1 PT" Investigative Ophthalmlgy & Visual Science, Vl. 30, N. 6, June 989 Cpyright Assciatin fr Research in Visin and Ophthalmlgy Retinal Damage in Macaque after White Light Expsures Lasting Ten Minutes t Twelve Hurs Jan J. M. Kremers and Dirk van Nrren We induced phtchemical damage in small parts f the retinas f anesthetized macaques after light expsures f varying intensity, lasting between 0 min and 2 hr. Damage was assessed bth with funduscpy and densitmetry at several perids after expsure. Damage was mst extensive 2 days pstexpsure, with similar threshlds fr bth methds. Reciprcity between expsure time and irradiance was fund fr all expsures at a threshld irradiant dse f 230 J/cm 2. This is in gd agreement with part f the literature data n mnkeys, yet cntradicts anther reprt (Sykes et al) in which a much lwer threshld dse was fund. The latter data prbably cncern a different class f damage. It remains unclear what critical factrs distinguish the tw classes. Observatins mre than 70 days pstexpsure shw a divergence between funduscpic and densitmetric threshlds. Althugh the appearance f funduscpic lesins had changed, the threshld dse remained 230 J/cm 2. Densitmetry shwed full recvery f the amunt f visual pigment fr dses belw 600 J/cm 2. Invest Ophthalml Vis Sci 30:032040,989 When the primate retina is expsed t intense light fr perids varying between several secnds and 4 hr, extensive damage t the pigment epithelium and t the neural retina may be fund. " 4 In patients such damage is als reprted after cular surgery in which use was made f bright light surces. 5 " 8 Fr perids between 0 and 000 sec, Ham et al 290 verified that reciprcity hlds, that is, irradiance is exchangeable fr expsure time. The threshld dse fr white light in Ham's experiments varied between 200 t 400 J/cm 2. With expsures shrter than 0 t 00 sec, depending n the size f the retinal image, reciprcity fails because the rise in retinal temperature is such that the dmain f thermal damage is entered. It is unclear hw far reciprcity hlds fr expsures beynd 000 sec. One reprt is available in which macaque mnkeys were expsed t 2 hr f cntinuus flurescent light.'' We calculated that the threshld dse in the latter experiment was abut 6 J/cm 2, an rder f magnitude lwer than Ham et al's J/cm 2. The directin f the deviatin frm reciprcity is unexpected. Naively, it is expected that with increasing expsure time (and decreasing irradiances) repair prcesses gradually vertake damage inductin. As a result the ttal dse t reach thresh Frm the TNO Institute fr Perceptin, Sesterberg, The Netherlands. Supprted by the Netherlands Organizatin fr Scientific Research, thrugh the Fundatin fr Biphysics. Submitted fr publicatin: May 23, 988; accepted December 5, 988. Reprint requests: D. van Nrren, PhD, TNO Institute fr Perceptin, P.O. Bx 23, 3769 ZG Sesterberg, The Netherlands. ld damage shuld increase, rather than decrease. Griess and Blankenstein 2 fund the time cnstant f the repair prcesses t be almst exactly 4 days. Frm this study alne reciprcity is expected t hld up t abut 2 days. But, as Griess and Blankenstein determined the time cnstant in an indirect way, this is nly true when n ther, unexpected, prcesses interfere at lng expsures. Sykes'" experiments actually suggest such an interference. The aim f the present study was t investigate whether r nt there is a deviatin frm reciprcity after lng expsures, as described abve. Therefre, we explred the expsure range frm a few hundred secnds t 2 hr. The cnditins were, apart frm irradiance and time, similar t thse used by Ham et al, 9 that is, anesthetized macaque mnkeys and expsures restricted t small patches f retina. In additin t funduscpy, we intrduced retinal densitmetry as a new technique fr assessing damage. This technique has the advantage f being bth quantitative and nninvasive. Als, direct infrmatin is btained n the kinetics f visual pigments after phtchemical damage. Finally, damage was als assessed between 2 and 7 mnths after expsure, t study the effect f repair mechanisms. Materials and Methds Animal Preparatin Mnkeys were sedated with 2540 mg ketamine hydrchlride (Ketalar, ParkDavis, Barcelna, Spain) and anesthetized with an initial intravenus 032
2 N. 6 RETINAL DAMAGE AFTER WHITE LIGHT EXPOSURES / Kremers and van Nrren 030 dse f 20 mg/kg f pentbarbital (Nembutal, CEVA, Paris, France), fllwed by a cntinuus infusin f 23 mg/kg/hr. After intubatin, artificial respiratin was started with a mixture f 70% nitrus xide and 30% xygen. T prevent eye mvements an intravenus infusin f a muscle relaxant pancurnium brmide (Pavuln, Organn, Oss, The Netherlands) was given. The initial dse was 30 Mg/kg fllwed by a cntinuus infusin f 30 jtg/kg/hr. Pupils were dilated with a drp f Phenylephrin (BurnnvillePharma, Almere, The Netherlands), cmbined with a drp f Cyclgyl (Schieffelin and C., New Yrk, NY). The head was fixed in place with ear bars and a jaw rest. A hard cntact lens was,used t prevent drying f the crnea. All preparatin was dne in yellw light t minimize the pssibility f retinal damage befre expsure. This investigatin adhered t the ARVO Reslutin n the Use f Animals in Research. Irradiatin Whenever we use the term irradiatin, we refer t expsures f white light t establish damage threshlds. We used a dual beam phthalmscpic stimulatr fr irradiatin under Maxwellian view cnditins. The light surce was a 450 W xenn arc with light stabilized pwer supply. Infrared radiatin was eliminated by a Schtt KG 3 filter. UV radiatin was reduced by the glass lenses. Details f this apparatus can be fund in Valetn and van Nrren. 3 Fur patches f retina were defined using a diaphragm with fur hles imaged n the retina. The hles measured 4 diameter and were arranged in a tw by tw array, abut separated. The center f the array was psitined abut 8 abve the fvea. T vary the irradiance level f individual patches, neutral density filters were placed n the hles. The irradiances f the fur patches were regularly calibrated with a Laser Precisin RK500 Pyrelectric Radimeter. The spectral utput f the white light at the crneal level was measured with a scanning spectrradimeter (Pht Research Spectrascan S.N. 286). The results f the latter measurement are presented in Figure. The average clr temperature was 5400 K. Retinal irradiance (E ret ) was calculated frm the measured irradiance (E air ) with 4 : Jret ''air ^ ' in which d is the distance between fcus and the irradiated plane f the measuring device f the radimeter, f the fcal length f the mnkey eye (abut.35 cm), n the refractive index (abut.33), and t the cular transmissin (abut 0.9). The maximal available retinal irradiance was 400 mw/cm 2. Fig.. Spectral distributin f the damageinducing light at the crneal level. Funduscpy The irradiated patch (seen thrugh the phthalmic stimulatr) was marked n a fundus phtgraph. Tw days after expsure, changes were visible as whiteyellwish spts. Funduscpic bservatins were perfrmed with an indirect phthalmscpe (28 dipter lens), because the large field f view made lesins easier t recgnize due t the cmparisn with the undamaged surrundings. We classified the bservatins int three categries: () n change, indicating subthreshld damage r absence f damage; (2) a just visible change (a patch smewhat smaller than the irradiated spt, and with fuzzy edges), as an indicatin fr threshld damage; and (3) a distinct funduscpic change (a patch with a size cmparable t the irradiated spt r smewhat larger, and with sharp edges), indicating suprathreshld damage. Funduscpic bservatins were made at fur different time intervals after expsure: () 0.52 hr; (2) 42 hr; (3) abut 2 days; and (4) minimally 70 days. The mst cmplete bservatins were made 2 days pstexpsure because at that time funduscpic changes were mst clearly present (in accrdance with bservatins f, eg, Ham et al u0 ). Densitmetry In retinal densitmetry a beam f light is shne int the eye, reflected at the fundus and cllected by a lightsensitive device, usually a phtmultiplier (PM). Essential in the technique is: first, that measuring light bleaches nly a small fractin f the phtpigment. Secnd, measurements are dne in tw cnditins, ne with high adapting illuminance which virtually bleaches all visual pigment, resulting in a relatively high number f reflected phtns, and
3 034 INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE / June 989 Vl. 30 ne with lwer adapting illuminances in which the visual pigment is partially regenerated, resulting in a lwer number f reflected phtns. Cmparisn f the tw cnditins yields a quantity bearing a relatin t the density f the visual pigment. In ur experiments, the density f the rd visual pigment was assessed with a labratrybuilt device in which several features f the Utrecht densitmeter 4 were incrprated, but which had the advantage f measuring at seven wavelengths in rapid successin. It was the prttype f a densitmeter described by van Nrren and van de Kraats. 5 Briefly, in a 00 msec cycle the eye is repetitively expsed t seven perids f light with different wavelengths, a dark perid, and fur perids f high adapting illuminance, each perid lasting 5 msec. The mean retinal level f bleaching light in the mnkey eye was equivalent t 3.2 X 0 5 td (2.2 X 0 5 sct td) fr humans; the retinal illuminance due t the sequential expsure t the varius wavelengths f the measuring light amunted an average f 3000 equivalent td (0 4 sct td). The measuring beam illuminated a field f 4.3 ; the bleaching beam was 0. The phtmultiplier in phtn cunting mde cllected light frm a 2.6 area cncentric with the illuminated field. The bleaching light was yellw (cut ff at 530 nm) in rder t avid interference between bleaching and damaging light. A micrprcessr srted the cunts f the phtmultiplier fr the prper wavelengths int seven channels, and these were all subsequently crrected fr the cunts cllected in the dark perid. The running average (with a time cnstant f fur sec) f the cunts at a chsen wavelength culd be displayed as a functin f time n a mnitr, and all results culd be stred n disk. Density was defined as the lgarithm f the rati f the number f cunts at 5 nm and at that at 730 nm, 4 the latter being a wavelength nt appreciably absrbed by the visual pigment. Densitmetric damage was defined by the damage index (D): D = (A B)/A (2) where A and B are the density differences between high and lw light level cnditins, befre and after expsure, respectively. Prcedure At the beginning f an experimental sessin the anesthetized animal was placed behind the irradiating device and the blck f fur patches f retina was selected and marked n a fundus phtgraph. Next, the animal was placed behind the densitmeter and the density f rhdpsin was measured at minimally tw f the fur selected patches f retina. When these densities were similar, the ther tw patches were nt measured. Then, the animal was placed back behind the irradiating device and irradiatin was started. At predetermined times subsequent hles f the diaphragm were cvered t allw fr different expsure times. T assess shrtterm damage, density was measured at a number f patches between 0.5 hr and 2 hr after irradiatin was cmpleted. On ther ccasins the bservatins and measurements were dne between 4 and 2 hr pstexpsure. Therefre, they were gruped int a separate categry. Density was nearly always measured 2 days after irradiatin. Depending n the length f the irradiatin this was between 3340 hr after cmpletin f irradiatin. Additinal density measurements were btained between 7020 days after irradiatin. Whenever density was measured, ntes were made n the appearance f the fundus. Sme eyes were used mre than nce. Eye mvements during expsure excluded sme patches frm evaluatin. Results Funduscpy Tw days pstexpsure, the retinal patches that underwent a funduscpical change shwed a brighter appearance than undamaged retina. The size f the damaged patches varied slightly, depending n the irradiant dse. Figure 2A thrugh 2D summarizes the results f funduscpic bservatins fr different irradiances and expsure times. The data are based n bservatins n 4 irradiated patches in ten eyes f seven animals. Up t 2 hr pstexpsure nt much damage was bserved; nly in a limited number f cases were threshld funduscpic lesins visible (halfpen circles in Fig. 2A, B). In Figure 2C the results f the mst extensive bservatins, made 2 days pstexpsure, are given. In any single experiment, we nted that the transitin between n damage and evident damage always was within a factr f tw f irradiant dse. The spread in threshld dse between individuals was nt large either: it was easy t draw a line by eye with slpe (cnstant dse) which separated sub frm suprathreshld data. This line represents a well defined and remarkably cnstant threshld dse f 230 J/cm 2 ver tw decades f expsure times. T enable cmparisns, the threshld dse line was drawn in all plts f Figure 2. It shws that it represents a cnservative estimate f a threshld curse fr the pstexpsure bservatins at ther times. With the lngest expsure time used, 2 hr, threshld damage is fund at abut 5 mw/cm 2. Fr a human eye, this wuld crrespnd t abut 3 X 0 6 td white light.
4 N. 6 RETINAL DAMAGE AFTER WHITE LIGHT EXPOSURES / Kremers nd vn Nrren 035 Fig. 2. Data n funduscpic bservatins 0.52 hr (A),42hr(B), 2 days (C), and mre than 70 days (D) pstexpsure. Filled circles represent a clear funduscpic lesin (suprathreshld damage), halffilled circles a just visible lesin (threshld damage), and pen circles n visible lesin (subthreshld damage). The dashed line represents an irradiant dse f 230 J/cm 2, which is the bestfitby eye fr threshld damage 2 days pstexpsure. 0 3 a.0' < ^ «0 A 0 3 * V^»«O _ A:0.52hrs C: 2dys * s ""* * N.* O 3 ^.» ' B:42hrs en D:>70 days j ""* * i i 0' 0 u retinal irradiance (mw.cnrr 2 ) After 70 r mre days, damaged patches which tw days pstexpsure were brighter than undamaged retina, nw appeared darker and had a granular texture. They were surrunded by an annulus f abut half a degree, with a smewhat brighter appearance than the rest f the retina. Recvery, in the sense that patches returned t nrmal, was minimal, as can be seen frm Figure 2D. Densitmetry An example f densitmetric measurements at 5 nm is given in the left part f Figure 3. In the upper panel a measurement befre expsure is given. The recrd starts with the bleaching light n; after 2 min the light was switched ff and pigment regeneratin was fllwed fr 5 min in the dark. Thereafter, the bleaching light was switched n again and the trace is seen t return t its riginal fully bleached level. The density difference between bleached and regenerated was 0.09, fairly typical fr the recrds btained in these experiments. The accuracy with which the density differences culd be assessed was between 0 and 20%. In the right part f Figure 3, density difference is given as functin f wavelength. The difference is maximal at 5 nm, indicative fr rd invlvement. The middle panel f Figure 3 presents the results f measurements taken 2 days after 4800sec expsure with an irradiance f 220 mw/cm 2, which was 4.6 times the funduscpic threshld dse. N changes in density are bserved fllwing an identical bleaching and regeneratin sequence, which is indicative fr a serius disturbance in the regeneratin cycle f rhdpsin. In the lwer panel f Figure 3, a measurement in the same patch 85 days after expsure is presented. Partial recvery f the density f rhdpsin was fund. In Figure 4A densitmetric damage indices btained fr 2 days pstexpsure are given as a functin f irradiant dse. The threshld dse btained frm funduscpy, the vertical line, prvides a satisfactry separatin between high and lw damage. In Figure 4B the same mde f presentatin is chsen fr densitmetric changes after prlnged recvery. The threshld dse fr lngterm densitmetric damage, thugh less accurately determined, lies at abut 600 J/cm 2, which is a factr f 2.6 higher than the dse fr funduscpic and densitmetric threshld damage 2 days pstexpsure. S, again, the fundu
5 006 INVESTIGATIVE OPHTHALMOLOGY & VI5UAL SCIENCE / June 989 Vl. 30 pre ij) c kmim I.**"* 2 days pst 85 days pst U 6 time (min) ^ VMUMMJ a> Jl 0 Ui 0 CD " days pst 85 days pst wavelength (nm) Fig. 3. Example f densitmetry befre expsure (tp panels), 2 days after a 4800sec expsure t 220 mw/cm 2 (middle panels), and 85 days after the same expsure (bttm panels). The left panels shw the density traces fr the measuring light f 5 nm wavelength. A trace starts with the pigment bleached. After 2 min the bleaching light is turned ff, and the visual pigment is allwed t regenerate fr 5 min. Then, the bleaching light is turned n again, and the density trace is seen t return t its previus level. The right panels shw the difference spectrum, which resembles the rhdpsin density spectrum. Nte the absence f visual pigment 2 days pstexpsure and the partial recvery f visual pigment after 85 days. scpic criterin 2 days pstexpsure prves t be the mst cnservative damage criterin. In Figure 5, funduscpic and densitmetric results are cmpared fr 2 days, and mre than 70 days pstexpsure, respectively. Crrespndence is high fr bservatins 2 days pstexpsure, but much prer after prlnged recvery. In distinct funduscpic lesins partial r even cmplete densitmetric recvery was measured in many instances. The data btained between 0.5 and 2 hr pstexpsure are nt presented in a figure, because nne f the ten measurements shwed a densitmetric change, despite the fact that the irradiant ttal dse was abut 550 J/cm 2, and despite the fact that in ne f the measured patches a vague funduscpic change was bserved (after a 2 hr expsure t.5 mw/cm 2 ). Only tw measurements were dne between 4 and 2 hr pstexpsure. The irradiant dses in the tw patches were 35 and 200 J/cm 2, respectively, and bth displayed a vague funduscpic change. Only the high dse expsure resulted in a densitmetric damage (D = ). Discussin Relatin between Irradiance and Expsure Time at Threshld The funduscpic threshld damages, btained 2 days pstexpsure, (Fig. 2C) ccurred at a cnstant 230 J/cm 2 irradiant dse fr expsure cnditins f up t 2 hr. This result is interesting in tw ways. In the first place it extends the dmain f timeirradiance reciprcity. Frm Ham et al's 9 data, reciprcity was clear up t at least 000 sec. By cmbining data in the literature fr varius animal mdels, we culd already tentatively extend that perid t abut 4 hr. 6 This study nw prvides experimental evidence fr reciprcity up t 2 hr in ne animal mdel, the macaque. In the secnd place the value f the threshld dse f 230 J/cm 2 merits attentin. It is nly slightly lwer than the 40 J/cm 2 value derived frm the data f Ham et al. 9 This difference may have a technical explanatin. Ham et al 9 used the integrated value frm nm, whereas urs ranged frm nm. Since all evidence suggests that wavelengths ver 700 nm d nt cntribute t phtchemical damage (prvided they d nt increase retinal temperature), ur threshld data are cmparable t Ham's data. Hwever, ur results are clearly at variance with thse f Sykes et al," wh fund threshld damage already at 6 J/cm 2 in an animal mdel clsely related t urs. The cntradictin with Ham's data was nt bvius as Sykes' expsure was utside the irradiance/time dmain cvered by Ham. The cntrversy has nw becme much mre manifest by ur extensin f the reciprcity dmain t 2 hr. Despite similarities in expsure time and animal mdel, there are differences between ur and Sykes' experiments, which might explain the different threshld irradiant dses. These differences are the use f anesthetics, the size f the expsed retinal area,
6 N. 6 RETINAL DAMAGE AFTER WHITE LIGHT EXPOSURES / Kremers and van Nrren 037 the technique f damage assessment and the light surce.. Anesthetics: We expsed the mnkey's eye under Nembutal anesthesia, whereas the animals in Sykes' experiments were unanesthetized. There is evidence indeed that Nembutal prvides prtectin. 7 On the ther hand, rugh estimatins f the damage dse in (unanesthetized) human sungazers are certainly nt lwer than ur 230 J/cm 2 value, because nly minr damages were reprted even after hr f sungazing 8 (retinal irradiance estimated t be abut 0 4 mw/cm 2, n crrectins fr eye mvements). 2. Size f expsed retinal area: Sykes et al used largefield expsure, whereas we used 4 field sizes A: 2 days x 0.4 I l_ * Q) r n= n=2 2 days >70days. n= B:>70days I irradiant dse (J.cnr 2 ) Fig. 4. Densitmetric damage index as a functin f the irradiant dse, fr measurements 2 days (A) and mre than 70 days (B) pstexpsure. The dashed lines represent the best fitting dses fr threshld densitmetric damage: 230 J/cm 2 after 2 days, and 600 J/cm 2 after mre than 70 days. n just clear funduscpic damage Fig. 5. Relatin between funduscpic and densitmetric damage indices tw days and mre than 70 days after expsure. The mean densitmetric damage and standard deviatin are presented at three funduscpic damage indices, tgether with the number f bservatins. Crrespndence between bth indices is mst clearly present 2 days after expsure. As a matter f fact, Ham et al 9 have suggested, but never substantiated, such an explanatin. 3. Technique f damage assessment: Sykes used histlgic criteria, whereas ur data were based n funduscpic and densitmetric bservatins. Bth this study and ur earlier literature survey have shwn, hwever, that different techniques d nt markedly differ in results. Fuller et al 20 fund that the irradiant dse fr a funduscpic threshld was nly
7 038 INVESTIGATIVE OPHTHALMOLOGY & VI5UAL 5CIENCE / June 989 Vl B CD e O Q. a 0 3 a a a A a A A class I O i90580 V. 0' 0" 3 0,2 0 A 0 V ^ irradiance (mw.crrr 2 ) class n week* day* 2hrs* hr* Fig. 6. Funduscpic data frm the present experiments (circles), brught tgether with literature data. Open symbls dente subthreshld damage, halffilled symbls threshld damage, and clsed symbls represent suprathreshld damage. The drawn curve is a theretical threshld curve fr Class II damage. 26 The fllwing Class I data were used: V: rats 2 (dented with , indicating the wavelength cntents f the irradiant light); D: rats 23 ; A: pigens 24 ; >: mnkeys". The literature data n Class II damage shwn here (0) riginate frm Ham et al. 9 Except fr the experiments f Nell et al 2 all expsures invlved white light surces. One f ur bservatins (2 hr expsure t 0.7 mw/cm 2 ) was nt shwn in Figure 2, as it did nt prvide additinal infrmatin n threshld data, but it has been included in this figure t emphasize the cntrversy with the data f Sykes etal." abut a factr f tw higher than the dse fr a histlgic threshld. 4. Light surce: We used a xenn arc lamp, whereas flurescent bulbs were used in Sykes' experiments. Hwever, taking accunt fr the actin spectra f phtchemical damage, it is very unlikely that the difference in spectral distributin f the radiatin might cause such large differences in threshld dses. Anther difference might be the flicker in the flurescent lights due t the AC pwer supply. We d nt find any mechanistic justificatin fr this pssibility. Therefre, it seems very imprbable that the differences in threshld dses wuld have been caused by the use f different light surces. The imprtance f these pssible differences may becme clear when things are put in a different perspective by nting that the results f the Sykes experiments d nt frm just an dd pint in a further cnsistent picture f threshld dses (Fig. 6). They seem t fit int a series f threshld data mainly fund in rats (eg, 223) but als in pigens 24 and in ther mnkey experiments These are the scalled Class I damages as defined by Mainster 27 and Kremers and van Nrren. 6 Class I damage is fund in experiments that have the fllwing characteristics in cmmn: unanesthetized animals, mainly rats, are expsed t largefield, lngterm (2 hr r lnger) irradiatin, with retinal irradiance seldm exceeding mw/cm 2 (data n white light surces 6 ). On histlgical examinatin f the retina, damage is mainly restricted t the phtreceptr level (fr a review see Lanum 28 ). The actin spectrum, fund in rats, is similar t the absrptin spectrum f visual pigment Harwerth and Sperling's 25 experiments, in which phtreceptr systems culd be selectively damaged by clred light, suggest an actin spectrum resembling visual pigment absrptin spectrum als exists in mnkeys. The damages prduced in ur experiments are typically f the Class II type. Cnditins in which phtchemical damage f Class II is fund can be characterized as fllws. Small patches f retina in usually anesthetized animals were expsed, fr limited perids f time, t irradiances typically exceeding 0 mw/cm 2 using white light surces. Damage is assessed at least 24 hr after expsure; in general the first signs f damage appear in the pigment epithelium. 9 The actin spectrum, in macaque mnkeys, shwed
8 N. 6 RETINAL DAMAGE AFTER WHITE LIGHT EXPOSURES / Kremers and vn Nrren 039 maximum sensitivity in the UV. Animal mdels in these experiments invlved primates and rabbits. 29 " 32 Human subjects, abut t underg eye enucleatin, were als studied. 833 The amunt f unbleached visual pigment has been suggested as crucial factr fr class determinatin, resulting in lwer threshld dses than expected fr Class II damage fr expsures f 2 hr r lnger. 6 Althugh this hypthesis seemed attractive fr explaining literature data, ur experiments d nt supprt it. Pssibly, a cmbinatin f sme f the afrementined factrs is required fr class determinatin. The unreslved cntrversy between Sykes' and ur results shuld, therefre, nt be viewed as just differences between tw experiments, but shuld be placed in the mre interesting, unreslved distinctin between Class I and Class II damage. Recvery Tw days pstexpsure, damage seems t be mst distinct. Thereafter, the appearance f the funduscpic lesins changes and the regeneratin cycle f the visual pigments may recver. Tw days after expsure, the damaged part f the retina appeared lighter than the rest and ccasinally it seemed edematus. This is in line with reprted depigmentatin and mild edema. ' 34 ' 35 After mre than 70 days, the lesin was less bvius (als bserved by Ham et al ), darker than the rest f the retina, and it had a granular appearance. The granularity after prlnged recvery culd be attributed t the irregular pigmentatin f the RPE cells as described by Ts. 35 We fund substantial recvery frm damage with densitmetry. Thus, the disturbance f the visual cycle may vanish cmpletely with the funduscpic lesin still present. The extent f recvery was fund t depend n the irradiant dse: when the dse was higher than abut 600 J/cm 2, recvery was never cmplete. These results are in qualitative agreement with the effects reprted by Mn et al. 36 After expsing the macula f a rhesus mnkey t 44 nm light, inducing a funduscpic threshld lesin, they fund visual perfrmance (visual acuity measured with Landlt rings) t be temprarily impaired, and returning t nrmal in abut 0 days. After a suprathreshld expsure (.5 times threshld dse) visual perfrmance nly shwed partial recvery. We fund incmplete recvery nly after an irradiant dse f 2.6 times threshld. This might indicate a lingering damage t the neural retina despite full recvery f the visual pigment regeneratin cycle. Key wrds: retina, phtchemical damage, white light, irradiant dse, densitmetry Acknwledgments The authrs thank Drs. J. J. Vs and B. de Graaf fr useful discussins, Dr. G. Szant fr crrecting the manuscript's grammar, and Mr. F. Fiirrer and Mrs. N. Blkland fr assistance during the experiments. References. 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