the cornea. Previous reported absorption values for the human retinal pigment epi- thelium and choroid include light scattered and reflected by the various structures of the eye 2^ , 25 . This resulted in excessively high ab- sorption values. Though this fact lets one be on the safe side when estimating retinal hazards, correction of these data for reflection seemed to be desirable. More recently completed work 26 nas resulted in such corrected absorption characteristics (Figs. 1-3). The influence of blood upon ocular spectral absorption has been discussed in previous communications 25 and in vivo reflection mea- surements allowed an estimation of retinal thermal injury 27. The energy density gradiant in the fundus depends upon the con- centration of the pigment within the granules and the space distribu- tion of the pigment granules within a given cell and cell layer. The 22

100 90 80 §60 50 30 20 10 PERCENT ABSORPTION IN RETINA AND CHOROID 28 Human Eyes 3ata uncorrected for reflection s **% \ Data corrected for spectral reflection (mean) 1 \l v • A , -> r\ • I 7 s* s :\ Range _j s n \ \ Si > x I \1 \ "^ \| \ % fi|4 / s s 1 y \ . > ^ ,'' ^ I •^. « ! \s* !" I, !=! tsz. te* 400 500 600 700 800 900 1000 MOO WAVE LENGTH(nm) 1200 1300 1400 1500 Figure 1. Percent absorption in retinal pigment epithelium and choroid for equal intensities and light incident on the cornea. (Human data) R = Ruby laser wavelength. NO = Neodynium laser wavelength. 23

O o PERCENT ABSORPTION IN RETINA ANDCHOROID 56 Rabbit Eyes -- Data uncorrected fo reflection (mean) f — Data corrected for reflection (mean) -~~ J Range . i • ^S // \ I s \ 1 Si S \j \ 1 \ I s *\v > r\ I\ • \ \ N \ **' s \ ** ^. \ f 1 rt, >—> ^ 400 500 600 700 800 900 1000 IIOO 1200 1300 1400 1500 WAVE LENGTH(nm) Figure 2. Percent absorption in retinal pigment epithelium and choroid for equal intensities and light incident on the cornea. (Rabbit data) R = Ruby laser wavelength. NO = Neodynium laser wavelength. 2k

PERCENT ABSORPTION IN RETINA AND CHOROID 100 90 I80 I70 §60 & 50 90 20 10 — Dofo uncorrected for reflection ~ Data corrected for reflection 400 500 600 700 800 900 1000 1100 1200 1300 1400 1500 WAVE LENGTH (nm) Figure 3. Percent absorption in retinal pigment epithelium and choroid for equal intensities and light incident on the cornea. (Rhesus monkey data) R = Ruby laser wavelength. NO = Neodynium laser wavelength. 25

distribution of pigment granules varies in both pigment epithelium and choroid but more markedly in the latter. Absorption of radiant energy in human and rabbit pigment epithelium may be greater than in the choroid, or vice versa, depending on the individual. Though the pigment density may vary from one area to another in one and the same eye, an even greater variation of pigment density exists from one species to the other. It is for this reason that in previous investi- gations mainly chinchilla rabbits were used to study the thermal effect on retina and choroid with the intention of finding a suitable model for the human fundus. It should be stressed that the rabbit eye in its anatomy and optics is quite different from the human eye (i.e. the absence of a foveal region in the rabbit eye and the lack of retinal vascularization). However, the transmission and absorption characteristics of the ocular fundus, particularly the retinal pigment epithelium and the choroid, are very similar in the rabbit and human. 0n the other hand, the anatomical and optical characteristics of the eye of the Rhesus monkey are quite similar to the human eye; the foveal region and retinal vascularization are similar to the human eye. However, at long exposure times and/or at energy levels greater than that required for the production of minimal retinal injury, the more intense choroidal pigmentation of the Rhesus eye contributes markedly to the development of retinal thermal lesions. It is for these reasons that data obtained in the Rhesus monkey eyes require cautions when correlating human ocular hazard from light exposure. Zaret and co-workers 2o in their studies have used the Douroucouli monkey, and according to these investigators the retinal and choroidal pigment density and distribution in this animal are very similar to the human eye. 0cular spectral reflectance. Preliminary spectral reflectance mea- surements have been made on human, Rhesus monkey, dutch and chinchilla rabbit eyes 2b. jhe measurements were taken from 350 nm through 1500 nm with the neural retina still attached to the retinal pigment epithelium and were repeated with the neural retina removed. The earlier reported values for absorption in retinal pigment epithelium and choroid 24,25 were corrected for these reflection data. The new absorption data thus more closely represent true absorption and give a more accurate estimate of absorbed energy at individual wavelength (Figs. 1-3). 0PHTHALM0SC0PIC FINDINGS IN MINIMAL RETINAL INJURY The ophthalmoscopic visible findings for minimal retinal injury can be grouped in three sub-divisions: 1) for long exposure times (ms to sec.), 2) for short exposure times (us to ms ranges), and 3) q-switched laser lesions (ns ranges). Lesions in the fundus of the human, monkey, or rabbit eye can be de- scribed collectively since their gross ophthalmoscopic appearance is so similar that small deviations in the different species may be neglected. When the exposure time is varied, however, the lesion produced have chat— acteristic differences. 26

Lesions Produced With Long Exposure Times. Minimal retinal lesions produced at long exposure times, approximately 30 ms to 300 ms, are usually smaller than the actual image size of the light beam on the retina. This feature can be explained by phenomena of heat conduction. The thermal flux at the periphery of the irradiated field causes a notably smaller temperature rise, one inadequate for producing thermal injury. The clinical picture of such a lesion is characterized by slightly darker discoloration of the fundus under observation with red free light. Usually the edges of these lesions are somewhat blurred. With slightly higher intensity the lesion becomes greyish, usually with a pearly white center and a peripheral zone of retinal edema. A small orange-colored halo then ensures, fading out peripherally in a zone of darker reddish color possibly due to hyperemia of the choroidal vessels. Due to thermal conduction in the periphery the size of these lesions might be larger than the image size of the light beam. Heavy lesions show eventually chorio-retinal rupture in the center of the exposed field and possible preretinal or vitreous hemorrhages in the center of the lesion. Such explosive chorio-retinal lesions are pro- duced with energies many times greater than those required for production of mild retinal lesions. They are always larger than the retinal image size of the light beam. Subretinal hemorrhages are usually not observed at this long exposure time for heat general causes early coagulation of the adjacent structures as well as of choroidal vessels, thus preventing the spread of choroidal and subretinal hemorrhages. Lesions Produced at Microsecond and Millisecond Ranges. In this range of exposure times, retinal lesions have a similar ap- pearance whether they are produced with the Xenon high pressure light coagulator or with a laser with an emission within the visible spectrum. These lesions appear somewhat different from those produced at long ex- posure times. Minimal lesions usually present slightly darker coloration than the surrounding fundus and moderate to severe lesions show a uniform, greyish area. For minimal and above minimal lesions the size of the lesion is approximately equal to the image size of the exposure light beam or laser beam. This might indicate that the effect of heat conduction is min- imal during short exposure times (i.e. within this exposure range). This effect of minimal spreading of cellular injury peripherally to the boundary of the irradiated area has been confirmed and demonstrated in histochemica1 and other studies ^»^5. Moderate lesions show a rather unifrom grey appearance with a pale, narrow halo surrounding it, while very heavy lesions often present cen- trally located pigment accumulation and hemorrhages, either intraretinal or preretinal. This ia a common feature for rather heavy lesions produced with both white light or laser exposures. The center of the lesion with the hemorrhage and pigment accumulation is mostly surrounded by a snow 27

white area border 1 i neci by a small cuff of irregular pigment distribution. Coagulation apparently prevents subretinal spreading of hemorrhages, for this usually does not occur. Q-switched Laser Lesions in Nanosecond Ranges. Retinal lesions produced at extremely short exposure times present a characteristic feature different from the one described in microseconds or milliseconds. Very minimal lesions appear as small dark reddish areas. They usually change to a mild or greyish appearance after several minutes. This phenomenon can particularly be well observed by red free light. Very minimal lesions usually do not demonstrate any intraretinal or subretinal hemorrhages; however, there is frequently a slight pigment irregularity observable within the irradiated area. After several days this becomes more pronounced with irregularly distributed pigmentation. If the energy dose is slightly increased, subretinal and intraretinal hemorrhages occur that frequently spread slowly, separating the neural retinal layer from the pigment epithelium. In severe lesions, intraretinal and preretinal hemorrhages become pronounced, sometimes following channel formation through the retina and into the vitreous. This appearance has been ex- plained by the discharge of pigment clumps from the pigment epithelium through the neural retina into the vitreous. Along their course, hemor- rhages originating from the choroidal capillary layer follow these channels and give this strange appearance. The surrounding retina is usually grey- ish white and widespread subretinal and choroidal hemorrhages are assoc- iated with these lesions. This particular clinical feature leads to assume that a "typical" thermal coagulation effect during or after irrad- iation is absent. The total diameter of these lesions is determined by the extent of the subretinal hemorrhages. HIST0LOGICAL FINDINGS Histological description of the produced lesions, either by light coagulation or various laser coagulations, is subdivided into the same three groups as the clinical observations: long exposures, intermediate exposures, and short exposures. Since the histological alterations after exposures are very similar for different species (human, Rhesus monkey, and rabbit), typical histopathological changes after irradiation are described for these three species together. It should be understood that the similarities of the lesion are mainly in the range of minimal or so-called threshold lesions, since for the production of these minimal lesions, apparently only the retinal pigment epithelium is primarily involved. For longer exposure times or more intense lesions (which means an increase in energy or power density), the choroidal pigmentation plays a significant role, and therefore, the histopathological feature of the produced chorioretinal lesion varies de- pending on the amount and distribution of pigmented cells. 28

Long Exposure Times (30-300 ms). For long exposure times, the histological findings have been de- scribed by many investigators. Meyer-Schwickerath l5 gave an excellent presentation of the histological changes after light coagulation with the Xenon high pressure lamp. The characteristic features for mild lesions are a narrowing of the receptor cell layer and an increased susceptibility for certain stains such as eosin and periodic acid Schiff reaction (PAS). Both stainings, because of their apparently higher affinity for coagulated tissue, represent in a moderate way an indicator for detection of minimal retinal thermal injury. Probably somewhat more pronounced and more sen- sitive is alcian blue for acid mucopolysaccharides, which are present in higher concentration between the outer segments of the receptor cells. Also the pentachrome stain seems to show more intense staining in the areas of thermal damage. Nitro BT tetrazolium studies for cytochemical localization of oxidative enzyme systems represent another useful method *, At long exposure times, minimal lesions already show definite ad- herence to the underlying retinal pigment epithelium which becomes very obvious during sectioning and preparation of the histological material, for otherwise the neural retinal layers become easily detached during processing of the histological specimen. In addition one can see even in mild lesions, that the nuclei of the outer and inner nuclear layers become somewhat less sharply defined. There seems to be a certain "loosen- ing" between the nuclei, with interspaces, and there is a darker staining with hematoxylin. Mild edema is frequently present in the inner retinal layers. In moderate lesions the outer nuclear layer is often in this layer. However, the most likely one might be that in moderate lesions the coagulation effect of the proteins causes tight adherence of the coagu- lated outer layers of the retina and pigmented structures of the eye, whereas severe edema occurs in the most vulnerable layers of the retina, the nuclear layers, with regard to structural stability with resulting spatial disruption of the cellular elements. If the energy is further increased, all inner layers of the retina are involved, and the severe coagulation effect coexists with disruption and distortion of the normal anatomical architecture. The choroid us- ually shows hyperemia and thickening with pyknosis of the nuclei, a fea- ture which may be seen in the sclera as well. Intermediate Exposure Times (microsecond to millisecond ranges). Very mild lesions show minimal changes in the retinal pigment epi- thelium and the receptor cell layer only. There may be some vacuoliza- tion in the PE cells, and the receptor organs often seem more adherent with increased staining of affinity to various stains. At slightly higher energy levels there is some darker staining of the nuclei in the outer nuclear layer and loosening of the pigment epithelial cells. This feature is very characteristic and is seen after exposures with the Xenon light coagulator as well as with a normal pulsed ruby laser. 29

A similar affinity to certain histological stains as mentioned for lesions produced at relative long exposure times has also been reported for those produced with ruby laser at 500 jus ^9. shuman and Maloney ™ examined laser exposed retinae by phosphotungstic acid hematoxylin and PAS techniques as well as by naphthol ASTR acid phophatase and nitro BT tetrazolium succinic oxidase cryostate methods. While they observed an increase in staining affinity for PAS and ASTR and a marked decrease in PTAH, 2k hours after exposure formazan deposition showed only minimal change. These authors concluded from their observations that non-thermal components of the interaction could be postulated since they did not ob- serve injury of the pigment cells with their method. If the energy is increased above that which results in minimal lesions, the diameter of the lesion does not increase as markedly as it does with the longer exposure times. The involvement of the choroid is markedly less and no scleral changes are demonstrable by ordinary histological techniques. The histological changes seem to be more con- fined to the outer layers of the retina and with less involvement of the inner layers of neural retina. Hemorrhages into the retina or choroid are not observed in moderate injury inflicted at these exposure times. If the energy is increased still further, disruption of pigment epithelial cells occurs with dislodging of pigment granules. These granules are dispersed through neighboring retinal pigment epithelial cells and throughout the outer segment of the retinal receptor cells. Choroidal and intraretinal hemorrhages may occur. The extent of damage to the inner retinal layers is proportional to the power density in- cident on the retina. At high irradiances disruption of choroid and retina will ensue with resulting hemorrhages in these structures which may extend into the vit- reous. Q.-Switched Ruby Laser Effect (nanosecond ranges). At this very short exposure time two outstanding features are present: 1) there seems to be no adherent effect between the outer retinal layers and the pigment epithelium, and 2) there seems to be, even in minimal le- sions, displacement of pigment epithelium cells and pigment granules anter- iorly. Usually there is slight swelling of the outer segment of the recep- tor cell layer. The remaining neural layers of the more inner retinal structures seem to be undisturbed. The displacement of the retinal pig- ment epithelium anteriorly, increases with increasing intensity of the incident flash. Even at slight increases of the power density, hemorrh- ages deriving from the chorio-capi1laries prevail and are usually seen as small aggregates of red blood cells between the PE layer and the re- ceptor cell layer. The PE cells in these areas are disrupted, and the rods and cones show swelling and distortion. In moderate lesions, disruption of pigment epithelium cells is always present and pronounced, with retinal pigment granules throughout the outer and inner retinal layers. Fractions of choroidal tissue are frequently 30

found, displaced forward into the subretinal space along with profuse hemorrhages. Subretinal and intraretinal hemorrhages are evident, though the retinal architecture is normally well recognizable. If the energy density is further increased, explosion-1ike dis- ruption takes place with discharge of accumulated pigment clumps. These can be observed through the retinal layers to various extents. It would appear that the distance through which the pigment clumps travel is directly related to the energy density of the exposure beam. Some of the pigment clumps come to rest within the retinal layers themselves; others might be dislocated in the preretinal space, and more intense ones may travel for considerable distances through the vitreous body, leaving channels through which choroidal hemorrhage follows. In the immediate surrounding of these retinal channels, multiple diffracting globules are frequently seen which stain positive with fat - 0 - red for free lipoids. In very large areas of exposed retina, as described by Jones and McCartney 5 j the border of the lesion is not as sharply demarcated as seen in smaller burns. Such lesions as produced in Maxwellian view in the intact monkey eye and at low energy densities on the retina are frequently not visible by ophthalmoscopy. However, under histological examination, damage could always be demonstrated and consisted primarily of retinal detachment, pigment loss from the retinal pigment epithelium, choroidal damage, micro-lesions with scattered pigment granules, degen- eration of the inner and outer segments of the receptor cell layers, pyknotic nuclei, and free blood cells. Histochemical Findings. f\ It has been stressed that ophthaImoscopic visible minimal lesions and histological minimal lesions certainly do not represent even an ap- proximation of true visual functional lesions. Therefore, other avenues have been explored in order to approach the actual "threshold" level for retinal damage. It was assumed that enzyme inactivation should repre- sent a more critical and sensitive method of determining damage, either transient or permanent, to the retina than obtainable with ordinary histological staining techniques. The two systems studied were succinic dehydrogenase and DPNH diaphorase. Since the study was performed in rabbit eyes, (because of the similarily to the human eye in the respects as outlined previously), DPNH diaphorase was finally selected as the more sensitive indicator of damage in spite of the fact that it has been argued that there is no "real" enzyme in the retina of that de- scription. Succinic dehydrogenase intensively stains within the ellip- soids of the receptor cell layer, presumably identifying mitochondria; however, this is the only location within the neural retina where stain- ing can be observed histochemically. 0n the other hand, OPNH diaphorase activity, as evidenced by its staining reaction, can be demonstrated in the ellipsoids of the receptor cell layer as well as Muellers fibers and also in the ganglion cell layer of the retina of the rabbit eye31,33. 31

This fact is of value in studying the extent of the destruction after laser or light coagulation to layers of the retina other than the retinal pigment epithelium and receptor cell layers. 0ne phenomenon found in this study should be briefly mentioned. The borderline pattern of lesions produced at long exposure times showed a sloping margin of inactivation of enzyme activity whereas the borderline between exposed and nonexposed retina at short exposure times (microsecond ranges) showed a very sharp delineation of enzyme inaction. This phenomenon may have been caused by the different ther- mal gradient in the periphery of the lesions, though this can only be explained with difficulties on a theoretical basis ^ . n A previously mentioned study has made it evident that histo- chemical methods are important in studying various enzyme systems and should be included in future investigation to determine lower thres- hold data for vital physiological systems, though one should be aware of the fact that different enzyme systems react quite differently to thermal and other insults. More critical data may be obtained if histochemica1 methods are combined with electron microscopic techniques to study enzyme activity in the pigment epithelial cells themselves. With "routine" histochem- ical methods in normal cryostat sections, possible mitochondrial staining is obscured by the melanin granules; however, with refined Nitro-tetro- zolium staining for electron microscopic sections, this difficulty can be overcome. Electron-mi croscopy. An electron microscopic comparison of retinal lesions produced by white light and laser radiation.at equal exposure times was conducted to study the details of morphological changes at a cellular level 35~37. This comparison has shown that for both types of irradiation the apparent site of the earliest tissue changes seem to lie within the pigment epi- thelial cells. Though the examined lesions were slightly above threshold, examination of peripheral zones of such lesions reveal, to some degree, threshold cellular damage on a morphological basis. Within these marg- inal cells the fragile system of smooth-surfaced endoplasmic reticulum occupying the apical and midzonal cytoplasm was grouped into two major features: 1) patchy and focal dens ificat ion of the adjacent ground sub- stance to membranes and 2) focal densificat ion of membranes. This gran- ulation effect was particularly prominent in the lamellated receptor outer segments. However, a similar granular effect was also seen in the pigmented epithelial villi, in the mitochondria, and within the photoreceptor synaptic expansions. Since within the latter structure the normal synaptic densities become exaggerated with densification of the limiting plasma membranes, whereas such changes were not observed in the apposed plasma membranes of either the second order of neurons or the adjacent glial cells, it has been considered as evidence for 32

lack of transsynaptic degeneration within the time interval of the experimental observation (5 hrs. post irradiation). There was no specific difference in the intercellular degeneration in lesions pro- duced by light coagulation or laser exposures. The boundary between exposed and nonexposed retinal pigment epithelium was rather sharply demarcated, showing granulation effect of the photoreceptor outer segments, vacuolization of the endoplasmic reticulum, and disturbances of the infolding of the basal membrane of the pigment epithelium of the exposed cells, while the immediate neighboring cells did not show any pathological changes. In general, the observations support the hypothesis that the intercellular changes are non-specific to this particular insult. Similar morphological changes can be produced with various forms of trauma. It is of interest that minimal lesions examin- ed by this technique required retinal energies (density and irradiance) identical to those visible with histological techniques. As mentioned under "Histochemistry", refined techniques, utilizing histochemical techniques in combination with electron microscopy in order to demon- strate enzyme activity within the mitochondria of the retinal pigment epithelial cells, may lead to observations and demonstration of damage to enzymes systems below energy levels which produce the morphological changes as described in this paragraph. 0ther Examination Methods. Chan e± a_K ^ has shown by agar-tissue electrophoresis that altera- tions of soluble retinal protein occur after light coagulation. In this particular study it was found that certain alterations were greater if long exposure times had been used (500 ms) in comparison with short ex- posures (175 fJS). The exposure energy used in that study was ^0% above the energy level for producing minimal visible ophthalmoscopic lesions. The image diameter of the exposure beam on the retina was 1 mm in dia- meter. The alteration of soluble retinal protein due to the coagulation effect was demonstrable not only within the area of irradiation but also outside the lesion in the adjacent retina, more than 2 mm from the center of the lesion. McNeer e_t a_[. 3 showed by rather gross electroretinographic tech- niques that a significant reduction of the b-wave could be observed at energy levels 50% below that which produced ophthalmoscopic minimal visible lesions. The disadvantage in this particular experiment was the necessity of multiple exposures in the posterior pole of the eye in order to demonstrate this electroretinographic finding. Although the observa- tion of the reduction in the b-wave was reproducible, it is not possible to conclude a loss of visual function. However, more refined techniques utilizing the retinal response to stimulation after light exposure may provide valuable information. The temporary interference with ERG recordings after laser exposure reported by Allwood and Nicholson ™ is certainly of interest and raises the question of interferences by vibrational disruption of physiologic transport. 33

High speed cinephotography during actual laser exposure in order to study effects other than thermal had been emphasized by the reviewer 39 using STL image converter camera which allows sequence photography at retinal exposure itself and in addition precise timing of those events in vivo and in vitro systems. Any other high speed cinematography is limited by the relatively slow recording. Zaret e± a_|_. 2° nevertheless showed valuable data with normal high speed cinematography documenting pressure waves in biological systems upon exposure, a phenomenon described before by Amar e£ al. ^**. Also the method of fluorescein cinematography recently advertised by various investigators for studying retinal damage after laser or light exposure was first suggested by Zaret e± a_K 28 and this technique has added another interesting examination and evaluation technique to the existing armamentarium in evaluating retinal injury. REVIEW AND DISCUSSI0N 0F EXPERIMENTAL W0RK In this chapter, only articles dealing with accurately measured phy- sical parameters in the production of minimal retinal lesions are reviewed. Because of the great variety of physical parameters, differences in applied units of measurement and constantly new published values, this most impor- tant facet of laser evaluation is at the same time the most vulnerable, most changing, most critical, and most controversial one. The production of mild ophthalmoscopic visible retinal lesions in the rabbit retina by white light of the Xenon high pressure arc, pulsed ruby laser and q-switched ruby laser as a function of average irradiance and exposure time has been studied by various investi gators 1~7|28-30,3^-37,^l~t> Work conducted by Ham, Geeraets, Guerry and co-workers *'~^" ranged in ex- posure times from three minutes with the Xenon high pressure arc down to 28.5 ns for the q-switched ruby laser with an overlap of white light and pulsed laser radiation in the microsecond range (200 /usec). The image sizes of the exposure beams on the retina were equal for all three sources of ir- radiation and measured from 100 u to 1 mm in diameter. White light exposures longer than k.Q ms were obtained by operating the Xenon lamp continuously (CW) with a KG-3 filter introduced in the beam to remove wavelengths greater than 950 mju. For exposure times between 175 jus and k ms, the white light source was electronically pulsed, which resulted in a shift of the emission spectrum almost entirely into the vis- ible range ^ . It was found that for longer exposure times, say longer than approximately 10 ms, the lesion size depended markedly on the exposure time. The lesion size appeared to be smaller than the image size for low doses of thermal energy, while for large doses of energy, the lesion ex- ceeded in size the image size of the exposure beam on the retina. For short exposure times, in microsecond ranges, the image size and size of the lesion (minimal lesion) were approximately equal. This holds true for laser exposures as well as white light exposures. The required irradiance for producing mild lesions with the pulsed ruby laser source (200 to 300 /us) and the pulsed Xenon lamp (175 ps) measured approximately

I07 I0« ^ 10s K>2 10' X XV K> 10 IQ-" io IO'3 10"' TIME- SECONDS 10' IOZ Figure k. Log-log plot of average irradiance in watts/cm^ vs exposure time in seconds for mild lesions in the rabbit retina. Image diameter on the retina BOO /J. • data for white light < 950 nm. x data for ruby laser, b94.3 nm. (Ham et al., Trans. N. Y. Acad. Scl. 28:520, 1966) 35

3-4 KW/cm2 for an image size of 800 u diameter on the retina. For q-switched ruby laser irradiation (30 ns) the average irradiance measured 2-5 MW/cm^ for the production of mild lesions. The ophthalmo- scopic and histological appearance of those lesions in comparison with those produced with the normal pulsed ruby laser and the Xenon light source were different as described in the previous chapter on the histo- logy. The region between 175 f-is and 30 ns exposure times needs to be investigated. Figure 4 shows graphically the average irradiance in watt/cm as a function of exposure time in seconds for mild lesions in the rabbit retina. The image size on the retina for the computation of this plot was 800 p. From this figure it becomes obvious that for long exposure times the curve tends to become parallel to the abscissa, thus defining for a given image size a limiting retinal irradiance for mild lesions. This means that at some temperature above ambiant and for rela- tively long periods of time, the retinal tissue apparently is not under- going any ophthalmoscopically visible alteration. Though it has been demonstrated in experiments by Ham £t a_l . ' that at long exposure times the required energy apparently decreases with the increase of image size of the lesion, studies performed by Jacobson are not in accordance with this observation. Jacobson and co-workers ^7 grey chinchilla rabbits for their retinal burn threshold data. The range of retinal image sizes in their experiment varied from 0.65 to b.k mm in diameter and the exposure times ranged from 25 to 150 ms. The instrument used was a Xenon high pressure lamp in the Zeiss light coagulator, with provisions for short exposure times. The lesions were produced and characterized as a function of time of exposure, irradiance, image size, and spectral characteristics of the incident energy. Lesions in the ocular fundus were clinically subdi- vided into seven subgroups of intensity: a score of 1 meant no lesion was observed after five minutes and 3 + was the heaviest lesion, with explosion of the retina. A so-called "E-burn" was chosen by the in- vestigators to represent the threshold lesion for several reasons: 1) the minimun lesion is one that the observer could discover with indirect ophthalmoscopy with some degree of consistency; 2) damage produced was irreversible as proven by a pathological study of the lesion and 3) there was no evidence at the time of injury of any co- agulation of the involved tissue. The authors further remarked that they did not consider the "E-burn" as an absolutely minimal insult. In their discussion the investigators come to the conclusion that for a given irradiance the threshold dose increases with increase of the retinal image size. This conclusion is in contradiction to the find- ings reported by Ham, Geeraets et aj_. '»**, 0ne must not forget that the image sizes with which the two groups of investigators have experi- mented are different, and therefore extrapolation of Jacobson's data down to the image sizes of the experimentation by Ham, Geeraets et a 1. is probably not justified. This becomes even more evident since in regions where the image sizes of the exposure beams on the retina were the same in both investigations (about 1 mm in diameter), the data of Jacobson and Ham e£a_KVU are in agreement at approximately 1-2 cal/cm2. 36

Furthermore Jacobson and co-workers stated that a higher energy dose was necessary to produce a lesion when the near infrared was included in the spectrum of the irradiating beam as compared with exposures to light within the visible range only. This is in agreement with data reported by Ham, Geeraets e_t a_l . and in accordance with experimental results by Bredemeyer et a_K 61. Irradiation of large areas of the retina were also reported by Jones and McCartney *. These investigators, however, used the normal pulsed ruby laser instead of a white light source. The pulsed ruby laser radi- ation in their experiment was presented in Maxwellian view to the intact monkey eye. The pulse duration was about 2.0 ms, and the flash energy was varied between 1 and 250 j. The investigators stated that energy levels above 100 j produced a marked degree of periorbital edema. But even below these high energy levels the gross findings showed cornea 1 pitting, hemorrhages into vitreous with bubble formation, and loss of light reflex. Histologically the authors observed extensive damage in the pigment epithelium and choroid associated with secondary retinal de- tachment and degeneration which extended peripherally to the area which had been exposed. These investigators state that at a large retinal sub- tense moderately severe lesions show significantly different clinical ap- pearance as compared to those of small retinal image size, the lesions were frequently not visible by ophthalmoscopy whereas the lesion could be demonstrated by his to logical techniques. • The authors used Macaca cynomolgus and cercocedus torquatus atys. The retinal area exposed under Maxwellian view measured about 78.5 sq mm or 2k% of the total retinal area. The eyes were enucleated at different time intervals, up to fifteen months after exposure. Histological sections were stained with hemotoxylin and eosin, gallocyanin or Mallor's azan an- iline blue. Four Macaca cynomolgus received single pulsed laser exposures in both eyes; the retinal subtense of these exposures was ^3.2 degree which gave a retinal area of 1.13 cm2. The energy per flash ranged from 1.2 to 7 j, delivered in 1.5 ms, and the energy density ranged from 1.0 to 6.2 j/ cm2. These animals were sacrificed six days after exposure. According to the authors' outline and tables I and 2 (see ref. 5] the lowest exposure energy was 5.0 j and an energy density of 1.53 cal/cnr and the examinations were carried out one and six days after exposures. These exposures were performed on Macaca cynomolgus. In a second series of exposures on four Macaca cynomolgus, the energy density ranged from 1.0 to 6.2 j/cm2 with a calculated image diameter of 11.25 mm. The authors stated that at close examination and energy densi- ties below 2.6 j/cm2 delivered in 1.5 ms no clinically observable lesions could be seen. However, six days after exposure they observed in three eyes some cobblestoning and small irregularites of the fundus. They also described a grayish appearance of the fundus immediately after exposures and a loss of definition of small surface vessels six days after exposure. At energy levels between 3 and 6 j/cm2 they observed immediate elevation of the retina and loss of light reflex. In these cases the retina became 37

completely detached within six days after exposure. The authors postulate that the primary damage after exposure to the pulsed ruby laser occurs in the retinal pigment epithelium, caused by localized temperature elevation with involvement of the outer segments of the receptor cells. The primary injury then creates secondary de- generative changes involving the receptor cell layer with degeneration, loosing of the outer segment-pigment epithelial junction, fluid infil- tration, and finally complete retinal detachment. This assumption can well be compared with the electron microscopic findings as described by Fine and Geeraets 35 which presented similar observations at the pri- mary site of injury in the retinal pigment epithelium and outer segments of the receptor cell layer with secondary degeneration of the first neuron. If one takes the lower value of energy levels quoted by Jones and McCartney 5 1.0 to 6.2 j/cm^ for image diameter of 11.25 mm) in con- junction with their statement that for all energy levels histological damage could be demonstrated, one finds that their minimal dose for this particular exposure time and large irradiated areas are in fair agreement with the minimal dose for production of lesions of relatively small image diameter i.e. 1.0 j/cm^ vs. 0.8 j/cm^, respectively reported by Ham et a_l . The exposed areas of the retina were almost equal in the experiments of Jacobson e_t a 1. ' and Jones and McCartney •* , but the exposure times were different, 2 ms as opposed to 25-150 ms, The extrapolation of the data is, therefore, of doubtful value. The threshold values for lesions produced with a normal pulsed laser and with the q-switched laser of Bergqvist, Kelman and Tengroth ^".54 are in fair agreement with data of Ham and Geeraets, who used equal image sizes For lesions smaller than 100 p in diameter, - in Bergqvist's 50 p, - the power density for q-switched lesions required 400 MW/cm^. This is an in- crease of approximately 1000 times above the threshold for normal pulsed laser lesions in their study. The possibility of the introduction of art- ifacts pertaining to such high energy levels is discussed in a following section. Zaret, Ripps, Siegel and Breinin (1963) ^ gave as an appropriate threshold dose for lesions (produced with a pulsed ruby laser of 2.5 ms duration and an image diameter of 150 u), a value between 6.45 and 0.65 cal/sq cm. However, since the image diameter was only an estimate, these results have to be taken with caution, as the authors implied. In a more recent report Zaret and co-workers 50 used the Douroucouli monkey eye for their investigation of minimal retinal lesions produced with q-switched laser action. The laser used was a TRG model 104 q-switch- ed laser action. The laser used was a TRG model 104 q-switched ruby laser. The output of the laser was 0.3 j with a peak power of 10 MW. The image sizes on the retina were experimentally verified by implanting stainless steel microspheres of 0.025 inches in diameter into the vitreous and mea- suring these microspheres photographically after they had been attached to 38

the retina by retrobulbar magnets. The magnification factor by photo- graphic recordings was 3.15- The authors calculated from these measure- ments that the focal length of this monkey eye was 18.3 mm. The retinal image sizes measured 0.^7 mm, 0.67 mm and 1.86 mm. They described the ophthaImoscooic findings of minimal lesions as an initial darkening or graying of the exposed retinal area which sometimes seemed to be transient. Two annular zones could usually be distinguished for minimal lesions which surrounded the exposed portion. In moderate lesions choroidal hemorrhage occurred that extended within the plane of the choroid and in deep retinal layers. A further increase in intensity resulted in hemorrhages which were confined to the area of chorio-retinal junction. With still higher energy density, profuse hemorrhaglng occurred extending through the retinal layers and frequently into the vitreous. The energy density range for the production of minimal lesions to the more severe ones extended from 0.06 to 1.8 j/crtr^. The findings described by the authors, that different area size of illumination did not noticeably influence their threshold for injury, agree with the observations of Geeraets and Ham at that exposure time. However, their observations that heavily pigmented fundi, although gen- erally requiring lower threshold energy for the production of minimal lesions than that for normal pigmented fund!, were not statistically sig- nificant, does not correspond with observations made by Ham and Geeraets, nor are they in agreement with measurements made in vitro examination on pigmented cells exposed to q-switched laser 63,64. Interesting observations were made by Zaret e_t a_K 50 using high speed cinephotography. During the exposure of the retina with the un- focused beam intensity of 10 MW/cm^ they observed two phenomena: 1) pro- duction of a mechanical force and 2) indirect evidence of the production of aplasma within the eye. These observations support reported findings by Geeraets(39) on the production of a plasma under q-switched exposure of the retinal pigment epithelium in which the exposure time measured 30 nsec, whereas the duration of the plasma lasted for several micro- seconds and the duration for the produced shock-wave lasted about 5 ms. Vassiliadis and co-workers ° reported observations on exposures of rabbit retinas to normal pulsed ruby laser exposures. Examination was carried out 2k hrs. after exposure. In the section on long pulsed ruby laser exposures, the authors do not give any image sizes of their ex- posure beam on the rabbit retina; however, it may be assumed from their q-switched ruby laser exposures that the image sizes on the retina are equal (100 to 150 p diameter). In this report, the authors recommend histochemica1 methods for determination of retinal threshold lesion which supports similar recommendations made previously . They added other techniques to those used previously and mentioned in this report under "Histological Findings". Energy levels for the production of minimal visible retinal lesions produced with normal pulsed ruby laser are not contained in the report by these investigators since exposure times, exact image size, and exact energy were not clearly defined. Taking, however, their threshold energy 39

dose for q-switched ruby laser radiation, which is in agreement with Ham e_t a_[. and other experiments discussed in this paper, the quoted threshold dose for normal pulsed ruby laser and the human eye by one of the co-authors (Zweng)^' was quoted as 20 j/cm . This value appears extremely high and needs verification. Beside their work with effects of normal pulsed laser action on rabbit eyes, the authors have conducted studies with q-switched ruby laser on the rabbit retina and the Rhesus monkey. The authors defined clinical visible threshold lesion as just barely visible changes by ophthalmoscopy within kS to 60 minutes after exposure. They state that the only method of in- vestigating the sub-visible lesions that produce irreversibl« damage would be by histochemica1 techniques. Their stated retinal dose for the pro- duction of minimal lesions produced by q-switched laser action (8 nsec), and "assumed retinal spot size of 100 to 150 ju." was given as 0.05 to 0.1 i/cnr for a 50% probability of the development of the lesion. This energy level is in agreement with the above mentioned values quoted by various investigators for this retinal image size. The authors feel that the threshold for histological visible lesions would be lower than the quoted threshold for ophthalmoscopic visible les- ions although they do not demonstrate histological proof for this assump- tion. In investigations carried out by Geeraets e_t aj_. it has been shown that the threshold level for histological and even electron-microscopic examination techniques was essentially the same as that for ophthalmo- scopic visible lesions, providing special ophthalmoscopic techniques were used. The only techniques by which lesions could be identified below the clinically visible threshold were histochemical staining techniques for enzyme inactivation and electrophoretic examination for possible demon- stration of protein alterations of the retina *»'. 0ther observations by these authors, particularly with regard to histological description of the differences in the appearance of lesions produced with normal pulsed ruby laser and those produced with q-switched lasers, correspond generally to the descriptions given by other investi- gators during the last several years and are discussed in this report. In more recent studies using long-pulse ruby laser, q-switched ruby laser, and a mode-locked ruby laser Vassiliadis e_t a_l . °5 an(j £weng e£ a_K 66 presented data for minimum spot sizes on the retina of Rhesus monkey. The data were obtained for exposure of the paramacular region. Macular threshold lesions were produced with long-pulse laser exposures. The authors stated that the threshold for macular lesions indicated that this location is 2.2 times more sensitive to laser-induced injury than the paramacular region. Threshold criteria were based on ophthalmoscopic visible lesions one hour after laser irradiation. About 1.1 mj was given for a 50% probability of retinal damage in the paramacular region for long-pulse ruby laser irradiation, corresponding to an energy density of 56 j/cm2. For the macular region approximately 0.5 mj (2.6 j/cm^) were required for similar conditions and criteria. Spot sizes were given as kO to 60 p and pulse duration with about 1.7 ms. It should, however, be stated that the lesions illustrated in this report appear to be well kO

above the general criteria adapted for ophthalmoscopic visible minimal lesions. Data given for minimal lesions produced by q-switched laser irrad- iation in the rabbit eye were given with 8pj for a 50% probability and for 8 ns exposure time and about 100 /i retinal diameter. This corre- sponds to about 0.1 j/cm^ retinal energy density. In the Rhesus monkey eye spot sizes of approximately 25 p were estimated although for the most part they averaged about 50 \i in diameter. The retinal energy den- sity for these spot sizes was calculated with 0.8 j/cm^ or peak power density of about 100 MW/cm^ for clinically visible minimal lesion. For histological detection of retinal injury about half of this energy density was sufficient according to these investigators. In a more recent paper by Kohitiao and co-workers ', who used normal pulsed laser and q-switched laser for production of minimal retinal lesions in gray chinchilla rabbits, the quoted energy levels for the production of minimal retinal lesions for both modes of laser action were quite differ- ent from any of the previously published reports. For the normal pulsed laser an exposure time of 500 fjs was implied. The retinal image size of the exposure beam measured 250 /* in diameter. Their criteria for a mini- mal threshold lesion was based on a LF 50 (lesion factor of 50%). The authors accepted as threshold lesions those which appeared 24 to 48 hours after exposure. Their retinal dose for minimal lesions produced by the normal pulsed ruby laser was given as 0.l6 i/cm^, which is about 5 times lower than the threshold given by other investigators. The same investigators gave a threshold dose for lesions produced with q-switched pulses of 80 ns duration and equal image size of 250 u- on the retina as .0045 j/cm . The latter value is about 16 times lower than the ones reported by Ham, Geeraets e_t a_K, and other investigators. In other words, between the threshold level for production of minimal lesions with normal pulsed ruby laser action and q-switch action, their data show a factor of 40, whereas the same factor in Ham's experimenta- tion is only 10. Ruby vs. Neodymium Laser Little has been reported in the literature on retinal lesions pro- duced by neodymium laser either in the pulsed or the q-switched mode 5i§«7, In particular no exact energy levels for the production of such lesions has been presented. In the following, a comparison of lesions produced with the ruby laser and neodymium laser is made. At the wavelength of the ruby laser (694.3 nm) the ocular media absorb approximately 6% of energy incident on the cornea; for the neodymium wave- length (1060.0 nm), approximately 50% of the energy incident on the cornea 24-26 is absorbed. The loss of energy by absorption, scattering, and reflection in the darkest human retinal pigment epithelium (PE), amounts to about 40% for ruby laser wavelength rather than the 15% of neodymium *5 41

in the human eye. Reflection from the pigment epithelium and choroid is approximately 3 to 5 times greater for the neodymium wavelength than for the ruby wavelength(2^) in the human eye. The data for loss of ener- gy at these two wavelengths within the darkest pigmented human choroid are approximately 56% (69^.3 nm) and 23% (1060 nm) 25 for ruby and neo- dymium respectively. It should be pointed out that for short pulse durations, such as those present in normal pulsed ruby or neodymium laser (fis to a few ms), and low energy levels which produce only minimal ophthaImoscopic and/or histological lesions in the retina, only the retinal pigment epithelium and its immediate neighboring structures are involved. The reason for this has been discussed previously 1,2,M*,68. p0r longer exposure times, that is greater than 10 ms, and for moderate to heavy lesions produced with higher energy levels, absorption within the choroid contributes in- creasingly to the extent of the lesion produced. At very high energy levels, even with short pulses, the absorption of neodymium wavelength (1060 nm) within the ocular media certainly makes for an additional com- plicating factor, though one may state that with a single, heavy accidental exposure severe chorioretinal disruption can occur, thus causing injury to the ocular media to be relatively insignificant. However, the greater absorption of the neodymium wavelength in the 0M makes this wavelength less desirable where relatively frequent and repetitious exposures (1 sec inter- vals) are required with energy levels resulting in mild to medium chorio- retinal reactions, that is, in the range of clinical therapeutic use. Although the absorption for 1060 nm in the 0M is considerably greater (50%) than that for the ruby wavelength (6%) and lower in PE (15% as op- posed to ^0%), one cannot conclude that for those two wavelengths the primary site of injury is at different topographic locations within the retina. The PE measures about 10 p. in thickness, while that of 0M for the human eye can be given at a minimum of approximately 22000 /i. The neural retina measures about 500 p. in thickness posteriorly and about 250^Ltat the center of the fovea. These considerable differences in "thickness" of the absorbing structures make it evident that the energy lost by the various means of energy dissipation per unit thickness is still considerably greater in the PE as compared to the neural retina. This becomes evident in comparing the hiStomorphological changes which occur in the retinal pigment epithelium and in the adjacent retinal and choralaaI structures after exposure to the ruby and neodymium laser wave- length. Preliminary data for energy densities and power densities of neo- dymium laser radiation were obtained in chinchilla and dutch rabbit eyes. With exposure times of 200 /us and image size of the exposure beam of approximately 800 /j in diameter on the retinal pigment epithelium, the energy density for an RD 50 lesion (lesion produced in 50% for exposures at this energy level) was about 5 to 6 times higher for the neodymium wave- length than that of the ruby laser wavelength. The same observation was made using both lasers in the q-switched mode (30 ns exposure time). This factor of roughly 5 to 6 in required energy density for the neodymium wave- length for production of minimal retinal injury can in part be explained

by the greater reflection from and lesser absorption within the retinal pigment epithelium 26. In the past, rabbits and monkeys have been the experimental animals of choice in determining levels of retinal damage after exposure to radi- ation sources like the sun, nuclear fireballs, xenon lamps, and lasers. The demand for a realistic evaluation of the retinal burn hazard from nuclear weapons and the growing hazard from laser sources accentuate the need for an accurate extrapolation of animal data to humans. The clinical technique of light coagulation of the retina has provided some information which can be correlated with animal data but generally speaking such data are difficult to use because they are obtained under pathological condi- tions and do not involve exposure of the fovea. Foveal exposure in a human volunteer, a 51 year old white male, has been performed recently **. The eye had to be enucleated for a choroid- al melanoma. A complete ocular examination revealed clear ocular media, visual acuity of 20/20-1 (corrected) and normal foveal reflex. A cho- roidal melanoma was located in the upper nasal quadrant with intra - and preretinal hemorrhages present. There was no central visual field defect (1 and 3 mm white test targets). Photopic and scotopic adaptation times (Goldman-Weeks Adaptometer technique) were within normal limits. The focal length, as determined by ultrasonogram, was calculated to be 17.5 mm. Retinal light exposure was than performed, using the "research light coagulator" described in a previous paper(70)» which utilizes a Xenon high pressure lamp as the light source and a KG~3 filter introduced in the optical pathway. This filter restricts the radiation spectrum to the vis- ible region, eliminating wavelengths beyond 950 nm. The angle of diver- gence of the light beam entering the eye was ^.5°. The calculated image diameter of the beam on the retina, based on a focal length of 16.5 mm for the 2 dpt. myopia of this patient was 1.37 mm in diameter. The ex- posure times ranged between 130-1^0 ms, and each exposure was monitored and recorded separately. The first exposure was made in the midperiphery in the 11 o'clock meridian. The calculated retinal dose for this exposure was 7.9 j/cm^ No ophthalmoscopic visible lesion developed within the next 18 hours. Another exposure was made in the 10 o'clock meridian, increasing the retinal dose to 9.2 j/cm^. This exposure caused a very mild change in the retina within about 5 minutes after exposure and seen with the ophthalmoscope using red free light. Another exposure using 9.b j/cm2 as the calculated retinal dose was made in the 9 o'clock meridian and produced results comparable to the 9.2 j/cm2 exposure. Accordingly, 9.6 J/cm2 Was accepted as a valid estimate of threshold dose according to the criteria used in this experiment. A diaphragm was then inserted in the light beam, reducing the energy output by 50% but leaving all other experimental parameters unchanged. The macula was exposed to this retinal dose (k.B j/cm2). Immediately

after exposure, visual acuity, visual field and adaptometry were repeated under the same conditions as carried out prior to the exposure. Corrected visual acuity was 20/25 + 3; the visual field was unchanged, and there was a slight delay in cone and rod adaptation times. However, all tests showed pre-experimental data within 2 hours and 30 minutes after exposure. Another exposure was then performed. This time it was decided to irradiate the macula with a retinal dose equal to that required to produce a minimal visible lesion in the midperiphery. The first exposure in the midperiphery was made with a retinal dose of 10 j/cm^. No visible lesion developed over the next 15 minutes and did not appear over another 15 hours of observation. Accordingly, a second exposure to a calculated retinal dose of 12.2 j/cm2 was given to the midperiphery. A very mild lesion de- veloped within three to four minutes after exposure. The macula was then exposed to a calculated dose of 13.0 j/cm^. No ophthalmoscopically vis- ible lesion could be detected over the next 15 hours. There was loss of the foveal reflex which was still present the following morning when the patient received his last examination. Immediately after this exposure, visual acuity, visual field, and adaptometry tests were performed again. The visual acuity corrected was similar to the previous experiment, 20/25 + 3 corrected. There was no scotoma, but the patient reported an after image which was "about the size of a goose egg" at 1 meter distance from the screen. Viewing a black back- ground the center of the image was "greenish, surrounded by a bluish ring". Viewing a white background the after image was purple. This after image faded slowly but was still noted by the patient 5 hours after the exposures. The adaptometry curve for cone and rod adaptation was almost identical to the one obtained after the first experimental light exposure. There was again a slight delay in cone adaptation and rod adaptation beginning about 10 minutes after the completion of light adaptation. 0riginal values were approached after approximately 30 minutes, at which time the test was dis- continued because of the increasing tension of the patient. Fourteen hours after last macular exposure the visual acuity was 20/20-2 corrected and no visual field loss could be detected with various size of white or colored test objects. There was no after image observ- able by the patient (9 hours after the last exposure) and the adaptometric values had returned to pre-exposure levels. Steady State Laser Hazard With the increase of power output from CW or steady state operation of gas lasers and semi-conductor diodes, special precaution has to be taken to prevent retinal damage. Injury may derive from prolonged single exposures or accumulated exposures with the possibility of late sequellae. The latter are at present only mentioned as theoretical possibility since no well controlled experimental results have been made available to sub- stantiate this assumption. However, the data reported by Noell 57, kk

Dowling "° , Kuwabara and Corn » certainly call for meticulous in- vestigation of such potential photodynamic retinal injury. Under normal conditions the output beam from these laser sources are extremely parallel, and hence the image size of the beam on the retina is diffraction limited if no optical systems are used in the pathway of the exposure beam. Jones and Montan 71 nave described ocular hazard for exposure to CW laser such as the He-Ne gas device. These authors calculated that 10~6 watts could be regarded as a safe power level on the retina even if the energy is confined to a 10 p image diameter on the retina. Though this image size may be an underestimate /z , it provides a factor of safety in so far as the energy density is concerned. This safety factor, however, is opposed by the factor of energy dissipation by conduction from the irradiated image to the surrounding unirradiated tissue in proportion to the temperature gradient. For long exposure times it has been shown l that the energy required for producing irreversible retinal injury de- creases with the image size of the exposure beam on the retina. DISCUSSI0N AND C0NCLUSI0NS The reported data on energy density incident on the retina for the pro- duction of ophthalmoscopically visible, minimal lesions, utilizing white light, are in fair agreement among several independent research groups if exposure times and retinal spot sizes are taken into account. Apparent discrepancies between data reported by Jacobson e_t a_K ^7 and those ob- tained by Ham e_t aJL " may not be true disagreements since exposure techniques and image sizes were quite different in the two studies. For lesions produced with pulsed ruby lasers, the reported data are again in agreement if the physical parameters relating to the production of these lesions are equal. For image sizes ranging from 100 \JL to 1.0 mm diameter on the retina and exposure times ranging from 200 ^is to approxi- mately 2 ms, the retinal dose (j/cm^) range from 0.7 to 1.0 j/cm^). This value is in agreement with Jones and McCartney 5 Up to lesions as large as k.k mm in diameter, although these investigators had quoted their vis- ible threshold prior to this last report with 0.01 j/cm^ for a-switched ruby laser exposures and large image sizes in the monkey eye 52 . -rne only large scale deviation known to the author has been reported by Kohtiao and co-workers ' who give retinal energy densities of 0.16 j/cnr for image di- ameters of 250 ft and exposure times of 500/us. .Jhgir values are lower by a factor of 5 from the data obtained by others ^*»^° . Discrepancies occur if the image size on the retina is reduced below 100 fj. diameter. However, with the in vivo examination techniques employed, it becomes increasingly more difficult to recognize very small lesions by ophthalmoscopy because of the lack of contrast between very mild lesions and the surrounding normal retina. This in turn requires higher energies to obtain more severe lesions so that they may be recognized. Moreover,

it is doubtful whether the rabbit eye, because of its poor optical quality, can resolve images smaller than 100 ^i. Similar observations hold for q-switched ruby laser lesions. For ex- posure times ranging from 5 to 50 ns, the retinal irradiances required for the production of minimal visible lesions range between 2 and 5 MW/cnr for image diameters from 100 fi to 1 mm. The threshold value for an RD jj0 les- ion reported by Ham £t al. ** and Qeeraets £t al. ^' Is 0.07 j/cm2 or 2.3 MW/cm2 at an exposure time of 28.5 ns. The only large scale discrep- ancy from this value as of now is that reported by Kohtiao and co-workers '. While their value for multiple-spiked ruby pulse was 5 times lower than ours, their lesion, which was produced with a q-switched ruby laser 250 j* in di- ameter and 80 ns exposure time, was .00^5 |/cnr, a value 16 times lower than that reported by us and other, a discrepancy discussed in this paper. How- ever, there are many possible explanations for this discrepancy when one considers the method used by these authors to produce lesions. When the image diameter is reduced below 100 /n it would appear that the retinal dose for production of minimal retinal lesions is significantly greater than that for larger image diameters '. Bergqvist, Kelman and Tengroth *+& reported power densities of ^00 MW/cm2 when the image size was reduced to 50 p in diameter. However, in more recent communications •>* these investigators indicated that artifacts caused by previously mentioned difficulties in recognizing minimal lesions of very small diameters may well have contributed to high dosage levels. Moreover, there is no real agree- ment among authorities as to the limiting size of retinal spots for the human, monkey, or rabbit eye. This in itself may introduce another source of error if irradiances are calculated on the basis of estimated spot sizes of the exposure beam on the retina. In recently published data by these investigators 5 , tne required power density for q-switched ruby laser lesions of the retina were even of a wider range depending on "calculated" image sizes on the retina. In this report the power density for an 8 ft in diameter lesion in the rabbit eye was given with 36000 MW/cm2. Realiz- ing that an image size of a diameter that small is almost impossible to achieve in the rabbit eye with its relatively poor optical qualities, these published data certainly call for a very detailed, exhaustive and final clarification of the question of the influence of image size and energy levels. An in vitro attempt to clarify these discrepancies has been made '*. While the thermal concept of retinal injury most likely holds for ex- scon d ranges Vos 7^.75^ Ridgeway 76, posure times in microsecond _..„__ , _, , workers *" Geeraets and Ridgeway °°, Hayes and Wolbarsht '', Makous and Gould 56f Wray 78 and Spells 62 , this concept is inadequate to explain all biological effects occuring in retina and choroid, particularly at high power densities (MW/cm2) and short exposure times (nanoseconds) as produced by q-switched laser exposures. During these extremely short exposure times heat conduction does not extend beyond 0.1 /j from the site of absorption. Taking an average diameter for a retinal pigment epithelial cell as being approximately 10 yu and a melain granule size of from I to 3 ft, the incident energy from a giant pulse of laser light would in the early stages of the pulse be absorbed by the anterior portions of the pigment granules with a

resulting high temperature rise in these structures. This in turn may lead to ionization and possible formation of a plasma which would be opaque to additional incoming photon. Shock waves and acoustic signals, Raman and Brillouin scattering, frequency doubling and other non-linear phenomena may produce biological effects in addition to thermal effects and before heat conduction would play a significant role. It seems that these biological effects of q-switched lasers are relatively independent of image size on the retina. Some support for this viewpoint comes from in vitro observations on cellular death for chick retinal epithelial cells in tissue culture when exposed to a q-switched ruby laser beam at 30 ns 73. The LD 50 dose (50% change of cellular death from this energy density) was identical for an approximate spot size of 20 /u and 135 f* diameter at the cellular plane. This energy dose was 1.2 |/cm2, or an irradiance of 3.^ MW/cm2, which is in agreement with the in vivo observations for retinal image diameters greater than 100 ju ^*. 0bservations in support of this but using normal pulsed ruby laser radiation have been made by Feick and co-workers '9. It should be stressed that retinal injury may occur from photochemi- cal processes as described most recently by Noell 57, Qowling ^0f Gorn and Kuwabara 58,59^ Rounds et jaK ". Data obtained from the one human volunteer should be evaluated separately. The calculated retinal energy densities required to produce minimal lesions in the periphery of this human fundus were significantly higher than those required to produce similar lesions in the monkey or rabbit retina. This is in agreement with recent observations published by Campbell e_t a_K 55. These authors, using a ruby laser, report "the energy values necessary to produce a threshold lesion are significantly lower in rabbits than in human subjects". However, their observation that "in one human subject the threshold was lower in the macula than in other areas of the retina" is not in agreement with our observations where retinal energy densities which produced minimal lesions in the periphery failed to produce any permanent physical manifestation in the macula area. The reasons for this discrepancy may reside in the different con- ditions inherent in the two experiments. Campbell trt a_K 55 used a pulsed ruby laser (exposure time 0.7 ms), where Geeraets Q a_K ° em- ployed a high pressure xenon lamp and the exposure time was 137~1^0 ms. Also, the lesion sizes were quite different (our retinal image covered the entire macular area) in the two experiments; the criteria used to define minimal lesions were different, and the observation period on the patient was more restricted in our case than in Campbell's. Nevertheless, both sets of observations are encouraging and emphasize that rabbit data on retinal lesions are at lease on the safe side insofar as retinal energy density is concerned. It must be remembered that the eyes of such patients are not free of pathology, and although the location of this melanoma was well removed from the light exposure sites, there were present in the fundus choroidal hyperemia and stromal exudates. Caution must be observed in attributing too much significance to these observations until more human data become available.

Although visual acuity was reduced slightly immediately after exposure of the entire macular area to 13 j/cm*, recovery was complete within 15 hours. Campbell ^t a_[. also reported this slight reduction of visual acuity (20/12 to 20/20 - 3) although the lesion in their experiment was observable and located slightly off center from the fovea. The fact that the calculated retinal dose or incident energy density required to produce a minimal lesion in the periphery was higher (from 9.6 to 12.2 |/cnr) in the second group of exposures is not fully understood. The possible selection of a lighter pigmented area of the fundus, mild vitreous reaction following the earlier exposures, and an increasing number of cells in the vitreous associated with the preretinal hemorrhage may have been contributing factors. Vassiliadis and co-workers' •*' reported their findings of human ex- perimental exposures. However, the ocular malignancy in their human volun- teer was apparently quite advanced, thus greatly interfering with ocular transmission. This factor may have caused the widespread of required energy which caused or did not cause retinal injury. Visible lesions oc- curred with energy output as low as 44 uj while on the other hand 150 pj energy output did not result in a visible lesion. Though the authors tried to explain this discrepancy by possible errors in estimated spot sizes due to incomplete paralysis of accommodation as well as to vitreous haziness and possible obscuration of the laser beam by the tumor, the last two factors seem to be the most important ones. Vitreous haziness and general inflamma- tory reactions caused by the ocular pathology represent major difficulties in this kind of human experimentation. This factor is even potentiated by the unknown biological response to insults superimposed on the already evi- dent pathological condition. SUMMARY 1. In this report only measured data are used; no extrapolations are quoted or made, for such extrapolations are misleading and in many instances erroneous. 2. 0cular spectral characteristics: a. absorption of radiant energy by the retinal pigment epithelium and choroid in the human and chinchilla rabbit eye are similar and occur primarily in the range 400-950 nm, the peak absorption occurring at approximately 575 nm. b. choroidal pigmentation in the Rhesus monkey is significantly heavier than that in man. c. spectral transmission through the ocular media is similar for man, monkey and rabbit. d. spectral reflectance from the pigmented structures of the ocular fundus is approximately 3 to 5 times greater for the neodymium wavelength (1060 nm) than for the ruby wavelength (694.3 nm). 48

3. OphthaImoscopic findings of minimal retinal lesions: a. for relatively long exposure times (millisecond-second lesions are usually smaller in diameter in comparison with the image diameter of the exposure beam on the retina. This is a heat conduction phenonenon. b. for short exposure times (microsecond ranges): lesion diameter is almost equal to image diameter of the exposure beam on the retina. Borders of lesions are sharply demarcated. There is no difference in appearance for lesions produced by white light or ruby laser. c. for extremely short exposure times (nanosecond): lesions show signs of cell disruption and subretinal hemorrhages at levels slightly above "threshold" for visible lesions. ^. Histological findings of minimal retinal lesions: a. for long exposures (millisecond-second ranges): coagulation effect of PE and retinal receptor cell layer is prominent with hyperemia in choroid and pyknotic nuclei. Retinal edema present in the en- tire neural retina overlaying the lesion. b. for short exposures (microsecond ranges): sharp borderlines of de- fect. Coagulation effect evident with involvement of PE and outer layers of the neural retina. Little or no effect demonstrable in choroid. c. for extremely short exposures (nanosecond ranges): disruption of PE cells and scattering of pigment granules into receptor cell layer. Free blood cells may be seen protruding through ruptures in Bruch's membrane. 5. Staining techniques, using DPN diaphorase as one possible sensitive in- dicator for demonstration of extent of retinal injury after light or laser exposure to various stains. Among those are Hematoxylin-Eosin, pentachrome and PAS. Also the use of acid phosphatase and phospho- tungstic acid hematoxylin staining of Newcomer-fixed material has been proven useful as an indicator of retinal injury. 6. Electron-microscopic findings for mild lesions produced in microsecond ranges by white light or by ruby laser showed identical changes in PE and receptor outer segments. Borderlines between exposed and non-exposed cells are very sharp. 0bserved cellular changes appear to be non-specific for this type of injury. 7. Electro-phoretic techniques represent a sensitive method of evaluating thermal injury to retinal proteins; denuaturation occurs within and peripheral to the exposed retina. 8. Retinal doses for retinal injury:

a. preliminary investigations of retinal lesions produced in the chin- chilla or dutch rabbit eye with white light (kOO to 9^0 nm), very long exposure times (3 mins.)* and an image size of 800 p. in dia- meter on the retina required an average irradiance of 6 watts/cm2. b. retinal doses for production of minimal ophthalmoscopic visible lesions in rabbit eyes for pulsed ruby lasers (200 jis - 2 ms ranges), and image sizes on the retina ranging from 100/4 to 1 mm in dia- meter, are given in various investigators within a range of 0.8 to l.6 j/cm2, exception: 0.16 j/cm2, Kohtiao e_t a_l . (7). c. retinal doses for production of minimal ophthalmoscopic visible lesions for q-switched ruby laser (5 ~ 50 ns) and image sizes of the beam on the retina ranging from 100 ^ to 1 mm in diameter, are given within a range of 0.05 to 0.1 j/cm2, exception: 0.0045 j/cm2, Kohtiao e_t aj[.(7). d. retinal doses presented for very small image sizes on the retina have to be treated with caution since inherent artifacts may result in erroneous energy for the production of minimal cellular damage. Such artifacts are twofold: 1) either the retinal image size has been underestimated; thus, the calculated irradiance per unit area is too high and 2) the required irradiance for production of a very small lesion has to be increased to give sufficient contrast for identifying these lesions clinically. 9. The primary site of retinal injury after exposure to neodymium and ruby laser wavelengths is in the retinal pigment epithelial cell and immedi- ate adjacent structures; there is also the possibility of harmful effects on structures of the ocular media and neural retina for wavelengths in the infrared because of greater absorption. 10. The power density at the retina for production of minimal lesions is approximately 5 to 6 times higher for neogymium laser than for the ruby laser wavelength. This fact may be in part explained by the greater reflection of the neodymium wavelength (l060 nm) from the retinal pigment epithelium and lesser absorption within this layer. 11. At high power densities (MW/cm2) delivered in nanoseconds, retinal injury may result from events other than thermal. Such effect may include ionization from intense electric field gradients, shock waves, Raman and Brillouin scattering, double photon effects, and other non- linear effects. 12. Presenting minimal irradiances or doses for various wavelengths and exposure times for every incident on the retina rather than on the cornea has the advantage that such physical considerations as pupil- lary diameter, ocular transmission co-efficient and spectral absorp- tion characteristics of retina and choroid are already incorporated in the data. 50

13. The threshold for biological effects from q-switched laser exposures are apparently independent of the image size of the laser beam on the retina. 14. Required energy for production of retinal lesions in the human eye appears to be significantly greater than energy levels causing retinal injury in the rabbit eye. REFERENCES 1. Ham, W. T., Jr., Wiesinger, H., Schmidt, F. H., Williams, R. C., Ruffin, Shaffer, M. C. and Guerry, 0., Ill, Flash Burns in the Rabbit Retina as a Means of Evaluating the Retinal Hazard from Nuclear Weapons. Am. J. 0phthal.. 46:700, 1958. 2. Geeraets, W. J., Burkhart, J., Guerry, D. Ill, Enzyme Activity in the Coagulated Retina. Acta 0phth. Suppl., 76, 79:93, 1963. 3. McNeer, K., Ghosh, M., Geeraets, W. J., Guerry, D. Ill, Electroretino- graphy After Light Coagulation. Acta 0phth. Suppl. 76, 94:100, 1963. 4. Chan, G., Berry, E. R.,. Geeraets, W. J., Alterations of Soluble Retinal Proteins due to Thermal Injury. Acta 0phth. Suppl. 76, 101-108, 1963. 5. Jones, A. E. and McCartney, A. J., Ruby Laser Effects on the Monkey Eye. Invest. 0phth. 5:474, 1966. D. Geeraets, W. J., Untersuchungen zur Deutung von Netzhautverbrennungen. AJ.brecht V. Graefes Archiv, 165:452-463, 1963. 7. Kohtiao, A., Resmick, I., Newton, J. and Schwell, H. Threshold Lesions in Rabbit Retinas Exposed to Pulsed Ruby Laser Radiation. Am. J. 0phth. 62:664, 1966. 8. Eccles, J. C. and Flynn, A. J., Experimental photo-retinitis. Med. J. Australia. 1:339, 1954. 9. Walker, A. M., The Pathological Effect of Radiatnt Energy on the Eye: A Systematic Review of the Literature. Prac. Am. Acad. Arts and Science 51:760, 1916. 10. Birch - Hirschfeld, A. and Stimmel, L., Beitrag zur Schadigung des Auges durch Blendung. Arch of 0phth. 90:138, 1915. 11. Verhoeff, F. H. and Bell, L., The Pathological Effects of Radiant Energy on the Eye. Proc. Am. Acad. Arts and Science, 51:630, 1916. 12. Flynn, A. J., Photo-retinitis in Anti-aircraft Lookouts. Med. J. Australia. 2:400, 1942. 51

13. Buettner, K. and Rose, H. W., Eye Hazards from Atomic Bomb, Si ght Savings Rev., 23; 1, 1953. 14. Pickering, J. E., Culver, W. T., Allen, R. G., Jr., Benson, R. E., Morris, F. M., Williams, D. B., Wilson, S. G., Zellmer, R. W., and Richey, E. 0., Effects on eyes from Exposure to very high Altitude Bursts. WT-l633. 0peration Hardtack, Apr.-0ct. 1958 (S/FRD). 15. Meyer-Schwickerath, G., Light Coagulation. The C. V. Mosby Company, St. Louis, 1960. 16. Guerry, D. Ill, Wiesinger, H. and Ham, W. T., Jr., Photocoagulation of the Retina: report on a successfully treated case of angiomatosis retinae. Am. J. 0phth. 46:463, 1958. 17. Gordon, J. P., Zeiger, H. J. and Townes, C. H., The Maser - New Type of Amplifier, Frequency Standard, and Spectrometer. Phys. Rev. 99:l264, 1955. 18. Maiman, T. H., Stimulated 0ptical Radiation in Ruby. Nature, 187:493, 1959. 19. Ludnigh, E. and McCarthy, E. F., Absorption-of Visible Light in the Refractive Media of the Human Eye. Arch. 0pth. 20:37, 1938 20. Kinsey, V. E., Spectral Transmission of the Eye to Ultra-violet radi- ations. Arch. 0phth. 39:508, 19^8 21. Wiesinger, H., Schmidt, F. H., Williams, R. C., Tiller, C. 0., Ruffin, R. S., Guerry, D. Ill, and Ham, W. T., Jr., The Transmission of Light Through the 0cular Media of the Rabbit Eye. A.J_.0., 42:907, 1956. 22. Prince, J. H., Spectral Absorption of the Retina and Choroid from 340-1770 m. Final Report Proj. 1069. Mar. 1962. Contr. No. AF 41 (657)-306. Institute for Research in Vision, 0hio State Univ., Col. 0hio. 23. Graham, W. P., The Absorption of the Eye for Ultra-violet Radiation. Am. J. Physiol. 0pt.. 4:152, 1923. 24. Geeraets, W. J., Williams, R. C., Chan, G., Ham, W. T., Guerry, D., Schmidt, F. H., The Loss of Light Energy in Retina and Choroid. A.M.A. Arch. 0phth.. 64:b06-615, 1960. 25. Geeraets, W. J., Williams, R. C., Chan, G., Ham, W. T., Jr., Guerry, D., Schmidt, F. H., The Relative Absorption of Thermal Energy in Retina and Choroid. Invest. 0phth.. 1:3^0-347, 1962. 26. Geeraets, W. J., Light Reflectance from the Retinal Pigment Epithelium. (Unpublished data). 52

27. Geeraets, W. J., Williams, R. C., Ghosh, M., Ham, W. T., Jr., Guerry, D., Ill, Schmidt, F. and Ruffin, R., Light Reflectance from the 0cular Fundus. Arch. 0phth., 69:112, 1963. 28. Zaret, M. M., 0cular Exposure to Q-switched Laser Irradiation. Techn. Rep. AFAL-TR-65-279, April 1966. 29. Vassiliadis, A., Rosan, R. C., Peabody, R. R., Zweng, H. C. and Honey, R. C., Investigation of Retinal Damage Using a Q-switched Ruby Laser. Spec. Techn. Rep., SRI, Project 5571, August 1966. (requests) AFAL (AVTL) Wright-Patterson AFB, 0hio 45^33. 30. Shuman, R. M. and Maloney, D. H., Minimal Cellular Damage to Rabbit Retinae Following Exposure to Focussed Long-pulse Ruby Laser. Fed. Proc. 26:793, 1967 (Abstract 2995). 31. Cogan, D. G. and Kuwabara, T., Tetrazolium Studies of the Retina (II and IV). The Joun. of Histochem. and Cytochem. 7:334, 1959 and 8:380, 1959. 32. Niew, M. and Mercumies, E., Cytochemical Localization of the 0xidative Enzyme Systems in the Retina (I and II). J. of Neurochem., 6:200, 1961 33. Pearse, A. G. E., Hi stochemi stry, Churchhill, London, I960. 3^. Vos, J. J., Ham. W. T., Jr. and Geeraets, W. J., What is the Functional Damage Threshold for Retinal Burns. AGARD Report, Paris, 1966. 35. Fine, B. S. and Geeraets, W. J., 0bservations on Early Pathologic Ef- fects of Photic Injury to the Rabbit Retina. Acta 0phthal., 43:684-691, 1965. 36. Fine, B. S. and Geeraets, W. J., Membranes and Ground Substance in Photic Injury to the Retina. Proc. Vlth Internat. Congress Elect. Microsk., Kyoto, Japan, Maruzen Company, 1966. 37. Fine, B. S. and Geeraets, W. J., Delayed Effects of Photo Injury in the Retina. Proc. Vlth Internat. Congress Electr. Microsk., Kyoto, Japan, Maruzen Company, 1966. 38. Allwood, M. J. and Nicholson, A. N., Transient Changes in the Electro- retinagram and 0ptic Tract Discharges Following Laser Irradiation. Royal Air Force Institute of Aviation Medicine, Farnborough, Hants, 1967. "~ 39. Geeraets, W. J., Laserstrahlung und Biologische Effekte. Bruns1 Klin. Chir. 210:259-277, 1965. 40. Amar, L., Bruma, M., Desvignes, P., Leblane, M., Perdriel, G., and Velghe, M., Detection d'0ndes Elastiques (Ultrasonores) sur I1 0s 0ccipital Induites par Impulsions Laser dans I1 0ei1 d'un Lapin Comptes Rendus. Acad. de Sci. (Paris) 259:3653, 1964. 53

41. Geeraets, W. J., Ham, W. T., Jr., Williams, R. C., Mueller, H. A., Burkhart, J., Guerry, D. Ill, and Vos, J. J., Laser vs. Light Coagulator: A Funduscopic and Histologic Study of Chorioretinal Injury as Function of Exposure Time. Fed. Proc. Suppl. 14, 24 (No. 1, Part III): S-48, 1965. 42. Discussion to 26, Page S-80. 43. Ham, W. T., Williams, R. C., Geeraets, W. J., Ruff in, R. S., Mueller, H. A., 0ptical Maser (Laser). Acta 0phth. Suppl.. 76, 60:78, 1963. 44. Ham, W. T., Williams, R. C., Mueller, H. A., Guerry, D., Clarke, A. M., and Geeraets, W. J., Effects of Laser Radiation on the Mammalian Eye. Transact. N. Y. Acad. Sc.. 28:517-526, 1966. 45. Ham, W. T., Williams, R. C., Mueller, H. A., Ruffin, R. S., Schmidt, F. H., Vos, J. J., Geeraets, W. J., 0cular Effects of Laser Radiation. Part 1, Acta 0phthaImologica, 43:390-409, I965. 4fa. Geeraets, W. J., Some Aspects of Laser Coagulation. International 0phtha1. Clinics 6:263, 1966. 47. Jacobson, J. H., Cooper, B., and Najac, H. W., Effects of Thermal Energy on Retinal Function. Techn. Document. Rep. No. AMRL-RDR 62-96, August I9b2. 48. Bergqvist, T., Kelman, B. and Tengroth, B., Laser Irradiance Levels for Retinal Lesions. Acta 0phth., 43:331, 1965. 49. Zaret, M. M., Ripps, H., Siegel, L. M. and Breinin, G. M., Laser Photo- coagulation of the Eye. Arch. 0phth., 69:97, 1963. 50. Zaret, M. M., 0cular Exposure to Q-switched Laser Irradiation. Techn. Rep. AFAL-TR-65-279. April 1966. 51. Wolbarsht, M. L., Fligsten, K. E. and Hayes, R., Retina: Pathology of Neodymium and Ruby Laser Burns. Science, 150:1453» 1965. 52. Jones, A. E., Scientific Exhibit: Laser Effect on the Monkey Retina Northeast Electronic Research and Engineering (NEREM) Meeting Nov. 3~5, 1965, Boston, Mass. ~ 53» Bergqvist, T. and Tengroth, B., (Personal communication to the author). 54. Bergqvist, T., Kelman, B. and Tengroth, B., Retinal Lesions Produced by Q-switched Lasers. Acta. 0phth.. 44:853, 1966. 55. Campbell, C. J., Rittler, M. C., Noyori, K. S., Swope, C. H., and Koester, C. J., The Threshold of the Retina of Damage by Laser Energy. Arch. 0phth. 76:437, 1966. 56. Makous, W. L., and Gould, J. D., Vision and Lasers: The Effects of Lasers on the Human Visual System, with some Implication for the Design of Laser Displayers. IBM Research, 0ct. 28, 1966, RC-1702. 5**

57. Noell, W. K., Walker, V. S., Bok Soon Kang, and Berman, S., Retinal Damage by Light in Rats. Invest. 0phth., 5:450, 1966. 58. Corn, R. A. and Kuwabara, T., Retinal Damage by Visible Light. Arch. 0phth.. 77:115, 1967. 59. Kywabara, T. and Gorn, R. A., Retinal Damage by Visible Light. Arch. 0phth.. 79:69, 1968. 60. Dowling, J. E., Discussion to Noell (64). Invest. 0phth., 5:472, 1966. 61. Bredemeyer, H. G., Wiegmann, 0. A., Bredemeyer, A. and Blackwell, H. R., Radiation Thresholds for Chorioretina1 Burns. Techn. Doc. Rep. AMRL- TDR-63-71. Wright-Patterson AFB, 0hio, July 1963. 62. Spells, K. W., The Production of Radiation Burns of the Retina at the Threshold Level of Damage. R.A.F. Institute of Aviation Medicine. Farnborough, Hants, March 1964. 63. Rounds, D. E., Effects of Laser Radiation on Cell Cultures. Fed. Proc. Suppl.. 14, 24 (No. 1, Part III): S-116, 1965. 64. Geeraets, W. J. and King, R. G., Jr., In Vitro Exposure of Retinal Pigment Cells to 0_-swi tched Ruby Laser Radiation as a Function of Pigment Density. 65. Vassiliadis, A., Peppers, N. A., Peabody, R. R., Rosan, R. C., Zweng, H. C., Flocks, M. and Honey, R. C., to 0cular Tissues. Techm. Rep. AFAL-TR-67-170, March 1967, Wright- Patterson AFB, 0hio. 66. Zweng, H. C., Rosan, R. C., Peabody, R. R., Shuman, R. M., Vassiliadis, A. and Honey, R. C. Experimental Q-switched Ruby Laser Retinal Damage. Arch 0phth. 78:634, 1967. 67. Geeraets, W. J., Retinal Injury by Ruby and Neodymium Laser. In press. Acta 0phth. 68. Geeraets, W. J. and Ridgeway, D., Retinal Damage from High Intensity Light. Acta 0phth. Suppl.. 76:109, lg63. 69. Geeraets, W. J., Ham, W. T., Jr., Guerry, D., Nooney, T., Williams, R. C. and Mueller, H. A., The Determination of Threshold Dose for Visual Impairment of the Human Macula After Exposure to a White Light Source. DASA Report, Feb. 1967, Contr. DA 49-146 XZ 416. 70. Ham, W. T., Williams, R. C., Ruffin, R. S., Schmidt, F. M., Mueller, H. A., Guerry, D., Ill, and Geeraets, W. J., Am. J. Med. Electronics, 2:308-315, 1963. 71. Jones, D. E. and Montan, D. N., Eye Protection Criteria for Laser Radiation. From Ham, e_t a_K, Acta 0phth., 43:395, 1965. 55

72. Westheimer, G., 0ptical and Motor Factors in the Formation of the Retinal Image. Journ. 0phth. Soc. Am. 53:86, 1963. 73. King, R. G., Jr., Geeraets, W. J., Q-switched Ruby Laser Radiation on Retinal Pigment Epithelium in Vitro: Cellular Reaction as a Means of Irradiated Spot Size. In press. Acta 0phth. 7*+. Vos, J. J., A Theory of Retinal Burns. Bull. Math. Biophysics, 2^:115, 1962. 75. Vos. J. J., Digital Computations of Temperature in Retinal Burn Problems. Inst. for Perception, RVQ-TN0, Report No. IZF 1965016, Soesteberg, The Netherlands, 1963. 76. Ridgeway, D., Steady-state Three Dimensional Heat Conduction from Cylinders and Randomly 0riented Collections of Circular Discs (to be published). 77. Hayes, J. R. and dolbarsht, M. L., A New Theory of Laser Induced Retinal Damage. Acta Biochem. Biophys. (in press). 78. Wray. J. L., Model for Prediction of Retinal Burns. Techm. Rep. No. AD-277-363, 1962. 79. Feick, J. R., (personal communication to the author). 80. Rounds, D. E., Chamberlaine, E. C. and 0kigaki, T., Laser Radiation of Tissue Culture. Ann. N. Y. Acad. Sci ., 122:713, 1965. 56

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