acomparative histopathological of argon and krypton laser ...observed in any ofthe krypton exposures...

British Journal of Ophthalmology, 1979, 63, 657-668

A comparative histopathological study of argonand krypton laser irradiations of the human retinaJOHN MARSHALL AND ALAN C. BIRD

From the Department of Visual Science and Clinical Ophthalmology, Institute of Ophthalmology,Moorfields Eye Hospital, Judd Street, London WC1H 9QS

SUMMARY A series of comparative exposures to both argon and krypton lasers have been madeat 3 locations in a human retina-the fovea, the macula, and intraretinal vessels. In the fovea argonirradiations resulted in damage to both the inner and outer retinal layers as a result of absorptionwithin the pigment epithelium and the macular pigment, while krypton exposures damaged theouter retina and the choroid. In the macula both systems resulted in damage to the outer retina,and again sufficient krypton radiation passed into the choroid to induce blood vessel occlusion,haemorrhage, and oedema. When intraretinal vessels were irradiated, only with argon was sufficientenergy absorbed within the vessels to damage them or their surroundings in the inner retina. Theimplications of these findings are discussed in relation to the therapeutic uses of lasers.

Both the initial destruction and the secondary tissueresponses induced by the coagulative action oflaser radiation on retinal tissue are exploited thera-peutically in ophthalmology. The primary reactionin most clinical exposures is one of tissue destructionresulting from the forces generated by the thermaldegradation of the incident energy absorbed in thetarget tissue (Marshall, 1970). The amount ofenergy absorbed is a function of the wavelength ofthe incident radiation and the absorption charac-teristics of the irradiated media. The degree andextent of destruction within a tissue are also relatedto the magnitude of the exposure energy, the areaof irradiation, and the duration of the exposure.Throughout the visible spectrum the predominantabsorption site in the retina is the pigment epithe-lium, and the physical parameters of most clinicalexposures are such that only this layer and theoverlying photoreceptor cells are damaged. In the1960s such a burn configuration with damageconfined to the outer retina was not considereduseful for the treatment of many neovascularconditions, especially those in which forward newvessels occurred. At that time the ideal system wasconsidered to be one with which vessels could bedirectly irradiated by a source with a wavelengthwhich would be absorbed by haemoglobin. Theargon laser met such requirements (L'Esperance,1968), and for some time various protocols for

Correspondence to Professor Bird.

direct irradiation of neovascular systems weredeveloped (Little et al., 1970). Such techniquescontinue to be used in the treatment of subretinalneovascular complexes or disciform lesions (Gass,1971, 1973; Bird, 1974).

Direct treatment of new blood vessels in diabetes(Little, 1973) has been largely replaced by peripheralablation, whereby large areas of the outer retinallayers in the peripheral fundus are destroyed(L'Esperance, 1975a). Furthermore, in disciformlesions at least part of the new vessels are close tothe pigment epithelium, and therefore, irradiationenergy absorbed within this layer may be responsiblefor blood vessel closure. Thus, at present, treatmentregimens for both these neovascular lesions areutilising the pigment epithelium as the absorptionsite and are not dependent upon the blue-green(488, 514 5 nm) emission of the argon laser. Insome circumstances there is evidence that the use ofthese wavelengths may be counterproductive, re-sulting in undesirable complications. For example,when treating disciform lesions close to the foveaapproximately 70% of the incident energy at 488 nmwill be absorbed by macular pigment and mayresult in nontherapeutic destruction in the innerretinal layers and prevent irradiation of the targettissue (Marshall et al., 1974, 1975). Further, whenargon irradiation falls upon intraretinal vascularelements, unnecessary damage may be induced inadjacent neurones (McLeod et al., 1977). For thesereasons it may be desirable to use lasers that emit

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John Marshall and Alan C. Bird

red light. Historically such lasers have not beenfavourably received by ophthalmologists, but theproblems with these early lasers have now beenshown to be unrelated to wavelength and to haveresulted from instrument design. The poor resultsobtained with the ruby lasers (694-3 nm) may havebeen due to short pulse duration of these devices,and the limited experiments with helium neon(632 8 nm) failed mainly because of inefficientoptics in the delivery systems (Manson et al., 1972).There are now commercial systems available thatenable either argon (488 nm) or krypton (641 nm)i-adiation to be used for the treatment of retinaldisease. Thus for the first time the relative merits ofred and green light may be assessed by using con-tinuous wave lasers with similar optical systems.The present paper describes the histopathology

of both argon and krypton irradiations in a varietyof locations on the fundus and relates their mor-phology to the physical parameters of the irradiatingsources.

Methods and materials

Two different laser systems were used in the presentstudy, a Coherent Radiation 800 argon laser, anda Lasertek krypton laser. Although the Laserteksystem may be used to deliver either krypton orargon radiation we thought that the use of theCoherent Radiation argon system would allow amore useful comparison as this model has beenwidely adopted in clinical centres. Both of theselasers have integral power monitors and all figuresquoted are those registered on the manufacturers'instruments. No study was undertaken of therelative energy distribution within the laser beams.

Exposures were delivered via the integral slit-lamp systems in conjunction with a Goldmannfundus contact lens. One eye of a single patient wasexposed 20 hours prior to enucleation for a malig-nant melanoma of the anterior choroid; the retinaldetachment in this patient did not involve theposterior pole.

In a peripheral area of retina trial exposures wereundertaken in order to adjust power levels so thatapproximately equal tissue responses were achieved.These exposures showed that for any given imagesize and exposure time krypton exposures alwaysrequired higher power levels to achieve an equi-retinal response to that of argon.Two groups of 0-2 to 0 5 second exposures were

made with each type of laser. In the macula a seriesof 8 argon exposures were made in a line on thesuperonasal to inferotemporal axis and whichtraversed the fovea (50 ,um image size, 87 mW). Asimilar number of krypton exposures were made at

similar distances from the fovea at right-angles tolines of argon burns (50 ,um image size, 200 mW).One 150 mW krypton exposure was made at thefoveola.The second group of exposures involved the

irradiation of similar calibre arterial and venouselements of the intraretinal circulation with bothargon (200 ,urm, 300 mW) and krypton (200 ,im,600 mW) systems.The eye was enucleated and processed for both

light and electron microscopy as previously des-cribed (Marshall et al., 1975).

Results

Ophthalmoscopic observations on the central groupof argon lesions confirmed earlier findings thatwithin 2° of the fovea the morphology of the lesionschanged with a coagulation site becoming apparentin the inner retina, and that the intensity of suchcoagulations increased as the distance from thefovea decreased. No such inner retinal damage wasobserved in any of the krypton exposures (Fig. 1).

Differences were also observed between the twotypes of irradiation on the vascular elements. Bothkrypton and argon induced lesions were seen aspale white areas of coagulation at the level of thepigment epithelium. With krypton lesions the vesseland inner retina appeared unaffected clinically(Fig. 2) whereas with argon the vessel lum-n wasnarrowed, there was haemorrhages, and opacifica-tion of the inner retina (Fig. 2). At 20 hours these

Fig. 1 Fundus photographs of the macular regionimmediately after irradiation by both argon (AA') andkrypton (KK') lasers. Damage within the inner retinallayers can be seen in the 3 argon lesions nearest tothe fovea (arrowed). Such damage was not producedby any of the krypton exposures

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A comparative histopathological study of argon and krypton laser irradiations

Fig. 2 Fundus photograph ofmajor retinal vessels immediatelyafter irradiation by either argon(A) or krypton (K) lasers. Thevessels irradiated with the argonlaser characteristically show anarrowed lumen, while thoseexposed to krypton radiationshow little effect

argon lesions acquired an increased opacificationconsisting of small fluffy white crescent-shapedchanges in the inner retinal layers on the side of thelesion adjacent to the optic disc.

RETINAL DAMAGEIrradiations of the maculaAll irradiations resulted in damage to the pigmentepithelium and overlying photoreceptor cellsthroughout the area of exposure (Fig. 3).At distances greater than 2° from the fovea

argon and krypton lesions had similar morphology,except that pigment epithelial changes appearedmore severe in the former. Thus in both cases thecells were either shrunken or swollen, but moreextracellular space was apparent in argon inducedlesions, especially in the region between the base ofthe cells and Bruch's membrane. In the periphery ofboth types of lesion the changes between irradiatedand nonirradiated epithelial cells were quite marked,and cell movement had resulted in an annular zoneof denuded Bruch's membrane (Fig. 3b). Someepithelial cells adjacent to irradiated areas hadbudded off Bruch's membrane and could be seentogether with macrophages in the subretinal spacebetween the outer segments of the photoreceptorcells (Fig. 3b, c).The electron microscopy of subcellular changes

within argon irradiated pigment epithelial cells hasbeen previously described (Marshall et al., 1975),

and in the present study a similar spectrum ofdamage was seen in cells irradiated by krypton.Damage to the neural retina in this region was

confined to the photoreceptor cells. Both argon andkrypton irradiations resulted in areas of disorganisedouter and inner segments of photoreceptor cells,which were always associated with, but smaller than,the areas of pigment epithelial disturbance. Receptornuclei in the irradiated areas were pyknotic, thoughin all lesions some nuclei appeared normal. De-generative changes were also seen in the innerconnecting fibres of damaged photoreceptor cells,which were abnormally densely stained where theytraversed the fibre layer of Henle. No laser inducedchanges were observed in the inner retinal layers ofany lesions in this region of retina.

Irradiations of the foveaIrradiation within 20 of the fovea showed markeddifferences in damage distribution in the neuralretina which were related to the irradiating wave-length (Fig. 4a).

In argon lesions in this area damage to the outerretinal layers was less severe than those seen in theouter macula. The pigment epithelial cells stillshowed displacement of their cell boundaries, butin equienergetic exposures the volume changes andvacuolation were less than in the more peripherallesions. In the photoreceptor cell layer changessimilar to those previously described were observed,

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Fig. 3 (a) Light micrograph ofa krypton laser induced lesionin the macula, 20 hours afterexposure. Damage is confined tothe pigment epithelium and theoverlying photoreceptor cells.The marker is 100 l.m. (b) (c)Light micrographs of humanpigment epithelium adjacent tokrypton laser lesions (arrowed)in the macula. In (b) pigmentepithelial cells (P) can be seenbudding off Bruch's membrane,while in (c) a macrophage (M)can be seen in the subretinalspace. The marker is 10 plm

but again fewer cells were involved (Fig. 4b). Allargon exposures resulted in gross vacuolation andtissue displacement in the inner retinal layers (Fig.4). This second damage locus was centred on theinner nuclear layer but involved both of the plexi-form layers and the ganglion cells. In all cases

serial sections demonstrated that, while the innerand outer retinal damage sites were coaxial, theywere discrete.

Krypton induced lesions in this region of theretina were identical to those produced in the outermacula, in that damage was confined to the outerretina, with the exception of a slightly more markedresponse within the pigment epithelium (Fig. 4).

Thus in the fovea argon and krypton inducedchanges in this layer appeared quite similar.

Irradiations of intraretinal blood vesselsThe larger image sizes and higher power densitiesused in this part of the study resulted in larger areasof damage with more severe cellular changes in theouter retina.

In the argon induced lesions changes wereobserved both in the irradiated vessels, and in theadjacent nerve fibres (Fig. 5). Both arterial andvenous vessels showed damage or displaced endo-thelial cells, and a high incidence of white bloodcells within the irradiated areas. Immediately

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Fig. 4 (a) Light micrograph ofboth an argon (A), and a krypton(K) induced laser lesion in thefovea. While both lesions showdamage to the retinal pigmentepithelium and overlyingphotor-eceptor cells, only theargon induced lesion shows adiscrete area ofdamage withinthe inner retina. The marker is100 Ftm. (b) Electron micrographof the damaged outer segmentswithin an area of argonirradiated retina at the fovea.Within 20 hours of exposuremacrophages (arrowed) can beseen engulfing these elements ofdamaged cells. The marker is4 [JJn.

adjacent to the basement membranes of somevessels small annular areas of vacuolation wereobserved, and in other lesions small haemorrhagesoccurred into the inner plexiform layer (Fig. 5).The most striking changes seen in association withareas of argon irradiated vessels were large spheroi-dal axonal swellings in the nerve fibre layer. Thecross-section diameters of axons in this region ofthe retina were normally in the range of betweenO-5 and 4 ,um; however, those of the swollen portionswere between 8 ,um and 16 ,um. These swellings,sometimes designated 'cytoid bodies', were foundon both sides of blood vessels that ran parallel withthe ganglion cell axons, but only on the side adjacentto the disc where vessels crossed the ganglion cellaxons at right angles (Figs. 5, 6). On electron micro-

scopy these axonal swellings were seen to containlarge numbers of degenerate mitochondria, neuro-filaments, and lysosomes, so densely packed thatthe normal axoplasm was almost excluded (Fig. 6).There were also membranous whorls and lipidbodies indicating membrane breakdown. Wherevessels that ran at right-angles to the ganglion cellaxons had been irradiated, less swollen but abnor-mally enlarged axons were also observed on theside of the vessel remote from the optic disc byelectron microscopy. These swollen regions con-tained few organelles but had abnormal concentra-tion of neurofilaments lining the axolemma. In alllesions some axons within the irradiated areaappeared normal.

Increase in the staining density of some compo-

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Fig. 5 Light micrographs of (a)an artery and (b) a vein 20hours after irradiation by anlargon laser. (a) The nervefibres in this region ranobliquely over the artery ontheir passage to the disc andhence distended nerve fibres(arrowed) can be seen surroundingthe vessel. This lesion alsoshows a central region of lessdamaged pigment epitheliunmlying under the artery resultingfrom the attenuation of inicidentenergy by absorption within thevessel. (b) In this lesion thenerve fibres ran more at right-angles to the vein and the hencedistended axons (arrowed) arepredominantly on the sidenearest to the disc. Thisexposure resulted in a smallhaemorrhage into the innernuclear layer. The marker is100 [±m

nents of the Muller's fibres were seen, but this waslargely unrelated to damage associated with intra-retinal vasculature.Damage to the neural retina induced by krypton

irradiation of blood vessels was almost exclusivelyconfined to photoreceptor cells, the exceptionsbeing occasional densely stained Muller's fibreelements in the inner retinal layers (Fig. 7a). Nodamage was observed in any of the irradiatedvessels, and no changes could be found in theadjacent axons of ganglion cells (Fig. 7b).

CHOROIDAL DAMAGEIn both argon and krypton irradiations there werechanges in the underlying choriocapillaris adjacentto damaged pigment epithelial cells. In most lesions

the capillaries were occluded throughout the irra-diated areas. Blood stasis had resulted in the lumenof the vessels being either packed with degenerateblood cells or collapsed and containing remnants ofendothelial cells and fibrin. Associated with thesevascular changes were areas of oedema in theinner layers of the choroid. In most argon lesionsdamage was limited to the choriocapillaris.By contrast vascular damage deep in the choroid

was a characteristic of krypton lesion. These vascularlesions were always associated with morphologicalchanges in adjacent choroidal melanocytes. In manthese cells are usually relatively uniformly pigmented,with many branch-like processes extending fromtheir cell bodies (Fig. 8a, b, c). Beneath areas ofkrypton induced damage to the retina they had lost

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Fig. 6 (a) Light micrograph ofdistended axons adjacent to anirradiated retinal vein. Thepseudonuclei (arrowed) resultedin the term 'cytoid bodies'being given to these systems.The marker is 20 lsm. (b)Electron micrograph of onesuch swollen axon showingthat the pseudonuclei are aregion filled with neurotubules,while the periphery containsmany shrunken and degeneratemitochondria. Axons of normaldimensions (arrowed) can beseen adjacent to those showingdamage, and (V) is the vein.The marker is 2 usm

their lateral processes and become rounded anddarkly pigmented (Fig. 8d). Macrophages wereobserved in the choroid associated with thesedamaged cells.

Three types of vascular lesions were observed,which were, in order of increasing severity, endo-thelial sloughing, endothelial loss with exudates,and small haemorrhages (Fig. 9). Endothelialsloughing was observed in vessels of all sizes but inlarge vessels was often highly focal and only inareas immediately adjacent to melanocytes (Fig.9a). In smaller vessels, where endothelial cell lossand leakage of vessels contents had occurred smallclots of platelets could be seen associated with theformer areas of leakage (Fig. 9b). Exudates frommany of these lesions had resulted in disorganisationof adjacent tissues.

Discussion

In any analysis of radiation induced damage to abiological system a fundamental requirement is theseparation of acute radiation induced change in andadjacent to the absorption sites from the secondarytissue responses to such primary lesions. The presentstudy involves the examination of damage producedby nonionising radiation 20 hours after exposure,and therefore much of the pattern of histologicaldisturbance is due to tissue reorganisation inresponse to injury.

RETINAL ABSORPTION SITES AND PRIMARY

DAMAGEThe retinal pigment epithelium is the major site ofabsorption of both argon and krypton radiation,

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Fig. 7 (a) Light micrograph ofa vein 20 hours after irradiationby a krypton laser. In this lesiondamage is confined to the outerlayers of the retina and noswollen axons are observed. Themarker is 100 Fm. (b) Electronmicrograph of the axonsadjacent to the irradiated vein(V) shown in (a). The markeris 2 Vm

and in the time domain of clinical exposures alldamage results from thermal processes. The mostquoted studies of absorption of retinal pigmentepithelium and choroid as a function of wavelengthsshow that, at the argon wavelength (488 nm), 73%of the incident energy will be absorbed, while only65% of absorption will occur at that of krypton(641 nm) (Geeraets and Berry, 1968). This 15%differential in absorption between the 2 wavelengthsseems inadequate to explain the factor of 2 betweenargon and krypton exposure energies for an equal

retinal response in the macula and when exposingintraretinal vessels. However, our results indicatethat in argon exposures very little energy passesthrough the pigment epithelium, so that in compara-tive studies it is the relative absorption of this layeralone that should be considered. Such measurementshave been carried out by Gabel and colleagues(1977), who show that in human pigment epitheliumthere is a 40% differential in absorption betweenthese 2 wavelengths and that at both wavelengths33% less energy is absorbed in the perimacular

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Fig. 8 (a) Light micrograph ofpigment epithelium and choroidin an unirradiated area showingthe discontinuous array ofchoroidal melanocytes. (b) Lightmicrograph of a flat preparationof choroid showing the ameboidlike processes of the choroidalmelanocytes. The marker is100 l±m. (c) Light micrographof unirradiated choroidalmelanocytes showing theirpigment distribution and thecollagenous interstitial elements.(d) Light micrograph of kryptonirradiated choroidal melanocytesshowing abnormal cell profileswith pigment clumping, and thepresence of both macrophagesand oedema. The marker is10 [m

region than in the macula. Differences of thismagnitude would be consistent with our observa-tions. Further factors may have arisen due todifferentials in energy distributions within thebeams of the 2 systems used (Borland et al., 1978).Beam energy profiles were not determined, butobservations indicated that neither of the beamshad a Gaussian distribution of energy.The absorption characteristics of the macular

pigment have been determined as a function ofwavelength and retinal location both in vivo(Ruddock, 1963) and in vitro (Gabel and Birn-gruber, 1979). While the absolute absorption variesbetween both individuals (Bone and Sparrock,1971; Gabel and Birngruber, 1979) and races(Ishak, 1952), the relative absorption as a function

of wavelength is remarkably constant. It has beenshown that between 15% and 80% of the incidentenergy at the argon wavelength is absorbed in thispigment but less than 1% is absorbed at that ofkrypton. A similar differential in relative absorptionexists when haemoglobin is irradiated, where,depending on the state of oxygenation, between10 and 50 times more light is absorbed at 488 nmthan at 630 nm (L'Esperance, 1975b).

In argon exposures these intraretinal absorptionsystems attenuate the radiation falling upon thepigment epithelium, and therefore damage in thislayer is less marked in the fovea and under retinalvessels (Bowbyes et al., 1973). Very little kryptonradiation is absorbed in either of these chromato-phores, and only about 15% of the incident energy

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at this wavelength is dissipated within the pigmentepithelium. It is therefore not surprising that inthese exposures absorption within the choroidalmelanocytes is of sufficient magnitude to inducedamage to this layer (Figs. 8, 9).The location of the various damage sites in the

present study are clearly coincident with the sites ofabsorption. However, in determining the degree ofdamage associated with each site, not only is therelative absorption important but also the pathlength in which such absorption occurs. In generalfor any given value of absorption the shorterdistance in which it occurs the greater the absorbedenergy density and, above threshold, the greaterthe associated damage. If the thermal tolerancelevels are similar for all cells throughout the retina,then damage associated with absorption by thepigment epithelium should be the most severe, asthe pigment in this layer is confined to the apical3 sum of the epithelial cells, while in most cases both

Fig. 9 (a) (b) Light micro-graphs of choroidal vessels 20hours after irradiation with akrypton laser. (a) A smallvascular lesion showing endothelialcell sloughing (arrowed)adjacent to an area ofoedemaand tissue disruption (E). (b)A more severe vascular lesionshowing clotting (arrowed)subsequent to a choroidalhaemorrhage, and the presenceof both oedema and denaturedmelanocytes in the surroundingtissue. The marker is 20 l±m

macular and blood pigments are more diffuselydistributed. In the present study this concept issupported by the large regions of coagulatedphotoreceptor cells adhering to the pigment epi-thelium throughout both argon and krypton irra-diated areas (Figs. 3, 4, 5, 7). The extensive distur-bances in the inner retinal layers in argon exposuresof the macula arise through bulk tissue displacementby secondary processes of fluid leakage. Secondaryprocesses also amplify the damage site in argonirradiation of the intraretinal vessels.The absorption parameters of the choroid are

extremely difficult to describe, as the local variationsare enormous (Fig. 8). Individual choroidal melan-ocytes are relatively large cells, being about 80 sumin length and 10 ,um in depth, and can be extremelydensely pigmented. This discontinuous array ofhighly absorbing cells probably accounts for thefocal distribution of vascular lesions seen in thekrypton irradiations, where up to 85% of the

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energy incident on the pigment epithelium passesthrough into the choroid. In the present study allchoroidal changes associated with argon irradiationswere confined to the choriocapillaris and resultedfrom thermal dissipation of energy absorbed withinthe pigment epithelium.

SECONDARY RESPONSES TO LASERIRRADIATIONThe responses of retinal cells to various types ofinjury are a characteristic of the cells and not theinjury. Thus the differences in topographic pathologybetween lesions induced by lasers of differentwavelengths arise through either variations in thedegree of damage to individual cell types or varia-tions in the cell types damaged. In the present studywithin 20 hours of exposure in both argon andkrypton lesions the pigment epithelial cells imme-diately adjacent to the irradiated area were under-going changes in order to contain and clear thedamaged site. The rounded cells protruding intothe intra receptor matrix eventually bud off Bruch'smembrane and join the blood-borne macrophagesin clearing the debris of coagulated cells. Thesewandering epithelial cells are formed either bybudding from multinucleate cells (Marshall andMelleiio, 1970) or by mitotic division (Ham et al.,1978), though in the present study we did notobserve any mitotic figures.The responses observed in irradiated photo-

receptor cells were of degeneration and decay, andeven in this short postexposure period many cellshad lost large portions of their outer segments dueto activity of macrophages. The degenerativechanges resulting in the abnormally dense stainingof the inner connecting fibres of some photoreceptorcells were shown to be extremely rapid in a previousstudy (Marshall et al., 1975). Both the angularinclinations with respect to the axis of radiationand the length of these degenerative fibres confirmthat they result from secondary degenerative pro-cesses within the cell bodies of photoreceptor cells.Primary damage resulting from intrafibre absorptionwas observed in the innermost part of the fibrelayer of Henle in the most central argon exposures,but this damage never resulted in the complementaryproduction of densely stained fibres radiating toremote outer portions of receptor cells. In many ofthese inner retinal lesions the exudates arising fromadjacent damaged cells resulted in a cleavage ofinner and outer retinal layers along the line of theouter plexiform layer.The axonal swellings seen in the nerve fibre

layer in areas of argon irradiation of intraretinalvessels were the most striking secondary response inthe inner retina (Figs. 5, 6). Terminal swellings on

either side of interrupted axons in areas of intensephotocoagulation have been previously reported(Okun and Collins, 1962; Marshall and Mellerio,1967), but it was not appreciated until recently thatsuch swellings arise through the interruption of thebidirectional flow of axoplasmic constituents alongthe axon. In an autoradiographic study of both laserand ischaemic lesions in pig retina it has beendemonstrated that the swelling of damaged axonsoccurs as a passive response to the damming ofaxonal flow (McLeod et al., 1977). The observationsin the present study are identical with those ofMcLeod and colleagues in that swelling due tointerruption of retrograde transport in the isolatedaxonal segment adjacent to the optic disc was alwayslarger than that due to orthograde flow in thesegment attached to the cell body. The significanceof this type of axonal damage to field loss followingirradiation would be very difficult to assess, as inall lesions in this study some normal looking axonswere present in the exposed areas.The presence of oedema and macrophages in the

choroid in areas of krypton irradiation is clearly asecondary response to changes in the vascularelements in this tissue, and represents an earlyphase of wound repair (Fig. 9).

Laser technology is now capable of producingreliable systems with a variety of emission wave-lengths, and therefore there is a potential for theselective exploitation of ocular absorption sites. Todo this effectively a better understanding of theparticular aspects of photocoagulation which resultin the beneficial changes in various types of neo-vascular lesions is essential. At present none of thetherapeutic procedures are fully understood interms of their reaction sequence. Thus in thesuccessful treatment of disciform lesions we do notknow whether the therapeutic response is 1° or 2°in either the new vessels, the pigment epithelium,the choroid, or some combination of these, orwhich tissue absorption is important in generatingthis change. Even more complex conceptual prob-lems arise in optimising peripheral ablation treat-ment. Several authors (see L'Esperance, 1975c) havesuggested that the large areas of retinal destructionresult in a reduced metabolic demand and that thisin turn influences neovascular atrophy. However,given the dual circulating system of the retina witha choroidal supply to the photoreceptor cells, andan intraretinal system which feeds all the innerretinal layers, it is difficult to understand howdestruction of the photoreceptor cells and theunderlying choroid would achieve this end inrespect of the intraretinal vascular system. A furtherconsideration is the increase in bulk fluid flowthrough the retinal pigment epithelium following

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photocoagulation, which would result in loss fromthe vitreous of any diffusible agent which may beinfluencing blood vessel behaviour (Foulds, 1976).With this uncertainty it is impossible to predict

the relative clinical values of lasers with differentwavelengths with their different absorption charac-teristics, and different spectra of tissue damage, butas we now have the capability to damage selectedregions of the retina it is hoped that future clinicalstudies will optimise the selection of laser wave-lengths for specific retinal diseases. In particular thekrypton laser allows damage to be restricted to theouter retina and choroid.

We thank Miss E. Clarke and Mr P. L. Ansell for technicalassistance and Miss Julie Bramley for secretarial help. Wewould like to express our gratitude to Lasertek for the loanof their krypton laser. We are also indebted to the BritishCommittee for the Prevention of Blindness, the GarrickTrust, and the Wellcome Trust for gifts of capital equipment.

References

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Bone, R. A., and Sparrock, J. M. B. (1971). Comparison ofmacular pigment densities in human eyes. Vision Research,11, 1057-1064.

Borland, R. G., Brennan, D. H., Marshall, J., and Viveash,J. P. (1978). The role of fluorescein angiography in thedetection of laser-induced damage to the retina: a thresholdstudy for Q-switched, neodymium and ruby lasers.Experimental Eye Research, 27, 471-493.

Bowbyes, J. A., Hamilton, A. M., Bird, A. C., Blach, R. K.,Marshall, J., and Kohner, E. M. (1973). The argon laser:The effect on retinal tissues and its clinical applications.Transactions of the Ophthalmological Societies of theUnited Kingdom, 93, 439-453.

Foulds, W. S. (1976). Clinical significance of trans-scleralfluid transfer. Transactions of the OphthalmologicalSocieties of the United Kingdom, 96, 290-308.

Gabel, V. P., and Birngruber, R. (1979). Klinishe folgerungenaus der xanthophylleinlargerung in der Netzhautmitte.In press.

Gabel, V. P., Birngruber, R., and Hillenkamp, F. (1977).Individuelle Unterschiede der Lichtabsorption am Augen-hintergrund in sichtbaren und infraroten Spectralbereich,Deutsche Ophthalmologische Gessellschaft, Berichtuberdie74. Zusammenkunft, 418-421.

Gass, J. D. M. (1971). Photocoagulation of macular lesions.Transactions of the American Academy of Ophthalmologyand Otolaryngology, 75, 580-608.

Gass, J. D. M. (1973). Drusen and disciform maculardetachment and degeneration. Archives of Ophthalmology,90, 206-217.

Geeraets, W. J., and Berry, B. S. (1968). Ocular spectral

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acomparative histopathological of argon and krypton laser ...observed in any ofthe krypton exposures...

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