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Investigative Ophthalmology & Visual Science, Vol. 30, No. 6, June 1989
Copyright © Association for Research in Vision and Ophthalmology
Retinal Damage in Macaque after White Light
Exposures Lasting Ten Minutes to Twelve Hours
Jan J. M. Kremers and Dirk van Norren
We induced photochemical damage in small parts of the retinas of anesthetized macaques after light
exposures of varying intensity, lasting between 10 min and 12 hr. Damage was assessed both with
funduscopy and densitometry at several periods after exposure. Damage was most extensive 2 days
post-exposure, with similar thresholds for both methods. Reciprocity between exposure time and
irradiance was found for all exposures at a threshold irradiant dose of 230 J/cm2. This is in good
agreement with part of the literature data on monkeys, yet contradicts another report (Sykes et al) in
which a much lower threshold dose was found. The latter data probably concern a different class of
damage. It remains unclear what critical factors distinguish the two classes. Observations more than
70 days post-exposure show a divergence between funduscopic and densitometric thresholds. Although the appearance of funduscopic lesions had changed, the threshold dose remained 230 J/cm2.
Densitometry showed full recovery of the amount of visual pigment for doses below 600 J/cm2. Invest
Ophthalmol Vis Sci 30:1032-1040,1989
old damage should increase, rather than decrease.
Griess and Blankenstein12 found the time constant of
the repair processes to be almost exactly 4 days. From
this study alone reciprocity is expected to hold up to
about 2 days. But, as Griess and Blankenstein determined the time constant in an indirect way, this is
only true when no other, unexpected, processes interfere at long exposures. Sykes'" experiments actually suggest such an interference.
The aim of the present study was to investigate
whether or not there is a deviation from reciprocity
after long exposures, as described above. Therefore,
we explored the exposure range from a few hundred
seconds to 12 hr. The conditions were, apart from
irradiance and time, similar to those used by Ham et
al,9 that is, anesthetized macaque monkeys and exposures restricted to small patches of retina. In addition to funduscopy, we introduced retinal densitometry as a new technique for assessing damage. This
technique has the advantage of being both quantitative and noninvasive. Also, direct information is obtained on the kinetics of visual pigments after photochemical damage.
Finally, damage was also assessed between 2 and 7
months after exposure, to study the effect of repair
mechanisms.
When the primate retina is exposed to intense light
for periods varying between several seconds and 4 hr,
extensive damage to the pigment epithelium and to
the neural retina may be found.1"4 In patients such
damage is also reported after ocular surgery in which
use was made of bright light sources.5"8 For periods
between 10 and 1000 sec, Ham et al 2 9 1 0 verified that
reciprocity holds, that is, irradiance is exchangeable
for exposure time. The threshold dose for white light
in Ham's experiments varied between 200 to 400
J/cm2. With exposures shorter than 10 to 100 sec,
depending on the size of the retinal image, reciprocity
fails because the rise in retinal temperature is such
that the domain of thermal -damage is entered. It is
unclear how far reciprocity holds for exposures
beyond 1000 sec. One report is available in which
macaque monkeys were exposed to 12 hr of continuous fluorescent light.'' We calculated that the threshold dose in the latter experiment was about 16 J/cm2,
an order of magnitude lower than Ham et al's
200-400 J/cm2. The direction of the deviation from
reciprocity is unexpected. Naively, it is expected that
with increasing exposure time (and decreasing irradiances) repair processes gradually overtake damage
induction. As a result the total dose to reach threshFrom the TNO Institute for Perception, Soesterberg, The Netherlands.
Supported by the Netherlands Organization for Scientific Research, through the Foundation for Biophysics.
Submitted for publication: May 23, 1988; accepted December 5,
1988.
Reprint requests: D. van Norren, PhD, TNO Institute for Perception, P.O. Box 23, 3769 ZG Soesterberg, The Netherlands.
Materials and Methods
Animal Preparation
Monkeys were sedated with 25-40 mg ketamine
hydrochloride (Ketalar®, Park-Davis, Barcelona,
Spain) and anesthetized with an initial intravenous
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RETINAL DAMAGE AFTER WHITE LIGHT EXPOSURES / Kremers and van Norren
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dose of 20 mg/kg of pentobarbital (Nembutal®,
CEVA, Paris, France), followed by a continuous infusion of 2-3 mg/kg/hr. After intubation, artificial
respiration was started with a mixture of 70% nitrous
oxide and 30% oxygen. To prevent eye movements
an intravenous infusion of a muscle relaxant pancuronium bromide (Pavulon®, Organon, Oss, The
Netherlands) was given. The initial dose was 30 Mg/kg
followed by a continuous infusion of 30 jtg/kg/hr.
Pupils were dilated with a drop of Phenylephrin®
(Bournonville-Pharma, Almere, The Netherlands),
combined with a drop of Cyclogyl® (Schieffelin and
Co., New York, NY). The head was fixed in place
with ear bars and a jaw rest. A hard contact lens was
,used to prevent drying of the cornea. All preparation
•was done in yellow light to minimize the possibility of
retinal damage before exposure.
This investigation adhered to the ARVO Resolution on the Use of Animals in Research.
Irradiation
Whenever we use the term irradiation, we refer to
exposures of white light to establish damage thresholds. We used a dual beam ophthalmoscopic stimulator for irradiation under Maxwellian view conditions.
The light source was a 450 W xenon arc with light
stabilized power supply. Infrared radiation was eliminated by a Schott KG 3 filter. UV radiation was reduced by the glass lenses. Details of this apparatus
can be found in Valeton and van Norren. 13 Four
patches of retina were defined using a diaphragm
with four holes imaged on the retina. The holes measured 4° diameter and were arranged in a two by two
array, about 1 ° separated. The center of the array was
positioned about 8° above the fovea. To vary the
irradiance level of individual patches, neutral density
filters were placed on the holes. The irradiances of the
four patches were regularly calibrated with a Laser
Precision RK-5100 Pyroelectric Radiometer. The
spectral output of the white light at the corneal level
was measured with a scanning spectroradiometer
(Photo Research Spectrascan S.N. 2186). The results
of the latter measurement are presented in Figure 1.
The average color temperature was 5400°K. Retinal
irradiance (Eret) was calculated from the measured
irradiance (Eair) with4:
J-ret
'-'air
^'
in which d is the distance between focus and the irradiated plane of the measuring device of the radiometer, f the focal length of the monkey eye (about 1.35
cm), n the refractive index (about 1.33), and t the
ocular transmission (about 0.9). The maximal available retinal irradiance was 400 mW/cm2.
1030
Fig. 1. Spectral distribution of the damage-inducing light at the
corneal level.
Funduscopy
The irradiated patch (seen through the ophthalmic
stimulator) was marked on a fundus photograph.
Two days after exposure, changes were visible as
white-yellowish spots.
Funduscopic observations were performed with an
indirect ophthalmoscope (28 diopter lens), because
the large field of view made lesions easier to recognize
due to the comparison with the undamaged surroundings. We classified the observations into three
categories: (1) no change, indicating subthreshold
damage or absence of damage; (2) a just visible
change (a patch somewhat smaller than the irradiated
spot, and with fuzzy edges), as an indication for
threshold damage; and (3) a distinct funduscopic
change (a patch with a size comparable to the irradiated spot or somewhat larger, and with sharp
edges), indicating suprathreshold damage.
Funduscopic observations were made at four different time intervals after exposure: (1) 0.5-2 hr; (2)
4-12 hr; (3) about 2 days; and (4) minimally 70 days.
The most complete observations were made 2 days
post-exposure because at that time funduscopic
changes were most clearly present (in accordance
with observations of, eg, Ham et al u 0 ).
Densitometry
In retinal densitometry a beam of light is shone
into the eye, reflected at the fundus and collected by a
light-sensitive device, usually a photomultiplier
(PM). Essential in the technique is: first, that measuring light bleaches only a small fraction of the photopigment. Second, measurements are done in two
conditions, one with high adapting illuminance
which virtually bleaches all visual pigment, resulting
in a relatively high number of reflected photons, and
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INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE / June 1989
one with lower adapting illuminances in which the
visual pigment is partially regenerated, resulting in a
lower number of reflected photons. Comparison of
the two conditions yields a quantity bearing a relation
to the density of the visual pigment. In our experiments, the density of the rod visual pigment was assessed with a laboratory-built device in which several
features of the Utrecht densitometer14 were incorporated, but which had the advantage of measuring at
seven wavelengths in rapid succession. It was the
prototype of a densitometer described by van Norren
and van de Kraats.15 Briefly, in a 100 msec cycle the
eye is repetitively exposed to seven periods of light
with different wavelengths, a dark period, and four
periods of high adapting illuminance, each period
lasting 5 msec. The mean retinal level of bleaching
light in the monkey eye was equivalent to 3.2 X 105 td
(2.2 X 105 scot td) for humans; the retinal illuminance due to the sequential exposure to the various
wavelengths of the measuring light amounted an
average of 3000 equivalent td (104 scot td). The measuring beam illuminated a field of 4.3°; the bleaching
beam was 10°. The photomultiplier in photon
counting mode collected light from a 2.6° area concentric with the illuminated field. The bleaching light
was yellow (cut off at 530 nm) in order to avoid interference between bleaching and damaging light. A microprocessor sorted the counts of the photomultiplier
for the proper wavelengths into seven channels, and
these were all subsequently corrected for the counts
collected in the dark period. The running average
(with a time constant of four sec) of the counts at a
chosen wavelength could be displayed as a function
of time on a monitor, and all results could be stored
on disk.
Density was defined as the logarithm of the ratio of
the number of counts at 511 nm and at that at 730
nm,14 the latter being a wavelength not appreciably
absorbed by the visual pigment. Densitometric damage was defined by the damage index (D):
D = (A - B)/A
(2)
where A and B are the density differences between
high and low light level conditions, before and after
exposure, respectively.
Procedure
At the beginning of an experimental session the
anesthetized animal was placed behind the irradiating device and the block of four patches of retina was
selected and marked on a fundus photograph. Next,
the animal was placed behind the densitometer and
the density of rhodopsin was measured at minimally
two of the four selected patches of retina. When these
Vol. 30
densities were similar, the other two patches were not
measured. Then, the animal was placed back behind
the irradiating device and irradiation was started. At
predetermined times subsequent holes of the diaphragm were covered to allow for different exposure
times. To assess short-term damage, density was
measured at a number of patches between 0.5 hr and
2 hr after irradiation was completed. On other occasions the observations and measurements were done
between 4 and 12 hr post-exposure. Therefore, they
were grouped into a separate category. Density was
nearly always measured 2 days after irradiation. Depending on the length of the irradiation this was between 33-40 hr after completion of irradiation. Additional density measurements were obtained between 70-210 days after irradiation. Whenever
density was measured, notes were made on the appearance of the fundus.
Some eyes were used more than once. Eye movements during exposure excluded some patches from
evaluation.
Results
Funduscopy
Two days post-exposure, the retinal patches that
underwent a funduscopical change showed a brighter
appearance than undamaged retina. The size of the
damaged patches varied slightly, depending on the
irradiant dose.
Figure 2A through 2D summarizes the results of
funduscopic observations for different irradiances
and exposure times. The data are based on observations on 41 irradiated patches in ten eyes of seven
animals. Up to 12 hr post-exposure not much damage was observed; only in a limited number of cases
were threshold funduscopic lesions visible (half-open
circles in Fig. 2A, B). In Figure 2C the results of the
most extensive observations, made 2 days post-exposure, are given. In any single experiment, we noted
that the transition between no damage and evident
damage always was within a factor of two of irradiant
dose. The spread in threshold dose between individuals was not large either: it was easy to draw a line by
eye with slope —1 (constant dose) which separated
sub- from suprathreshold data. This line represents a
well defined and remarkably constant threshold dose
of 230 J/cm2 over two decades of exposure times. To
enable comparisons, the threshold dose line was
drawn in all plots of Figure 2. It shows that it represents a conservative estimate of a threshold course for
the post-exposure observations at other times. With
the longest exposure time used, 12 hr, threshold damage is found at about 5 mW/cm2. For a human eye,
this would correspond to about 3 X 106 td white light.
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RETINAL DAMAGE AFTER WHITE LIGHT EXPOSURES / Kremers ond von Norren
1
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Fig. 2. Data on funduscopic observations 0.5-2 hr
(A),4-12hr(B), 2 days (C),
and more than 70 days (D)
post-exposure. Filled circles
represent a clear funduscopic lesion (suprathreshold
damage), half-filled circles a
just visible lesion (threshold
damage), and open circles
no visible lesion (subthreshold damage). The dashed
line represents an irradiant
dose of 230 J/cm2, which is
the bestfitby eye for threshold damage 2 days post-exposure.
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After 70 or more days, damaged patches which two
days post-exposure were brighter than undamaged
retina, now appeared darker and had a granular texture. They were surrounded by an annulus of about
half a degree, with a somewhat brighter appearance
than the rest of the retina. Recovery, in the sense that
patches returned to normal, was minimal, as can be
seen from Figure 2D.
Densitometry
An example of densitometric measurements at 511
nm is given in the left part of Figure 3. In the upper
panel a measurement before exposure is given. The
record starts with the bleaching light on; after 2 min
the light was switched off and pigment regeneration
was followed for 15 min in the dark. Thereafter, the
bleaching light was switched on again and the trace is
seen to return to its original fully bleached level. The
density difference between bleached and regenerated
was 0.09, fairly typical for the records obtained in
these experiments. The accuracy with which the density differences could be assessed was between 10 and
20%. In the right part of Figure 3, density difference is
given as function of wavelength. The difference is
102
10310°
retinal irradiance (mW.cnrr2)
i
103
maximal at 511 nm, indicative for rod involvement.
The middle panel of Figure 3 presents the results of
measurements taken 2 days after 4800-sec exposure
with an irradiance of 220 mW/cm2, which was 4.6
times the funduscopic threshold dose. No changes in
density are observed following an identical bleaching
and regeneration sequence, which is indicative for a
serious disturbance in the regeneration cycle of rhodopsin. In the lower panel of Figure 3, a measurement in the same patch 85 days after exposure is
presented. Partial recovery of the density of rhodopsin was found.
In Figure 4A densitometric damage indices obtained for 2 days post-exposure are given as a function of irradiant dose. The threshold dose obtained
from funduscopy, the vertical line, provides a satisfactory separation between high and low damage. In
Figure 4B the same mode of presentation is chosen
for densitometric changes after prolonged recovery.
The threshold dose for long-term densitometric damage, though less accurately determined, lies at about
600 J/cm2, which is a factor of 2.6 higher than the
dose for funduscopic and densitometric threshold
damage 2 days post-exposure. So, again, the fundu-
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INVESTIGATIVE OPHTHALMOLOGY & VI5UAL SCIENCE / June 1989
Vol. 30
0.12
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0
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c 0.1
2 days post
Ui
0
0.1
0
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2 days post
CD
85 days post
kMIM
0
"°0.04
85 days post
•VMUMMJ
8 10 12
time (min)
U
16
18 20
400
500
600
700
wavelength (nm)
Fig. 3. Example of densitometry before exposure (top panels), 2 days after a 4800-sec exposure to 220 mW/cm 2 (middle panels), and 85
days after the same exposure (bottom panels). The left panels show the density traces for the measuring light of 511 nm wavelength. A trace
starts with the pigment bleached. After 2 min the bleaching light is turned off, and the visual pigment is allowed to regenerate for 15 min.
Then, the bleaching light is turned on again, and the density trace is seen to return to its previous level. The right panels show the difference
spectrum, which resembles the rhodopsin density spectrum. Note the absence of visual pigment 2 days post-exposure and the partial recovery
of visual pigment after 85 days.
scopic criterion 2 days post-exposure proves to be the
most conservative damage criterion.
In Figure 5, funduscopic and densitometric results
are compared for 2 days, and more than 70 days
post-exposure, respectively. Correspondence is high
for observations 2 days post-exposure, but much
poorer after prolonged recovery. In distinct funduscopic lesions partial or even complete densitometric
recovery was measured in many instances.
The data obtained between 0.5 and 2 hr post-exposure are not presented in a figure, because none of the
ten measurements showed a densitometric change,
despite the fact that the irradiant total dose was about
550 J/cm2, and despite the fact that in one of the
measured patches a vague funduscopic change was
observed (after a 12 hr exposure to 11.5 mW/cm2).
Only two measurements were done between 4 and 12
hr post-exposure. The irradiant doses in the two
patches were 351 and 1200 J/cm2, respectively, and
both displayed a vague funduscopic change. Only the
high dose exposure resulted in a densitometric damage (D = 1).
Discussion
Relation between Irradiance and Exposure Time
at Threshold
The funduscopic threshold damages, obtained 2
days post-exposure, (Fig. 2C) occurred at a constant
230 J/cm2 irradiant dose for exposure conditions of
up to 12 hr. This result is interesting in two ways.
In the first place it extends the domain of time-irradiance reciprocity. From Ham et al's9 data, reciprocity was clear up to at least 1000 sec. By combining data in the literature for various animal models,
we could already tentatively extend that period to
about 4 hr.16 This study now provides experimental
evidence for reciprocity up to 12 hr in one animal
model, the macaque.
In the second place the value of the threshold dose
of 230 J/cm2 merits attention. It is only slightly lower
than the 410 J/cm2 value derived from the data of
Ham et al.9 This difference may have a technical explanation. Ham et al9 used the integrated value from
400-800 nm, whereas ours ranged from 400-700 nm.
Since all evidence suggests that wavelengths over 700
nm do not contribute to photochemical damage
(provided they do not increase retinal temperature),
our threshold data are comparable to Ham's data.
However, our results are clearly at variance with
those of Sykes et al," who found threshold damage
already at 16 J/cm 2 in an animal model closely related to ours. The contradiction with Ham's data was
not obvious as Sykes' exposure was outside the irradiance/time domain covered by Ham. The controversy has now become much more manifest by our
extension of the reciprocity domain to 12 hr.
Despite similarities in exposure time and animal
model, there are differences between our and Sykes'
experiments, which might explain the different
threshold irradiant doses. These differences are the
use of anesthetics, the size of the exposed retinal area,
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No. 6
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RETINAL DAMAGE AFTER WHITE LIGHT EXPOSURES / Kremers and van Norren
the technique of damage assessment and the light
source.
1. Anesthetics: We exposed the monkey's eye
under Nembutal anesthesia, whereas the animals in
Sykes' experiments were unanesthetized. There is evidence indeed that Nembutal provides protection.17
On the other hand, rough estimations of the damage
dose in (unanesthetized) human sungazers are certainly not lower than our 230 J/cm2 value, because
only minor damages were reported even after 1 hr of
sungazing18 (retinal irradiance estimated to be about
104 mW/cm 2 , no corrections for eye movements).
2. Size of exposed retinal area: Sykes et al used
large-field exposure, whereas we used 4° field sizes.
2 days
1.0
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-0.2
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1.0
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0.8
no just clear
funduscopic damage
0.6
Fig. 5. Relation between funduscopic and densitometric damage
indices two days and more than 70 days after exposure. The mean
densitometric damage and standard deviation are presented at
three funduscopic damage indices, together with the number of
observations. Correspondence between both indices is most clearly
present 2 days after exposure.
0.2
0.0
-0.2
500
1000
irradiant dose (J.cnr 2 )
Fig. 4. Densitometric damage index as a function of the irradiant
dose, for measurements 2 days (A) and more than 70 days (B)
post-exposure. The dashed lines represent the best fitting doses for
threshold densitometric damage: 230 J/cm2 after 2 days, and 600
J/cm2 after more than 70 days.
As a matter of fact, Ham et al19 have suggested, but
never substantiated, such an explanation.
3. Technique of damage assessment: Sykes used
histologic criteria, whereas our data were based on
funduscopic and densitometric observations. Both
this study and our earlier literature survey have
shown, however, that different techniques do not
markedly differ in results. Fuller et al20 found that the
irradiant dose for a funduscopic threshold was only
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1038
INVESTIGATIVE OPHTHALMOLOGY & VI5UAL 5CIENCE / June 1989
107
•• B
10
1 week-*
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a
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•i90-580
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2
irradiance (mW.crrr )
about a factor of two higher than the dose for a histologic threshold.
4. Light source: We used a xenon arc lamp,
whereas fluorescent bulbs were used in Sykes' experiments. However, taking account for the action spectra of photochemical damage, it is very unlikely that
the difference in spectral distribution of the radiation
might cause such large differences in threshold doses.
Another difference might be the flicker in the fluorescent lights due to the AC power supply. We do not
find any mechanistic justification for this possibility.
Therefore, it seems very improbable that the differences in threshold doses would have been caused by
the use of different light sources.
The importance of these possible differences may
become clear when things are put in a different perspective by noting that the results of the Sykes experiments do not form just an odd point in a further
consistent picture of threshold doses (Fig. 6). They
seem to fit into a series of threshold data mainly
found in rats (eg, 21-23) but also in pigeons24 and in
other monkey experiments. 2526 These are the socalled Class I damages as defined by Mainster27 and
Kremers and van Norren.16 Class I damage is found
Vol. 30
Fig. 6. Funduscopic data
from the present experiments (circles), brought together with literature data.
Open symbols denote
subthreshold damage, halffilled symbols threshold
damage, and closed symbols
represent suprathreshold
damage. The drawn curve is
a theoretical threshold
curve for Class II damage.1216 The following Class
I data were used: V: rats21
(denoted with 490-580, indicating the wavelength
contents of the irradiant
light); D: rats23; A: pigeons24; >: monkeys". The
literature data on Class II
damage shown here (0)
originate from Ham et al.9
Except for the experiments
of Noell et al21 all exposures
involved white light sources.
One of our observations
(12 hr exposure to 0.7
mW/cm2) was not shown in
Figure 2, as it did not provide additional information
on threshold data, but it has
been included in this figure
to emphasize the controversy with the data of Sykes
etal."
in experiments that have the following characteristics
in common: unanesthetized animals, mainly rats, are
exposed to large-field, long-term (12 hr or longer)
irradiation, with retinal irradiance seldom exceeding
1 mW/cm2 (data on white light sources16). On histological examination of the retina, damage is mainly
restricted to the photoreceptor level (for a review see
Lanum28). The action spectrum, found in rats, is similar to the absorption spectrum of visual pigment.21-22
Harwerth and Sperling's25 experiments, in which
photoreceptor systems could be selectively damaged
by colored light, suggest an action spectrum resembling visual pigment absorption spectrum also exists
in monkeys.
The damages produced in our experiments are typically of the Class II type. Conditions in which photochemical damage of Class II is found can be characterized as follows. Small patches of retina in usually
anesthetized animals were exposed, for limited periods of time, to irradiances typically exceeding 10
mW/cm2 using white light sources. Damage is assessed at least 24 hr after exposure; in general the first
signs of damage appear in the pigment epithelium.19
The action spectrum, in macaque monkeys, showed
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RETINAL DAMAGE AFTER WHITE LIGHT EXPOSURES / Kremers and von Norren
maximum sensitivity in the UV. Animal models in
these experiments involved primates and rabbits.29"32
Human subjects, about to undergo eye enucleation,
were also studied.1833
The amount of unbleached visual pigment has
been suggested as crucial factor for class determination, resulting in lower threshold doses than expected
for Class II damage for exposures of 12 hr or longer.16
Although this hypothesis seemed attractive for explaining literature data, our experiments do not support it. Possibly, a combination of some of the aforementioned factors is required for class determination.
The unresolved controversy between Sykes' and
our results should, therefore, not be viewed as just
differences between two experiments, but should be
placed in the more interesting, unresolved distinction
between Class I and Class II damage.
Recovery
Two days post-exposure, damage seems to be most
distinct. Thereafter, the appearance of the funduscopic lesions changes and the regeneration cycle of the
visual pigments may recover. Two days after exposure, the damaged part of the retina appeared lighter
than the rest and occasionally it seemed edematous.
This is in line with reported depigmentation and mild
edema.1'34'35 After more than 70 days, the lesion was
less obvious (also observed by Ham et al1), darker
than the rest of the retina, and it had a granular appearance. The granularity after prolonged recovery
could be attributed to the irregular pigmentation of
the RPE cells as described by Tso.35
We found substantial recovery from damage with
densitometry. Thus, the disturbance of the visual
cycle may vanish completely with the funduscopic
lesion still present. The extent of recovery was found
to depend on the irradiant dose: when the dose was
higher than about 600 J/cm 2 , recovery was never
complete. These results are in qualitative agreement
with the effects reported by Moon et al.36 After exposing the macula of a rhesus monkey to 441 nm
light, inducing a funduscopic threshold lesion, they
found visual performance (visual acuity measured
with Landolt rings) to be temporarily impaired, and
returning to normal in about 10 days. After a suprathreshold exposure (1.5 times threshold dose) visual performance only showed partial recovery. We
found incomplete recovery only after an irradiant
dose of 2.6 times threshold. This might indicate a
lingering damage to the neural retina despite full recovery of the visual pigment regeneration cycle.
Key words: retina, photochemical damage, white light, irradiant dose, densitometry
1039
Acknowledgments
The authors thank Drs. J. J. Vos and B. de Graaf for
useful discussions, Dr. G. Szanto for correcting the manuscript's grammar, and Mr. F. Fiirrer and Mrs. N. Blokland
for assistance during the experiments.
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