Cone Mosaic in Eyes with Varied Axial Length Using Adaptive Optics Scanning Laser Ophthalmoscopy

Cone Mosaic in Eyes with Varied Axial Length Using Adaptive Optics Scanning Laser Ophthalmoscopy | 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 Cone Mosaic in Eyes with Varied Axial Length Using Adaptive Optics Scanning Laser Ophthalmoscopy Wen-Da Zhou, Li Dong, Han-Xu Shi, Rui-Heng Zhang, Yu-hang Yang, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5471967/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 Background Abnormalities in cone photoreceptors are closely associated with the occurrence of many ocular diseases. Adaptive Optics Scanning Laser Ophthalmoscopy (AOSLO) allows visualization of the living human retina with exquisite single-cell resolution. Methods This study aimed to found the potential relationship between cone cells and and axial myopia using a commercial AOSLO system in cone moasic. 74 patients (148 eyes; 30 (40.5%) men) with a mean age of 31.8 ± 10.4 years were icluded in this study. Cone mosic was obtained from the 3° and 5° eccentricities of macular. The relationship between cone cell indexes (linear cone density, cone spacing, cone dispersion and cone regularity) and axial length were analyzed. Results The linear cone density significantly declined with increasing axial length at both 3° and 5° eccentricities (all P <0.001). The cone spacing was significantly increasing with the increasing of axial length and the reduce of cone density. After adjusting for axial length, cone spacing was significantly associated only with linear cone density, both at 3° and 5° eccentricities (all P <0.001). The cone dispersion was significantly increasing with the increasing of axial length and the reduce of cone density. After adjusting for axial length, cone dispersion remained significantly associated with linear cone density only at the inferior 3° (β=-0.43, P = 0.014) and inferior 5° eccentricities (β=-0.4, P = 0.003). Cone regularity significantly increasing with increasing linear cone density and after adjusting for axial length, cone dispersion remained significantly associated with linear cone density only at the nasal 3° (β = 0.71, P < 0.001) and temporal 3° eccentricities (β = 0.25, P < 0.001). Cone regularity significantly decreased with increasing axial length and after adjusting for linear cone density, cone dispersion remained significantly associated with axial length at temporal 5° eccentricity (β=-0.57, P < 0.001). Conclusions Cone cell density was significantly decreased in axial myopia. The uniformity of cone distribution was decreased in axial myopia, which may be the indirected caused by a decrease in cone density due to axial elongation. The cone morphology regularity was significantly decreased in axial myopia, which may result directly from the axial elongation or indirectly from the cone density decrease it causes. Myopia Axial length Adaptive Optics Scanning Laser Ophthalmoscopy Cone Introduction Abnormalities in cone photoreceptors are closely associated with many ocular diseases, and recent findings suggest that cone photoreceptors may be involved in the development of myopia[ 1 – 3 ]. The axial l elongation is the primary cause of myopia, and the definite growth-regulating mechanism remains unclear at present[ 4 ]. However, local retinal visual signal related to defocus is now well-established in the regulation of eye growth. Some studies revealed that the eye could detect the sign of defocus by detecting the presence or absence of a chromatic signal across cone channels[ 2 , 5 , 6 ]. Therefore, the morphology and distribution of cones in the macular region are crucial indexes for evaluating the impact of axial myopia. In the past decade, with the emergence of adaptive optics(AO)technology, live images of photoreceptor cells had been obtained[ 7 ]. AO use a wavefront sensor and deformable mirror to measure and compensate aberrations, which allows visualization of the living human retina with exquisite single-cell resolution[ 7 ]. Many groups routinely are using Adaptive optics scanning laser ophthalmoscopy (AOSLO) to obtain in vivo images of fovea cone photoreceptor mosaic[ 8 – 12 ]. However, the most common used indexes were cone density and cone spacing, which could not fully reveal the characteristic of cone morphology and distribution in eyes with varying axial lengths. Furthermore, previous studies utilizing AOSLO systems have primarily focused on laboratory-grade equipment, which are large in size and require manual intervention during data processing, resulting in high labor and time costs. These significant drawbacks have greatly limited the widespread application of AOSLO systems in clinical practice. To promote the adoption of AOSLO systems in the clinical field, it is imperative to overcome these technical bottlenecks. In this study, we used the first commercial AOSLO system (Mona II, Robotrak Technologies, Nanjing, China) in China to obtain the cone mosaic of macuar region of eyes with varying axial lengths. We analysis the relashionship of axial length and the cone indexes incluing cone density, cone spacing, cone dispersion and cone regularity, which could further refine the cone characteristic in axial myopia and promote the clinic application of AOSLO. Methods Subjects This study was performed at Beijing Tongren Hospital (Beijing, China). All subjects were recruited from the healthy examnation center of Beijing Tongren Hospital. The study protocol followed guidelines set by the Declaration of Helsinki. Written informed consent was obtained from each participant. Inclusion criterion was the absence of any retinal or optic nerve disease. Additional exclusion criteria were a history of major systemic diseases, such as diabetes mellitus or arterial hypertension, and previous intraocular surgery or ocular trauma. All subjects received a complete eye examination and no fundus abnormalities were found other than fundus tessellation. All had best corrected visual acuity of 20/20 or better. Ocular biometry such as axial length, anterior chamber depth and keratometry was measured with a biometer (IOL-Master, Carl Zeiss Meditec AG, Jena, Germany). It is worth noting that the longest axial length included in this study was 29mm, as patients with excessively long axial lengths often present with highly irregular astigmatism, along with posterior scleral expansion, making imaging with the AOSLO system challenging. AOSLO system Subjects were imaged using a commercialized AOSLO system (Mona II, Robotrak Technologies, Nanjing, China). This system utilizes an 840 nm light source with a full-width half-maximum (FWHM) of 40 nm. The field of view on the retina spans 2.4 × 2.4° (approximately 700 × 700 µm) and is designed to cover a 7mm exit pupil. Horizontal scanning is accomplished using an 8kHz resonant scanner mirror, while vertical scanning is achieved with a 14Hz galvo mirror, resulting in a 14 Hz frame rate. To maintain confocality, a pinhole with a diameter equal to approximately 2 Airy disks is placed before an Avalanche Photo Diode (APD) detector. For accurate correction of ocular aberrations, the system employs a high-speed deformable mirror, which operates in conjunction with a custom Shack-Hartmann wavefront sensor. This powerful combination ensures precise aberration correction, enhancing the imaging quality of the AOSLO system. To ensure subject safety, the imaging power entering the subject's pupil is meticulously controlled, remaining below 600 µW and well within the safety limits defined by ANSI (American National Standards Institute) standards. The AOSLO system is also equipped with a real-time retina tracking module, ensuring eye-motion stabilization and efficient imaging. To capture high-quality images, each retinal location is imaged for approximately 3 seconds, resulting in ~ 40 frames. These frames undergo a dewarping process to eliminate distortion introduced by the sinusoidal motion of the resonant scanner. Subsequently, an automatic detection system identifies and removes invalid frames caused by blinking or saccades, ensuring only the most reliable frames are retained. Finally, a strip-based registration process is employed. The aligned frames are averaged to improve the signal-to-noise ratio. The entire process takes place right after each imaging session and will automatically generate a registered image by the Mona II software. Image acquisition and cone indexes Both eyes of each subject were dilated and cyclopleged with 1% Tropicamide before imaging. All images were collected from the nasal, temporal, superior, and inferior orientations at 3° and 5° from the foveal in each eye. Three images were captured at each imaging point, and the imaging quality of each image was assessed by three different ophthalmologists. If two or more ophthalmologists deemed the imaging quality of a particular image acceptable, it was retained; otherwise, it was deleted. For quantitative cell analysis, the AOSLO system uses AI-based algorithm for automatic photoreceptor segmentation and generates statistical descriptors of photoreceptor morphology properties[ 13 ]. In this study, we utilized four metrics: cone density, cone spacing, cone dispersion, and cone regularity. The AOSLO system computed linear cone density. Cone spacing represents the average distance between the centers of nearest neighboring cones. At the foveal, all photoreceptor cells are cones. With increasing eccentricity, there is a gradual decrease in cone density, and the spaces between cones are filled with smaller rod cells. Analyzing the uniformity of cone distribution around the fovea is also clinically significant. However, cone spacing alone may not fully reflect the overall uniformity of cone distribution. To address this, we further calculated cone dispersion, which is the ratio of the mean to the standard deviation of cone spacing. Smaller cone dispersion values indicate a more uniform distribution of cones. Cone regularity is a metric that reflects the arrangement and distribution of cone cells, derived from the construction of Voronoi diagrams. Previous studies have suggested that cone cells tend to arrange around a single cell with approximately six neighboring cells, forming a hexagonal pattern on the Voronoi diagram[ 8 ]. Therefore, in this study, we defined cone regularity as the proportion of quadrilateral to octagonal shapes on the Voronoi diagram. A higher cone regularity indicates a more orderly arrangement of cone cells. Statistical analysis Statistical analyses were performed using SPSS software (version 27.0; IBM SPSS Statistics for Windows, Armonk, NY). The Shapiro–Wilk test was performed to determine whether the data were normally distributed. Data with a normal distribution were presented as mean ± standard deviation. Data not following a normal distribution were presented as the first quartile (Q1) and third quartile (Q3). We calculated the standardized regression coefficient beta and the non-standardized regression B with its 95% confidence intervals (CIs). Two-sided P -values smaller than 0.05 were considered to be statistically significant. Results The study included 74 patients (148 eyes; 30 (40.5%) men) with a mean age of 31.8 ± 10.4 years (range: 15–60 years) and a mean axial length of 25 ± 1.6 mm (range: 21.5–29 mm). All of them were East Asian ethnicity. Only the best-quality image from different eccentricities was retained, and poor-quality images were discarded. Basic data were presented in Table 1 . Table 1 Demographics and characteristics of the data sets Location Number of qualified images Age (mean ± SD, y) Number of men (%) Axial length (mean ± SD, mm) Cone density (mean ± SD, mm 2 ) Cone spacing (mean ± SD, µm) Cone dispersion(mean ± SD) Cone regularity(mean ± SD) 3˚ eccentricity Temporal Nasal Superior Inferior 122 110 109 106 31.08 ± 9.35 30.44 ± 8.38 30.1 ± 10.32 30.8 ± 9.05 49 (40.2) 45 (40.9) 47 (43.1) 46 (43.4) 25.13 ± 1.58 25.2 ± 1.6 25.08 ± 1.63 25.2 ± 1.63 17357.21 ± 3025.08 17406.8 ± 2982.04 15398.74 ± 3033.77 15924.16 ± 3077.55 6.2 ± 0.76 6.20 ± 0.76 6.44 ± 0.79 6.37 ± 0.71 0.206 ± 0.036 0.204 ± 0.038 0.233 ± 0.038 0.221 ± 0.035 0.948 ± 0.014 0.947 ± 0.014 0.939 ± 0.013 0.940 ± 0.013 5˚ eccentricity Temporal Nasal Superior Inferior 110 104 107 96 31.2 ± 9.6 30.4 ± 8.9 30.8 ± 9.2 31 ± 9.8 46 (41.8) 44 (42.3) 46 (43.0) 43 (44.8) 25.13 ± 1.64 25.07 ± 1.62 25.08 ± 1.58 25.13 ± 1.69 15168.79 ± 3136.69 14766.87 ± 2941.16 13428.12 ± 2696.19 12877.75 ± 3369.75 6.42 ± 0.66 6.47 ± 0.69 6.68 ± 0.81 6.78 ± 0.85 0.232 ± 0.036 0.232 ± 0.037 0.251 ± 0.040 0.261 ± 0.042 0.937 ± 0.013 0.936 ± 0.014 0.928 ± 0.012 0.924 ± 0.014 Note: SD: standard deviation. Table 2 Associations (univariable analysis) between between cone indexes (cone spacing, cone dispersion and cone regularity) and cone density, and between cone indexes (linear cone density, cone spacing, cone dispersion and cone regularity) and axial length. Liner cone density* Standardized regression coefficient beta Non-standardized regression coefficient B 95% Confidence intervals of B P -value Axial length Nasal 3° eccentricity -0.77 -1435.2 -1661.3, -1209.1 < 0.001 Temporal 3°eccentricity -0.75 -1437.7 -1665.6, -1209.8 < 0.001 Superior 3° eccentricity -0.74 -1370.6 -1610.4, -1130.7 < 0.001 Inferior 3° eccentricity -0.84 -1587.3 -1787.3, -1387.3 < 0.001 Nasal 5° eccentricity -0.68 -1250.3 -1510.3, -990.4 < 0.001 Temporal 5°eccentricity -0.64 -1220.4 -1502.5, -938.2 < 0.001 Superior 5° eccentricity -0.55 -934.9 -1210.2, -659.6 < 0.001 Inferior 5° eccentricity -0.68 -1359.1 -1667.2, -1061.1 < 0.001 Cone spacing* Axial length Nasal 3° eccentricity 0.57 0.27 0.2,0.35 < 0.001 Temporal 3°eccentricity 0.57 0.27 0.2,0.35 < 0.001 Superior 3° eccentricity 0.69 0.33 0.27,0.4 < 0.001 Inferior 3° eccentricity 0.72 0.31 0.25,0.37 < 0.001 Nasal 5° eccentricity 0.59 0.25 0.18,0.32 < 0.001 Temporal 5°eccentricity 0.52 0.21 0.14,0.27 < 0.001 Superior 5° eccentricity 0.46 0.23 0.15,0.32 < 0.001 Inferior 5° eccentricity 0.62 0.31 0.23,0.39 < 0.001 Liner cone density Nasal 3° eccentricity -0.62 0 0,0 < 0.001 Temporal 3°eccentricity -0.67 0 0,0 < 0.001 Superior 3° eccentricity -0.85 0 0,0 < 0.001 Inferior 3° eccentricity -0.93 0 0,0 < 0.001 Nasal 5° eccentricity -0.89 0 0,0 < 0.001 Temporal 5°eccentricity -0.93 0 0,0 < 0.001 Superior 5° eccentricity -0.89 0 0,0 < 0.001 Inferior 5° eccentricity -0.89 0 0,0 < 0.001 Cone dispersion* Axial length Nasal 3° eccentricity 0.25 0.006 0.001,0.01 0.009 Inferior 3° eccentricity 0.25 0.006 0.001,0.01 0.008 Temporal 5°eccentricity 0.22 0.005 0.001,0.009 0.02 Inferior 5° eccentricity 0.21 0.005 0.00,0.01 0.04 Liner cone density Nasal 3° eccentricity -0.46 -0.00 0,0 < 0.001 Inferior 3° eccentricity -0.34 -0.00 0,0 < 0.001 Temporal 5° eccentricity -0.21 -0.00 0,0 0.02 Inferior 5° eccentricity -0.36 -0.00 0,0 < 0.001 Cone regularity* Liner cone density Nasal 3° eccentricity 0.34 0 0,0 < 0.001 Temporal 3°eccentricity 0.25 0 0,0 0.006 Inferior 3° eccentricity 0.2 0 0,0 0.04 Axial length Temporal 5°eccentricity -0.57 -0.002 -0.003,0 < 0.001 Note: * the dependent variable The linear cone density significantly declined with increasing axial length at both 3° (nasal: β=-0.77, P < 0.001; temporal: β=-0.75, P < 0.001; superior: β=-0.74, P < 0.001; inferior: β=-0.84, P < 0.001) and 5° eccentricities (nasal: β=-0.68, P < 0.001; temporal: β=-0.64, P < 0.001; superior: β=-0.55, P < 0.001; inferior: β=-0.68, P 0.2) or 5° eccentricities (all P > 0.05). Cone spacing was significantly increased with increasing axial length at 3° (nasal: β = 0.57, P < 0.001; temporal: β = 0.57, P < 0.001; superior: β = 0.69, P < 0.001; inferior: β = 0.72, P < 0.001) and 5° eccentricities (nasal: β = 0.59, P < 0.001; temporal: β = 0.52, P < 0.001; superior: β = 0.46, P < 0.001; inferior: β = 0.62, P < 0.001) and was significantly reduced with increasing linear cone density at 3° (nasal: β=-0.62, P < 0.001; temporal: β=-0.67, P < 0.001; superior: β=-0.85, P < 0.001; inferior: β=-0.80, P < 0.001) and 5° eccentricities (nasal: β=-0.89, P < 0.001; temporal: β=-0.93, P < 0.001; superior: β=-0.89, P < 0.001; inferior: β=-0.89, P < 0.001). After adjusting for axial length, cone spacing was significantly associated only with linear cone density, both at 3° (nasal: β=-0.44, P < 0.001; temporal: β=-0.56, P < 0.001; superior: β=-0.76, P < 0.001; inferior: β=-0.66, P < 0.001) and 5° eccentricities (nasal: β=-0.91, P < 0.001; temporal: β=-0.93, P < 0.001; superior: β=-0.92, P < 0.001; inferior: β=-0.87, P < 0.001). Cone dispersion significantly decreased with increasing linear cone density at 3° eccentricities (nasal: β=-0.46, P < 0.001; inferior: β=-0.34, P < 0.001) and 5° eccentricities (temporal: β=-0.21, P = 0.02; inferior: β=-0.36, P < 0.001). It also significantly increased with axial length at specific 3° eccentricities (nasal: β = 0.25, P = 0.009; inferior: β = 0.25, P = 0.008) and 5° eccentricities (temporal: β = 0.22, P = 0.02; inferior: β = 0.21, P = 0.04). After adjusting for axial length, cone dispersion remained significantly associated with linear cone density only at the inferior 3° (β=-0.43, P = 0.014) and inferior 5° eccentricities (β=-0.4, P = 0.003). Cone regularity significantly increasing with increasing linear cone density at certain 3° eccentricities (nasal: β = 0.34, P < 0.001; temporal: β = 0.25, P = 0.006; inferior: β = 0.2, P = 0.04). After adjusting for axial length, cone dispersion remained significantly associated with linear cone density only at the nasal 3° (β = 0.71, P < 0.001) and temporal 3° eccentricities (β = 0.25, P < 0.001). Cone regularity significantly decreased with increasing axial length at temporal 5° eccentricity (β=-0.24, P = 0.013), after adjusting for linear cone density, cone dispersion remained significantly associated with axial length at temporal 5° eccentricity (β=-0.57, P < 0.001). Discussion In this study, we utilized a commercial AOSLO system to establish the first dataset of cone mosaic in the Chinese population, mainly focusing on the relationship between axial length and cone morphology properties. As expected, we observed a decrease in the linear cone density with increasing axial length after adjusting the age and gender, consistent with findings from previous studies [ 8 – 10 ]. However, the linear cone density only revealed the cones number in the linear dimension, which could not fully explain decline in retinal resolution observed in the myopic population [ 11 , 14 – 16 ]. The cone spcing and was used to evaluated the uniformity of cone distribution and previous studies found the increasing of cone spacing with the axial elongation [ 8 – 10 ]. In our analysis, after adjusting the influence of axial length the increased cone spacing was only associated with the decreased linear cone density. Compared to the cone spacing, the cone dispersion chould better evaluated the uniformity of cone distribution. In our study, we found the cone dispersion was significiatly increased with the decreasing of cone density and increasing of axial length. However, after adjusting the influence of axial length the increased cone dispersion was only associated with the decreased cone density. These indicated that the uniformity of cone distribution was decreased in axial myopia, which may be the indirected caused by a decrease in cone density due to axial elongation. Cone regularity could evaluate the morphology of single cone cell, in our study, we found the cone regularity was significiatly decreased with the decreasing of cone density. The axial elongation cloud also causes the decrease of cone regularity independently of the decread of cone density, which provides a new perspective for understanding the decline in retinal resolution in myopic population. Cone density and distribution also changed with the eccentricity increased[ 9 , 10 ], After adjusting for the influence of axial length, the effect of cone density on cone regularity was observed at 3° eccentricity, while the independent effect of axial length on cell regularity occurred at 5° eccentricity. This suggests that as eccentricity increases, the influence of axial length on cell regularity may become more significant. However, it is regrettable that the range of eccentricities obtained in this study was limited, and further research can be conducted in the future.Cone photoreceptors may serve as the starting point for defocus signals and play a crucial role in the process of eyeball growth and myopia development[ 3 , 5 ]. Our study further suggests a relationship between cone abnormalities and myopia. Future studies should aim to validate the causal relationship between the cone abnormalities and defocus signals in lens-induced myopia models. The normal human cone mosaic consists of three types of cones, each sensitive to different regions of the visible spectrum[ 6 ]. The non-invasive differentiation of these distinct cell types is crucial for further validating the role of LCA in ocular growth[ 5 ]. The ability to visualize the trichromatic cone mosaic has led to numerous psychophysical studies[ 17 – 21 ]. These techniques provide essential support for future investigations into the role of cone photoreceptors in myopia development. With the clinical application of AOSLO systems in ophthalmology centers across the country, it will play a crucial role in early disease screening and diagnosis[ 22 – 25 ]. The AOSLO system employed in this study represents the first commercial AOSLO equipment approved in China. It boasts several features conducive to large-scale clinical applications: compact size, brief examination duration, minimal patient cooperation requirements, and automated operation with automatic analysis of examination results. These advantages lay the groundwork for establishing multicenter, large-scale clinical datasets in the future, marking a pivotal step in advancing the clinical utility of AOSLO. The findings of this study can guide future AOSLO clinical application in axial myopia population. There are several limitations in this study that need to be addressed. Firstly, we found that image quality is significantly affected by tear film interference, making it difficult to obtain clear cone mosaic images, particularly in patients with dry eye syndrome. This was a major factor contributing to the inadequate quality of images in this study. Furthermore, current AOSLO systems face challenges in imaging in patients with myopic maculopathy. Myopic maculopathy is a leading cause of irreversible blindness in myopic patients, and its pathogenesis remains unclear. In the future, if imaging of photoreceptor cells in the macular area of patients with pathological myopia can be achieved, it will further validate the relationship between axial length and cone metrics, thus greatly aiding research into the pathogenesis of pathological myopia. Conclusion This study established the first cone mosaic dataset in healthy Chinese individuals with various axial length, shedding light on the relationship between cone morphology properties and myopia. The AOSLO system used in this study is compact in size and capable of automatically performing cone mosaic analysis, which has greatly facilitated the integration of the AOSLO system into clinical practice. Declarations Ethics approval and consent to participate: This study adheres to the tenets of the Declaration of Helsinki. and was approved by The Institutional Review Board and Medical Ethics Committee at Beijing Tongren Hospital approved this study (TRECKY2018-056-GZ (2022)-07). The written informed consent was obtained from all subjects after the nature and possible complications of the study protocol were explained. Availability of data and materials The data that support the findings of this study are not publicly available due to their containing information that could compromise the privacy of research participants but are available from the corresponding author upon reasonable request. Consent for publication In this study, all participants provided written informed consent for the publication of their individual details and images. Additional consent was obtained from the participants for the publication of identifiable images. Funding This study was supported by the National Natural Science Foundation of China (82220108017, 82141128, 82401283); The Capital Health Research and Development of Special (2024-1-2052);Science & Technology Project of Beijing Municipal Science & Technology Commission (Z201100005520045)；Sanming Project of Medicine in Shenzhen (No. SZSM202311018); Scientific Research Common Program of Beijing Municipal Commission of Education (No. KM202410025011); The priming scientific research foundation for the junior researcher in Beijing Tongren Hospital, Capital Medical University (No. 2023-YJJ-ZZL-003). Author Contributions Concept and design: Wen-Da Zhou, Li Dong, Lei Shao, Wen-Bin Wei. Acquisition, analysis, or interpretation of data: Wen-Da Zhou, Li Dong, Han-Xu Shi, Rui-Heng Zhang, Yu-hang Yang, Han-qing Zhao, Yi-Tong Li, Chu-Yao Yu, He-Yan Li, Hao-Tian Wu. Critical revision of the manuscript for important intellectual content: All authors. 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Britten-Jones AC, Thai L, Flanagan JPM, Bedggood PA, Edwards TL, Metha AB, Ayton LN. Adaptive optics imaging in inherited retinal diseases: A scoping review of the clinical literature. Surv Ophthalmol. 2024;69(1):51–66. Ooto S, Hangai M, Takayama K, Sakamoto A, Tsujikawa A, Oshima S, Inoue T, Yoshimura N. High-resolution imaging of the photoreceptor layer in epiretinal membrane using adaptive optics scanning laser ophthalmoscopy. Ophthalmology. 2011;118(5):873–81. 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-5471967","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":382077554,"identity":"b99467cd-c068-472e-b420-01de26e3bdee","order_by":0,"name":"Wen-Da Zhou","email":"","orcid":"","institution":"Beijing Tongren Eye Centre, Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Wen-Da","middleName":"","lastName":"Zhou","suffix":""},{"id":382077556,"identity":"8e69f740-552b-40e4-86bc-777c879c3232","order_by":1,"name":"Li Dong","email":"","orcid":"","institution":"Beijing Tongren Eye Centre, Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Li","middleName":"","lastName":"Dong","suffix":""},{"id":382077557,"identity":"395692c2-7460-4dfd-943b-dbc898e77f34","order_by":2,"name":"Han-Xu Shi","email":"","orcid":"","institution":"Beijing Tongren Eye Centre, Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Han-Xu","middleName":"","lastName":"Shi","suffix":""},{"id":382077560,"identity":"46d16db4-e258-4a20-a586-007664f38631","order_by":3,"name":"Rui-Heng Zhang","email":"","orcid":"","institution":"Beijing Tongren Eye Centre, Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Rui-Heng","middleName":"","lastName":"Zhang","suffix":""},{"id":382077563,"identity":"ed0910bb-076d-4285-ac68-4d0ec57122b0","order_by":4,"name":"Yu-hang Yang","email":"","orcid":"","institution":"Beijing Tongren Eye Centre, Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yu-hang","middleName":"","lastName":"Yang","suffix":""},{"id":382077564,"identity":"b4a0b3fe-933e-4ece-93c4-6104d89f21a6","order_by":5,"name":"Han-qing Zhao","email":"","orcid":"","institution":"Beijing Tongren Eye Centre, Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Han-qing","middleName":"","lastName":"Zhao","suffix":""},{"id":382077565,"identity":"a919cec5-3fe5-4f9b-9199-7881aaae422a","order_by":6,"name":"Yi-Tong Li","email":"","orcid":"","institution":"Beijing Tongren Eye Centre, Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yi-Tong","middleName":"","lastName":"Li","suffix":""},{"id":382077567,"identity":"c4332a55-7685-4987-8a69-24176a5ab51d","order_by":7,"name":"Chu-Yao Yu","email":"","orcid":"","institution":"Beijing Tongren Eye Centre, Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Chu-Yao","middleName":"","lastName":"Yu","suffix":""},{"id":382077568,"identity":"5e2aae54-4d4c-4cd4-b4c3-c256c6fe279e","order_by":8,"name":"He-Yan Li","email":"","orcid":"","institution":"Beijing Tongren Eye Centre, Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"He-Yan","middleName":"","lastName":"Li","suffix":""},{"id":382077569,"identity":"87dd48f1-5a5e-42bd-9eaf-c935ede03cc0","order_by":9,"name":"Hao-Tian Wu","email":"","orcid":"","institution":"Beijing Tongren Eye Centre, Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Hao-Tian","middleName":"","lastName":"Wu","suffix":""},{"id":382077570,"identity":"9f995104-9351-491e-99b6-0796b99c1dc1","order_by":10,"name":"Lei Shao","email":"","orcid":"","institution":"Beijing Tongren Eye Centre, Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Lei","middleName":"","lastName":"Shao","suffix":""},{"id":382077571,"identity":"97437901-977a-4218-afd5-225d3cbdceb1","order_by":11,"name":"Wen-Bin Wei","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAz0lEQVRIiWNgGAWjYFACxgYgcYAHxHqQUFFDihY2BmaDB2eOEW3VAQagFjbJhy3MhNUaHG9uk/i4446MuXzvs4rEBjYG/vbuBPxazhxsk5x55hmPZRu72Y3EHTIMEmfObsCrBais7TZv22Eeg2NsbDcSz7AxGEjkEtBy/2Hb7b9QLQWJbcxEaLnB2HabEaqFgSgt9mcS23/2tj0Dakljlkg4c4yHoF8k248/NvjZdsfe4PAxxo8/Kmrk+Nt78WvBADykKR8Fo2AUjIJRgBUAANX1TNtCHWG5AAAAAElFTkSuQmCC","orcid":"","institution":"Beijing Tongren Eye Centre, Capital Medical University","correspondingAuthor":true,"prefix":"","firstName":"Wen-Bin","middleName":"","lastName":"Wei","suffix":""}],"badges":[],"createdAt":"2024-11-18 01:38:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5471967/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5471967/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":72581320,"identity":"c9b9b5ca-d167-4906-906e-58f16e27b75c","added_by":"auto","created_at":"2024-12-30 05:34:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":630992,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5471967/v1/3406446d-aff3-46a9-8d0d-0e0d7957c2c0.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Cone Mosaic in Eyes with Varied Axial Length Using Adaptive Optics Scanning Laser Ophthalmoscopy","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAbnormalities in cone photoreceptors are closely associated with many ocular diseases, and recent findings suggest that cone photoreceptors may be involved in the development of myopia[\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The axial l elongation is the primary cause of myopia, and the definite growth-regulating mechanism remains unclear at present[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. However, local retinal visual signal related to defocus is now well-established in the regulation of eye growth. Some studies revealed that the eye could detect the sign of defocus by detecting the presence or absence of a chromatic signal across cone channels[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Therefore, the morphology and distribution of cones in the macular region are crucial indexes for evaluating the impact of axial myopia.\u003c/p\u003e \u003cp\u003eIn the past decade, with the emergence of adaptive optics(AO)technology, live images of photoreceptor cells had been obtained[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. AO use a wavefront sensor and deformable mirror to measure and compensate aberrations, which allows visualization of the living human retina with exquisite single-cell resolution[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Many groups routinely are using Adaptive optics scanning laser ophthalmoscopy (AOSLO) to obtain in vivo images of fovea cone photoreceptor mosaic[\u003cspan additionalcitationids=\"CR9 CR10 CR11\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. However, the most common used indexes were cone density and cone spacing, which could not fully reveal the characteristic of cone morphology and distribution in eyes with varying axial lengths. Furthermore, previous studies utilizing AOSLO systems have primarily focused on laboratory-grade equipment, which are large in size and require manual intervention during data processing, resulting in high labor and time costs. These significant drawbacks have greatly limited the widespread application of AOSLO systems in clinical practice. To promote the adoption of AOSLO systems in the clinical field, it is imperative to overcome these technical bottlenecks.\u003c/p\u003e \u003cp\u003eIn this study, we used the first commercial AOSLO system (Mona II, Robotrak Technologies, Nanjing, China) in China to obtain the cone mosaic of macuar region of eyes with varying axial lengths. We analysis the relashionship of axial length and the cone indexes incluing cone density, cone spacing, cone dispersion and cone regularity, which could further refine the cone characteristic in axial myopia and promote the clinic application of AOSLO.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSubjects\u003c/h2\u003e \u003cp\u003eThis study was performed at Beijing Tongren Hospital (Beijing, China). All subjects were recruited from the healthy examnation center of Beijing Tongren Hospital. The study protocol followed guidelines set by the Declaration of Helsinki. Written informed consent was obtained from each participant. Inclusion criterion was the absence of any retinal or optic nerve disease. Additional exclusion criteria were a history of major systemic diseases, such as diabetes mellitus or arterial hypertension, and previous intraocular surgery or ocular trauma. All subjects received a complete eye examination and no fundus abnormalities were found other than fundus tessellation. All had best corrected visual acuity of 20/20 or better. Ocular biometry such as axial length, anterior chamber depth and keratometry was measured with a biometer (IOL-Master, Carl Zeiss Meditec AG, Jena, Germany). It is worth noting that the longest axial length included in this study was 29mm, as patients with excessively long axial lengths often present with highly irregular astigmatism, along with posterior scleral expansion, making imaging with the AOSLO system challenging.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eAOSLO system\u003c/h3\u003e\n\u003cp\u003eSubjects were imaged using a commercialized AOSLO system (Mona II, Robotrak Technologies, Nanjing, China). This system utilizes an 840 nm light source with a full-width half-maximum (FWHM) of 40 nm. The field of view on the retina spans 2.4 \u0026times; 2.4\u0026deg; (approximately 700 \u0026times; 700 \u0026micro;m) and is designed to cover a 7mm exit pupil. Horizontal scanning is accomplished using an 8kHz resonant scanner mirror, while vertical scanning is achieved with a 14Hz galvo mirror, resulting in a 14 Hz frame rate. To maintain confocality, a pinhole with a diameter equal to approximately 2 Airy disks is placed before an Avalanche Photo Diode (APD) detector. For accurate correction of ocular aberrations, the system employs a high-speed deformable mirror, which operates in conjunction with a custom Shack-Hartmann wavefront sensor. This powerful combination ensures precise aberration correction, enhancing the imaging quality of the AOSLO system. To ensure subject safety, the imaging power entering the subject's pupil is meticulously controlled, remaining below 600 \u0026micro;W and well within the safety limits defined by ANSI (American National Standards Institute) standards. The AOSLO system is also equipped with a real-time retina tracking module, ensuring eye-motion stabilization and efficient imaging. To capture high-quality images, each retinal location is imaged for approximately 3 seconds, resulting in ~\u0026thinsp;40 frames. These frames undergo a dewarping process to eliminate distortion introduced by the sinusoidal motion of the resonant scanner. Subsequently, an automatic detection system identifies and removes invalid frames caused by blinking or saccades, ensuring only the most reliable frames are retained. Finally, a strip-based registration process is employed. The aligned frames are averaged to improve the signal-to-noise ratio. The entire process takes place right after each imaging session and will automatically generate a registered image by the Mona II software.\u003c/p\u003e\n\u003ch3\u003eImage acquisition and cone indexes\u003c/h3\u003e\n\u003cp\u003eBoth eyes of each subject were dilated and cyclopleged with 1% Tropicamide before imaging. All images were collected from the nasal, temporal, superior, and inferior orientations at 3\u0026deg; and 5\u0026deg; from the foveal in each eye. Three images were captured at each imaging point, and the imaging quality of each image was assessed by three different ophthalmologists. If two or more ophthalmologists deemed the imaging quality of a particular image acceptable, it was retained; otherwise, it was deleted.\u003c/p\u003e \u003cp\u003eFor quantitative cell analysis, the AOSLO system uses AI-based algorithm for automatic photoreceptor segmentation and generates statistical descriptors of photoreceptor morphology properties[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In this study, we utilized four metrics: cone density, cone spacing, cone dispersion, and cone regularity. The AOSLO system computed linear cone density. Cone spacing represents the average distance between the centers of nearest neighboring cones. At the foveal, all photoreceptor cells are cones. With increasing eccentricity, there is a gradual decrease in cone density, and the spaces between cones are filled with smaller rod cells. Analyzing the uniformity of cone distribution around the fovea is also clinically significant. However, cone spacing alone may not fully reflect the overall uniformity of cone distribution. To address this, we further calculated cone dispersion, which is the ratio of the mean to the standard deviation of cone spacing. Smaller cone dispersion values indicate a more uniform distribution of cones. Cone regularity is a metric that reflects the arrangement and distribution of cone cells, derived from the construction of Voronoi diagrams. Previous studies have suggested that cone cells tend to arrange around a single cell with approximately six neighboring cells, forming a hexagonal pattern on the Voronoi diagram[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Therefore, in this study, we defined cone regularity as the proportion of quadrilateral to octagonal shapes on the Voronoi diagram. A higher cone regularity indicates a more orderly arrangement of cone cells.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed using SPSS software (version 27.0; IBM SPSS Statistics for Windows, Armonk, NY). The Shapiro\u0026ndash;Wilk test was performed to determine whether the data were normally distributed. Data with a normal distribution were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. Data not following a normal distribution were presented as the first quartile (Q1) and third quartile (Q3). We calculated the standardized regression coefficient beta and the non-standardized regression B with its 95% confidence intervals (CIs). Two-sided \u003cem\u003eP\u003c/em\u003e-values smaller than 0.05 were considered to be statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe study included 74 patients (148 eyes; 30 (40.5%) men) with a mean age of 31.8\u0026thinsp;\u0026plusmn;\u0026thinsp;10.4 years (range: 15\u0026ndash;60 years) and a mean axial length of 25\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6 mm (range: 21.5\u0026ndash;29 mm). All of them were East Asian ethnicity. Only the best-quality image from different eccentricities was retained, and poor-quality images were discarded. Basic data were presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\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\u003eDemographics and characteristics of the data sets\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" 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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLocation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber of qualified images\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003cp\u003e(mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, y)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNumber of men (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAxial length (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, mm)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCone density (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, mm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eCone spacing (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, \u0026micro;m)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eCone dispersion(mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eCone regularity(mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3˚ eccentricity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTemporal\u003c/p\u003e \u003cp\u003eNasal\u003c/p\u003e \u003cp\u003eSuperior\u003c/p\u003e \u003cp\u003eInferior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e122\u003c/p\u003e \u003cp\u003e110\u003c/p\u003e \u003cp\u003e109\u003c/p\u003e \u003cp\u003e106\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31.08\u0026thinsp;\u0026plusmn;\u0026thinsp;9.35\u003c/p\u003e \u003cp\u003e30.44\u0026thinsp;\u0026plusmn;\u0026thinsp;8.38\u003c/p\u003e \u003cp\u003e30.1\u0026thinsp;\u0026plusmn;\u0026thinsp;10.32\u003c/p\u003e \u003cp\u003e30.8\u0026thinsp;\u0026plusmn;\u0026thinsp;9.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e49 (40.2)\u003c/p\u003e \u003cp\u003e45 (40.9)\u003c/p\u003e \u003cp\u003e47 (43.1)\u003c/p\u003e \u003cp\u003e46 (43.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25.13\u0026thinsp;\u0026plusmn;\u0026thinsp;1.58\u003c/p\u003e \u003cp\u003e25.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003cp\u003e25.08\u0026thinsp;\u0026plusmn;\u0026thinsp;1.63\u003c/p\u003e \u003cp\u003e25.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e17357.21\u0026thinsp;\u0026plusmn;\u0026thinsp;3025.08\u003c/p\u003e \u003cp\u003e17406.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2982.04\u003c/p\u003e \u003cp\u003e15398.74\u0026thinsp;\u0026plusmn;\u0026thinsp;3033.77\u003c/p\u003e \u003cp\u003e15924.16\u0026thinsp;\u0026plusmn;\u0026thinsp;3077.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.76\u003c/p\u003e \u003cp\u003e6.20\u0026thinsp;\u0026plusmn;\u0026thinsp;0.76\u003c/p\u003e \u003cp\u003e6.44\u0026thinsp;\u0026plusmn;\u0026thinsp;0.79\u003c/p\u003e \u003cp\u003e6.37\u0026thinsp;\u0026plusmn;\u0026thinsp;0.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.206\u0026thinsp;\u0026plusmn;\u0026thinsp;0.036\u003c/p\u003e \u003cp\u003e0.204\u0026thinsp;\u0026plusmn;\u0026thinsp;0.038\u003c/p\u003e \u003cp\u003e0.233\u0026thinsp;\u0026plusmn;\u0026thinsp;0.038\u003c/p\u003e \u003cp\u003e0.221\u0026thinsp;\u0026plusmn;\u0026thinsp;0.035\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.948\u0026thinsp;\u0026plusmn;\u0026thinsp;0.014\u003c/p\u003e \u003cp\u003e0.947\u0026thinsp;\u0026plusmn;\u0026thinsp;0.014\u003c/p\u003e \u003cp\u003e0.939\u0026thinsp;\u0026plusmn;\u0026thinsp;0.013\u003c/p\u003e \u003cp\u003e0.940\u0026thinsp;\u0026plusmn;\u0026thinsp;0.013\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e5˚ eccentricity\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTemporal\u003c/p\u003e \u003cp\u003eNasal\u003c/p\u003e \u003cp\u003eSuperior\u003c/p\u003e \u003cp\u003eInferior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e110\u003c/p\u003e \u003cp\u003e104\u003c/p\u003e \u003cp\u003e107\u003c/p\u003e \u003cp\u003e96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31.2\u0026thinsp;\u0026plusmn;\u0026thinsp;9.6\u003c/p\u003e \u003cp\u003e30.4\u0026thinsp;\u0026plusmn;\u0026thinsp;8.9\u003c/p\u003e \u003cp\u003e30.8\u0026thinsp;\u0026plusmn;\u0026thinsp;9.2\u003c/p\u003e \u003cp\u003e31\u0026thinsp;\u0026plusmn;\u0026thinsp;9.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46 (41.8)\u003c/p\u003e \u003cp\u003e44 (42.3)\u003c/p\u003e \u003cp\u003e46 (43.0)\u003c/p\u003e \u003cp\u003e43 (44.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25.13\u0026thinsp;\u0026plusmn;\u0026thinsp;1.64\u003c/p\u003e \u003cp\u003e25.07\u0026thinsp;\u0026plusmn;\u0026thinsp;1.62\u003c/p\u003e \u003cp\u003e25.08\u0026thinsp;\u0026plusmn;\u0026thinsp;1.58\u003c/p\u003e \u003cp\u003e25.13\u0026thinsp;\u0026plusmn;\u0026thinsp;1.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15168.79\u0026thinsp;\u0026plusmn;\u0026thinsp;3136.69\u003c/p\u003e \u003cp\u003e14766.87\u0026thinsp;\u0026plusmn;\u0026thinsp;2941.16\u003c/p\u003e \u003cp\u003e13428.12\u0026thinsp;\u0026plusmn;\u0026thinsp;2696.19\u003c/p\u003e \u003cp\u003e12877.75\u0026thinsp;\u0026plusmn;\u0026thinsp;3369.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6.42\u0026thinsp;\u0026plusmn;\u0026thinsp;0.66\u003c/p\u003e \u003cp\u003e6.47\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69\u003c/p\u003e \u003cp\u003e6.68\u0026thinsp;\u0026plusmn;\u0026thinsp;0.81\u003c/p\u003e \u003cp\u003e6.78\u0026thinsp;\u0026plusmn;\u0026thinsp;0.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.232\u0026thinsp;\u0026plusmn;\u0026thinsp;0.036\u003c/p\u003e \u003cp\u003e0.232\u0026thinsp;\u0026plusmn;\u0026thinsp;0.037\u003c/p\u003e \u003cp\u003e0.251\u0026thinsp;\u0026plusmn;\u0026thinsp;0.040\u003c/p\u003e \u003cp\u003e0.261\u0026thinsp;\u0026plusmn;\u0026thinsp;0.042\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.937\u0026thinsp;\u0026plusmn;\u0026thinsp;0.013\u003c/p\u003e \u003cp\u003e0.936\u0026thinsp;\u0026plusmn;\u0026thinsp;0.014\u003c/p\u003e \u003cp\u003e0.928\u0026thinsp;\u0026plusmn;\u0026thinsp;0.012\u003c/p\u003e \u003cp\u003e0.924\u0026thinsp;\u0026plusmn;\u0026thinsp;0.014\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eNote: 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=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssociations (univariable analysis) between between cone indexes (cone spacing, cone dispersion and cone regularity) and cone density, and between cone indexes (linear cone density, cone spacing, cone dispersion and cone regularity) and axial length.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLiner cone density*\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStandardized regression coefficient beta\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNon-standardized regression coefficient B\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e95% Confidence intervals of B\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e \u003cp\u003eAxial length\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNasal 3\u0026deg; eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1435.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-1661.3, -1209.1\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTemporal 3\u0026deg;eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1437.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-1665.6, -1209.8\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSuperior 3\u0026deg; eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1370.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-1610.4, -1130.7\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInferior 3\u0026deg; eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1587.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-1787.3, -1387.3\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNasal 5\u0026deg; eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1250.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-1510.3, -990.4\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTemporal 5\u0026deg;eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1220.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-1502.5, -938.2\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSuperior 5\u0026deg; eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-934.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-1210.2, -659.6\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInferior 5\u0026deg; eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1359.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-1667.2, -1061.1\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCone spacing*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e \u003cp\u003eAxial length\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNasal 3\u0026deg; eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.2,0.35\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTemporal 3\u0026deg;eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.2,0.35\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSuperior 3\u0026deg; eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.27,0.4\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInferior 3\u0026deg; eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.25,0.37\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNasal 5\u0026deg; eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.18,0.32\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTemporal 5\u0026deg;eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.14,0.27\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSuperior 5\u0026deg; eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.15,0.32\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInferior 5\u0026deg; eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.23,0.39\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e \u003cp\u003eLiner cone density\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNasal 3\u0026deg; eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,0\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTemporal 3\u0026deg;eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,0\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSuperior 3\u0026deg; eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,0\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInferior 3\u0026deg; eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,0\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNasal 5\u0026deg; eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,0\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTemporal 5\u0026deg;eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,0\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSuperior 5\u0026deg; eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,0\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInferior 5\u0026deg; eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,0\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCone dispersion*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eAxial length\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNasal 3\u0026deg; eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001,0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.009\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInferior 3\u0026deg; eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001,0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTemporal 5\u0026deg;eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001,0.009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInferior 5\u0026deg; eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.00,0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eLiner cone density\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNasal 3\u0026deg; eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,0\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInferior 3\u0026deg; eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,0\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTemporal 5\u0026deg; eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInferior 5\u0026deg; eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,0\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCone regularity*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eLiner cone density\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNasal 3\u0026deg; eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,0\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTemporal 3\u0026deg;eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInferior 3\u0026deg; eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAxial length\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTemporal 5\u0026deg;eccentricity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-0.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.003,0\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 \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eNote: * the dependent variable\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe linear cone density significantly declined with increasing axial length at both 3\u0026deg; (nasal: β=-0.77, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; temporal: β=-0.75, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; superior: β=-0.74, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; inferior: β=-0.84, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and 5\u0026deg; eccentricities (nasal: β=-0.68, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; temporal: β=-0.64, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; superior: β=-0.55, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; inferior: β=-0.68, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). No significant associations were observed with age or gender at either 3\u0026deg; (all P\u0026thinsp;\u0026gt;\u0026thinsp;0.2) or 5\u0026deg; eccentricities (all P\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003eCone spacing was significantly increased with increasing axial length at 3\u0026deg; (nasal: β\u0026thinsp;=\u0026thinsp;0.57, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; temporal: β\u0026thinsp;=\u0026thinsp;0.57, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; superior: β\u0026thinsp;=\u0026thinsp;0.69, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; inferior: β\u0026thinsp;=\u0026thinsp;0.72, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and 5\u0026deg; eccentricities (nasal: β\u0026thinsp;=\u0026thinsp;0.59, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; temporal: β\u0026thinsp;=\u0026thinsp;0.52, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; superior: β\u0026thinsp;=\u0026thinsp;0.46, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; inferior: β\u0026thinsp;=\u0026thinsp;0.62, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and was significantly reduced with increasing linear cone density at 3\u0026deg; (nasal: β=-0.62, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; temporal: β=-0.67, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; superior: β=-0.85, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; inferior: β=-0.80, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and 5\u0026deg; eccentricities (nasal: β=-0.89, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; temporal: β=-0.93, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; superior: β=-0.89, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; inferior: β=-0.89, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). After adjusting for axial length, cone spacing was significantly associated only with linear cone density, both at 3\u0026deg; (nasal: β=-0.44, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; temporal: β=-0.56, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; superior: β=-0.76, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; inferior: β=-0.66, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and 5\u0026deg; eccentricities (nasal: β=-0.91, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; temporal: β=-0.93, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; superior: β=-0.92, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; inferior: β=-0.87, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eCone dispersion significantly decreased with increasing linear cone density at 3\u0026deg; eccentricities (nasal: β=-0.46, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; inferior: β=-0.34, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and 5\u0026deg; eccentricities (temporal: β=-0.21, P\u0026thinsp;=\u0026thinsp;0.02; inferior: β=-0.36, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). It also significantly increased with axial length at specific 3\u0026deg; eccentricities (nasal: β\u0026thinsp;=\u0026thinsp;0.25, P\u0026thinsp;=\u0026thinsp;0.009; inferior: β\u0026thinsp;=\u0026thinsp;0.25, P\u0026thinsp;=\u0026thinsp;0.008) and 5\u0026deg; eccentricities (temporal: β\u0026thinsp;=\u0026thinsp;0.22, P\u0026thinsp;=\u0026thinsp;0.02; inferior: β\u0026thinsp;=\u0026thinsp;0.21, P\u0026thinsp;=\u0026thinsp;0.04). After adjusting for axial length, cone dispersion remained significantly associated with linear cone density only at the inferior 3\u0026deg; (β=-0.43, P\u0026thinsp;=\u0026thinsp;0.014) and inferior 5\u0026deg; eccentricities (β=-0.4, P\u0026thinsp;=\u0026thinsp;0.003).\u003c/p\u003e \u003cp\u003eCone regularity significantly increasing with increasing linear cone density at certain 3\u0026deg; eccentricities (nasal: β\u0026thinsp;=\u0026thinsp;0.34, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; temporal: β\u0026thinsp;=\u0026thinsp;0.25, P\u0026thinsp;=\u0026thinsp;0.006; inferior: β\u0026thinsp;=\u0026thinsp;0.2, P\u0026thinsp;=\u0026thinsp;0.04). After adjusting for axial length, cone dispersion remained significantly associated with linear cone density only at the nasal 3\u0026deg; (β\u0026thinsp;=\u0026thinsp;0.71, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and temporal 3\u0026deg; eccentricities (β\u0026thinsp;=\u0026thinsp;0.25, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Cone regularity significantly decreased with increasing axial length at temporal 5\u0026deg; eccentricity (β=-0.24, P\u0026thinsp;=\u0026thinsp;0.013), after adjusting for linear cone density, cone dispersion remained significantly associated with axial length at temporal 5\u0026deg; eccentricity (β=-0.57, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we utilized a commercial AOSLO system to establish the first dataset of cone mosaic in the Chinese population, mainly focusing on the relationship between axial length and cone morphology properties. As expected, we observed a decrease in the linear cone density with increasing axial length after adjusting the age and gender, consistent with findings from previous studies [\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. However, the linear cone density only revealed the cones number in the linear dimension, which could not fully explain decline in retinal resolution observed in the myopic population [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The cone spcing and was used to evaluated the uniformity of cone distribution and previous studies found the increasing of cone spacing with the axial elongation [\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In our analysis, after adjusting the influence of axial length the increased cone spacing was only associated with the decreased linear cone density. Compared to the cone spacing, the cone dispersion chould better evaluated the uniformity of cone distribution. In our study, we found the cone dispersion was significiatly increased with the decreasing of cone density and increasing of axial length. However, after adjusting the influence of axial length the increased cone dispersion was only associated with the decreased cone density. These indicated that the uniformity of cone distribution was decreased in axial myopia, which may be the indirected caused by a decrease in cone density due to axial elongation. Cone regularity could evaluate the morphology of single cone cell, in our study, we found the cone regularity was significiatly decreased with the decreasing of cone density. The axial elongation cloud also causes the decrease of cone regularity independently of the decread of cone density, which provides a new perspective for understanding the decline in retinal resolution in myopic population.\u003c/p\u003e \u003cp\u003eCone density and distribution also changed with the eccentricity increased[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], After adjusting for the influence of axial length, the effect of cone density on cone regularity was observed at 3\u0026deg; eccentricity, while the independent effect of axial length on cell regularity occurred at 5\u0026deg; eccentricity. This suggests that as eccentricity increases, the influence of axial length on cell regularity may become more significant. However, it is regrettable that the range of eccentricities obtained in this study was limited, and further research can be conducted in the future.Cone photoreceptors may serve as the starting point for defocus signals and play a crucial role in the process of eyeball growth and myopia development[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Our study further suggests a relationship between cone abnormalities and myopia. Future studies should aim to validate the causal relationship between the cone abnormalities and defocus signals in lens-induced myopia models. The normal human cone mosaic consists of three types of cones, each sensitive to different regions of the visible spectrum[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The non-invasive differentiation of these distinct cell types is crucial for further validating the role of LCA in ocular growth[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The ability to visualize the trichromatic cone mosaic has led to numerous psychophysical studies[\u003cspan additionalcitationids=\"CR18 CR19 CR20\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. These techniques provide essential support for future investigations into the role of cone photoreceptors in myopia development.\u003c/p\u003e \u003cp\u003eWith the clinical application of AOSLO systems in ophthalmology centers across the country, it will play a crucial role in early disease screening and diagnosis[\u003cspan additionalcitationids=\"CR23 CR24\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe AOSLO system employed in this study represents the first commercial AOSLO equipment approved in China. It boasts several features conducive to large-scale clinical applications: compact size, brief examination duration, minimal patient cooperation requirements, and automated operation with automatic analysis of examination results. These advantages lay the groundwork for establishing multicenter, large-scale clinical datasets in the future, marking a pivotal step in advancing the clinical utility of AOSLO. The findings of this study can guide future AOSLO clinical application in axial myopia population.\u003c/p\u003e \u003cp\u003eThere are several limitations in this study that need to be addressed. Firstly, we found that image quality is significantly affected by tear film interference, making it difficult to obtain clear cone mosaic images, particularly in patients with dry eye syndrome. This was a major factor contributing to the inadequate quality of images in this study. Furthermore, current AOSLO systems face challenges in imaging in patients with myopic maculopathy. Myopic maculopathy is a leading cause of irreversible blindness in myopic patients, and its pathogenesis remains unclear. In the future, if imaging of photoreceptor cells in the macular area of patients with pathological myopia can be achieved, it will further validate the relationship between axial length and cone metrics, thus greatly aiding research into the pathogenesis of pathological myopia.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study established the first cone mosaic dataset in healthy Chinese individuals with various axial length, shedding light on the relationship between cone morphology properties and myopia. The AOSLO system used in this study is compact in size and capable of automatically performing cone mosaic analysis, which has greatly facilitated the integration of the AOSLO system into clinical practice.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003eThis study adheres to the tenets of the Declaration of Helsinki. and was approved by The Institutional Review Board and Medical Ethics Committee at Beijing Tongren Hospital approved this study (TRECKY2018-056-GZ (2022)-07). The written informed consent was obtained from all subjects after the nature and possible complications of the study protocol were explained.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are not publicly available due to their containing information that could compromise the privacy of research participants but are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this study, all participants provided written informed consent for the publication of their individual details and images. Additional consent was obtained from the participants for the publication of identifiable images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the National Natural Science Foundation of China (82220108017, 82141128, 82401283); The Capital Health Research and Development of Special (2024-1-2052);Science \u0026amp; Technology Project of Beijing Municipal Science \u0026amp; Technology Commission (Z201100005520045)；Sanming Project of Medicine in Shenzhen (No. SZSM202311018); Scientific Research Common Program of Beijing Municipal Commission of Education (No. KM202410025011); The priming scientific research foundation for the junior researcher in Beijing Tongren Hospital, Capital Medical University (No. 2023-YJJ-ZZL-003).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConcept and design: Wen-Da Zhou, Li Dong, Lei Shao, Wen-Bin Wei. Acquisition, analysis, or interpretation of data: Wen-Da Zhou, Li Dong, Han-Xu Shi, Rui-Heng Zhang, Yu-hang Yang, Han-qing Zhao, Yi-Tong Li, Chu-Yao Yu, He-Yan Li, Hao-Tian Wu. Critical revision of the manuscript for important intellectual content: All authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eRucker FJ, Wallman J. Chick eyes compensate for chromatic simulations of hyperopic and myopic defocus: evidence that the eye uses longitudinal chromatic aberration to guide eye-growth. Vis Res. 2009;49(14):1775\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRucker FJ, Wallman J. Chicks use changes in luminance and chromatic contrast as indicators of the sign of defocus. J Vis 2012, 12(6).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRucker FJ. The role of luminance and chromatic cues in emmetropisation. Ophthalmic Physiol Opt. 2013;33(3):196\u0026ndash;214.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJonas JB, Ang M, Cho P, Guggenheim JA, He MG, Jong M, Logan NS, Liu M, Morgan I, Ohno-Matsui K, et al. IMI Prevention of Myopia and Its Progression. Invest Ophthalmol Vis Sci. 2021;62(5):6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTaylor CP, Shepard TG, Rucker FJ, Eskew RT Jr.. Sensitivity to S-Cone Stimuli and the Development of Myopia. Invest Ophthalmol Vis Sci. 2018;59(11):4622\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMustafi D, Engel AH, Palczewski K. Structure of cone photoreceptors. 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PLoS ONE. 2018;13(1):e0191141.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang Y, Bensaid N, Tiruveedhula P, Ma J, Ravikumar S, Roorda A. Human foveal cone photoreceptor topography and its dependence on eye length. eLife 2019, 8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSong H, Chui TY, Zhong Z, Elsner AE, Burns SA. Variation of cone photoreceptor packing density with retinal eccentricity and age. Invest Ophthalmol Vis Sci. 2011;52(10):7376\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi K, Yin Q, Ren J, Song H, Zhang J. Automatic quantification of cone photoreceptors in adaptive optics scanning light ophthalmoscope images using multi-task learning. Biomedical Opt express. 2022;13(10):5187\u0026ndash;201.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAtchison DA, Schmid KL, Pritchard N. Neural and optical limits to visual performance in myopia. Vis Res. 2006;46(21):3707\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJaworski A, Gentle A, Zele AJ, Vingrys AJ, McBrien NA. Altered visual sensitivity in axial high myopia: a local postreceptoral phenomenon? Invest Ophthalmol Vis Sci. 2006;47(8):3695\u0026ndash;702.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eColetta NJ, Watson T. Effect of myopia on visual acuity measured with laser interference fringes. Vis Res. 2006;46(5):636\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHofer H, Singer B, Williams DR. Different sensations from cones with the same photopigment. J Vis. 2005;5(5):444\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSabesan R, Hofer H, Roorda A. Characterizing the Human Cone Photoreceptor Mosaic via Dynamic Photopigment Densitometry. PLoS ONE. 2015;10(12):e0144891.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSabesan R, Schmidt BP, Tuten WS, Roorda A. The elementary representation of spatial and color vision in the human retina. Sci Adv. 2016;2(9):e1600797.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchmidt BP, Boehm AE, Foote KG, Roorda A. The spectral identity of foveal cones is preserved in hue perception. J Vis. 2018;18(11):19.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchmidt BP, Sabesan R, Tuten WS, Neitz J, Roorda A. Sensations from a single M-cone depend on the activity of surrounding S-cones. Sci Rep. 2018;8(1):8561.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNesper PL, Scarinci F, Fawzi AA. Adaptive Optics Reveals Photoreceptor Abnormalities in Diabetic Macular Ischemia. PLoS ONE. 2017;12(1):e0169926.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMakiyama Y, Ooto S, Hangai M, Ogino K, Gotoh N, Oishi A, Yoshimura N. Cone abnormalities in fundus albipunctatus associated with RDH5 mutations assessed using adaptive optics scanning laser ophthalmoscopy. Am J Ophthalmol. 2014;157(3):558\u0026ndash;e570551.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBritten-Jones AC, Thai L, Flanagan JPM, Bedggood PA, Edwards TL, Metha AB, Ayton LN. Adaptive optics imaging in inherited retinal diseases: A scoping review of the clinical literature. Surv Ophthalmol. 2024;69(1):51\u0026ndash;66.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOoto S, Hangai M, Takayama K, Sakamoto A, Tsujikawa A, Oshima S, Inoue T, Yoshimura N. High-resolution imaging of the photoreceptor layer in epiretinal membrane using adaptive optics scanning laser ophthalmoscopy. Ophthalmology. 2011;118(5):873\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e\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":"Myopia, Axial length, Adaptive Optics Scanning Laser Ophthalmoscopy, Cone","lastPublishedDoi":"10.21203/rs.3.rs-5471967/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5471967/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eAbnormalities in cone photoreceptors are closely associated with the occurrence of many ocular diseases. Adaptive Optics Scanning Laser Ophthalmoscopy (AOSLO) allows visualization of the living human retina with exquisite single-cell resolution.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis study aimed to found the potential relationship between cone cells and and axial myopia using a commercial AOSLO system in cone moasic. 74 patients (148 eyes; 30 (40.5%) men) with a mean age of 31.8\u0026thinsp;\u0026plusmn;\u0026thinsp;10.4 years were icluded in this study. Cone mosic was obtained from the 3\u0026deg; and 5\u0026deg; eccentricities of macular. The relationship between cone cell indexes (linear cone density, cone spacing, cone dispersion and cone regularity) and axial length were analyzed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe linear cone density significantly declined with increasing axial length at both 3\u0026deg; and 5\u0026deg; eccentricities (all \u003cem\u003eP\u003c/em\u003e\u0026lt;0.001). The cone spacing was significantly increasing with the increasing of axial length and the reduce of cone density. After adjusting for axial length, cone spacing was significantly associated only with linear cone density, both at 3\u0026deg; and 5\u0026deg; eccentricities (all \u003cem\u003eP\u003c/em\u003e\u0026lt;0.001). The cone dispersion was significantly increasing with the increasing of axial length and the reduce of cone density. After adjusting for axial length, cone dispersion remained significantly associated with linear cone density only at the inferior 3\u0026deg; (β=-0.43, P\u0026thinsp;=\u0026thinsp;0.014) and inferior 5\u0026deg; eccentricities (β=-0.4, P\u0026thinsp;=\u0026thinsp;0.003). Cone regularity significantly increasing with increasing linear cone density and after adjusting for axial length, cone dispersion remained significantly associated with linear cone density only at the nasal 3\u0026deg; (β\u0026thinsp;=\u0026thinsp;0.71, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and temporal 3\u0026deg; eccentricities (β\u0026thinsp;=\u0026thinsp;0.25, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Cone regularity significantly decreased with increasing axial length and after adjusting for linear cone density, cone dispersion remained significantly associated with axial length at temporal 5\u0026deg; eccentricity (β=-0.57, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eCone cell density was significantly decreased in axial myopia. The uniformity of cone distribution was decreased in axial myopia, which may be the indirected caused by a decrease in cone density due to axial elongation. The cone morphology regularity was significantly decreased in axial myopia, which may result directly from the axial elongation or indirectly from the cone density decrease it causes.\u003c/p\u003e","manuscriptTitle":"Cone Mosaic in Eyes with Varied Axial Length Using Adaptive Optics Scanning Laser Ophthalmoscopy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-02 13:16:04","doi":"10.21203/rs.3.rs-5471967/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":"368c7ce4-0588-4f3f-93bd-1965954001cd","owner":[],"postedDate":"December 2nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-12-30T05:24:26+00:00","versionOfRecord":[],"versionCreatedAt":"2024-12-02 13:16:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5471967","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5471967","identity":"rs-5471967","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}