Download Dependency between light intensity and refractive development

Experimental Eye Research 92 (2011) 40e46
Contents lists available at ScienceDirect
Experimental Eye Research
journal homepage: www.elsevier.com/locate/yexer
Dependency between light intensity and refractive development under
lightedark cycles
Yuval Cohen*, Michael Belkin, Oren Yehezkel, Arieh S. Solomon, Uri Polat
Goldschleger Eye Research Institute, Tel Aviv University, 52621 Tel Hashomer, Israel
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 25 February 2010
Accepted in revised form 27 October 2010
Available online 3 November 2010
The emmetropization process involves fine-tuning the refractive state by altering the refractive
components toward zero refraction. In this study, we provided lightedark cycle conditions at several
intensities and examined the effect of light intensity on the progression of chicks’ emmetropization.
Chicks under high-, medium-, and low-light intensities (10,000, 500, and 50 lux, respectively) were
followed for 90 days by retinoscopy, keratometry, as well as ultrasound measurements.
Emmetropization was reached from days 30e50 and from days 50e60 for the low- and mediumintensity groups, respectively. On day 90, most chicks in the low-intensity group were myopic, with
a mean refraction of 2.41D (95% confidence interval (CI) 2.9 to 1.8D), whereas no chicks in the highintensity group developed myopia, but they exhibited a stable mean hyperopia of þ1.1D. The mediumintensity group had a mean refraction of þ0.03D. The low-intensity group had a deeper vitreous chamber
depth and a longer axial length compared with the high-intensity group, and shifted refraction to the
myopic side. The low-intensity group had a flatter corneal curvature, a deeper anterior chamber, and
a thinner lens compared with the high-intensity group, and shifted refraction to the hyperopic side. In all
groups the corneal power was correlated with the three examined levels of log light intensity for all
examined times (e.g., day 20 r ¼ 0.6 P < 0.0001, day 90 r ¼ 0.56 P < 0.0001). Thus, under lightedark
cycles, light intensity is an environmental factor that modulates the process of emmetropization, and the
low intensity of ambient light is a risk factor for developing myopia.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
myopia
hyperopia
emmetropization
light intensity
ambient light
1. Introduction
In newborns, most eyes are short in relation to their optic power,
resulting in hyperopic refraction in a non-accommodative state.
During ocular development, the rate of axial growth is matched to
the optical powers of the eye in a process known as emmetropization, resulting in the development of a near emmetropic
refractive error. Emmetropization includes an active process that is
regulated by visual feedback both from the eye’s refractive state
and the induced optical defocus (Norton and Siegwart, 1995;
Schaeffel et al., 1988; Smith, 1998; Wildsoet, 1997).
The emmetropization process and myopia development in
humans is both genetically and environmentally determined
(Dirani et al., 2006; Gottlieb et al., 1987; Hammond et al., 2001;
Lyhne et al., 2001; Mandel et al., 2008; Rose et al., 2008a, 2008b;
Sorsby, 1979). However, the rapid increase in the prevalence of
school myopia suggests strong environmental influences, such as
* Corresponding author. Tel.: þ972 3 5354481; fax: þ972 3 5351577.
E-mail address: [email protected] (Y. Cohen).
0014-4835/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.exer.2010.10.012
the burden of urbanization (Ip et al., 2008). Low exposure to
outdoor activates in a natural environment was found to be associated with higher rates of myopia in school children, which was
attributed to low exposure to the protective effect of higher light
intensities present outdoors (Ashby et al., 2009; Dirani et al., 2009;
Rose et al., 2008a, 2008b).
Light intensity was examined for its possible involvement in the
chicks’ emmetropization process (Ashby et al., 2009; Cohen et al.,
2008; Feldkaemper et al., 1999; Lauber and Kinnear, 1979). In
chicks, five days exposure to high-light intensity indoors retards
the development of deprivation myopia. Chicks that wore diffusers
continuously under high-light intensity had less myopic refractions
compared with chicks reared under normal light levels. However,
when chicks were exposed to low or medium ambient light
intensities, there was no statistically significant difference in
refraction of the form-deprived eyes (Ashby et al., 2009).
Short-term exposure to a low intensity of ambient light did not
induce changes in chicks’ refraction; however, mild myopia
developed when light intensity was reduced by a neutral density
filter (Feldkaemper et al., 1999). The optical imperfections of the
neutral density filter, rather than the critically low retinal image
Y. Cohen et al. / Experimental Eye Research 92 (2011) 40e46
brightness, were considered as the trigger for developing myopia
(Feldkaemper et al., 1999). Long-term exposure of chicks to varied
intensities of continuous light revealed a significant difference of
more than 10D between the high- to low-intensities (Cohen et al.,
2008). We hypothesize that light intensity might also be a covariant for developing refraction in chicks reared under lightedark
cycles if it is examined for longer periods.
Our aim was to examine the effect of ambient low-, medium-,
and high-light intensities of lightedark cycle on chicks’ emmetropization during the first 3-month post-hatching period.
2. Materials and methods
2.1. Animals and their rearing conditions
Forty newly hatched Rock male chicks were obtained from
a local hatchery and raised in continuously temperature-controlled
cages by means of air circulation and ventilation (days 1e7,
33 0.5 C; days 7e90, 23 1 C). The chicks were supplied with
food and water ad libitum and their weight was measured on days
10, 30, 60, 90. The experiment and animal handling were approved
by the Animal Welfare Commission of Tel Aviv University and was
in adherence with the ARVO Statement for the Use of Animals in
Ophthalmic and Vision Research. During the first 10 days after
hatching, the chicks were placed in a cage (120 60 60 cm) with
lighting according to a 12-h/12-h lightedark cycle with an intensity
of 500 lux. Ten days after hatching, the chicks were subjected to
baseline optical measurements, after which the chicks were
divided randomly into three groups and placed in 2.3 1.7 4-m
cages. The light duration was a 12-h/12-h lightedark cycle and it
was the same for all groups throughout the study; light was turned
off at 8:00 o’clock P.M.
During the light hours, the chicks were exposed to incandescent
light at three different levels of light intensity. Group 1 (highintensity, n ¼ 13) was raised under bright light with an intensity of
about 10,000 lux; group 2 (medium-intensity, n ¼ 14) was raised
under moderate lighting of about 500 lux; and group 3 (low
intensity, n ¼ 13) was raised under dim light with an intensity of
about 50 lux. After day 20, two chicks did not survive: one from the
low-intensity group, and the other from the high-intensity group.
The measurements were performed for both eyes.
The cages’ illumination was standardized to incandescent light
bulbs that were placed 2 m above the floor level, and light intensity
was measured at the center of the room at the floor level. The cages
of the low- and medium-intensity groups were illuminated with
one bulb of 5 W (OSRAM GmbH) and 40 W (Panasonic Corporation), respectively. The cage of the high-intensity group was illuminated with four 100-W (Panasonic Corporation) bulbs at each
corner, and one 300-W (Hyundai Light & Electric (HZ) Co. Ltd) bulb
at the center. Light intensity and the spectral compositions of the
emitted light were measured at floor level at the center of the cage,
using a calibrated Megatron spectroradiometer (Megatron, London,
UK), and an Ocean Optics spectrometer USB4000 XR-1 (Ocean
Optics, Inc.). The high-, medium-, and low-intensity groups were
exposed to light spectra of 280e1050; 620 nm, 300e1000; 580 nm,
and 450e950; 630 nm (range; peak), respectively. Illumination, as
a function of distance from the light source, was not equal across
the cage. We did not monitor the chicks’ movement across the cage;
thus, chicks located just under the bulb had greater radiance
exposure than a chick that had moved away from the bulb. We
reduced individual chicks’ exposure variance to light intensity by
placing the bulb at the center of the cage. The high-intensity light
used in this study is lower than outdoor levels (30,000e50,000 lux)
and its spectral makeup is different from daylight.
41
2.1.1. Optical measurements
In all three groups, optical measurements were carried out in
anesthetized chicks at 10, 20, 30, 50, 60, and 90 days after
hatching. Subcutaneous xylazine solution 2%, 5 mg/kg, and ketamine, 20 mg/kg, were administered as an anesthesia. Cycloplegic
ocular refraction was assessed using a Nikon Streak Retinoscope.
Binocular cycloplegia was induced with eye drops containing 0.1%
vecuronium bromide (Schwahn and Schaeffel, 1994). The refractive state was determined at a 66-cm working distance, the length
of the examiner’s arm, using lens bars to neutralize the two
principal meridians. Refraction was corrected for the measurement distance and was expressed as spherical equivalents
(sphere cylinder/2).
For keratometry, we used a calibrated JavaleSchiotz (HaagStreit) keratometer and calculated the mean of the two meridians.
Because the radius of the cornea of the newly hatched chick is
steep, we extended the measuring range of the instrument by
adding convex lenses (þ1.25 to þ6D). A correction for the true
radius of the cornea was made on the basis of measuring the
apparent radii of metal balls of known radii (range:
3.95e9.55 mm) through these convex lenses. The central 3-mm
anterior corneal radius is transformed to diopters and is presented
as corneal power.
For axial length, we measured by a calibrated Allergan Humphrey ultrasound biometer (model 820) operated in the manual
mode. Measurements of axial length were taken on days 10, 20, 30,
60, and 90. The mean of three to five measurements of axial length
was taken. On day 90 after hatching, we determined the means of
3e5 in-vivo measurements of the vitreous chamber depth, the
anterior chamber depth, and the lens thickness using an A-mode
ultrasound device (EchoScan US-1800; Nidek, Fremont, CA).
We used a 10 MH-z solid transducer for both devises (sonic
velocity at 1550 m/s). The Ecoscan US-1800 was selected for
measuring anterior and posterior segments since it was proven to
be reliable. It presents the vitreous chamber depth digitally and
simplifies the recording of measurements (Hashemi et al., 2005).
An ultrasound pachymeter (Paxis; Biovision) was used for
measuring corneal thickness. The mean limbus-to-limbus corneal
diameter along the 180 and 90 meridians was calculated from
measurements made on day 90, using a calibrated manual
micrometer.
Following the optical and ultrasound examinations, the chicks
were euthanized with pentobarbitone sodium (60 mg/kg, i.v.).
Their eyes were enucleated and the equatorial diameter was
measured immediately afterwards, using a calibrated micrometer,
and the average values of the horizontal and vertical meridians
were calculated.
3. Data analyses
Data are reported as means SD. Refraction’s confidence
interval (CI) was calculated for each group at each measurement
time, and used for the assessment of time to emmetropia. Means of
the optical measurements of the eyes and ocular components were
evaluated for each group and compared between the groups by
one-way analysis of variance (ANOVA). Post-hoc pair-wise multiple
comparisons were made using Dunnett’s t-test for unequal variances. The multiple repeat designs ANOVA, and the dependent ttest were used to compare the measurements within the groups.
Pearson analysis was used to correlate refraction, corneal power
and log light-intensity exposure. For statistical analysis of the
results, we used the SigmaStat program (version 18, SPSS, Inc.,
Chicago, IL). Differences of P < 0.05 were considered statistically
significant.
42
Y. Cohen et al. / Experimental Eye Research 92 (2011) 40e46
4. Results
greatly declined in all measurements, on days 10e20, days 20e30,
days 30e50, days 50e60, and days 60e90 (paired t-test, P < 0.0001,
0.01, 0.0001, 0.0001, 0.01, respectively). Three chicks (6 from 28
eyes) developed myopia with a maximal value of 1.2D on day 90.
The low-intensity group reached emmetropia between day 30
(þ1.3 0.3D) and day 50 (þ0.5 0.4D), with a mean refraction of
2.4D on day 90 (CI: 2.9 to 1.8).
The changes in refraction between the days: 10e30 (period 1),
30e60 (period 2), and 60e90 (period 3) are depicted in Fig. 1d. The
low-intensity group was the only group that did not show signs of
declining with respect to the change in refraction; this was noted
during the measurement periods. The change in refraction is the
first parameter that helps predict further changes in refraction. The
second parameter, which can assist in predicting further changes
in refraction, is the change in the variability of the intragroup
refraction. This change is tantamount to the standard deviation
of refraction. Until day 50, the calculated variability of the intragroup refraction in all groups ranged from 0.2 to 0.5. From day 50
onwards, the low-intensity group’s intragroup refraction variability
increased, whereas that of the high-intensity group decreased.
Thus, both the variability in refraction and the previous changes in
refraction can facilitate in predicting further changes regarding the
refraction of the groups.
4.1. Refraction
In emmetropia the refraction values ranged from þ1D to
0.25D, as is defined in humans (Zadnik et al., 2004). We measured
the time to emmetropia, when at least 95% of the chicks’ eyes had
a refraction value between þ1 and 0.25D. The refraction’s confidence interval (CI) was used to evaluate whether emmetropia was
reached and to measure the time to emmetropia. The mean baseline refraction of all chicks on day 10 was þ4.15 0.77D (CI:
3.9e4.3); thereafter, the mean refraction of all groups gradually
declined (Fig. 1aed, Table 1).
The changes in individual ocular refraction, as a function of time,
for each group, are presented in Fig. 1aec. A significant decline in the
hyperopic refraction of the highest-intensity group was noted until
day 60 (Multiple repeat designs ANOVA, P < 0.0001). The refraction
on day 90 did not change much from day 60 (dependent t-test for
days 60 and 90, P ¼ 0.68) and was mildly hyperopic, with a mean
refraction of þ1.1D (CI: þ1.1 to þ1.2D). The medium-intensity group
reached emmetropia on days 50e60, with a mean refraction on day
60 of þ0.4D (CI: þ0.3 to þ0.6D) and it remained emmetropic on day
90 (CI: 0.2 to þ0.3D). The refraction of the medium-intensity group
High-intensity group
6
d
5
6
4
Refraction (D)
2
4
1
0
-1
10
20
30
40
50
60
70
80
90
2
Refraction (D)
-3
-4
-5
Day of examination
-6
Refraction (D)
3
100
-2
b
High-intensity group
Medium-intensity group
Low-intensity group
5
3
Medium-intensity group
6
1
0
10
20
30
40
50
60
70
80
5
4
-2
3
-3
Day of examination
2
0
-1
0.5
-4
1
N=
10
20
30
40
50
60
70
80
90
90
-1
13
14
13
12
14
12
12
14
12
100
0.25
0
-2
-3
-0.25
-4
-0.5
-5
Day of examination
-6
c
-0.75
Low-intensity group
6
-1
High-intensity group
Medium-intensity group
Low-intensity group
5
4
Refraction (D)
3
Change in refraction
per 10 days (D)
a
-1.25
-1.5
2
days 10 to 30
1
0
-1
10
20
30
40
50
60
70
80
90
100
days 30 to 60
days 60 to 90
Examined period
-2
-3
-4
-5
-6
Day of examination
Fig. 1. Refraction throughout the examined period. Individual ocular refraction as a function of time for each group is presented in Fig. 1aec. Refractive measurements are presented
as spherical equivalent and are denoted as a (B) e non-filled circle, the individual refraction of each chick was connected with a solid black line to the corresponding consecutive
measurement. Fig. 1d (Top) Mean ocular refraction, mean SD through the examined period for the three groups. Third-order polynominals were used to fit lines to the data points.
The change in refraction per 10 days at three examined period is presented in the lower part of Fig. 1d. Data columns represent the means SD (bars). The changes in refraction
gradually decline in the high- and intermediate-intensity groups. However, the low-intensity group had no reduction in refraction change throughout the examined periods. N e
number of chicks.
Y. Cohen et al. / Experimental Eye Research 92 (2011) 40e46
The Pearson correlation test, used for assessing the refraction of
all groups regarding the three log light-intensity levels examined,
revealed strong correlations for all the examined times. The
correlations were r ¼ 0.58 (P < 0.0001), 0.63 (P < 0.0001), 0.64
(P < 0.0001), 0.71 (P < 0.0001), 0.88 (P < 0.0001) for days 20, 30, 50,
60, and 90, respectively.
4.2. Keratometry
The mean corneal power values (Fig. 2, Table 1) of the low-,
medium-, and high-intensity groups on day 10 were about the
same: 102.9 1.8D, 103.3 2.6D, and 102.4 2.4D, respectively
(One-way ANOVA, P ¼ 0.35). The rate of decline in corneal power
from days 10e90 differed among the groups. The low-intensity
group had flatter corneas than the medium- and high-intensity
groups had, as measured on day 20. The corneal power values of the
low-, medium-, and high-intensity groups were 84.5 2.1D,
86.7 1.4D, and 88 1.8D, respectively (One-way ANOVA,
P < 0.0001, Post-hoc tests, P < 0.0001, P < 0.0001, P < 0.018 for low
to medium, low to high, and medium to high, respectively). Even
though the corneal power declined faster during the period first
measured (the decline was 4 times faster from days 10e30, as
compared with the period from days 60e90), the difference
between the low- and the high-intensity groups in terms of corneal
power was steady (w3D) throughout the examined period. The
Pearson correlation test revealed strong-to-moderate correlations
for all the examined times. The correlations were r ¼ 0.60
(P < 0.0001), 0.40 (P < 0.0001), 0.52 (P < 0.0001), 0.53 (P < 0.0001),
0.56 (P < 0.0001) for days 20, 30, 50, 60, and 90, respectively.
4.3. Other corneal parameters
Corneal thickness values (Table 2), measured on day 90 by
ultrasound pachymetry, were 259.2 12.4, 241.8 11.2, and
233.7 8.7 mm for the high-, medium-, and low-intensity groups,
respectively (One-way ANOVA, P < 0.0001). The mean limbus-tolimbus corneal diameter (Table 2) did not differ among the groups
(One-way ANOVA, P ¼ 0.26).
4.4. Ultrasound and micrometer measurements
The mean axial length (Table 1) was 9.4 0.3 mm on day 10 and
did not differ between the groups (One-way ANOVA, P ¼ 0.27). The
low-intensity group had the longest axial length, noted on day 20,
and it was 0.7 mm greater than that of the high-intensity group on
day 90 (Independent t-test, P ¼ 0.013, and 0.005 for days 20 and 90,
respectively). The equatorial diameter (Table 2) was 0.6 mm longer
in the low-intensity group than in the medium- and high-intensity
groups (Independent t-test, 0.02, 0.006, respectively).
The myopia of the low-intensity group is attributed to the
deepening of the vitreous chamber. The median value of the
vitreous chamber depth (VCD) in all groups on day 90 was 9.5 mm.
Interestingly, ninety percent of the low-intensity group had greater
VCD values. However, lens thinning, corneal curvature, and the
anterior chamber depth (ACD) counteracted and reduced the
severity of the myopia in the low-intensity group. The median value
of lens thickness in all groups on day 90 was 3.35 mm and 84% of
the eyes in the low-intensity group had thinner lenses. For
example, the cornea was 3D flatter in the low-intensity group than
in the high-intensity group. The median value of ACD for all groups
on day 90 was 2.8 mm. The ACD of the low-intensity group was
found to be deeper than that of the high-intensity group, and 68% of
the low-intensity group had an anterior chamber that was deeper
than 2.8 mm.
43
4.5. Body weight
The mean body weights in the groups were not affected by light
intensity (Table 1), and on day 90 all chicks had gained comparable
body masses that were 3381, 3330, and 3248 g for the low-,
medium-, and high-intensity groups, respectively (One-way
ANOVA, P ¼ 0.365).
5. Discussion
In the present study, we examined how diurnal cycles of light
intensity affect chicks’ ocular parameters and refraction. According
to our results, diurnal cycles of light intensity under play a major
role in modulating refraction, corneal curvature and thickness, ACD,
lens thickness, vitreous chamber depth, and axial length
throughout the emmetropization process. Thus, low-light intensity
is an environmental risk factor for the development of myopia in
chicks. The effects of medium-light intensity should be further
evaluated for its potential to create a myopogenic effect.
In chicks, at hatching the vast majority of their eyes are hyperopic (Wallman et al., 1981). During the emmetropization process of
chicks reared under lightedark cycles, the postnatal hyperopic
refraction is reduced to emmetropia within 8 weeks (Wallman
et al., 1981). However, in our study we showed that the time to
reach emmetropia in chicks reared under diurnal lightedark cycles
and with undisturbed form vision was dependent on the light
intensity. For example, under low-light intensity conditions,
emmetropia was achieved within 30e50 days and then it progressed toward myopia. Under medium-light intensity conditions,
however, the emmetropization process took longer and lasted more
than 50 days. Moreover, the high-intensity group did not reach
emmetropia at all, and the refraction remained on the hyperopic
side even after 90 days. The emmetropization process thus seems to
be environmentally guided by ambient light intensity.
The oldest study that examined the effect of dim light measured
an increase in equatorial diameter and eye weight when compared
to that of bright light (Lauber and Kinnear, 1979). In our study we
added the long-term effect of dim light intensity on refraction, and
showed that dim light is a risk factor to myopia. Dim light-induced
myopia in over 90% of the chicks, but the effect was heterogeneous
with one chick remaining emmetropic. Myopia of dim light is
a slow process, spanning 50e60 days, as compared with extreme
myopia, which develops within days when the chicks are formdeprived (Irving et al., 1992; Stone et al., 1995). Thus, apparently
dim light is a mild inducer of myopia when compared with form
deprivation.
Twenty-one percent of the chicks from the medium-light
intensity group were myopic on day 90, and their exposure to
indoor light intensity induced a large decrease in refraction even at
the end of the experiment. Apparently this decrease in refraction is
continuous and a greater number of myopic chicks may be found
for longer experimental periods. Previous emmetropization studies
examining chicks reared under medium-light intensity ended with
different results. Chicks’ emmetropization measured at the age of
80 days post-hatching revealed a mean refraction of 2.8D; however,
in that study fluorescent light was used with a light intensity of
700 lux (Li et al., 1995). In another study, chicks reared for 7 weeks
under a light source of combined fluorescent and incandescent
lamps, with a light intensity of 700 lux, had a refraction of þ2.8D
and þ3D in the chicks’ K strain and H/N strain, respectively (Troilo
et al., 1995). Wallman et al. (1981) measured refraction in the range
of 0 to þ1D in 8-week old chicks reared under room light. The
differences in refraction found in different experimental conditions
may be partially attributed to the age of the animals, to the type of
illumination used, i.e., incandescent vs. fluorescent lighting, and to
44
Y. Cohen et al. / Experimental Eye Research 92 (2011) 40e46
b
110
High intensity group: 10 000 lux
105
Medium intensity group: 500 lux
100
Low intensity group: 50 lx
Anterior corneal power (D)
A n ter io r co rn eal p o w er (D )
a
95
90
85
80
80
High intensity group: 10 000 lux
Medium intensity group: 500 lux
75
Low intensity group: 50 lx
70
65
60
55
75
10
20
50
30
Day of examination
c
90
Examined period
days 10 to 30
Change in anterior corneal power
/ 10 da ys
60
Day of examination
days 30 to 60
0
-1
-2
-3
-4
-5
-6
-7
-8
-9
days 60 to 90
High intensity group: 10000 lux
Medium intensity group: 500 lux
Low intensity group: 50 lux
Fig. 2. Corneal power of the three groups. Anterior corneal power of the three groups as a function of time is presented in Fig. 2a. Data columns represent the means SE (bars). The
corneal power was steeper as light intensity was increased; however, the difference between the high- to low-intensity groups remained relatively constant throughout the
examined periods. Change in Corneal power per 10 days of the groups during three examined periods is presented in Fig. 2c. Data columns represent the means SE (bars).
Between days 10e30, the change in corneal power was greater in the low-intensity group then the high-intensity group (independent t-test, P ¼ 0.037). However, between days
30e60, and days 60e90 the change in corneal power did not differ between the groups (independent t-test, P ¼ 0.09, and 0.68, respectively). N e number of chicks.
strain differences. Thus, we think that an indoor light intensity of
500 lux is insufficient to prevent the evolution of myopia.
During the normal emmetropization process, the intragroup
variability of refraction was shown to decrease while refraction
approaches zero (Wallman et al., 1981). However, according to our
data, the intragroup variability and the change in refraction during
the chicks’ growth behaved different in each group depending on
light intensity. We showed that under dim lighting conditions, the
emmetropization process becomes less accurate and hence displays
larger variance than under brighter lighting condition. Low intensity of light appears to uncover the individual chicks’ sensitivity to
the effect of light intensity.
We showed that the higher the light intensity, the greater the
refractive power of the cornea and the lens, resulting from steepening of the corneal curvature and thickening of the lens. Light
intensity dependent modulation of corneal curvature occurred at
Table 1
Refraction, corneal curvature, axial length and body weight measurements. The table presents the mean SD for the refraction, corneal curvature, axial length and chicks’ body
weight of all groups throughout the examined period. Post-hoc tests were examined for the differences among the groups; a significance of P < 0.05 was denoted as (1), (2), and
(3) for high-intensity vs. medium-intensity groups, medium-intensity vs. low-intensity groups, and low-intensity vs. high-intensity groups, respectively. NA e not available.
Low: low-intensity group, Medium: medium-intensity group, High: high-intensity group.
Measurements
Measurement day
10
Refraction (D)
Low
Medium
High
Corneal curvature (D)
Low
Medium
High
Axial length (mm)
Low
Medium
High
Body weight (g)
Low
Medium
High
20
4 0.2
4.1 0.5
4.2 0.2
102.9 1.8
103.3 2.6
102.4 2.2
9.4 0.3
9.3 0.3
9.4 0.3
147 7
141 7.6
142 12
30
50
60
90
1.5 0.4(1)
1.8 0.2(2)
2.1 0.2(3)
1.3 0.3(1)
1.6 0.3(2)
2.1 0.3(3)
0.5 0.4(1)
1.2 0.3
1.4 0.4(3)
0.2 0.8(1)
0.4 0.3(2)
1.1 0.1(3)
2.4 1.2(1)
0.03 0.5(2)
1.1 0.2(3)
84.5 0.4(1)
86.7 0.2(2)
88 0.3(3)
77.3 1.8(1)
78.5 1.4
79.3 2.1(3)
71.7 2(1)
73.5 2
74.5 1.2(3)
65.3 2(1)
66.9 1.6(2)
68.2 1.5(3)
59.9 1.9(1)
61.8 1.8
62.8 1.3(3)
11.4 0.1
11.4 0.1
11.3 0.1
12.3 0.3
12.2 0.2
11.9 0.2(3)
NA
14.6 0.4
14.4 0.5
14.3 0.3(3)
16.2 0.5(1)
15.6 0.4
15.5 0.4(3)
NA
917 85
910 109
879 88
NA
2324 149
2343 205
2253 166
3381 216
3330 232
3248 218
Y. Cohen et al. / Experimental Eye Research 92 (2011) 40e46
45
Table 2
In-vivo ultrasound and Ex-vivo micrometer measurements on day 90. Post-hoc tests were examined for the differences among the groups; a significance of P < 0.05 was denoted
as (1), (2), and (3) for high-intensity vs. medium-intensity groups, medium-intensity vs. low-intensity groups, and low-intensity vs. high-intensity groups, respectively. In-vivoy;
Ex-vivoz.
Groups
High-intensity group (10,000 lux)
Medium-intensity group (500 lux)
Low-intensity group (50 lux)
Number of examined eyes
24
28
24
Corneal thicknessy (mm)
Lens thicknessy (mm)
Anterior chamber depthy (mm)
Vitreous chamber depthy (mm)
Limbus-to-limbus corneal diametery (mm)
Equatorial diameterz (mm)
233.7
3.44
2.72
9.33
9.9
21.15
1.7
0.02(1)
0.4
0.1
0.35
0.7
the first month post-hatching. Ashby et al. (2009) reported no
changes in the corneal radius of curvature in chicks exposed to
high-light levels over a period of four days under lightedark cyclic
conditions compared with those chicks exposed to either medium
or low intensities (Ashby et al., 2009). Further, Blatchford et al.
(2009) also reported no changes in corneal radius among chicks
raised for 5 weeks under one of the three lighting conditions (5, 50,
200 lux) under a photoperiod of 16 light: 8 dark hours. The corneal
radius measurements in the latter study were performed ex-vivo
after fixation with formalin (Blatchford et al., 2009). We suggest
that the differences in the observations between the studies could
be partially attributed to the duration of the experiment, light
intensity differences between the groups, and the method used for
measuring corneal power.
The chick’s neural retina contains a complete circadian clockwork system that is regulated by the lightedark cycle, and is
partially affected by dopamine, which was shown to be involved in
controlling the chicks’ ocular growth and changes in axial length.
The levels of retinal dopamine and vitreal dopamine derivative
drop during the development of form deprivation myopia (Iuvone
et al., 1989; Stone et al., 1989). The development of form deprivation myopia can be prevented either by intraviteal injection of
dopamine agonists or by light-induced dopamine release
(McCarthy et al., 2007; Stone et al., 1989). Dopamine release was
shown to be dependent on light intensity and dopamine antagonists can prevent the ability of high-light levels to retard the
development of deprivation myopia (Ashby et al., 2009; Ashby and
Schaeffel, 2010). Thus, light can affect the expression of specific
neuromodulators proposed to be involved in the regulation of
ocular growth.
An intriguing question is, whether these results from chickens
are applicable to human myopia? Light intensity-related environmental factors were shown to affect human myopia prevalence,
specifically the time spent outdoors and the season of birth. In
school children, a greater period of time spent outdoors was
associated with a reduced risk of developing myopia; this was
partially attributed to the effect of exposure to higher light intensities (Ashby et al., 2009; Dirani et al., 2009; Rose et al., 2008a,
2008b). The season of birth was found to be associated with
refraction changes (Mandel et al., 2008), and it was suggested that
the seasonal effect on refraction might represent a complex effect of
light intensity and light duration (McMahon et al., 2009).
In conclusion, under lightedark cycle conditions, dim ambient
light is a risk factor for developing myopia in chicks and bright light
is a risk factor for hyperopia. The time to reach emmetropia and the
emmetropization process in chicks is possibly modulated by
ambient light intensity. Lighting conditions should be strictly
controlled when examining chicks’ ocular development, thus preventing artifactual induction of myopia by low-intensity laboratory
light. The length of such experiments should be extended in order
to further study the effect of medium- and low-intensity groups.
241.8
3.34
2.83
9.44
9.8
21.16
2.1(1)
0.02
0.4(2)
0.1(2)
0.19
0.45(2)
259.2
3.26
2.93
10.07
9.9
21.75
2.5(3)
0.02(3)
0.7(3)
0.1(3)
0.25
0.55(3)
ANOVA P-value
<0.0001
<0.0001
0.03
<0.0001
0.26
0.006
References
Ashby, R., Ohlendorf, A., Schaeffel, F., 2009. The effect of ambient illuminance on the
development of deprivation myopia in chicks. Invest. Ophthalmol. Vis. Sci. 50,
5348e5354.
Ashby, R.S., Schaeffel, F., 2010. The effect of bright light on lens-compensation in
chicks. Invest. Ophthalmol. Vis. Sci. Epub ahead Print.
Blatchford, R.A., Klasing, K.C., Shivaprasad, H.L., Wakenell, P.S., Archer, G.S.,
Mench, J.A., 2009. The effect of light intensity on the behavior, eye and leg
health, and immune function of broiler chickens. Poult. Sci. 88, 20e28.
Cohen, Y., Belkin, M., Yehezkel, O., Avni, I., Polat, U., 2008. Light intensity modulates
corneal power and refraction in the chick eye exposed to continuous light. Vis.
Res. 48, 2329e2335.
Dirani, M., Chamberlain, M., Garoufalis, P., Chen, C., Guymer, R.H., Baird, P.N., 2006.
Refractive errors in twin studies. Twin Res. Hum. Genet. 9, 566e572.
Dirani, M., Tong, L., Gazzard, G., Zhang, X., Chia, A., Young, T.L., Rose, K.A.,
Mitchell, P.R., Saw, S.M., 2009. Outdoor activity and myopia in Singapore
teenage children. Br. J. Ophthalmol. 93, 997e1000.
Feldkaemper, M., Diether, S., Kleine, G., Schaeffel, F., 1999. Interactions of spatial and
luminance information in the retina of chickens during myopia development.
Exp. Eye Res. 68, 105e115.
Gottlieb, M.D., Fugate-Wentzek, L.A., Wallman, J., 1987. Different visual deprivations
produce different ametropias and different eye shapes. Invest. Ophthalmol. Vis.
Sci. 28, 1225e1235.
Hammond, C.J., Snieder, H., Gilbert, C.E., Spector, T.D., 2001. Genes and environment
in refractive error: the twin eye study. Invest. Ophthalmol. Vis. Sci. 42,
1232e1236.
Hashemi, H., Yazdani, K., Mehravaran, S., Fotouhi, A., 2005. Anterior chamber depth
measurement with a-scan ultrasonography, Orbscan II, and IOLMaster. Optom.
Vis. Sci. 82, 900e904.
Ip, J.M., Rose, K.A., Morgan, I.G., Burlutsky, G., Mitchell, P., 2008. Myopia and the
urban environment: findings in a sample of 12-year-old Australian school
children. Invest. Ophthalmol. Vis. Sci. 49, 3858e3863.
Irving, E.L., Sivak, J.G., Callender, M.G., 1992. Refractive plasticity of the developing
chick eye. Ophthalmic Physiol. Opt. 12, 448e456.
Iuvone, P.M., Tigges, M., Fernandes, A., Tigges, J., 1989. Dopamine synthesis and
metabolism in rhesus monkey retina: development, aging, and the effects of
monocular visual deprivation. Vis. Neurosci. 2, 465e471.
Lauber, J.K., Kinnear, A., 1979. Eye enlargement in birds induced by dim light. Can. J.
Ophthalmol. 14, 265e269.
Li, T., Troilo, D., Glasser, A., Howland, H.C., 1995. Constant light produces severe
corneal flattening and hyperopia in chickens. Vis. Res. 35, 1203e1209.
Lyhne, N., Sjolie, A.K., Kyvik, K.O., Green, A., 2001. The importance of genes and
environment for ocular refraction and its determiners: a population based
study among 20e45 year old twins. Br. J. Ophthalmol. 85, 1470e1476.
Mandel, Y., Grotto, I., El-Yaniv, R., Belkin, M., Israeli, E., Polat, U., Bartov, E., 2008.
Season of birth, natural light, and myopia. Ophthalmology 115, 686e692.
McCarthy, C.S., Megaw, P., Devadas, M., Morgan, I.G., 2007. Dopaminergic agents
affect the ability of brief periods of normal vision to prevent form-deprivation
myopia. Exp. Eye Res. 84, 100e107.
McMahon, G., Zayats, T., Chen, Y.P., Prashar, A., Williams, C., Guggenheim, J.A., 2009.
Season of birth, daylight hours at birth, and high myopia. Ophthalmology 116,
468e473.
Norton, T.T., Siegwart Jr., J.T., 1995. Animal models of emmetropization: matching
axial length to the focal plane. J. Am. Optom. Assoc. 66, 405e414.
Rose, K.A., Morgan, I.G., Ip, J., Kifley, A., Huynh, S., Smith, W., Mitchell, P., 2008a.
Outdoor activity reduces the prevalence of myopia in children. Ophthalmology
115, 1279e1285.
Rose, K.A., Morgan, I.G., Smith, W., Burlutsky, G., Mitchell, P., Saw, S.M., 2008b.
Myopia, lifestyle, and schooling in students of Chinese ethnicity in Singapore
and Sydney. Arch. Ophthalmol. 126, 527e530.
Schaeffel, F., Glasser, A., Howland, H.C., 1988. Accommodation, refractive error and
eye growth in chickens. Vis. Res. 28, 639e657.
Schwahn, H.N., Schaeffel, F., 1994. Chick eyes under cycloplegia compensate for
spectacle lenses despite six-hydroxy dopamine treatment. Invest. Ophthalmol.
Vis. Sci. 35, 3516e3524.
46
Y. Cohen et al. / Experimental Eye Research 92 (2011) 40e46
Smith 3rd, E.L., 1998. Spectacle lenses and emmetropization: the role of optical
defocus in regulating ocular development. Optom. Vis. Sci. 75, 388e398.
Sorsby, A., 1979. In: Duene, T.D. (Ed.), Clinical Ophthalmology. Harper & Row,
Philadelphia, pp. 1e17.
Stone, R.A., Lin, T., Desai, D., Capehart, C., 1995. Photoperiod, early post- natal eye
growth, and visual deprivation. Vis. Res. 35, 1195e1202.
Stone, R.A., Lin, T., Laties, A.M., Iuvone, P.M., 1989. Retinal dopamine and formdeprivation myopia. Proc. Natl. Acad. Sci. USA 86, 704e706.
Troilo, D., Li, T., Glasser, A., Howland, H.C., 1995. Differences in eye growth and the
response to visual deprivation in different strains of chicken. Vis. Res. 35,1211e1216.
Wallman, J., Adams, J.I., Trachtman, J.N., 1981. The eyes of young chickens grow
toward emmetropia. Invest. Ophthalmol. Vis. Sci. 20, 557e561.
Wildsoet, C.F., 1997. Active emmetropizationeevidence for its existence and ramifications for clinical practice. Ophthalmic Physiol. Opt. 17, 279e290.
Zadnik, K., Mutti, D.O., Mitchell, G.L., Jones, L.A., Burr, D., Moeschberger, M.L., 2004.
Normal eye growth in emmetropic schoolchildren. Optom. Vis. Sci. 81, 819e828.