Eye damage control by reduced blue illumination
Toshihiko Uedaa,*, Takako Nakanishi-Uedab, Hajime Yasuharab, Ryohei Koidea, William W. Dawsonc
aDepartment of Ophthalmology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
bDepartment of Pharmacology, School of Medicine, Showa University, 1-5-8, Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
cDepartment of Ophthalmology, University of Florida, M119 Medical Sciences, PO Box 100284, Gainesville, FL 32610, USA
a r t i c l e i n f o
Received 5 February 2009
Accepted in revised form 19 July 2009
Available online 4 August 2009
a b s t r a c t
The aim of this study was to demonstrate that a blue light and ultraviolet cut-off filter (blue filter) could
reduce short-wavelength retina/RPE damage threshold by a continuous spectrum source. Sixteen normal
eyes of two rhesus monkeys and six cynomolgus monkeys were subjected to macular irradiation of 20,
24, 27.4, 30, 35, 45, 50 and 60 J/cm2energy densities. The values of energy density were measured before
the blue filter. Lesions were measured before and at 2 and 30 days after irradiation of a 2.8 mm diameter
region within the macular arcade. Measures were fundoscopy, fluorescein angiography and long wave-
length scanning by the Heidelberg Retinal Tomograph (HRT) unit. The lesions, which were produced,
were scored and compared to irradiant energy density of the blue LED (NSPB500S, Nichia, Tokushima,
Japan). The exposure at the 20 J/cm2produced no detectable result at 2 or 30 days. Exposure at 35 J/cm2
showed definite lesion production without blue filter. With the filter added there was one indication of
minor change. At 60 J/cm2there was extensive heavy, enduring damage without the filter and with the
filter damage was present but was significantly attenuated. These results strongly support the conclusion
that the blue filter attenuation reduces the frequency of damage by exposure. This experimental system
is a useful model for normal human eye aging and continuous spectrum environment irradiance.
? 2009 Elsevier Ltd. All rights reserved.
It is well known that visible light can produce damage to the
retina and pigmented supporting tissue (Lawwill,1982). Especially,
blue light increases the risk of light damage to the retina (Ham
et al., 1978; Nilsson et al., 1989; Taylor et al., 1992). We also
demonstrated that the continuous spectrum, blue light from light
emitting diodes (LED) is a hazard to retinas in normal young rhesus
monkeys (Dawson et al., 2001). Histological examinations 30 days
after exposure, showed that blue LED irradiation greater than
60 J/cm2caused a marked disruption of the disks of photoreceptor
cells, damaged retinal pigmented epithelium (RPE) apical villi, and
reduced RPE melanin (Koide et al., 2001). A blue light and ultravi-
olet cut-off filtering intraocular lens (blue-filtering IOL) was
developed to prevent cyanopisia after cataract surgery (Ishida et al.,
1994). Recently, the use of blue-filtering intraocular lenses (IOLs)
has increased. Basic studies of RPE (Sparrow et al., 2004; Nilsson,
2004) and animal experiments which used rodent eyes (Lawwill
et al., 1980; Tanito et al., 2006), have demonstrated the protective
effect on the retina of blue-filtering IOLs.
Blue-light toxicity studies before year 2000 had only line
emission (laser or xenon) sources available. At that time LED’s
produced small amounts of output power. Now the continuous-
band emission LED’s can approach ‘‘filtered’’ sunlight power. The
continuous emission characteristic is more consistent with modern
blue-filtering IOL’s. In this study we report that this combination is
an effective model (LED-short-wavelength filter) for normal human
eye aging and environment irradiance.
2. Materials and methods
Two young adult rhesus monkeys (Macaca mulatta) and six
cynomolgus (Macaca nemestrina) monkeys were screened for
normal eyes including a dilated examination of the fundus, anterior
segment and pupillary responsiveness. Screened monkeys were
assigned, right eyes to the non filter and left eyes to the blue light
cut-off filter (blue filter) condition (Table 1). All procedures
involving the animals were approved by the University of Florida
Institutional Animal Care and Use Committee as required by the
U.S. Department of Agriculture. Anesthesia for retinal exposures
* Corresponding author. Tel.: þ81 3 3784 8553; fax: þ81 3 3784 5048.
E-mail addresses: firstname.lastname@example.org
showa-u.ac.jp (T. Nakanishi-Ueda), email@example.com (H. Yasuhara),
firstname.lastname@example.org (R. Koide), email@example.com (W.W. Dawson).
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Experimental Eye Research 89 (2009) 863–868
and measurements was achieved by the administration of 10 mg/kg
ketamine, 0.25 mg/kg promethazine and 0.02 mg/kg of xylazine.
Premedication with glycopyrrolate (0.001 mg/kg) managed cardiac
and secretory variables. Eye movement was eliminated when, after
sedation, the trachea was intubated and neuromuscular relaxation
was achieved by the use of pancuronium bromide (0.03 mg/kg/h).
Respiration was mechanically assisted and endtidal CO2 was
controlled between 4.5 and 5.8%. During exposure and subsequent
testing all relevant vital signs were monitored including mean
arterial pressure. Body temperature was continuously controlled by
a thermal blanket with covers. Hydration was maintained by
continuous intravenous fluids and each eye was fitted with a hard
corneal contact lens.
The blue LED (NSPB500SE, Nichia Co., Tokushima, Japan)
exhibited a power-peak at 465 nm. As shown in Fig. 1 the diode
output falls to zero at 410 nm and 540 nm. The transmission curve
for the blue and UV light filter (filter) provided by Menicon Co. Ltd.
(Nagoya, Japan) is shown in Fig. 1. Roll-off of the filter begins at
approximately 540 nm and falls sharply at approximately 420 nm.
The maximum LED input current was 80 mA (mA). The LED was
located in the optical axis of the slit-lamp biomicroscope (Topcon,
Tokyo, Japan, Dawson et al., 2001). This modification set the image
plane stop dimension. An aerial focal plane containing the image of
source/stop was formed approximately 1 cm proximal to the
aspheric objective lens (60 diopter, Volk). The irradiant power in
the aerial plane, before the 60 D lens, was measured by an
Advantest optical power meter (model TQ8210, Tokyo, Japan). The
power was controlled, at about 850 mW, during exposures. The
projected stop images were approximately 2.8 mm in diameter as
measured by Heidelberg Engineering Retinal Tomograph (HRT).
Thisimageplanewas parfocal with the fundus and allowed viewing
and control of the source position on the fundus. The images on the
temporal fundus appeared to be slightly larger than the optic disc,
uniform, and positioned so that they were within the vascular
arcade and mainly in a melanin pigmented portion of the macula
about one disc diameter from the fovea. The image was placed to
avoid major blood vessels. The blue light cut-off filter was inserted
into the Topcon’s illumination channel so that it could be swung
away for normal viewing. The right eye (OD) was exposed without
the filter. The left eye (OS) was exposed at the same prefilter energy
density level. Exposures proceeded in series with increased times
so that maximum efficiencycould be utilized fromthe results of the
previous animals. The sequence of exposures was 20, 24, 27.4, 30,
35, 45, 50 and 60 J/cm2. The duration of the exposures ranged from
27 to 82 min. The exposures at the cornea were reduced by the blue
light cut-off filter from 24 to 15.8 J/cm2, from 27.4 to 18 J/cm2, from
30 to 21.3 J/cm2, from 45 to 29 J/cm2, and from 50 to 35.5 J/cm2,
2.3. Damage measurement
There were three periodic measurement and recording events.
One set of measures and records were complete two days before
exposure, two days after exposure and 30 days after exposure. Eyes
were dilated with 2% phenylephrine HCl and accommodation was
controlled with Tropicamide topical drops. Contact lenses were
placed to maintain corneal quality. Color fundus photographs
covering a 30?area centered on the perifovea were made using
a Zeiss F series clinical fundus camera. The same fundus camerawas
used with appropriate excitor and barrier filters for the production
of sequenced fluorescein angiograms. Before rapid (saphenous
vein) injection of fluorescein (0.3 mL, 10%) red-free photographs
were taken by a Cannon EOS digital camera back modification of
the fundus camera. The same system was used subsequently to
record the fluorescence frames where early filling was recording at
Results of blue LED exposures.
Period FundusL. Fluor HRT
No filter 242–
No filter 27.42
No filter 302
No filter 352
No filter 452
There is a range of energy densities at 2 and 30 days (period) after the exposure.
Fundus, late fluorescence and HRT signs are rated as strong (þþ), mild (þ) and weak
(?/þ). No lesion was given a dash (?). Comments:
afoveal artifact present.
bFoveal avascular regions or pigment clumps.
cWeak pigment redistribution.
Fig. 1. Transmission curve of the blue light cut-off filter (doted line). The square area
between 410 and 540 nm is the area that influences the irradiation by the NSPB500S
light emitting diode. A solid line shows the emission of the blue LED (NSPB500S).
T. Ueda et al. / Experimental Eye Research 89 (2009) 863–868864
0.8 s and 5 s intervals followed with late phase photographs ending
at 3 min.
When the photography was completed, tomograms of the
central retina were acquired digitally by the confocal, scanning
Heidelberg Engineering Retinal Tomograph (HRT). Each tomogram
consisted of 32 pooled confocal slices which stepped at 10 mm
increments into the z-axis of a 20?field which contained the blue
light exposure site, fovea and an edge of the optic disc for reference
purposes. When lesions were seen, z-axis profiles of the averaged
reflected light tomogram were taken through the lesion site to
evaluate fiber-layer height changes associated with lesions.
Lesion results were evaluated by an experienced observer at one
time without knowledge of the exposures. The late fluorescein
angiograms, fundus photographs and HRT lesion results for day 2
and 30 were rated as strong (þþ), mild (þ) and weak (?/þ). No
lesion was given a dash (?).
Eyes were from T69 and G81 (50 and 35.5 J/cm2). Enucleations
were done within 30 days (?24 h) of the exposure. Enucleations
were performed and a 3–4 mm slit made posterior to the ora
serrata. Ten ml 4% buffered paraformaldehyde was injected into the
mid vitreous which was slowly forced out the slit. Then the slit was
extended 3–5 mm and fixation was continued by immersion. After
fixation the posterior eye segment was flattened and samples for
histology were removed. Fixed tissue was dehydrated and infil-
trated with paraffin, blocked, and sections were cut perpendicular
to the fundus. After mounting and drying the sections were cover
slipped and microscopy was done with a Normarski optical system
providing interference contrast images.
2.5. Statistical analysis
with and without filter was performed using the Wilcoxon test.
P value was considered statistically significant when less than 0.05.
The color fundus photographs after 60 J/cm2exposure are
shown in Fig. 2 (monkey 8904). Arrows inserted into the images
show the general areawherethe exposures weremade. The color in
the lesion region was changed for the right eyes (no filter), but it
was not changed in the left eye (with filter) at 2 days and 30 days
(Fig. 2). After a 35 J/cm2exposure (monkey CA9V, not pictured),
a small and clearly present lightening of the exposure region was
observed at 2 days for the right eye (no filter). Avery mild change in
color in the lesion region is also present in the right eye at 30 days.
The left eye (with filter) showed an extremely subtle pigmentary
change in the general region of the lesion at two days. There is no
evidence of a lesion in the 30 days image.
The late fluorescein result of the 60 J/cm2exposure showed
regional hyperfluorescence equal to the lesion dimensions in the
righteye (no filter) at day 2 and30. The left eye (with filter)exposed
region, showed a clear fluorescence at two days and a minimal
fluorescent residual at 30 days (Fig. 3). At 35 J/cm2(monkey CA9V),
the fluorescein stain showed a faint but late fluorescence at 2 days
for the right eye (no filter). The fluorescent abnormality was not
observed in the 30 days image for the right eye (no filter). The
apparently exposed region was not observed for the left eye (with
filter) at 2 or 30 days after 35 J/cm2exposure.
The HRT images in Fig. 4 show the evidence of a lesion at two
days in the right eye (no filter) after 60 J/cm2exposure. The HRT in
right eye (no filter) showed surprisingly small change at 2 days, and
at 30 days. There was clear evidence of pigment migration in an
almost fully circular lesion. The left eye (with filter) response was
observed as a small, local change in reflectance at two days, which
was reduced in dimensions at 30 days (Fig. 4). The HRT evidence of
a lesion was not observed in the left eye (with filter) at two or 30
days after the exposure after a 35 J/cm2exposure.
Table 1 shows the ratings of the various signs of pathology. Signs
were rated as strong (þþ), mild (þ) and weak (?/þ). No lesion was
given a dash (?). Energy density was measured in the optical
pathway in the absence of the filter. The more strong damage was
Fig. 2. Color fundus images recorded digitally before and at 2 and 30 days following blue exposure. Right eye (OD) was exposed with no filter. Left eye (OS) was similarly exposed
with the blue-cut filter added (with filter). Fig. 2 exposure energy density was 60 J/cm2. Arrows indicate exposed area.
T. Ueda et al. / Experimental Eye Research 89 (2009) 863–868865
observed in the right eyes (without filter) compared to those in the
left eyes (with filter) (P < 0.001).
The histopathological results from the right eye (no filter) after
50 J/cm2exposure showed in Fig. 5. The panoramic center figure
shows a tissue region responding to the lesion on the left and
then fading into more normal tissue on the right. The lesion area
shows a partial loss of receptor outer segments and a reduction
in cone inner segment dimensions and little pigment remains in
the epithelium. These pathological changes correspond to the
regional area of hyperfluorescence at 30 days in both early
(choroidal or arterial phase) and late fluorescein angiograms.
However there was no visible change in the density of the layer of
Fig. 4. Retinal tomograms before and after exposure at 60 J/cm2, monkey 8904. Left optic pathway has the blue-cut filter. Otherwise as Fig. 2.
Fig. 3. Late fluorescein images (monkey 8904) produced after 60 J/cm2. OS pathway had the blue-cut filter. Otherwise as Fig. 2.
T. Ueda et al. / Experimental Eye Research 89 (2009) 863–868866
receptor cell nuclei. It seems likely that the degeneration of the
receptors would continue, if time had been extended. The bipolar
cell layer and ganglion cell layer characteristics are within normal
limits. Fig. 6 shows the results of the left eye (with filter) after the
50 J/cm2exposure. At a distance from the lesion area normal
receptor inner segments and outer segments are numerous
(Fig. 6). There is no clear evidence of alteration in the receptor cell
bodies. There were no clinically apparent changes in the eye (with
filter) at 30 days post exposure.
These data support the finding (Dawson et al., 2001) that the
primate macular blue-light lesion threshold is within about 0.5 log
units of 30 J/cm2. This data further establishes that in the presence
of a blue-cut filter the extent and duration of the lesions are
If the area of the normalized diode emission curve is multiplied
by the filters transmission curve between 410 and 540 nm, the
product allows for the calculation of the relative affect of the filter
on transmission from the diode. The calculated result indicates,
assuming a perfect optical system, an attenuation of 29% of the
diodes output. Multiple measurements by radiometer of the loss
produced by the filter in its optical system resulted in attenuation
estimates ranging from 32 to 35%. The action spectrum of retinal
phototoxicity increases logarithmically as the wavelength of irra-
diation decreases (Wolbarshtet al.,1980). So, exposurenear 410 nm
may contribute to injury of the retina. In this study, exposure time
and irradiant power were adjusted to provide a total exposure of
50 J/cm2. With the blue-cut filter present this exposure at
the cornea was reduced to 35.5 J/cm2, animal T69. At 2 days after
a 50 J/cm2exposure, the rate of fundus photograph: þ, the rate of
the late fluorescein angiogram: þþ and the rate of HRT lesion: þþ
in the right (no filter) were observed, and in the left eye (with filter)
Fig. 5. Photomicrograph of the right retina (no filter) after 50 J/cm2, monkey T69, at 30 days post exposure. The lesion area showed a partial loss of receptor outer segments and
there was a reduction in cone inner segment dimensions.
Fig. 6. Photomicrograph of the left retina (with filter) after 50 J/cm2, monkey 8904, at 30 days post exposure. There were no clinically apparent changes.
T. Ueda et al. / Experimental Eye Research 89 (2009) 863–868867
were ?, ? and þ/?, respectively. And at 30 days, the left eye Download full-text
Other authors have found early changes in the pigmented
epithelium and have generated threshold values. By using the
formula which was described by Lund et al. (2006), the retinal
irradiance (E) of the right eye, animal T69 at 465-nm is calculated.
E ¼ 4 ? T ? TIP/pd2, T is the transmittance through the ocular media
(0.69 for 457.9 nm, Ham et al.,1978), TIP is a total intraocular energy
(0.85 mW) and d is a retinal irradiance diameter (2.8 mm). E is
9.53 mW/cm2. And the exposure duration was 4154 s, so the esti-
mated the retinal total exposure was 39.6 J/cm2. Lund et al. (2006)
reported that E and TIP at the ED50for retinal alteration induced by
exposure to laser irradiation for 48-h minimum visible lesion
endpoint. When TIP was 0.61 mW at 457.9-nm, 327 mm: d, and the
exposure duration was 100 s, the total exposure was estimated
50 J/cm2. They also estimated assuming a non-thermal damage
mechanism at the 1 s, 327 mm, 441.6-nm ED50. Previously, Ham
et al. (1979) reported at 457.9-nm and 350 mm of the retinal irra-
diance diameter, and 100 s exposure, TIP was 0.74 mWand the total
exposure was 52 J/cm2. The maximum temperature above ambient
on the retina during irradiation, 1?, was calculated by the mathe-
matical model of Clarke et al. (1969). These data suggest that the
retinal damage in right eye of animal T69 was non-thermal
Morgan et al. (2008) described a novel retinalchange, a decrease
in the autofluorescence intensity with an adaptive optics scanning
laser ophthalmoscope (AOSLO) as a result of light exposure to the
retina. The threshold as defined by a funduscopically visible lesion
at 48 h after exposure (Ham et al., 1976; Lund et al., 2006) may be
re-estimate by using AOSLO.
In the human retina, documented lesions from solar radiation
range from the acute effects of sun-gazing to injuries resulting from
prolonged periods of exposure in brightly illuminated environ-
ments (Young,1988). However, cumulative UV-A or UV-B exposure
was not related to the development of visual loss from age-related
macular degeneration (AMD) (Taylor et al., 1992). Early-stage AMD
progression occurs more readily in patients who have undergone
cataract surgerycomparedwith those have not(Pollacket al.,1997).
It is well known that human lenses gradually transmit less short-
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that have undergone cataract extraction, short-wavelength irradi-
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cataract surgeons prefer blue light attenuating IOLs over conven-
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These results suggest that visible short-wavelength reducing
optical products improve human safety.
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