Thickened Photoreceptor Outer Segment Layer in Children with Hyperopic Anisometropic Amblyopia

Thickened Photoreceptor Outer Segment Layer in Children with Hyperopic Anisometropic Amblyopia | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Thickened Photoreceptor Outer Segment Layer in Children with Hyperopic Anisometropic Amblyopia Wenli Zhang, Fan Yang, Shirong Chen, Tingkun Shi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4178975/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose To quantitatively investigate the reflectivity and structure of the outer retinal layers in children with hyperopic anisometropic amblyopia using swept-source optical coherence tomography (SS-OCT). Methods Seventy-eight patients with amblyopia and 64 age-matched children with normal vision were included in this study. All participants underwent SS-OCT and detailed ophthalmic examinations. Longitudinal reflectance profile measurements (LRP) were measured by Image J. The reflectivity of outer retinal layers was measured at the three selected positions: subfovea, 1 mm nasal to the fovea and 1 mm temporal to the fovea. The reflectivity ratios were calculated by outer retinal layers divided by the nuclear layer (ONL) for normalization. Photoreceptor outer segment layer thickness was also measured. The results were compared between the amblyopia and normal controls. The possible effects of age, sex and axial length on results were adjusted by generalized estimating equations (GEE). Results Photoreceptor outer segment layer thickness was significantly greater in amblyopic eyes than in normal control eyes at all three regions (18.41 ± 1.83 vs 16.84 ± 1.39, p < 0.001 at fovea; 14.78 ± 1.34 vs 14.19 ± 1.40, p = 0.030 at 1mm nasal to the foveal; 14.92 ± 1.48 vs 14.41 ± 1.32, p = 0.049 at 1mm temporal to the fovea). The reflectivity ratio of outer segment/ONL was higher only at 1mm nasal to the fovea (2.94 ± 0.61 vs 2.70 ± 0.42, p = 0.02). Subfoveal OS thickness was positively correlated with choroidal thickness (r = 0.248, p = 0.018), but was not correlated with spherical equivalent, age, axial length or LogMAR visual acuity. Conclusions Quantitative measurement of SS-OCT images revealed that greater photoreceptor outer segment in both eyes of children with amblyopia than in normal control eyes. A thicker OS thickness is somehow related to amblyopia, and this may be a new useful diagnostic parameter for amblyopia. Hyperopic anisometropic amblyopia Photoreceptor outer segment Optical coherence tomography reflectivity choroidal thickness Figures Figure 1 Figure 2 Introduction Amblyopia is a developmental visual disorder in the eye characterised by decreased vision, which cannot be immediately improved by refractive correction and has no obvious structural abnormality. The common causes of amblyopia include strabismus, anisometropia and form deprivation. Results from human and animal studies indicated that each of these causes exerts a functional or morphologic effect on the visual cortex and lateral geniculate nucleus [ 1 – 3 ] . Possible structural changes compared with normal eyes have been reported, since the advent of optical coherence tomography, including differences in macular thickness, retinal nerve fibre layer, and individual retinal layers [ 4 – 6 ] . Nonetheless reports have shown discordant results. Nishi et al. [ 7 ] found that the length of the photoreceptor outer segment (OS) was significantly thinner in amblyopic eyes than in fellow eyes although relatively small sample size. Nishikawa et al. found that there were no significant differences in outer retinal layer thickness values between amblyopic eyes and fellow eyes, except that the parafoveal outer segment photoreceptor/retinal pigment epithelium complex thickness was significantly greater in the fellow eyes [ 8 ] . It was also reported that the bulge of the foveal ellipsoid zone (EZ) was frequently absent and the reflectivity of the EZ was lower in amblyopic eyes compared with normal eyes [ 9 ] . However, the change of reflectivity reported in the literature was only an observation and has not been quantitatively studied, in addition, the thickness of each retinal layer is measured manually, and there is the possibility of measurement error. Therefore, the purpose of this study was to investigate quantitatively the reflectivity and other morphological changes of the photoreceptors in patients with unilateral amblyopia using the longitudinal-reflectance-profile (LRP) on OCT images, and to compare these findings with normal fellow eyes. Methods Patients and controls A cross-sectional comparative study was designed involving patients with hyperopic anisometropic amblyopia who visited the tertiary hospital from November 2020 to December 2022. This study adhered to the tenets of the Declaration of Helsinki and was approved by the institution ethics committee board. Written informed consent was obtained from the parents or legal guardians of all participants prior to recruitment. All the recruited patients had an age range of 5–15 years and were diagnosed with hyperopic anisometropic amblyopia. Comprehensive ophthalmic examinations were conducted in all patients, including best corrected visual acuity (BCVA), intraocular pressure (IOP), cycloplegic refraction, axial length (AL), slit lamp microscopy and dilated fundoscopy. BCVA was measured using a standard logarithmic decimal chart, and decimal BCVA was converted into the logMAR value for further analysis. Refraction was measured using Topcon K-800 (Tokyo, Japan). The AL and corneal curvature were measured with an IOL-Master (Carl Zeiss Meditec, Germany). Anisometropic amblyopia was defined as a 2.0 D or more difference in spherical equivalent refractive error between two eyes and eyes with BCVA of 0.6 or worse in the amblyopic eye and 1.0 or better in the fellow eye. There should have been no prior spectacle wear or other treatment for amblyopia. Patients with any identifiable organic lesions accounting for decreased vision, history of intraocular surgery, history of ocular trauma, cataract, glaucoma, uveitis, premature infants, or any other retinal diseases were excluded. Microtropia or strabismic amblyopia were also excluded. The control group was composed of age-matched subjects whose spherical equivalent less than − 1 D and BCVA were equal to or better than 1.0 in both eyes. The right eye of the controls was included in the study. Measurement of choroidal thickness All eyes were scanned with swept-source optical coherence tomography (SS-OCT) (Triton DRI-OCT; Topcon, Japan; wavelength: 1050 nm). The SS-OCT provides 100000 A scans/second according to a protocol of 12 mm line scan with an average of 128 consecutive, overlapping single B-scan OCT images. Eye traction was used to obtain each section. The line scan was made horizontally across the fovea. We recognised the fovea according to the centre of the vessel-free region on the fundus photograph during scanning and the area absent of inner retinal layers on the OCT. Any image quality scores lower than 60 (range 0–100) obtained using software for each volumetric OCT scan were excluded. Other significant image artefacts were excluded from analysis as we previously reported [ 10 ] . Choroidal thickness (CT) was measured between the outer border of the retinal pigment epithelial and the inner sclera surface. Two independent investigators (T. S. and W. Z.) who were masked to the diagnosis and other clinical information measured the CTs. The mean values were used for the final analysis. Interobserver reproducibility analysis of the measurements was performed using an intraclass correlation coefficient. Longitudinal reflectance profile measurements The horizontal and vertical B-scans across the fovea were exported from SS-OCT as grayscale JPEG images. The LRP measurement protocol was adopted using ImageJ software (National Institutes of Health, Bethesda, MD), as we previously reported [ 10 , 11 ] . Each layer of retinal reflectance was automatically calculated using ImageJ software and presented as several peaks on a curved line at the three selected points. Outer limiting membrane, EZ, interdigitation zone and RPE at outer retinal layers corresponded to the four peaks, as shown in Fig. 1 . The photoreceptor OS layer thickness was defined as the distance between the EZ peak and the RPE peak. The OS thickness was measured by an experienced observer (T.S.). Statistical analysis Statistical analysis was performed using SPSS 19.0 software (SPSS, Chicago, IL, USA). The descriptive statistics of the continuous variables were expressed as mean ± standard deviation (SD). Normal distributions were confirmed in age, AL, corneal curvature, spherical equivalent, visual acuity of amblyopic eyes, body mass index (BMI) and other morphological parameters. An analysis of variance (ANOVA) was used to compare the differences in baseline demographics among amblyopic eyes, fellow eyes, and control eyes. Bonferroni test was performed for the post hoc test. The correlation between OS thickness and the choroidal thickness, spherical equivalent, age, and axial length of amblyopic eyes was analyzed using Pearson correlation. Generalised estimating equation (GEE) was used to compare the differences in retinal reflectivity and other morphological parameters between amblyopic eyes and control eyes, as well as between fellow eyes of amblyopia and control eyes after adjusting for the possible effects of age and AL. A P < 0.05 was considered statistically significant. Results Demographic data Seventy-eight patients with anisometropic amblyopia and 64 age-matched controls were included in the study. All the participants were Chinese. Among the amblyopic patients, 39 were male and 39 were female. The mean age ± SD was 8.54 ± 2.98 (range 5–15 years). The mean BMI was 16.38 ± 2.50 in amblyopic eyes. The range of BCVA in amblyopic eyes was 0.1–0.6. BCVA in fellow eyes and control eyes was equal to or better than 1.0. Among the controls, 32 were male and 32 were female. The mean age ± SD was 8.39 ± 2.28 (range 5–15 years). The mean BMI was 16.52 ± 1.68 in control eyes (Table 1 ). There were no significant differences in age, BMI or gender distribution. Table 1 Demographic characteristics of amblyopes and normal controls Amblyopic eyes(n = 78) Fellow eyes (n = 78) Control eyes(n = 64) Ages (years) 8.54 ± 2.98 8.54 ± 2.98 8.39 ± 2.28 Gender (Male: Female) 39/39 39/39 32/32 Body mass index (BMI) 16.38 ± 2.50 16.38 ± 2.50 16.52 ± 1.68 Visual acuity (LogMAR) 0.54 ± 0.26 -0.02 ± 0.06 -0.02 ± 0.04 Average anterior corneal radius of curvature 7.92 ± 0.24 7.89 ± 0.23 7.77 ± 0.23 Spherical equivalent (diopter) 5.35 ± 1.67 1.63 ± 1.79 0.17 ± 1.10 Axial length (mm) 21.49 ± 0.74 22.91 ± 0.87 23.29 ± 1.01 The mean spherical equivalent was 5.35 ± 1.67 D in amblyopic eyes, 1.63 ± 1.79 D in fellow eyes, and 0.17 ± 1.10 D in control eyes. The mean AL was 21.49 ± 0.74 mm in amblyopic eyes, 22.91 ± 0.87 mm in fellow eyes, and 23.29 ± 1.01 mm in control eyes. Amblyopic eyes were significantly more hyperopic and had a shorter axial length than fellow eyes and control eyes ( p < 0.001, p < 0.001, ANOVA). Fellow eyes were also significantly more hyperopic amblyopic and had a shorter axial length than control eyes (p < 0.001 and p = 0.005, ANOVA). Examples of LRP measurements are presented in Fig. 1 and Fig. 2 . The main results of different retinal layers reflectivity were summarized in Table 2 , Table 3 and Table 4 . The reflectivity ratio of retinal pigment epithelium/ONL was higher in amblyopia than in normal controls at fovea (4.19 ± 0.66 vs 3.83 ± 0.52, p = 0.001) and at 1mm nasal to the fovea (3.89 ± 0.69 vs 3.52 ± 0.51, p = 0.001) but not at 1mm temporal to the fovea. The reflectivity ratio of outer segment/ONL was higher only at 1mm nasal to the fovea (2.94 ± 0.61 vs 2.70 ± 0.42, p = 0.02). Table 2 Comparison of quantitative OCT measurements between amblyopic eyes, fellow eyes, and normal vision control eyes at subfovea. Amblyopic eyes(n = 78) Fellow eyes (n = 78) Control eyes (n = 64) Amblyopia vs Fellow Amblyopia vs Control Fellow vs Control ONL reflectivity 47.97 ± 8.18 50.73 ± 8.10 53.18 ± 8.15 0.062 < 0.001 0.213 EZ reflectivity 159.87 ± 19.26 171.67 ± 19.88 179 ± 16.88 < 0.001 < 0.001 0.05 OS reflectivity 82.74 ± 22.55 90.20 ± 19.52 92.96 ± 18.32 0.021 0.008 0.99 RPE reflectivity 195.94 ± 13.01 199.84 ± 11.56 199.57 ± 11.08 0.107 0.21 0.998 EZ/ONL reflectivity ratio 3.41 ± 0.41 3.45 ± 0.55 3.43 ± 0.55 0.956 0.978 0.99 OS/ONL reflectivity ratio 1.75 ± 0.48 1.79 ± 0.34 1.77 ± 0.35 0.996 0.997 0.999 RPE/ONL reflectivity ratio 4.19 ± 0.66 4.03 ± 0.61 3.83 ± 0.52 0.285 0.001 0.092 OS thickness 18.41 ± 1.83 17.68 ± 0.34 16.84 ± 1.39 0.007 < 0.001 0.004 Choroidal thickness (µm) 352.71 ± 77.46 279.81 ± 74.52 252.95 ± 66.88 < 0.001 < 0.001 0.070 ONL outer nuclear layer, EZ ellipsoid zone, OS outer segment, RPE retinal pigment epithelium, SD standard deviation Table 3 Comparison of quantitative OCT measurements between amblyopic eyes, fellow eyes, and normal vision control eyes at 1 mm nasal to the fovea. Amblyopic eyes(n = 78) Fellow eyes (n = 78) Control eyes (n = 64) Amblyopia vs Fellow Amblyopia vs Control Fellow vs Control ONL reflectivity 50.4 ± 9.46 53.46 ± 8.22 56.01 ± 8.95 0.085 0.001 0.232 EZ reflectivity 191.63 ± 17.51 197.28 ± 16.53 191.65 ± 34.24 0.103 0.996 0.675 OS reflectivity 143.56 ± 18.65 148.82 ± 17.60 149.06 ± 19.84 0.121 0.266 0.996 RPE reflectivity 190.27 ± 11.76 192.43 ± 12.57 192.95 ± 10.48 0.598 0.446 0.998 EZ/ONL reflectivity ratio 3.92 ± 0.71 3.76 ± 0.53 3.51 ± 0.75 0.334 0.003 0.077 OS/ONL reflectivity ratio 2.94 ± 0.61 2.83 ± 0.42 2.70 ± 0.42 0.47 0.02 0.218 RPE/ONL reflectivity ratio 3.89 ± 0.69 3.68 ± 0.55 3.52 ± 0.51 0.084 0.001 0.236 OS thickness 14.78 ± 1.34 14.45 ± 1.34 14.19 ± 1.40 0.291 0.03 0.771 Choroidal thickness (µm) 327.90 ± 78.94 243.46 ± 66.14 218.70 ± 64.05 < 0.001 < 0.001 0.087 ONL outer nuclear layer, EZ ellipsoid zone, OS outer segment, RPE retinal pigment epithelium, SD standard deviation Table 4 Comparison of quantitative OCT measurements between amblyopic eyes, fellow eyes, and normal vision control eyes at 1 mm temporal to the fovea. Amblyopic eyes(n = 78) Fellow eyes (n = 78) Control eyes (n = 64) Amblyopia vs Fellow Amblyopia vs Control Fellow vs Control ONL reflectivity 53.14 ± 8.72 55.56 ± 8.68 55.38 ± 8.07 0.232 0.333 0.998 EZ reflectivity 195.19 ± 20.40 200.17 ± 159.59 199.99 ± 17.95 0.228 0.4 0.997 OS reflectivity 147.47 ± 19.92 151.20 ± 19.76 149.27 ± 17.75 0.477 0.998 0.996 RPE reflectivity 191.67 ± 13.15 194.85 ± 12.54 193.75 ± 11.78 0.372 0.948 0.994 EZ/ONL reflectivity ratio 3.76 ± 0.66 3.68 ± 0.57 3.67 ± 0.50 0.996 0.998 0.999 OS/ONL reflectivity ratio 2.83 ± 0.49 2.77 ± 0.47 2.74 ± 0.43 0.998 0.721 0.999 RPE/ONL reflectivity ratio 3.69 ± 0.55 3.59 ± 0.57 3.56 ± 0.47 0.771 0.409 0.999 OS thickness 14.92 ± 1.48 14.59 ± 1.28 14.41 ± 1.32 0.258 0.049 0.991 Choroidal thickness (µm) 341.74 ± 80.62 287.86 ± 70.80 269.45 ± 76.88 < 0.001 < 0.001 0.410 ONL outer nuclear layer, EZ ellipsoid zone, OS outer segment, RPE retinal pigment epithelium, SD standard deviation Photoreceptor outer segment layer thickness was significantly greater in amblyopic eyes than in normal control eyes at all three regions (18.41 ± 1.83 vs 16.84 ± 1.39, p < 0.001 at fovea; 14.78 ± 1.34 vs 14.19 ± 1.40, p = 0.030 at 1mm nasal to the fovea; 14.92 ± 1.48 vs 14.41 ± 1.32, p = 0.049 at 1mm temporal to the fovea) and greater than in fellow eyes (18.41 ± 1.83 vs 17.68 ± 0.34, p = 0.007) only at fovea. CT was significantly greater in amblyopic eyes than in fellow eyes and normal control eyes at three selected points (all p values < 0.001). However, there was no significant difference between fellow eyes and normal control eyes. Pearson correlation was conducted to determine correlations between OS thickness and the choroidal thickness, spherical equivalent, age, and axial length of amblyopic eyes. Subfoveal OS thickness was positively correlated with choroidal thickness (r = 0.248, p = 0.018), but was irrelevant with spherical equivalent (r = 0.065, p = 0.575), age (r = 0.164, p = 0.202), axial length (r = 0.037, p = 0.747) or LogMAR VA (r = 0.043, p = 0.708). Discussion The main findings of this study were the bilateral changes in the reflectivity in the outer retinal layers on SS-OCT for children with hyperopic anisometropic amblyopia. The results showed that the reflectivity ratio of retinal pigment epithelium/ONL was higher in amblyopia than in normal controls at fovea and at 1 mm nasal to the fovea. The outer segment/ONL was increased in amblyopia than in normal controls only at 1mm nasal to the fovea. Photoreceptor outer segment layer thickness was greater at both fovea and parafovea. OS thickness was correlated with CT at subfovea. Interestingly, our results showed that optical intensities of the outer segment only raised at 1 mm nasal to the fovea, optical intensities of the RPE raised at fovea and 1 mm nasal to the fovea. The differences of reflectivity change in fovea and parafovea may be due to the mechanism of centripetal migration of the outer layers. In neonates’ study, Maldonado et al. [ 12 ] reported a centrifugal migration of the inner layers and a centripetal migration of the outer layers with development, and these findings were demonstrated by histological studies on human foveal, which showed progressive thickening of the foveal ONL after birth as cone packing occurred. Al-Haddad et al. [ 9 ] also found that temporal outer retinal layers were thinner in amblyopia than in normal controls. We can postulate that outer retina migrates from nasal to temporal, therefore, in the premature fovea of the amblyopia, the optical intensities of the outer segment raised at 1 mm nasal to the fovea. Because of more old OS discs were phagocytosed by the RPE, and then the reflectivity of RPE at fovea and 1 mm nasal to the fovea were increased. The retinal effect on amblyopia has been controversial. Bruce [ 4 ] included 85 amblyopes and 110 visually normal controls to examine foveal structure changes using Spectral domain-OCT and found that foveal thickness increased, and pit depth decreased in the horizontal meridian of amblyopes. Yen [ 13 ] found that retinal nerve fibre layer thickness was thicker in the amblyopic eyes of refractive amblyopia patients than in normal fellow eyes. The results from a population-based cross-sectional study [ 6 ] revealed that amblyopic eyes had slightly greater foveal thickness than normal fellow eyes and control eyes, but peripapillary RNFL thickness was not significantly different between amblyopic and fellow eyes or normal eyes. Al-Haddad et al. [ 9 ] studied macular morphology in amblyopic eyes using SD-OCT and found that the foveal pit was significantly shallower in the strabismic group but not in the anisometropic group and hypothesized that possibly different pathways are involved whereby suppression due to strabismus affects foveal maturation differently than anisometropia contributes to a blurred image. These inconsistent results among previous studies may be partially explained by the variation in the age of the subjects, the differences in ethnicity or the different measurement methods. In this study, we found that the OS length was significantly greater in amblyopic eyes than in fellow eyes or control eyes at fovea and parafovea, which was partially consistent with greater foveal thickness in amblyopes as previous reported. Chen et al. [ 14 ] found that fovea slightly but significantly thinner after treatment in eyes with amblyopia. Huynh et al. [ 6 ] also found that the interocular difference in foveal thickness was greater in amblyopic children who did not receive any treatment. The results from above studies suggested that foveal thickening occurs after onset of amblyopia and then regresses with treatment. However, examining 21 patients with hyperopic anisometropic amblyopia and 25 age-matched controls, Nishi [ 7 ] measured the foveal thickness and the thickness of the outer nuclear layer, photoreceptor inner segment layer and OS layer using SD-OCT and found that OS length was significantly thinner in amblyopic eyes than in fellow eyes. There are some differences between Nishi’s study and our study. First, the mean age of the subjects was younger (6.0 ± 2.3 years) in Nishi’s study than the subjects in our study (8.49 ± 2.31 years). A previous study reported that foveal thickness increases significantly with age [ 4 ] and that the retina is still in the process of normal development during childhood and adolescents [ 15 ] . Another pathological study suggested that human foveal cone density increases until around 5–8 years of age [ 16 ] . Second, the ethnicity of the subjects was different (Japanese vs. Chinese). Third, the measurement method for the OS was different. Retinal thickness was measured manually using the embedded OCT software used in Nishi’s study. Conversely, OS thickness was measured using longitudinal reflectance profile measurements in the present study. LRP can provide the coordinate site of the EZ and RPE, through which we can calculate exactly the OS length. Fourth, we enrolled more hyperopic anisometropic amblyopia patients (78 vs. 21 patients). The larger sample size and the more accurate measurements of retinal thickness are the strengths of this study. The difference of photoreceptor outer segment layer thickness between amblyopia and normal controls was only 0.5 to 2 pixels, which makes it difficult to identify this feature without the help of LRP quantitative measurement. Some studies investigated the correlation of retinal thickness with visual outcome in eyes with amblyopia and found that visual acuity was not correlated with retinal thickness or structure. Dickmann et al. [ 17 ] found that macular thickness in both strabismus and anisometropic amblyopia had no correlation with visual acuity. Chen et al. [ 14 ] also failed to find a correlation between macular thickness and visual acuity even during the recovery of the visual acuity after treatment. Similarly, in the present study, neither OS thickness nor outer retinal reflectivity was correlated with the visual outcome. Greater Choroidal thickness in amblyopic eyes than in normal controls have been reported by previous studies, and this finding was considered associated with amblyopia. This study not only found that the thickness of choroid thickens in amblyopic eyes, but also found that OS was correlated with choroid thickness. Studies aforementioned and ours indicate that a greater OS thickness or higher reflectivity of outer retinal may associated with amblyopia but are unrelated to the degree of amblyopia. Our study has some limitations. First, all the patients included were Chinese. Second, we only examined anisometropic amblyopia and did not study other types of amblyopia. Third, the measurement taken at 1 mm around the fovea was not corrected for axial length, which could have affected the lateral scale of the OCT datasets for peripheral measurements. Lastly, due to the study’s cross-sectional design, longitudinal OS changes were not observed. Future studies involving diversity ethnicity and more types of amblyopia are warranted to investigate the correlation of OS thickness changes with visual acuity improvement after amblyopia treatment. Conclusion, in the subfoveal area, the OS length was greater in amblyopic eyes than in fellow eyes of amblyopia. Moreover, differences were found in the OS thickness in both eyes of children with amblyopia compared to normal vision. For children with hyperopic anisometropia, the presence of amblyopia should be highly suspected if there is also a thickened OS, and it is necessary to detect changes in the thickness of OS during the amblyopia treatment. Declarations Acknowledgment: No applicable Funding: This work was supported by the Guangdong medical research under Grant (A2022467). Competing interests: None of the following authors have any proprietary interests or conflicts of interest related to this submission: Wenli Zhang, Tingkun Shi, Fan yang, Shirong Chen. Authors contribution: Concept and design (WZ, TS), data of collection (WZ, FY and SC), drafting manuscript (WZ, TS), critical revision (TS). The authors read and approved the final manuscript. Consent to participate: All patients gave their informed consent for their anonymized data to be submitted for audit and publication. 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A morphological study of retinal changes in unilateral amblyopia using optical coherence tomography image segmentation. PLoS One. 2014;9:e88363. Hendrickson A E. Primate foveal development: a microcosm of current questions in neurobiology. Invest Ophth Vis Sci. 1994;35:3129-33. Dickmann A, Petroni S, Perrotta V, Salerni A, Parrilla R, Aliberti S, et al. A morpho-functional study of amblyopic eyes with the use of optical coherence tomography and microperimetry. J AAPOS. 2011;15:338-41. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4178975","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":284878673,"identity":"3703b22d-abfc-4ebe-9356-4e710df6a00c","order_by":0,"name":"Wenli Zhang","email":"","orcid":"","institution":"Shantou University \u0026 the Chinese University of Hong Kong","correspondingAuthor":false,"prefix":"","firstName":"Wenli","middleName":"","lastName":"Zhang","suffix":""},{"id":284878675,"identity":"c3f3ba3d-e039-48d1-89ee-975a50657a72","order_by":1,"name":"Fan Yang","email":"","orcid":"","institution":"Shantou University \u0026 the Chinese University of Hong Kong","correspondingAuthor":false,"prefix":"","firstName":"Fan","middleName":"","lastName":"Yang","suffix":""},{"id":284878676,"identity":"ac1a4105-9e6e-4e76-9069-4e0b8fd6c9ac","order_by":2,"name":"Shirong Chen","email":"","orcid":"","institution":"Shantou University \u0026 the Chinese University of Hong Kong","correspondingAuthor":false,"prefix":"","firstName":"Shirong","middleName":"","lastName":"Chen","suffix":""},{"id":284878678,"identity":"365bc987-fdb1-4b21-bfb6-0baa3066d387","order_by":3,"name":"Tingkun Shi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAq0lEQVRIiWNgGAWjYFACNsYHEgwSJOlgYzYgWQsbSeoZGOTnt6VVWPyxkONvYD728QsxWgyOsR27IdkmYSxxgC15tgxRWtjY225INkgkbmDgMWYmyonybextBRJ/JOqJ18IAdBiDBJtEggFQC+MHohx2LC1ZAugXwxmH2ZKZibJEvvmY4WeJP3Xy/O3Nhxl/EKUHCCBeAFrBzEOsFrgXiLdlFIyCUTAKRhQAAOg6J1tzK+EUAAAAAElFTkSuQmCC","orcid":"","institution":"Shantou University \u0026 the Chinese University of Hong Kong","correspondingAuthor":true,"prefix":"","firstName":"Tingkun","middleName":"","lastName":"Shi","suffix":""}],"badges":[],"createdAt":"2024-03-28 02:59:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4178975/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4178975/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":53959464,"identity":"c84af3b5-4015-4f12-a7e9-f2496a9765de","added_by":"auto","created_at":"2024-04-02 17:51:36","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1774141,"visible":true,"origin":"","legend":"\u003cp\u003eCT and OS length measurement in an amblyopic eye. A. Red-free fundus photograph. B. Longitudinal reflectance profile. C. Swept-source OCT. (EZ ellipsoid zone, IZ interdigitation zone, RPE retinal pigment epithelium)\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4178975/v1/479ce7f7f70433ce62c68b38.png"},{"id":53959465,"identity":"a78bcd1e-2036-49db-ad8b-3d5759a56476","added_by":"auto","created_at":"2024-04-02 17:51:36","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1617339,"visible":true,"origin":"","legend":"\u003cp\u003eOptical coherence tomography (OCT, a, b) and longitudinal reflectance profile (LRP) at temporal (c, d), fovea (e, f) and nasal (g, h) of amblyopic eye (left column) and normal control eye. The yellow boxes on OCT images (a, b) indicate the regions for LRP at three selected points. (EZ ellipsoid zone, IZ interdigitation zone, RPE retinal pigment epithelium)\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4178975/v1/5d7402c13c8e0aab3fcc1449.jpg"},{"id":57491571,"identity":"12bdb4b5-31c9-4e9b-8a37-692781c1d414","added_by":"auto","created_at":"2024-05-31 11:32:10","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4362726,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4178975/v1/d6819b3e-7bec-484a-8dd4-77314d8c451f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eThickened Photoreceptor Outer Segment Layer in Children with Hyperopic Anisometropic Amblyopia\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAmblyopia is a developmental visual disorder in the eye characterised by decreased vision, which cannot be immediately improved by refractive correction and has no obvious structural abnormality. The common causes of amblyopia include strabismus, anisometropia and form deprivation. Results from human and animal studies indicated that each of these causes exerts a functional or morphologic effect on the visual cortex and lateral geniculate nucleus\u003csup\u003e[\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003ePossible structural changes compared with normal eyes have been reported, since the advent of optical coherence tomography, including differences in macular thickness, retinal nerve fibre layer, and individual retinal layers \u003csup\u003e[\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. Nonetheless reports have shown discordant results. Nishi et al.\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e found that the length of the photoreceptor outer segment (OS) was significantly thinner in amblyopic eyes than in fellow eyes although relatively small sample size. Nishikawa et al. found that there were no significant differences in outer retinal layer thickness values between amblyopic eyes and fellow eyes, except that the parafoveal outer segment photoreceptor/retinal pigment epithelium complex thickness was significantly greater in the fellow eyes\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. It was also reported that the bulge of the foveal ellipsoid zone (EZ) was frequently absent and the reflectivity of the EZ was lower in amblyopic eyes compared with normal eyes\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eHowever, the change of reflectivity reported in the literature was only an observation and has not been quantitatively studied, in addition, the thickness of each retinal layer is measured manually, and there is the possibility of measurement error. Therefore, the purpose of this study was to investigate quantitatively the reflectivity and other morphological changes of the photoreceptors in patients with unilateral amblyopia using the longitudinal-reflectance-profile (LRP) on OCT images, and to compare these findings with normal fellow eyes.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients and controls\u003c/h2\u003e \u003cp\u003eA cross-sectional comparative study was designed involving patients with hyperopic anisometropic amblyopia who visited the tertiary hospital from November 2020 to December 2022. This study adhered to the tenets of the Declaration of Helsinki and was approved by the institution ethics committee board. Written informed consent was obtained from the parents or legal guardians of all participants prior to recruitment.\u003c/p\u003e \u003cp\u003eAll the recruited patients had an age range of 5\u0026ndash;15 years and were diagnosed with hyperopic anisometropic amblyopia. Comprehensive ophthalmic examinations were conducted in all patients, including best corrected visual acuity (BCVA), intraocular pressure (IOP), cycloplegic refraction, axial length (AL), slit lamp microscopy and dilated fundoscopy. BCVA was measured using a standard logarithmic decimal chart, and decimal BCVA was converted into the logMAR value for further analysis. Refraction was measured using Topcon K-800 (Tokyo, Japan). The AL and corneal curvature were measured with an IOL-Master (Carl Zeiss Meditec, Germany). Anisometropic amblyopia was defined as a 2.0 D or more difference in spherical equivalent refractive error between two eyes and eyes with BCVA of 0.6 or worse in the amblyopic eye and 1.0 or better in the fellow eye. There should have been no prior spectacle wear or other treatment for amblyopia. Patients with any identifiable organic lesions accounting for decreased vision, history of intraocular surgery, history of ocular trauma, cataract, glaucoma, uveitis, premature infants, or any other retinal diseases were excluded. Microtropia or strabismic amblyopia were also excluded. The control group was composed of age-matched subjects whose spherical equivalent less than \u0026minus;\u0026thinsp;1 D and BCVA were equal to or better than 1.0 in both eyes. The right eye of the controls was included in the study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eMeasurement of choroidal thickness\u003c/h2\u003e \u003cp\u003eAll eyes were scanned with swept-source optical coherence tomography (SS-OCT) (Triton DRI-OCT; Topcon, Japan; wavelength: 1050 nm). The SS-OCT provides 100000 A scans/second according to a protocol of 12 mm line scan with an average of 128 consecutive, overlapping single B-scan OCT images. Eye traction was used to obtain each section. The line scan was made horizontally across the fovea. We recognised the fovea according to the centre of the vessel-free region on the fundus photograph during scanning and the area absent of inner retinal layers on the OCT. Any image quality scores lower than 60 (range 0\u0026ndash;100) obtained using software for each volumetric OCT scan were excluded. Other significant image artefacts were excluded from analysis as we previously reported\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. Choroidal thickness (CT) was measured between the outer border of the retinal pigment epithelial and the inner sclera surface. Two independent investigators (T. S. and W. Z.) who were masked to the diagnosis and other clinical information measured the CTs. The mean values were used for the final analysis. Interobserver reproducibility analysis of the measurements was performed using an intraclass correlation coefficient.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eLongitudinal reflectance profile measurements\u003c/h2\u003e \u003cp\u003eThe horizontal and vertical B-scans across the fovea were exported from SS-OCT as grayscale JPEG images. The LRP measurement protocol was adopted using ImageJ software (National Institutes of Health, Bethesda, MD), as we previously reported\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. Each layer of retinal reflectance was automatically calculated using ImageJ software and presented as several peaks on a curved line at the three selected points. Outer limiting membrane, EZ, interdigitation zone and RPE at outer retinal layers corresponded to the four peaks, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The photoreceptor OS layer thickness was defined as the distance between the EZ peak and the RPE peak. The OS thickness was measured by an experienced observer (T.S.).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was performed using SPSS 19.0 software (SPSS, Chicago, IL, USA). The descriptive statistics of the continuous variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD).\u003c/p\u003e \u003cp\u003eNormal distributions were confirmed in age, AL, corneal curvature, spherical equivalent, visual acuity of amblyopic eyes, body mass index (BMI) and other morphological parameters. An analysis of variance (ANOVA) was used to compare the differences in baseline demographics among amblyopic eyes, fellow eyes, and control eyes. Bonferroni test was performed for the post hoc test. The correlation between OS thickness and the choroidal thickness, spherical equivalent, age, and axial length of amblyopic eyes was analyzed using Pearson correlation. Generalised estimating equation (GEE) was used to compare the differences in retinal reflectivity and other morphological parameters between amblyopic eyes and control eyes, as well as between fellow eyes of amblyopia and control eyes after adjusting for the possible effects of age and AL. A \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eDemographic data\u003c/h2\u003e \u003cp\u003eSeventy-eight patients with anisometropic amblyopia and 64 age-matched controls were included in the study. All the participants were Chinese. Among the amblyopic patients, 39 were male and 39 were female. The mean age\u0026thinsp;\u0026plusmn;\u0026thinsp;SD was 8.54\u0026thinsp;\u0026plusmn;\u0026thinsp;2.98 (range 5\u0026ndash;15 years). The mean BMI was 16.38\u0026thinsp;\u0026plusmn;\u0026thinsp;2.50 in amblyopic eyes. The range of BCVA in amblyopic eyes was 0.1\u0026ndash;0.6. BCVA in fellow eyes and control eyes was equal to or better than 1.0. Among the controls, 32 were male and 32 were female. The mean age\u0026thinsp;\u0026plusmn;\u0026thinsp;SD was 8.39\u0026thinsp;\u0026plusmn;\u0026thinsp;2.28 (range 5\u0026ndash;15 years). The mean BMI was 16.52\u0026thinsp;\u0026plusmn;\u0026thinsp;1.68 in control eyes (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). There were no significant differences in age, BMI or gender distribution.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic characteristics of amblyopes and normal controls\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAmblyopic\u003c/p\u003e \u003cp\u003eeyes(n\u0026thinsp;=\u0026thinsp;78)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFellow eyes (n\u0026thinsp;=\u0026thinsp;78)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eControl \u003c/p\u003e \u003cp\u003eeyes(n\u0026thinsp;=\u0026thinsp;64)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAges (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.54\u0026thinsp;\u0026plusmn;\u0026thinsp;2.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.54\u0026thinsp;\u0026plusmn;\u0026thinsp;2.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.39\u0026thinsp;\u0026plusmn;\u0026thinsp;2.28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender (Male: Female)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39/39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39/39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32/32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody mass index (BMI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.38\u0026thinsp;\u0026plusmn;\u0026thinsp;2.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.38\u0026thinsp;\u0026plusmn;\u0026thinsp;2.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16.52\u0026thinsp;\u0026plusmn;\u0026thinsp;1.68\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVisual acuity (LogMAR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAverage anterior corneal radius of curvature\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.92\u0026thinsp;\u0026plusmn;\u0026thinsp;0.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.89\u0026thinsp;\u0026plusmn;\u0026thinsp;0.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.77\u0026thinsp;\u0026plusmn;\u0026thinsp;0.23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpherical equivalent (diopter)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.35\u0026thinsp;\u0026plusmn;\u0026thinsp;1.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.63\u0026thinsp;\u0026plusmn;\u0026thinsp;1.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.17\u0026thinsp;\u0026plusmn;\u0026thinsp;1.10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAxial length (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21.49\u0026thinsp;\u0026plusmn;\u0026thinsp;0.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.91\u0026thinsp;\u0026plusmn;\u0026thinsp;0.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23.29\u0026thinsp;\u0026plusmn;\u0026thinsp;1.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe mean spherical equivalent was 5.35\u0026thinsp;\u0026plusmn;\u0026thinsp;1.67 D in amblyopic eyes, 1.63\u0026thinsp;\u0026plusmn;\u0026thinsp;1.79 D in fellow eyes, and 0.17\u0026thinsp;\u0026plusmn;\u0026thinsp;1.10 D in control eyes. The mean AL was 21.49\u0026thinsp;\u0026plusmn;\u0026thinsp;0.74 mm in amblyopic eyes, 22.91\u0026thinsp;\u0026plusmn;\u0026thinsp;0.87 mm in fellow eyes, and 23.29\u0026thinsp;\u0026plusmn;\u0026thinsp;1.01 mm in control eyes. Amblyopic eyes were significantly more hyperopic and had a shorter axial length than fellow eyes and control eyes (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001, ANOVA). Fellow eyes were also significantly more hyperopic amblyopic and had a shorter axial length than control eyes (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 and \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005, ANOVA).\u003c/p\u003e \u003cp\u003eExamples of LRP measurements are presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The main results of different retinal layers reflectivity were summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e \u003cb\u003eand\u003c/b\u003e Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. The reflectivity ratio of retinal pigment epithelium/ONL was higher in amblyopia than in normal controls at fovea (4.19\u0026thinsp;\u0026plusmn;\u0026thinsp;0.66 vs 3.83\u0026thinsp;\u0026plusmn;\u0026thinsp;0.52, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001) and at 1mm nasal to the fovea (3.89\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69 vs 3.52\u0026thinsp;\u0026plusmn;\u0026thinsp;0.51, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001) but not at 1mm temporal to the fovea. The reflectivity ratio of outer segment/ONL was higher only at 1mm nasal to the fovea (2.94\u0026thinsp;\u0026plusmn;\u0026thinsp;0.61 vs 2.70\u0026thinsp;\u0026plusmn;\u0026thinsp;0.42, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of quantitative OCT measurements between amblyopic eyes, fellow eyes, and normal vision control eyes at subfovea.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAmblyopic\u003c/p\u003e \u003cp\u003eeyes(n\u0026thinsp;=\u0026thinsp;78)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFellow eyes (n\u0026thinsp;=\u0026thinsp;78)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eControl eyes\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;64)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAmblyopia vs Fellow\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAmblyopia vs Control\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFellow vs Control\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eONL reflectivity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e47.97\u0026thinsp;\u0026plusmn;\u0026thinsp;8.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e50.73\u0026thinsp;\u0026plusmn;\u0026thinsp;8.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e53.18\u0026thinsp;\u0026plusmn;\u0026thinsp;8.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.062\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.213\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEZ reflectivity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e159.87\u0026thinsp;\u0026plusmn;\u0026thinsp;19.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e171.67\u0026thinsp;\u0026plusmn;\u0026thinsp;19.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e179\u0026thinsp;\u0026plusmn;\u0026thinsp;16.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOS reflectivity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e82.74\u0026thinsp;\u0026plusmn;\u0026thinsp;22.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e90.20\u0026thinsp;\u0026plusmn;\u0026thinsp;19.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e92.96\u0026thinsp;\u0026plusmn;\u0026thinsp;18.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRPE reflectivity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e195.94\u0026thinsp;\u0026plusmn;\u0026thinsp;13.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e199.84\u0026thinsp;\u0026plusmn;\u0026thinsp;11.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e199.57\u0026thinsp;\u0026plusmn;\u0026thinsp;11.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.107\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEZ/ONL reflectivity ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e3.41\u0026thinsp;\u0026plusmn;\u0026thinsp;0.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e3.43\u0026thinsp;\u0026plusmn;\u0026thinsp;0.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.956\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.978\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOS/ONL reflectivity ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.79\u0026thinsp;\u0026plusmn;\u0026thinsp;0.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e1.77\u0026thinsp;\u0026plusmn;\u0026thinsp;0.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.996\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.997\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRPE/ONL reflectivity ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e4.19\u0026thinsp;\u0026plusmn;\u0026thinsp;0.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e4.03\u0026thinsp;\u0026plusmn;\u0026thinsp;0.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e3.83\u0026thinsp;\u0026plusmn;\u0026thinsp;0.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.285\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.092\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOS thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e18.41\u0026thinsp;\u0026plusmn;\u0026thinsp;1.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e17.68\u0026thinsp;\u0026plusmn;\u0026thinsp;0.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e16.84\u0026thinsp;\u0026plusmn;\u0026thinsp;1.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChoroidal thickness (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e352.71\u0026thinsp;\u0026plusmn;\u0026thinsp;77.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e279.81\u0026thinsp;\u0026plusmn;\u0026thinsp;74.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e252.95\u0026thinsp;\u0026plusmn;\u0026thinsp;66.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.070\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eONL outer nuclear layer, EZ ellipsoid zone, OS outer segment, RPE retinal pigment epithelium, SD standard deviation\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of quantitative OCT measurements between amblyopic eyes, fellow eyes, and normal vision control eyes at 1 mm nasal to the fovea.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAmblyopic\u003c/p\u003e \u003cp\u003eeyes(n\u0026thinsp;=\u0026thinsp;78)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFellow eyes (n\u0026thinsp;=\u0026thinsp;78)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eControl eyes\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;64)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAmblyopia vs Fellow\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAmblyopia vs Control\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFellow vs Control\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eONL reflectivity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e50.4\u0026thinsp;\u0026plusmn;\u0026thinsp;9.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e53.46\u0026thinsp;\u0026plusmn;\u0026thinsp;8.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e56.01\u0026thinsp;\u0026plusmn;\u0026thinsp;8.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.085\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.232\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEZ reflectivity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e191.63\u0026thinsp;\u0026plusmn;\u0026thinsp;17.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e197.28\u0026thinsp;\u0026plusmn;\u0026thinsp;16.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e191.65\u0026thinsp;\u0026plusmn;\u0026thinsp;34.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.103\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.996\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.675\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOS reflectivity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e143.56\u0026thinsp;\u0026plusmn;\u0026thinsp;18.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e148.82\u0026thinsp;\u0026plusmn;\u0026thinsp;17.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e149.06\u0026thinsp;\u0026plusmn;\u0026thinsp;19.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.121\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.266\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.996\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRPE reflectivity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e190.27\u0026thinsp;\u0026plusmn;\u0026thinsp;11.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e192.43\u0026thinsp;\u0026plusmn;\u0026thinsp;12.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e192.95\u0026thinsp;\u0026plusmn;\u0026thinsp;10.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.598\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.446\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEZ/ONL reflectivity ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e3.92\u0026thinsp;\u0026plusmn;\u0026thinsp;0.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.76\u0026thinsp;\u0026plusmn;\u0026thinsp;0.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e3.51\u0026thinsp;\u0026plusmn;\u0026thinsp;0.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.334\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.077\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOS/ONL reflectivity ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e2.94\u0026thinsp;\u0026plusmn;\u0026thinsp;0.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e2.83\u0026thinsp;\u0026plusmn;\u0026thinsp;0.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e2.70\u0026thinsp;\u0026plusmn;\u0026thinsp;0.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.218\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRPE/ONL reflectivity ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e3.89\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.68\u0026thinsp;\u0026plusmn;\u0026thinsp;0.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e3.52\u0026thinsp;\u0026plusmn;\u0026thinsp;0.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.084\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.236\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOS thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e14.78\u0026thinsp;\u0026plusmn;\u0026thinsp;1.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e14.45\u0026thinsp;\u0026plusmn;\u0026thinsp;1.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e14.19\u0026thinsp;\u0026plusmn;\u0026thinsp;1.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.291\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.771\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChoroidal thickness (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e327.90\u0026thinsp;\u0026plusmn;\u0026thinsp;78.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e243.46\u0026thinsp;\u0026plusmn;\u0026thinsp;66.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e218.70\u0026thinsp;\u0026plusmn;\u0026thinsp;64.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.087\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eONL outer nuclear layer, EZ ellipsoid zone, OS outer segment, RPE retinal pigment epithelium, SD standard deviation\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of quantitative OCT measurements between amblyopic eyes, fellow eyes, and normal vision control eyes at 1 mm temporal to the fovea.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAmblyopic\u003c/p\u003e \u003cp\u003eeyes(n\u0026thinsp;=\u0026thinsp;78)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFellow eyes (n\u0026thinsp;=\u0026thinsp;78)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eControl eyes\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;64)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAmblyopia vs Fellow\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAmblyopia vs Control\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFellow vs Control\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eONL reflectivity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e53.14\u0026thinsp;\u0026plusmn;\u0026thinsp;8.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e55.56\u0026thinsp;\u0026plusmn;\u0026thinsp;8.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e55.38\u0026thinsp;\u0026plusmn;\u0026thinsp;8.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.232\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.333\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEZ reflectivity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e195.19\u0026thinsp;\u0026plusmn;\u0026thinsp;20.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e200.17\u0026thinsp;\u0026plusmn;\u0026thinsp;159.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e199.99\u0026thinsp;\u0026plusmn;\u0026thinsp;17.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.228\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.997\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOS reflectivity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e147.47\u0026thinsp;\u0026plusmn;\u0026thinsp;19.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e151.20\u0026thinsp;\u0026plusmn;\u0026thinsp;19.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e149.27\u0026thinsp;\u0026plusmn;\u0026thinsp;17.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.477\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.996\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRPE reflectivity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e191.67\u0026thinsp;\u0026plusmn;\u0026thinsp;13.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e194.85\u0026thinsp;\u0026plusmn;\u0026thinsp;12.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e193.75\u0026thinsp;\u0026plusmn;\u0026thinsp;11.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.372\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.948\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.994\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEZ/ONL reflectivity ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e3.76\u0026thinsp;\u0026plusmn;\u0026thinsp;0.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.68\u0026thinsp;\u0026plusmn;\u0026thinsp;0.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e3.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.996\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOS/ONL reflectivity ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e2.83\u0026thinsp;\u0026plusmn;\u0026thinsp;0.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e2.77\u0026thinsp;\u0026plusmn;\u0026thinsp;0.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e2.74\u0026thinsp;\u0026plusmn;\u0026thinsp;0.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.998\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.721\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRPE/ONL reflectivity ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e3.69\u0026thinsp;\u0026plusmn;\u0026thinsp;0.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.59\u0026thinsp;\u0026plusmn;\u0026thinsp;0.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e3.56\u0026thinsp;\u0026plusmn;\u0026thinsp;0.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.771\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.409\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOS thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e14.92\u0026thinsp;\u0026plusmn;\u0026thinsp;1.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e14.59\u0026thinsp;\u0026plusmn;\u0026thinsp;1.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e14.41\u0026thinsp;\u0026plusmn;\u0026thinsp;1.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.258\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.049\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.991\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChoroidal thickness (\u0026micro;m)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e341.74\u0026thinsp;\u0026plusmn;\u0026thinsp;80.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e287.86\u0026thinsp;\u0026plusmn;\u0026thinsp;70.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e269.45\u0026thinsp;\u0026plusmn;\u0026thinsp;76.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.410\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eONL outer nuclear layer, EZ ellipsoid zone, OS outer segment, RPE retinal pigment epithelium, SD standard deviation\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePhotoreceptor outer segment layer thickness was significantly greater in amblyopic eyes than in normal control eyes at all three regions (18.41\u0026thinsp;\u0026plusmn;\u0026thinsp;1.83 vs 16.84\u0026thinsp;\u0026plusmn;\u0026thinsp;1.39, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001 at fovea; 14.78\u0026thinsp;\u0026plusmn;\u0026thinsp;1.34 vs 14.19\u0026thinsp;\u0026plusmn;\u0026thinsp;1.40, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.030 at 1mm nasal to the fovea; 14.92\u0026thinsp;\u0026plusmn;\u0026thinsp;1.48 vs 14.41\u0026thinsp;\u0026plusmn;\u0026thinsp;1.32, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.049 at 1mm temporal to the fovea) and greater than in fellow eyes (18.41\u0026thinsp;\u0026plusmn;\u0026thinsp;1.83 vs 17.68\u0026thinsp;\u0026plusmn;\u0026thinsp;0.34, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.007) only at fovea.\u003c/p\u003e \u003cp\u003eCT was significantly greater in amblyopic eyes than in fellow eyes and normal control eyes at three selected points (all \u003cem\u003ep\u003c/em\u003e values\u0026thinsp;\u0026lt;\u0026thinsp;0.001). However, there was no significant difference between fellow eyes and normal control eyes.\u003c/p\u003e \u003cp\u003ePearson correlation was conducted to determine correlations between OS thickness and the choroidal thickness, spherical equivalent, age, and axial length of amblyopic eyes. Subfoveal OS thickness was positively correlated with choroidal thickness (r\u0026thinsp;=\u0026thinsp;0.248, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.018), but was irrelevant with spherical equivalent (r\u0026thinsp;=\u0026thinsp;0.065, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.575), age (r\u0026thinsp;=\u0026thinsp;0.164, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.202), axial length (r\u0026thinsp;=\u0026thinsp;0.037, p\u0026thinsp;=\u0026thinsp;0.747) or LogMAR VA (r\u0026thinsp;=\u0026thinsp;0.043, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.708).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe main findings of this study were the bilateral changes in the reflectivity in the outer retinal layers on SS-OCT for children with hyperopic anisometropic amblyopia. The results showed that the reflectivity ratio of retinal pigment epithelium/ONL was higher in amblyopia than in normal controls at fovea and at 1 mm nasal to the fovea. The outer segment/ONL was increased in amblyopia than in normal controls only at 1mm nasal to the fovea. Photoreceptor outer segment layer thickness was greater at both fovea and parafovea. OS thickness was correlated with CT at subfovea.\u003c/p\u003e \u003cp\u003eInterestingly, our results showed that optical intensities of the outer segment only raised at 1 mm nasal to the fovea, optical intensities of the RPE raised at fovea and 1 mm nasal to the fovea. The differences of reflectivity change in fovea and parafovea may be due to the mechanism of centripetal migration of the outer layers. In neonates\u0026rsquo; study, Maldonado et al.\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e reported a centrifugal migration of the inner layers and a centripetal migration of the outer layers with development, and these findings were demonstrated by histological studies on human foveal, which showed progressive thickening of the foveal ONL after birth as cone packing occurred. Al-Haddad et al.\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e also found that temporal outer retinal layers were thinner in amblyopia than in normal controls. We can postulate that outer retina migrates from nasal to temporal, therefore, in the premature fovea of the amblyopia, the optical intensities of the outer segment raised at 1 mm nasal to the fovea. Because of more old OS discs were phagocytosed by the RPE, and then the reflectivity of RPE at fovea and 1 mm nasal to the fovea were increased.\u003c/p\u003e \u003cp\u003eThe retinal effect on amblyopia has been controversial. Bruce\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e included 85 amblyopes and 110 visually normal controls to examine foveal structure changes using Spectral domain-OCT and found that foveal thickness increased, and pit depth decreased in the horizontal meridian of amblyopes. Yen\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e found that retinal nerve fibre layer thickness was thicker in the amblyopic eyes of refractive amblyopia patients than in normal fellow eyes. The results from a population-based cross-sectional study\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e revealed that amblyopic eyes had slightly greater foveal thickness than normal fellow eyes and control eyes, but peripapillary RNFL thickness was not significantly different between amblyopic and fellow eyes or normal eyes. Al-Haddad et al.\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e studied macular morphology in amblyopic eyes using SD-OCT and found that the foveal pit was significantly shallower in the strabismic group but not in the anisometropic group and hypothesized that possibly different pathways are involved whereby suppression due to strabismus affects foveal maturation differently than anisometropia contributes to a blurred image. These inconsistent results among previous studies may be partially explained by the variation in the age of the subjects, the differences in ethnicity or the different measurement methods.\u003c/p\u003e \u003cp\u003eIn this study, we found that the OS length was significantly greater in amblyopic eyes than in fellow eyes or control eyes at fovea and parafovea, which was partially consistent with greater foveal thickness in amblyopes as previous reported. Chen et al.\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e found that fovea slightly but significantly thinner after treatment in eyes with amblyopia. Huynh et al.\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e also found that the interocular difference in foveal thickness was greater in amblyopic children who did not receive any treatment. The results from above studies suggested that foveal thickening occurs after onset of amblyopia and then regresses with treatment. However, examining 21 patients with hyperopic anisometropic amblyopia and 25 age-matched controls, Nishi\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e measured the foveal thickness and the thickness of the outer nuclear layer, photoreceptor inner segment layer and OS layer using SD-OCT and found that OS length was significantly thinner in amblyopic eyes than in fellow eyes. There are some differences between Nishi\u0026rsquo;s study and our study. First, the mean age of the subjects was younger (6.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3 years) in Nishi\u0026rsquo;s study than the subjects in our study (8.49\u0026thinsp;\u0026plusmn;\u0026thinsp;2.31 years). A previous study reported that foveal thickness increases significantly with age\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e and that the retina is still in the process of normal development during childhood and adolescents\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. Another pathological study suggested that human foveal cone density increases until around 5\u0026ndash;8 years of age\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. Second, the ethnicity of the subjects was different (Japanese vs. Chinese). Third, the measurement method for the OS was different. Retinal thickness was measured manually using the embedded OCT software used in Nishi\u0026rsquo;s study. Conversely, OS thickness was measured using longitudinal reflectance profile measurements in the present study. LRP can provide the coordinate site of the EZ and RPE, through which we can calculate exactly the OS length. Fourth, we enrolled more hyperopic anisometropic amblyopia patients (78 vs. 21 patients). The larger sample size and the more accurate measurements of retinal thickness are the strengths of this study. The difference of photoreceptor outer segment layer thickness between amblyopia and normal controls was only 0.5 to 2 pixels, which makes it difficult to identify this feature without the help of LRP quantitative measurement.\u003c/p\u003e \u003cp\u003eSome studies investigated the correlation of retinal thickness with visual outcome in eyes with amblyopia and found that visual acuity was not correlated with retinal thickness or structure. Dickmann et al.\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e found that macular thickness in both strabismus and anisometropic amblyopia had no correlation with visual acuity. Chen et al.\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e also failed to find a correlation between macular thickness and visual acuity even during the recovery of the visual acuity after treatment. Similarly, in the present study, neither OS thickness nor outer retinal reflectivity was correlated with the visual outcome. Greater Choroidal thickness in amblyopic eyes than in normal controls have been reported by previous studies, and this finding was considered associated with amblyopia. This study not only found that the thickness of choroid thickens in amblyopic eyes, but also found that OS was correlated with choroid thickness. Studies aforementioned and ours indicate that a greater OS thickness or higher reflectivity of outer retinal may associated with amblyopia but are unrelated to the degree of amblyopia.\u003c/p\u003e \u003cp\u003eOur study has some limitations. First, all the patients included were Chinese. Second, we only examined anisometropic amblyopia and did not study other types of amblyopia. Third, the measurement taken at 1 mm around the fovea was not corrected for axial length, which could have affected the lateral scale of the OCT datasets for peripheral measurements. Lastly, due to the study\u0026rsquo;s cross-sectional design, longitudinal OS changes were not observed. Future studies involving diversity ethnicity and more types of amblyopia are warranted to investigate the correlation of OS thickness changes with visual acuity improvement after amblyopia treatment.\u003c/p\u003e \u003cp\u003eConclusion, in the subfoveal area, the OS length was greater in amblyopic eyes than in fellow eyes of amblyopia. Moreover, differences were found in the OS thickness in both eyes of children with amblyopia compared to normal vision. For children with hyperopic anisometropia, the presence of amblyopia should be highly suspected if there is also a thickened OS, and it is necessary to detect changes in the thickness of OS during the amblyopia treatment.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgment:\u003c/strong\u003e No applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e This work was supported by the Guangdong medical research under Grant (A2022467).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eNone of the following authors have any proprietary interests or conflicts of interest related to this submission: Wenli Zhang, Tingkun Shi, Fan yang, Shirong Chen.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors contribution:\u0026nbsp;\u003c/strong\u003eConcept and design (WZ, TS), data of collection (WZ, FY and SC), drafting manuscript (WZ, TS), critical revision (TS). The authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate:\u0026nbsp;\u003c/strong\u003eAll patients gave their informed consent for their anonymized data to be submitted for audit and publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e: The Joint Shantou International Eye Center Institute Ethics Committee approved this study (EC 20201124(11)-P05).\u003c/p\u003e\n\u003cp\u003eThis submission has not been published anywhere previously and that it is not simultaneously being considered for any other publication. This manuscript has been read and approved by all the authors.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHeadon M P, Powell T P. Cellular changes in the lateral geniculate nucleus of infant monkeys after suture of the eyelids. J Ana. 1973;116:135-45.\u003c/li\u003e\n\u003cli\u003evon Noorden G K. Histological studies of the visual system in monkeys with experimental amblyopia. Invest Ophth. 1973;12:727-38.\u003c/li\u003e\n\u003cli\u003eBirch E E. Amblyopia and binocular vision. Prog Retin Eye Res. 2013;33:67-84.\u003c/li\u003e\n\u003cli\u003eBruce A, Pacey I E, Bradbury J A, Scally A J, Barrett B T. Bilateral changes in foveal structure in individuals with amblyopia. Ophthalmology. 2013;120:395-403.\u003c/li\u003e\n\u003cli\u003eCelik E, Cakir B, Turkoglu E B, Dogan E, Alagoz G. Evaluation of the retinal ganglion cell and choroidal thickness in young Turkish adults with hyperopic anisometropic amblyopia. Int Ophthalmol. 2016;36:515-20.\u003c/li\u003e\n\u003cli\u003eHuynh S C, Samarawickrama C, Wang X Y, Rochtchina E, Wong T Y, Gole G A, et al. Macular and nerve fiber layer thickness in amblyopia: the Sydney Childhood Eye Study. Ophthalmology. 2009;116:1604-9.\u003c/li\u003e\n\u003cli\u003eNishi T, Ueda T, Hasegawa T, Miyata K, Ogata N. Retinal thickness in children with anisohypermetropic amblyopia. Br J Ophthalmol. 2015;99:1060-4.\u003c/li\u003e\n\u003cli\u003eNishikawa N, Chua J, Kawaguchi Y, Ro-Mase T, Schmetterer L, Yanagi Y, et al. Macular Microvasculature and Associated Retinal Layer Thickness in Pediatric Amblyopia: Magnification-Corrected Analyses. Invest Ophth Vis Sci. 2021;62:39.\u003c/li\u003e\n\u003cli\u003eAl-Haddad C E, El Mollayess G M, Mahfoud Z R, Jaafar D F, Bashshur Z F. Macular ultrastructural features in amblyopia using high-definition optical coherence tomography. Br J Ophthalmol. 2013;97:318-22.\u003c/li\u003e\n\u003cli\u003eShi T, Zhang W, Chen S, Xia H, Chen H. Reduced Photoreceptor Outer Segment Layer Thickness and Association with Vision in Amblyopic Children and Adolescents with Unilateral High Myopia. Curr Eye Res. 2021;46:1892-9.\u003c/li\u003e\n\u003cli\u003eXia H, Ke X, Chen L J, Yan H, Chen H. Reduced photoreceptor outer segment layer thickness in mild commotio retinae without ellipsoid zone disruption. Graefes Arch Clin Exp Ophthalmol. 2020;258:1437-42.\u003c/li\u003e\n\u003cli\u003eMaldonado R S, O\u0026apos;Connell R V, Sarin N, Freedman S F, Wallace D K, Cotten C M, et al. Dynamics of Human Foveal Development after Premature Birth. Ophthalmology. 2011;118:2315-25.\u003c/li\u003e\n\u003cli\u003eYen M Y, Cheng C Y, Wang A G. Retinal nerve fiber layer thickness in unilateral amblyopia. Invest Ophth Vis Sci. 2004;45:2224-30.\u003c/li\u003e\n\u003cli\u003eChen W, Chen J, Zhang F, Zhu X, Lu F. Visual outcome in isoametropic amblyopic children with high hyperopia and the effect of therapy on retinal thickness. Am J Ophthalmol. 2013;155:536-43.e1.\u003c/li\u003e\n\u003cli\u003eSzigeti A, T\u0026aacute;trai E, Szamosi A, Vargha P, Nagy Z Z, N\u0026eacute;meth J, et al. A morphological study of retinal changes in unilateral amblyopia using optical coherence tomography image segmentation. PLoS One. 2014;9:e88363.\u003c/li\u003e\n\u003cli\u003eHendrickson A E. Primate foveal development: a microcosm of current questions in neurobiology. Invest Ophth Vis Sci. 1994;35:3129-33.\u003c/li\u003e\n\u003cli\u003eDickmann A, Petroni S, Perrotta V, Salerni A, Parrilla R, Aliberti S, et al. A morpho-functional study of amblyopic eyes with the use of optical coherence tomography and microperimetry. J AAPOS. 2011;15:338-41.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Hyperopic anisometropic amblyopia, Photoreceptor outer segment, Optical coherence tomography, reflectivity, choroidal thickness","lastPublishedDoi":"10.21203/rs.3.rs-4178975/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4178975/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo quantitatively investigate the reflectivity and structure of the outer retinal layers in children with hyperopic anisometropic amblyopia using swept-source optical coherence tomography (SS-OCT).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSeventy-eight patients with amblyopia and 64 age-matched children with normal vision were included in this study. All participants underwent SS-OCT and detailed ophthalmic examinations. Longitudinal reflectance profile measurements (LRP) were measured by Image J. The reflectivity of outer retinal layers was measured at the three selected positions: subfovea, 1 mm nasal to the fovea and 1 mm temporal to the fovea. The reflectivity ratios were calculated by outer retinal layers divided by the nuclear layer (ONL) for normalization. Photoreceptor outer segment layer thickness was also measured. The results were compared between the amblyopia and normal controls. The possible effects of age, sex and axial length on results were adjusted by generalized estimating equations (GEE).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePhotoreceptor outer segment layer thickness was significantly greater in amblyopic eyes than in normal control eyes at all three regions (18.41 ± 1.83 vs 16.84 ± 1.39, p \u0026lt; 0.001 at fovea; 14.78 ± 1.34 vs 14.19 ± 1.40, p = 0.030 at 1mm nasal to the foveal; 14.92 ± 1.48 vs 14.41 ± 1.32, p = 0.049 at 1mm temporal to the fovea). The reflectivity ratio of outer segment/ONL was higher only at 1mm nasal to the fovea (2.94 ± 0.61 vs 2.70 ± 0.42, \u003cem\u003ep\u003c/em\u003e = 0.02). Subfoveal OS thickness was positively correlated with choroidal thickness (r = 0.248, \u003cem\u003ep\u003c/em\u003e = 0.018), but was not correlated with spherical equivalent, age, axial length or LogMAR visual acuity.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eQuantitative measurement of SS-OCT images revealed that greater photoreceptor outer segment in both eyes of children with amblyopia than in normal control eyes. A thicker OS thickness is somehow related to amblyopia, and this may be a new useful diagnostic parameter for amblyopia.\u003c/p\u003e","manuscriptTitle":"Thickened Photoreceptor Outer Segment Layer in Children with Hyperopic Anisometropic Amblyopia","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-02 17:51:31","doi":"10.21203/rs.3.rs-4178975/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2df8b18a-ac83-4f49-aba0-7778e6cba6d0","owner":[],"postedDate":"April 2nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-05-31T11:24:02+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-02 17:51:31","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4178975","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4178975","identity":"rs-4178975","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}