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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. 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