New insights into changes in ocular structural parameters in a simulated hypobaric hypoxia plateau environment

New insights into changes in ocular structural parameters in a simulated hypobaric hypoxia plateau environment | 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 New insights into changes in ocular structural parameters in a simulated hypobaric hypoxia plateau environment Yuchen Wang, Anqi Guo, Xinli Yu, Yihe Liu, Zesong Wang, Jiaxing Xie, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4185123/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose High altitude is the main area for human exploration, and human eye is an important organ for obtaining visual signals. The changes of eye structure and function caused by hypobaric hypoxia environment need to be clarified. Methods Measurements were taken at five altitudes (1: ground; 2: 3500m; 3: 4000m; 4: 4500m; and 5: end of experiment). Refractive values were measured with the IOL Master (Carl Zeiss Shanghai Co. Ltd.). Data analysis was performed using the Kolmogorov–Smirnov (K-S) test, paired sample T-test, and Wilcoxon test. Results Subjects’ axial length (AL) increased with altitude, peaking at 4500m, then decreased. Significant differences in AL were observed across altitudes (p < 0.05), except between 2 and 5, and 3 and 5. Central corneal thickness (CCT) thickened then thinned with elevation changes, significantly thicker at altitudes 2–5 compared to the baseline (p < 0.05). Lens thickness (LT) followed a similar pattern, increasing up to altitude 4, then decreasing at 5. Correlations were found between AL and LT at altitudes 1 (r = 0.375, p < 0.05) and 5 (r = 0.341, p < 0.05), and between AL and CCT at altitude 4 (r = 0.337, p < 0.05), but not elsewhere. No significant relationship was observed between LT and CCT. Conclusions As altitude increases and the degree of acute low-pressure hypoxia worsens, the refractive parameters such as AL, CCT, and LT are altered, which could potentially affect the pilot's visual function after acute hypoxia, further affecting the pilot's information acquisition and decision-making during driving and posing a threat to flight safety. refractive values high-altitude hypobaric hypoxia environment axial length Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Introduction In recent years, aerospace technology has developed rapidly, and high-altitude, low-pressure hypoxic areas such as high-altitude plateaus have become the main places for human exploration. When the human body is in a high-altitude environment, 1 the human body system will be challenged by factors such as low air pressure, low oxygen partial pressure, and low temperature. Research shows that the relationship between a high-altitude environment and the degree of hypoxia can be roughly defined by the following stages: medium altitude (mild hypoxia) is 1520–2440 meters, high altitude (moderate hypoxia) is 2440–4270 meters, and ultra-high altitude (severe hypoxia) is 4270–5490 meters. 2 When the altitude exceeds 2440 meters, adverse consequences such as acute mountain sickness, high-altitude cerebral edema, and pulmonary edema may occur. As the altitude continues to increase, hypoxemia and hypocapnia are particularly obvious, and the local partial pressure of oxygen decreases, resulting in vascular disease. Uneven contraction and destruction of the blood barrier can cause irreversible damage to aerobic tissues, such as those in the brain, heart, and liver, and even threaten life. However, in addition to organs and tissues such as the heart, brain, and lungs, the human eye is the main organ that allows the brain to obtain visual information. Its structure and function depend on the nutritional and metabolic supply of retinal blood flow and are most obviously affected by hypoxia and ischemia. High-altitude retinopathy was first observed in early 1970 by Frayser et al., 3 manifesting as optic disc edema, retinal hemorrhage, optic nerve fiber infarction, etc. Since then, in 2008, Bosch et al. 3 repeatedly reported that exposure to a plateau environment leads to refractive changes and ocular pressure fluctuations, 4 but the specific mechanism is unclear. The impact of a high-altitude, low-pressure hypoxic environment on human ocular axial length (AL), central corneal thickness (CCT), keratometry (K), lens thickness (LT), anterior chamber depth (ACD), and other related physiological parameters has not yet been explored. 5 Therefore, we selected healthy volunteers from Beijing, a low-altitude area in China, to participate in this study to explore changes in ocular axial length, corneal curvature, and other data under acute exposure to different altitude changes, allowing us to objectively evaluate the human eye's response to low-pressure hypoxia. The results provide a research basis for further research on the mechanism of changes in refractive values in human eyes caused by a low-pressure hypoxic environment. Materials and methods Subjects This prospective study enrolled 16 healthy, physically fit volunteers aged 20–26 years, including 8 males and 8 females. All subjects were of Han descent and lived at altitudes between 40 and 250 m above sea level. None of the volunteers in this study had systemic or refractive diseases (e.g., glaucoma, shallow anterior chamber, narrow atrial angle, etc.) or a history of ophthalmic surgery, intraocular lenses, or contact lenses, and they did not take any medications that affect refraction. Subjects were required to get enough sleep before the test and not drink caffeinated beverages such as coffee or tea before the experiment. We adhered to the tenets of the Declaration of Helsinki, and the research was approved by the Biomedical Ethics Committee of BHU. Written and oral informed consent were obtained from the participants after a full explanation of the nature and possible consequences of the study. Ascent Profile and Measurements The experiment was safely conducted in a complex high-altitude simulation module at the BHU High-Precision Medicine Center under the supervision of a professional physician. The temperature and humidity inside the chamber were set to be between 23.3 and 26.5 ℃ and between 30 and 35%, respectively. The experimental chamber ascended at a speed of 5 m/s, and 2 minutes of habituation was included after every 1000 m. After the altitude of the simulation chamber reached 4500 m above sea level, the simulation chamber descended at a speed of 3 m/s, and 2 minutes of habituation was again included after every 1000 m. The ocular parameters in the subjects’ eyes was measured during all habituation periods. The specific experimental altitude changes are shown in Fig. 1 . Refractive values were measured in both eyes with the IOL master (Carl Zeiss Shanghai Co. Ltd), which uses non-contact infrared-light interferometry to measure the ocular refractive parameters, such as keratometry, axial length, anterior chamber depth, etc. These values were used to calculate the power and position of the intraocular lens, which can improve the accuracy and repeatability of the measurement. Statistical Analysis The K-S test was performed to determine normal distribution. The T-test or Wilcoxon test was applied to analyze the differences among the refractive values at five altitude points. The repeated measures ANOVA test was performed to eliminate the individual effects on the experimental results. A P-value < 0.05 was considered significant. All evaluations were performed using a commercially available statistical software package (SPSS for Windows, v. 26.0, IBM). Results All subjects safely reached the simulated altitude of 4500 m and completed the experiment safely without oxygen supplementation. Table 1 Measured values of AL, CCT, and LT at different altitudes (x ̅±s). altitude number AL (mm) CCT (um) LT (mm) ACD (mm) Altitude 1 32 24.056 ± 0.187 545.500 ± 5.999 3.748 ± 0.022 3.596 ± 0.042 Altitude 2 32 24.074 ± 0.187 546.875 ± 6.220 3.762 ± 0.021 3.600 ± 0.043 Altitude 3 32 24.082 ± 0187 547.688 ± 6.208 3.767 ± 0.021 3.593 ± 0.042 Altitude 4 32 24.088 ± 0.187 547.250 ± 6.071 3.752 ± 0.020 3.598 ± 0.042 Altitude 5 32 24.079 ± 0188 547.750 ± 6.034 3.729 ± 0.023 3.606 ± 0.042 altitude number K1 (D) K2 (D) TK1 (D) TK2 (D) Altitude 1 32 42.976 ± 0.236 43.987 ± 0.261 43.003 ± 0.244 43.888 ± 0.271 Altitude 2 32 42.974 ± 0.237 43.998 ± 0.262 43.991 ± 0.246 43.917 ± 0.271 Altitude 3 32 42.970 ± 0.236 44.012 ± 0.260 42.991 ± 0.244 42.934 ± 0.268 Altitude 4 32 42.970 ± 0.239 43.989 ± 0.256 42.982 ± 0.246 43.903 ± 0.263 Altitude 5 32 43.000 ± 0.238 43.996 ± 0.259 43.013 ± 0.247 43.921 ± 0.264 Altitude 1: ground; Altitude 2: 3500m; Altitude 3: 4000m; Altitude 4: 4500m; Altitude 5: back on the ground. It can be seen from Table 1 and Fig. 2 that the AL of the eyes of all subjects’ changes with elevation, increasing from 24.056 ± 0.187 mm at ground level (altitude 1) to 24.088 ± 0.187 mm at 4500 m (altitude 4), and finally, the AL of all subjects reduced to 24.079 ± 0.188 mm after returning to the ground level (altitude 5). Among them, the AL of most subjects showed a statistically significant growing trend with the increase in altitude, while the AL of a few subjects fluctuated between 3500m (altitude 2) and 4000m (altitude 3), but there was no statistical significance. After that, with the decrease in altitude, the AL gradually decreased toward its initial state, but the AL was still larger compared with its initial state (altitude 1) after returning to the ground (altitude 5). In reviewing the specific changes in AL at the five altitudes (Fig. 3 ), the AL of all subjects underwent a T-test and repeated measures ANOVA. Except for the AL between 3500m (altitude 2) and the ground (altitude 5) and that between 4000m (altitude 3) and the ground (altitude 5), which had no statistical significance, the AL showed a statistically significant increase among the other altitude pairs (P < 0.05). As can be seen from Table 1 and Fig. 4 , the CCT in all subjects showed fluctuating thickening with an increasing altitude and rolling thinning with a decreasing altitude. Specifically, as the altitude increased, the CCT increased from 545.500 ± 5.999 um on the ground (altitude 1) to 547.688 ± 6.208 um at 4000 m (altitude 3). The CCT fluctuated and changed to be 547.250 ± 6.071 um at 4500 m (altitude 4). After returning to the ground (altitude 5), the subjects’ CCT was 547.750 ± 6.034 um, which was slightly thinner than that at 3500m (altitude 2) but still thicker than the CCT at the initial state (altitude 1). After the repeated measures analysis of variance, paired t-test, and Wilcoxon test (Fig. 5 ) were performed, the CCT at the four altitudes of 3500m, 4000m, 4500m, and back on the ground (altitudes 2, 3, 4, and 5) was found to be statistically significantly thicker than at the initial state (p < 0.05); notably, the CCT values had a striking difference between altitude 1 and altitude 3 and altitude 1 and altitude 5 (p < 0.01) (Fig. 4 ). However, when comparing the CCT among all altitudes, no statistical difference was found; that is, there was no significant thickening or thinning in the CCT at 3500, 4000, 4500, and back on the ground (altitudes 2, 3, 4, and 5). As shown in Table 1 and Fig. 6 , the LT of more than half of the subjects increased when the altitude increased to 4000m, and the LT of more than half of the subjects became thinner when the altitude increased to 4500 m. After going back to the ground, at the initial ground level (altitude 1), the LT was 3.748 ± 0.022mm. The LT thickened with the increase in altitude and became 3.762 ± 0.021mm and 3.767 ± 0.021mm at the altitudes of 3500m (altitude 2) and 4000m (altitude 3), respectively. Then, the LT became thinner with the decrease in altitude. After returning to the ground (altitude 5), the LT was 3.729 ± 0.023mm. Through the paired T-test (Fig. 7 ) and repeated measures ANOVA, it can be seen that the LT at the four altitudes (3500m, 4000 m, and 4500 m) and back on the ground (altitudes 2, 3, 4, and 5) is statistically thicker or thinner than that at the initial altitude (altitude 1). Moreover, the repeated measures ANOVA showed that the difference between altitudes 2 and 5 was statistically significant, as was the difference between altitudes 3 and 5 (p < 0.01). (Fig. 6 ). There was no significant change in LT between different heights. Additionally, we also investigated the changes in ACD, K, and TK at different altitudes, which showed fluctuating changes with the increase or decrease in altitude, but no obvious pattern was observed; that is, no statistically significant changes were observed in those values among different altitudes. In order to determine whether there is a correlation between AL and ACD and between LT and CCT, and whether the measurement of AL is affected by these 3 values, we further explored the correlation between them. The statistics presented in Table 2 show that for AL and LT, there is a correlation between the two groups at ground level (altitude 1) (r = 0.375, p < 0.05) and after returning to ground level (altitude 5) (r = 0.341, p < 0.05), but there is no correlation between the two groups at the altitudes of 3,500m, 4,000m, and 4,500m; for AL and CCT, the two groups have the same change trend at 4,500m (altitude 4) (r = 0.337, p < 0.05), but no significant correlation is seen at the rest of the altitudes. For AL and CCT, the same trend was observed at 4500m (altitude 4) (r = 0.337, p < 0.05), but no significant correlation was observed at the remaining altitudes. Meanwhile, there was no significant relationship between LT and CCT or between AL and corneal curvature. In addition, we further explored the correlation between ACD and the changes in each parameter, and it was seen that at altitudes 2, 3, and 4, i.e., after ascending in altitude, ACD was positively correlated with AL; at altitudes 1, 2, 3, and 5, ACD was negatively correlated with LT. Thus, although acute low-pressure hypoxia did not cause statistically significant changes in ACD, it is still known that ocular axis growth and increased lens thickness can lead to changes in anterior chamber depth. Table 2 Correlation analysis between AL, LT, and CCT. altitude AL vs. LT AL vs. CCT LT vs. CCT r P r P r P Altitude 1 Altitude 2 Altitude 3 Altitude 4 Altitude 5 0.375* 0.103 0.087 0.254 0.341* 0.05 > 0.05 > 0.05 0.05 > 0.05 > 0.05 0.05 -0.069 -0.082 -0.036 0.046 -0.078 > 0.05 > 0.05 > 0.05 > 0.05 > 0.05 Table 3 Correlation analysis between AL, K, and TK. altitude AL vs. K1 AL vs. K2 AL vs. TK1 AL vs. TK2 r P r p r P r P Altitude 1 0.04 > 0.05 0.182 > 0.05 0.057 > 0.05 0.192 > 0.05 Altitude 2 0.04 > 0.05 0.188 > 0.05 0.058 > 0.05 0.201 > 0.05 Altitude 3 0.063 > 0.05 0.19 > 0.05 0.072 > 0.05 0.207 > 0.05 Altitude 4 0.041 > 0.05 0.208 > 0.05 0.053 > 0.05 0.22 > 0.05 Altitude 5 0.045 > 0.05 0.206 > 0.05 0.054 > 0.05 0.228 > 0.05 Table 4 Correlation analysis between ACD, LT, CCT, and AL. altitude ACD vs. AL ACD vs. LT ACD vs. CCT r P r P r P Altitude 1 Altitude 2 Altitude 3 Altitude 4 Altitude 5 0.224 0.357* 0.388* 0.337* 0.283 > 0.05 < 0.05* < 0.05* 0.05 -0.344 -0.358 -0.32 -0.268 -0.316 < 0.05* < 0.05* 0.05 0.05 > 0.05 > 0.05 > 0.05 > 0.05 Discussion There are many differences between high-altitude and sea-level environments, characterized by low oxygen concentrations, low temperatures, and high UV radiation. Some studies have shown that the ocular data of people living at a high altitude for long periods of time, such as in the Tibetan Plateau, show significant differences in ocular appearance in terms of nose bridge width (NBW), inner intercanthal distance (IICD), outer intercanthal distance (IOCD), and interpupillary distance (IPD), and changes in the inner eye, such as low intraocular pressure (IOP), shorter axial length of the eye, and high prevalence of lens cloudiness, have been observed. 6 The above suggests that there is an adaptive response to low-pressure hypoxia in the human eye at high altitudes, which results in differences from the human eye at sea level in a number of ways. The fluctuations in AL, LT, and CCT with altitude observed in the present study are similar to the physiologic changes observed in high-altitude populations. However, in the present study, we focused on the effects of acute hypoxia on the human eye by using healthy adults who lived on the plains and had never visited the plateau region before. This study was carried out in a high-altitude, low-pressure simulation chamber, which simulated the environment of low-pressure hypoxia and hypothermia in the plateau and rapidly elevated the subjects to altitudes of 3,500, 4,000, and 4,500 meters within a short period of time, to further clarify the physiological structural and functional effects of acute low-pressure hypoxia on the human eye. Through the long-term observation of high-altitude populations, one study found that Aboriginal people living at high altitudes had shorter axial lengths than white, black, and Asian people, averaging 23.05 millimeters (with a standard deviation of 0.77 millimeters). 6 This finding is inconsistent with the results of this study, which observed that the mean axial length of the subjects' eyes increased with altitude, reached a maximum at the highest altitude, and then gradually recovered after returning to the ground again, suggesting that acute hypoxia causes reversible changes in the axial length of the eyes. The reason for the increase in mean axial length with elevation observed in the subjects in this study was considered to be possibly related to choroidal blood supply, which can be broadly classified as having two functions: the first is to provide oxygen and nutrients to the outer retina, and the second is to regulate the position of the retina through changes in the thickness of the choroid, as well being involved in vascularization and scleral remodeling, which affect the release of ocular growth regulators such as VEGF, NO, etc. In 2021, Yilin L et al. 7 reviewed the correlation between choroidal blood flow and ocular axis length in myopic patients and found that when choroidal blood flow is reduced, the choroid and sclera show ischemic and hypoxic manifestations, which appear as a reduction in the diameter of the choroidal vessels; at the same time, there is a reduction in the molecules with osmotically active molecules such as hyaluronic acid, glycosaminoglycans, and proteoglycan in the choroidal vasculature, 8 resulting in a reduction in the permeability of choroidal tubular diameters and making it not possible for more fluids to be pulled into the choroid, which leads to a further reduction in the diameter of the choroid and a thinning of the choroid, 9 In addition, endogenous choroidal neurofactors are released by ischemic and hypoxic conditions, and they interfere with choroidal vascular and nonvascular smooth muscle, which can lead to changes in choroidal thickness, among other things. 8 In an in vitro study, 1-day-old rats were exposed to 5% oxygen and 95% nitrogen for 2 hours and recovered under normal oxygen for a time period from 3 hours to 21 days to observe the effects of acute hypoxia on retinal cellular and vascular factors in neonatal rats as well as the effects of these factors on choroidal vascular permeability. The results showed that the mRNA and protein expression of HIF-1α, VEGF, eNOS, nNOS, and iNOS, as well as the concentration of VEGF and the production of NO, significantly increased in the retina after hypoxia, which led to an increase in the permeability of the choroidal vasculature and leakage of RhIC and HRP from the vasculature, and further led to the narrowing of the vascular diameter of the choroidal vasculature and its thinning. Therefore, we speculate that when subjects are in a low-pressure hypoxic environment, blood oxygen saturation decreases, ocular choroidal blood flow decreases, ocular growth regulators and neurofactors are released, the vascular smooth muscle becomes constricted, the canaliculus narrows, the choroid thins, and the sclera thins. Studies have shown that the main area of choroidal sclera thinning is in the macular central pucker, 10 so there is an increase in the elasticity of the wall of the eyeball, a decrease in the eyeball's tolerance to the preexisting IOP, and the emergence of a detectable increase in the eye's axial length. As an important part of the optical pathway, the transparent cornea relies on the capillary network of the corneoscleral rim for the acquisition of nutrients as well as the maintenance of its function, and thus its response to hypoxia is more pronounced. For the central corneal thickness, previous articles confirmed that a stay of 1–2 weeks at a high altitude results in a decrease in the thickness of the tear film and an increase in the thickness of the corneal endothelium and the corneal mesenchymal stroma. Moreover, the central corneal thickness thickens with the increasing duration of stay at a high altitude, 11 , 12 and gradually decreases to baseline levels when returning to sea level. The present study demonstrated the onset of acute hypoxia with a relatively rapid increase in altitude and a gradual increase in CCT from altitude 1 to altitude 3, which is consistent with the literature findings. However, in this study, after staying at 4500 meters for 40 minutes, the CCT gradually decreased to what it was at sea level, and at altitude 5, compared with the initial state, the CCT was still thicker than the corneal thickness at its initial state, meaning it was not restored. The discrepancy may be due to the fact that most of the studies in the literature were experiments of chronic hypoxia and acclimatization training was conducted on the subjects, whereas the experiments in this paper were experiments of acute hypoxia, and therefore, there was a delay in the recovery of the ocular structures. To explain why CCT thickens with altitude, the following factors were considered: Low-pressure hypoxia leads to anaerobic glycolysis and lactic acid accumulation in corneal epithelial cells, and lactic acid diffuses through the corneal stroma and endothelium and is metabolized in atrial fluid, resulting in osmolality-dependent atrial reflux and an increase in corneal edema. 13 At the same time, anaerobic glycolytic products decrease the activity of the corneal endothelial pump, leading to corneal edema and increased corneal thickness. In addition, in vitro studies showed that DNA damage and apoptosis were observed in cells of ocular surface tissues, such as those from the conjunctival and corneal epithelium, in a single episode of acute hypoxia, and that corneal epithelial cells promoted corneal edema and angiogenesis under hypoxic conditions by increasing the expression of VEGF and cytochrome p4504B1, suggesting that hypoxia may lead to corneal epithelial cells affecting its thickness and that these factors may be important corneal hypoxic regulators of corneal injury. 14 , 15 In the present study, we also observed a statistically different change in lens thickness with increasing altitude, with the lens thickness being thicker at 4,000 and 4,500 meters above sea level than after returning to the ground. It is well known that the lens inherently exists in a relatively low-oxygen environment due to a lack of blood supply, with there being a gradual decrease in oxygen concentration from the surface to the core of the lens. One study measured the proliferation rate of lens epithelial cells in vitro at both high and low oxygen concentrations and found that the proliferative activity of the cells did not increase when the oxygen concentration was lower than normal. 16 In contrast, hypoxia leads to lens maturation through the activation of hypoxia-inducible factor (HIF1a), 17 which regulates hypoxia-responsive genes and promotes the elimination of epithelial cell organelles, enabling them to differentiate into lens fiber cells and achieve a regular arrangement. Therefore, previous studies concluded that low-pressure hypoxia does not cause changes in lens structure. However, in this experiment, an increase in the thickness of the lens alongside an increasing altitude was observed, which has not been previously reported in the literature, and so this specific mechanism needs to be further investigated. Previously, some scholars tested ACD at high altitudes for three consecutive days and observed more significant changes. 18 Unfortunately, we did not observe significant changes in the anterior chamber depth under acute hypoxic conditions in the present study, and we assume that this may be related to the duration of hypoxia, as acute hypoxia over a short period of time could not have a statistically significant effect on anterior chamber depth. In addition, the pattern of change in the curvature of the anterior surface of the cornea and in the total surface of the cornea with altitude in the present study showed a large fluctuation in the data, which is consistent with the results of the previous literature and is also in line with the previous long-term statistical follow-up data on the anterior chamber depth of the people who stayed at high altitudes, 3,300 meters or 1,700 meters, for a short period of time or for a long period of time. 12 A review of previous studies showed that the refractive error of the subjects changed with altitude; however, one of the possible mechanisms is that the epithelial cells of the tear film, conjunctiva, and cornea are affected by the low-oxygen environment, and the DNA in the epithelial cells of the cornea and conjunctiva breaks and undergoes apoptosis, destabilizing the tear film and conjunctiva, disrupting the regularity of the image, and disorganizing the arrangement of the corneal collagen, which leads to the clinical symptom of the subjective blurring of vision in subjects. In this present study, we found that the subjects' subjective vision was not clear. Secondly, through this study, we observed the change in the length of the ocular axis with altitude, and since the elongation of the ocular axis will change the morphology of the eyeball, affect the thickness of the ocular wall, and then affect the refractive error of the eyeball, we hope to study the correlation between the ocular axis and the refractive error in the future; regrettably, in this study we did not observe the change in the K and the TK with altitude (Table 3 ), and so we could not analyze the ocular axis and the refractive error in conjunction with each other. In the future, we hope to expand the sample size, further analyze the correlation of the data from each group, and perform choroidal blood flow monitoring to clarify the causes of altered visual function after acute hypoxia and explore the pathophysiological mechanisms. Conclusions A low-pressure hypoxic environment at a high altitude affects the ocular structure and refractive parameters in eyes, which tend to manifest themselves in the form of ocular axis elongation, increased central corneal thickness, and lens thickness, and these alterations can affect visual acuity and thus a pilot's ability to carry out information acquisition and decision making while driving. Our study provides, for the first time, more complete data on the values of refractive parameters, such as total eye axis length, central corneal thickness, and lens thickness, at different degrees of hypoxia under acute hypoxic conditions. In the future, we will expand the sample size to analyze each group of data and conduct choroidal blood flow monitoring in order to specifically study the reasons for the changes in eye physiology and pathophysiology at high altitudes, as well as the mechanisms that affect the biological parameters of the eye, so as to provide a reference basis for the design of safe aircraft. Declarations Acknowledgments : We would like to thank Li Ding and Xuemin Li and their team at the Peking University Third Hospital and Beihang University. We appreciate the kindness of the volunteers for cooperating in high-altitude experiments for the advancement of science. This article is solely dedicated to them. Conflicts of Interest: The authors declare no conflicts of interest. Funding: Peking University Third Hospital Key talent project, funding number: BYSYZD2021044. Author contributions: Yuchen Wang, Anqi Guo, and Xinli Yu made substantial contributions to the conception of this study; Anqi Guo processed the data; Yuchen Wang and Xinli Yu reviewed the literature and drafted the manuscript; Yihe Liu, Zesong Wang, Jiaxing Xie, Xinzuo Zhou, Haqin Xia, Jiaxi Li, Chao Sun, Jing Zhang, Zhongsheng Lv, Siru Liu, and Chengkai Zhou participated in the translation of articles; Ziyuan Liu reviewed the manuscript; Xuemin Li and Li Ding gave final approval of the version to be submitted and approved any revised versions. Institutional Review Board Statement : This study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Biomedical Ethics Committee of BHU. Informed Consent Statement : Informed consent was obtained from all subjects involved in the study. References Hou J, Zheng D, Wen X, Xiao W, et al. 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Influence of hypobaric hypoxic conditions on ocular structure and biological function at high attitudes: a narrative review. Front Neurosci. 2023;17:1149664. McKay TB, Hjortdal J, Priyadarsini S, Karamichos D. Acute hypoxia influences collagen and matrix metalloproteinase expression by human keratoconus cells in vitro. PLoS One. 2017;12(4):e0176017. Akberova SI, Markitantova YV, Ryabtseva AA, Stroeva OG. Hypoxia as pathogenic factor affecting the eye tissues: The selective apoptotic damage of the conjunctiva and anterior epithelium of the cornea. Dokl Biochem Biophys. Mar 2016;467(1):150-152. Morris DS, Somner J, Donald MJ, McCormick IJ, et al. The eye at altitude. Adv Exp Med Biol. 2006;588:249-70. Shui YB, Beebe DC. Age-dependent control of lens growth by hypoxia. Invest Ophthalmol Vis Sci. Mar 2008;49(3):1023-29. Brennan L, Disatham J, Kantorow M. Hypoxia regulates the degradation of non-nuclear organelles during lens differentiation through activation of HIF1a. Exp Eye Res. Sep 2020;198:108129. Willmann G, Schatz A, Zhour A, Schommer K, et al. Impact of acute exposure to high altitude on anterior chamber geometry. Invest Ophthalmol Vis Sci. Jun 21 2013;54(6):4241-48. 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-4185123","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":286496533,"identity":"abe3005d-fbf7-449f-b60c-8faaa706e3fa","order_by":0,"name":"Yuchen Wang","email":"","orcid":"","institution":"Peking University Third Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuchen","middleName":"","lastName":"Wang","suffix":""},{"id":286496534,"identity":"482655af-2d14-40d3-a640-12bc20bd9121","order_by":1,"name":"Anqi Guo","email":"","orcid":"","institution":"Peking University Third Hospital","correspondingAuthor":false,"prefix":"","firstName":"Anqi","middleName":"","lastName":"Guo","suffix":""},{"id":286496535,"identity":"b4041e5c-9cc0-461a-ac81-d43853c8f457","order_by":2,"name":"Xinli Yu","email":"","orcid":"","institution":"Beihang University","correspondingAuthor":false,"prefix":"","firstName":"Xinli","middleName":"","lastName":"Yu","suffix":""},{"id":286496536,"identity":"95a76ac0-0a0e-4b91-ac37-7400ae12fd01","order_by":3,"name":"Yihe Liu","email":"","orcid":"","institution":"Peking University Third Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yihe","middleName":"","lastName":"Liu","suffix":""},{"id":286496537,"identity":"cae731b3-789f-4e0c-a078-4a9ca73b4876","order_by":4,"name":"Zesong Wang","email":"","orcid":"","institution":"Peking University Third 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Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ziyuan","middleName":"","lastName":"Liu","suffix":""},{"id":286496547,"identity":"69e3088f-b7d8-41e3-a7e1-868f1fa73ba2","order_by":14,"name":"Xuemin Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAv0lEQVRIiWNgGAWjYBACPgYGxgMMDDZy/AyMDcRpYQNioJY0Y8kGErUcSjQ4QKzD2CSyEw7z5hxIMD5/uO3BDwY7OV1ClrHxnN1wcOa2O3lmNxLbDXsYko3NCFnHxt674cDHbc+KzW4wtknwMBxI3EZQCzPvBqCyw4mb+w+2Sf4hSgvElsOJGxgS26SJswXilzRjiRtALTIGRPiFXyJ342PebcCo7D/+TPJNhZ0cQS1owIA05aNgFIyCUTAKcAAAi4BFsBVddi4AAAAASUVORK5CYII=","orcid":"","institution":"Peking University Third Hospital","correspondingAuthor":true,"prefix":"","firstName":"Xuemin","middleName":"","lastName":"Li","suffix":""},{"id":286496548,"identity":"42c83271-4758-4a9a-ad81-712fd54ed4e8","order_by":15,"name":"Li Ding","email":"","orcid":"","institution":"Beihang University","correspondingAuthor":false,"prefix":"","firstName":"Li","middleName":"","lastName":"Ding","suffix":""}],"badges":[],"createdAt":"2024-03-29 02:14:24","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4185123/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4185123/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":54154577,"identity":"1342c489-0794-4d52-919b-7a2b442d21be","added_by":"auto","created_at":"2024-04-05 11:40:52","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":71638,"visible":true,"origin":"","legend":"\u003cp\u003eLow-pressure simulation chamber altitude rises and falls time points, lasting a total of 1 hour. altitude1: ground; altitude2: 3500m; altitude3: 4000m; altitude4: 4500m; altitude5: ground.\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4185123/v1/de5fa5a49b5c02f2c858818d.jpg"},{"id":54154576,"identity":"8a34bfd8-493d-461b-834e-49fdd5acf966","added_by":"auto","created_at":"2024-04-05 11:40:52","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":69688,"visible":true,"origin":"","legend":"\u003cp\u003eAL variation values of all subjects.\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4185123/v1/345126e8f1fb953ecd6c678b.jpg"},{"id":54154575,"identity":"6b77b0b0-1e64-4979-b23a-96c3363ed428","added_by":"auto","created_at":"2024-04-05 11:40:52","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":74145,"visible":true,"origin":"","legend":"\u003cp\u003eSignificant results of AL differences among different altitudes.\u003c/p\u003e","description":"","filename":"Picture3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4185123/v1/ddaf6d6500ceb733bf076cfd.jpg"},{"id":54154579,"identity":"7e304425-bb07-4609-b2f8-01ba6455cc02","added_by":"auto","created_at":"2024-04-05 11:40:52","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":87942,"visible":true,"origin":"","legend":"\u003cp\u003eCCT variation values of all subjects.\u003c/p\u003e","description":"","filename":"Picture4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4185123/v1/95c40749565eedd7cadb0e25.jpg"},{"id":54154583,"identity":"4fe150d8-36c8-4ee6-b5f4-5145750b9422","added_by":"auto","created_at":"2024-04-05 11:40:53","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":93933,"visible":true,"origin":"","legend":"\u003cp\u003eSignificant results of CCT differences among different altitudes.\u003c/p\u003e","description":"","filename":"Picture5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4185123/v1/79c9f1faa7f6cc3cc08154eb.jpg"},{"id":54154584,"identity":"ac62f628-3c1d-4d82-8dbc-a42cdcb39fed","added_by":"auto","created_at":"2024-04-05 11:40:53","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":66153,"visible":true,"origin":"","legend":"\u003cp\u003eLT variation values of all subjects.\u003c/p\u003e","description":"","filename":"Picture6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4185123/v1/ed83ce6bc8e44fad731a4d84.jpg"},{"id":54154580,"identity":"81d5e974-329f-4497-8ac3-28e26855e1f4","added_by":"auto","created_at":"2024-04-05 11:40:52","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":90840,"visible":true,"origin":"","legend":"\u003cp\u003eSignificant results of LT differences among different altitudes.\u003c/p\u003e","description":"","filename":"Picture7.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4185123/v1/39b8a01cbede2677792e5f48.jpg"},{"id":54154582,"identity":"24f7e2f3-3e3f-47d1-a465-3262588fc1c9","added_by":"auto","created_at":"2024-04-05 11:40:53","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":45792,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation analysis between AL and LT at altitude 1.\u003c/p\u003e","description":"","filename":"Picture8.png","url":"https://assets-eu.researchsquare.com/files/rs-4185123/v1/b4c0181aa8f3a7541cb1887b.png"},{"id":54154894,"identity":"62bb0333-2215-4db0-81c3-817a87a7d297","added_by":"auto","created_at":"2024-04-05 11:48:52","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":52330,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation analysis between AL and LT at altitude 5.\u003c/p\u003e","description":"","filename":"Picture9.png","url":"https://assets-eu.researchsquare.com/files/rs-4185123/v1/0898759a1cf0d778ac8f070c.png"},{"id":54154578,"identity":"a6c11de5-794c-48a1-8903-ee9c6b183bb6","added_by":"auto","created_at":"2024-04-05 11:40:52","extension":"png","order_by":10,"title":"Figure 10","display":"","copyAsset":false,"role":"figure","size":41063,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation analysis between AL and CCT at altitude 4.\u003c/p\u003e","description":"","filename":"Picture10.png","url":"https://assets-eu.researchsquare.com/files/rs-4185123/v1/c669163b427cc12c185930ea.png"},{"id":58576790,"identity":"dcd9edda-43e1-4130-b688-4752fc019692","added_by":"auto","created_at":"2024-06-18 12:17:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1188205,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4185123/v1/12b94e8f-2bea-427d-a268-05e847535c8e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"New insights into changes in ocular structural parameters in a simulated hypobaric hypoxia plateau environment","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIn recent years, aerospace technology has developed rapidly, and high-altitude, low-pressure hypoxic areas such as high-altitude plateaus have become the main places for human exploration. When the human body is in a high-altitude environment, \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e the human body system will be challenged by factors such as low air pressure, low oxygen partial pressure, and low temperature. Research shows that the relationship between a high-altitude environment and the degree of hypoxia can be roughly defined by the following stages: medium altitude (mild hypoxia) is 1520\u0026ndash;2440 meters, high altitude (moderate hypoxia) is 2440\u0026ndash;4270 meters, and ultra-high altitude (severe hypoxia) is 4270\u0026ndash;5490 meters. \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e When the altitude exceeds 2440 meters, adverse consequences such as acute mountain sickness, high-altitude cerebral edema, and pulmonary edema may occur. As the altitude continues to increase, hypoxemia and hypocapnia are particularly obvious, and the local partial pressure of oxygen decreases, resulting in vascular disease. Uneven contraction and destruction of the blood barrier can cause irreversible damage to aerobic tissues, such as those in the brain, heart, and liver, and even threaten life. However, in addition to organs and tissues such as the heart, brain, and lungs, the human eye is the main organ that allows the brain to obtain visual information. Its structure and function depend on the nutritional and metabolic supply of retinal blood flow and are most obviously affected by hypoxia and ischemia. High-altitude retinopathy was first observed in early 1970 by Frayser et al., \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e manifesting as optic disc edema, retinal hemorrhage, optic nerve fiber infarction, etc. Since then, in 2008, Bosch et al. \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e repeatedly reported that exposure to a plateau environment leads to refractive changes and ocular pressure fluctuations, \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e but the specific mechanism is unclear. The impact of a high-altitude, low-pressure hypoxic environment on human ocular axial length (AL), central corneal thickness (CCT), keratometry (K), lens thickness (LT), anterior chamber depth (ACD), and other related physiological parameters has not yet been explored. \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e Therefore, we selected healthy volunteers from Beijing, a low-altitude area in China, to participate in this study to explore changes in ocular axial length, corneal curvature, and other data under acute exposure to different altitude changes, allowing us to objectively evaluate the human eye's response to low-pressure hypoxia. The results provide a research basis for further research on the mechanism of changes in refractive values in human eyes caused by a low-pressure hypoxic environment.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSubjects\u003c/h2\u003e \u003cp\u003eThis prospective study enrolled 16 healthy, physically fit volunteers aged 20\u0026ndash;26 years, including 8 males and 8 females. All subjects were of Han descent and lived at altitudes between 40 and 250 m above sea level. None of the volunteers in this study had systemic or refractive diseases (e.g., glaucoma, shallow anterior chamber, narrow atrial angle, etc.) or a history of ophthalmic surgery, intraocular lenses, or contact lenses, and they did not take any medications that affect refraction. Subjects were required to get enough sleep before the test and not drink caffeinated beverages such as coffee or tea before the experiment. We adhered to the tenets of the Declaration of Helsinki, and the research was approved by the Biomedical Ethics Committee of BHU. Written and oral informed consent were obtained from the participants after a full explanation of the nature and possible consequences of the study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eAscent Profile and Measurements\u003c/h2\u003e \u003cp\u003eThe experiment was safely conducted in a complex high-altitude simulation module at the BHU High-Precision Medicine Center under the supervision of a professional physician. The temperature and humidity inside the chamber were set to be between 23.3 and 26.5 ℃ and between 30 and 35%, respectively. The experimental chamber ascended at a speed of 5 m/s, and 2 minutes of habituation was included after every 1000 m. After the altitude of the simulation chamber reached 4500 m above sea level, the simulation chamber descended at a speed of 3 m/s, and 2 minutes of habituation was again included after every 1000 m. The ocular parameters in the subjects\u0026rsquo; eyes was measured during all habituation periods. The specific experimental altitude changes are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eRefractive values were measured in both eyes with the IOL master (Carl Zeiss Shanghai Co. Ltd), which uses non-contact infrared-light interferometry to measure the ocular refractive parameters, such as keratometry, axial length, anterior chamber depth, etc. These values were used to calculate the power and position of the intraocular lens, which can improve the accuracy and repeatability of the measurement.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eThe K-S test was performed to determine normal distribution. The T-test or Wilcoxon test was applied to analyze the differences among the refractive values at five altitude points. The repeated measures ANOVA test was performed to eliminate the individual effects on the experimental results. A P-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered significant. All evaluations were performed using a commercially available statistical software package (SPSS for Windows, v. 26.0, IBM).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eAll subjects safely reached the simulated altitude of 4500 m and completed the experiment safely without oxygen supplementation.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eMeasured values of AL, CCT, and LT at different altitudes (x ̅\u0026plusmn;s).\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ealtitude\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003enumber\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eAL (mm)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCCT (um)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eLT (mm)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eACD (mm)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAltitude 1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e32\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e24.056\u0026thinsp;\u0026plusmn;\u0026thinsp;0.187\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e545.500\u0026thinsp;\u0026plusmn;\u0026thinsp;5.999\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e3.748\u0026thinsp;\u0026plusmn;\u0026thinsp;0.022\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e3.596\u0026thinsp;\u0026plusmn;\u0026thinsp;0.042\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAltitude 2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e32\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e24.074\u0026thinsp;\u0026plusmn;\u0026thinsp;0.187\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e546.875\u0026thinsp;\u0026plusmn;\u0026thinsp;6.220\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e3.762\u0026thinsp;\u0026plusmn;\u0026thinsp;0.021\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e3.600\u0026thinsp;\u0026plusmn;\u0026thinsp;0.043\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAltitude 3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e32\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e24.082\u0026thinsp;\u0026plusmn;\u0026thinsp;0187\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e547.688\u0026thinsp;\u0026plusmn;\u0026thinsp;6.208\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e3.767\u0026thinsp;\u0026plusmn;\u0026thinsp;0.021\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e3.593\u0026thinsp;\u0026plusmn;\u0026thinsp;0.042\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAltitude 4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e32\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e24.088\u0026thinsp;\u0026plusmn;\u0026thinsp;0.187\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e547.250\u0026thinsp;\u0026plusmn;\u0026thinsp;6.071\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e3.752\u0026thinsp;\u0026plusmn;\u0026thinsp;0.020\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e3.598\u0026thinsp;\u0026plusmn;\u0026thinsp;0.042\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAltitude 5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e32\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e24.079\u0026thinsp;\u0026plusmn;\u0026thinsp;0188\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e547.750\u0026thinsp;\u0026plusmn;\u0026thinsp;6.034\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e3.729\u0026thinsp;\u0026plusmn;\u0026thinsp;0.023\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e3.606\u0026thinsp;\u0026plusmn;\u0026thinsp;0.042\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Taba\" border=\"1\"\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ealtitude\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003enumber\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eK1 (D)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eK2 (D)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eTK1 (D)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eTK2 (D)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAltitude 1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e32\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e42.976\u0026thinsp;\u0026plusmn;\u0026thinsp;0.236\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e43.987\u0026thinsp;\u0026plusmn;\u0026thinsp;0.261\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e43.003\u0026thinsp;\u0026plusmn;\u0026thinsp;0.244\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e43.888\u0026thinsp;\u0026plusmn;\u0026thinsp;0.271\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAltitude 2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e32\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e42.974\u0026thinsp;\u0026plusmn;\u0026thinsp;0.237\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e43.998\u0026thinsp;\u0026plusmn;\u0026thinsp;0.262\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e43.991\u0026thinsp;\u0026plusmn;\u0026thinsp;0.246\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e43.917\u0026thinsp;\u0026plusmn;\u0026thinsp;0.271\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAltitude 3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e32\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e42.970\u0026thinsp;\u0026plusmn;\u0026thinsp;0.236\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e44.012\u0026thinsp;\u0026plusmn;\u0026thinsp;0.260\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e42.991\u0026thinsp;\u0026plusmn;\u0026thinsp;0.244\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e42.934\u0026thinsp;\u0026plusmn;\u0026thinsp;0.268\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAltitude 4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e32\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e42.970\u0026thinsp;\u0026plusmn;\u0026thinsp;0.239\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e43.989\u0026thinsp;\u0026plusmn;\u0026thinsp;0.256\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e42.982\u0026thinsp;\u0026plusmn;\u0026thinsp;0.246\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e43.903\u0026thinsp;\u0026plusmn;\u0026thinsp;0.263\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAltitude 5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e32\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e43.000\u0026thinsp;\u0026plusmn;\u0026thinsp;0.238\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e43.996\u0026thinsp;\u0026plusmn;\u0026thinsp;0.259\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e43.013\u0026thinsp;\u0026plusmn;\u0026thinsp;0.247\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\"\u0026plusmn;\"\u003e\n\u003cp\u003e43.921\u0026thinsp;\u0026plusmn;\u0026thinsp;0.264\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eAltitude 1: ground; Altitude 2: 3500m; Altitude 3: 4000m; Altitude 4: 4500m; Altitude 5: back on the ground.\u003c/p\u003e\n\u003cp\u003eIt can be seen from Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e that the AL of the eyes of all subjects\u0026rsquo; changes with elevation, increasing from 24.056\u0026thinsp;\u0026plusmn;\u0026thinsp;0.187 mm at ground level (altitude 1) to 24.088\u0026thinsp;\u0026plusmn;\u0026thinsp;0.187 mm at 4500 m (altitude 4), and finally, the AL of all subjects reduced to 24.079\u0026thinsp;\u0026plusmn;\u0026thinsp;0.188 mm after returning to the ground level (altitude 5).\u003c/p\u003e\n\u003cp\u003eAmong them, the AL of most subjects showed a statistically significant growing trend with the increase in altitude, while the AL of a few subjects fluctuated between 3500m (altitude 2) and 4000m (altitude 3), but there was no statistical significance. After that, with the decrease in altitude, the AL gradually decreased toward its initial state, but the AL was still larger compared with its initial state (altitude 1) after returning to the ground (altitude 5).\u003c/p\u003e\n\u003cp\u003eIn reviewing the specific changes in AL at the five altitudes (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e), the AL of all subjects underwent a T-test and repeated measures ANOVA. Except for the AL between 3500m (altitude 2) and the ground (altitude 5) and that between 4000m (altitude 3) and the ground (altitude 5), which had no statistical significance, the AL showed a statistically significant increase among the other altitude pairs (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\n\u003cp\u003eAs can be seen from Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e, the CCT in all subjects showed fluctuating thickening with an increasing altitude and rolling thinning with a decreasing altitude. Specifically, as the altitude increased, the CCT increased from 545.500\u0026thinsp;\u0026plusmn;\u0026thinsp;5.999 um on the ground (altitude 1) to 547.688\u0026thinsp;\u0026plusmn;\u0026thinsp;6.208 um at 4000 m (altitude 3). The CCT fluctuated and changed to be 547.250\u0026thinsp;\u0026plusmn;\u0026thinsp;6.071 um at 4500 m (altitude 4). After returning to the ground (altitude 5), the subjects\u0026rsquo; CCT was 547.750\u0026thinsp;\u0026plusmn;\u0026thinsp;6.034 um, which was slightly thinner than that at 3500m (altitude 2) but still thicker than the CCT at the initial state (altitude 1).\u003c/p\u003e\n\u003cp\u003eAfter the repeated measures analysis of variance, paired t-test, and Wilcoxon test (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e) were performed, the CCT at the four altitudes of 3500m, 4000m, 4500m, and back on the ground (altitudes 2, 3, 4, and 5) was found to be statistically significantly thicker than at the initial state (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05); notably, the CCT values had a striking difference between altitude 1 and altitude 3 and altitude 1 and altitude 5 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e). However, when comparing the CCT among all altitudes, no statistical difference was found; that is, there was no significant thickening or thinning in the CCT at 3500, 4000, 4500, and back on the ground (altitudes 2, 3, 4, and 5).\u003c/p\u003e\n\u003cp\u003eAs shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e, the LT of more than half of the subjects increased when the altitude increased to 4000m, and the LT of more than half of the subjects became thinner when the altitude increased to 4500 m. After going back to the ground, at the initial ground level (altitude 1), the LT was 3.748\u0026thinsp;\u0026plusmn;\u0026thinsp;0.022mm. The LT thickened with the increase in altitude and became 3.762\u0026thinsp;\u0026plusmn;\u0026thinsp;0.021mm and 3.767\u0026thinsp;\u0026plusmn;\u0026thinsp;0.021mm at the altitudes of 3500m (altitude 2) and 4000m (altitude 3), respectively. Then, the LT became thinner with the decrease in altitude. After returning to the ground (altitude 5), the LT was 3.729\u0026thinsp;\u0026plusmn;\u0026thinsp;0.023mm. Through the paired T-test (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003e) and repeated measures ANOVA, it can be seen that the LT at the four altitudes (3500m, 4000 m, and 4500 m) and back on the ground (altitudes 2, 3, 4, and 5) is statistically thicker or thinner than that at the initial altitude (altitude 1). Moreover, the repeated measures ANOVA showed that the difference between altitudes 2 and 5 was statistically significant, as was the difference between altitudes 3 and 5 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e). There was no significant change in LT between different heights.\u003c/p\u003e\n\u003cp\u003eAdditionally, we also investigated the changes in ACD, K, and TK at different altitudes, which showed fluctuating changes with the increase or decrease in altitude, but no obvious pattern was observed; that is, no statistically significant changes were observed in those values among different altitudes.\u003c/p\u003e\n\u003cp\u003eIn order to determine whether there is a correlation between AL and ACD and between LT and CCT, and whether the measurement of AL is affected by these 3 values, we further explored the correlation between them.\u003c/p\u003e\n\u003cp\u003eThe statistics presented in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e show that for AL and LT, there is a correlation between the two groups at ground level (altitude 1) (r\u0026thinsp;=\u0026thinsp;0.375, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) and after returning to ground level (altitude 5) (r\u0026thinsp;=\u0026thinsp;0.341, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), but there is no correlation between the two groups at the altitudes of 3,500m, 4,000m, and 4,500m; for AL and CCT, the two groups have the same change trend at 4,500m (altitude 4) (r\u0026thinsp;=\u0026thinsp;0.337, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), but no significant correlation is seen at the rest of the altitudes. For AL and CCT, the same trend was observed at 4500m (altitude 4) (r\u0026thinsp;=\u0026thinsp;0.337, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), but no significant correlation was observed at the remaining altitudes. Meanwhile, there was no significant relationship between LT and CCT or between AL and corneal curvature. In addition, we further explored the correlation between ACD and the changes in each parameter, and it was seen that at altitudes 2, 3, and 4, i.e., after ascending in altitude, ACD was positively correlated with AL; at altitudes 1, 2, 3, and 5, ACD was negatively correlated with LT. Thus, although acute low-pressure hypoxia did not cause statistically significant changes in ACD, it is still known that ocular axis growth and increased lens thickness can lead to changes in anterior chamber depth.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eCorrelation analysis between AL, LT, and CCT.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003ealtitude\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eAL vs. LT\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eAL vs. CCT\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eLT vs. CCT\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003er\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003er\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003er\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAltitude 1\u003c/p\u003e\n\u003cp\u003eAltitude 2\u003c/p\u003e\n\u003cp\u003eAltitude 3\u003c/p\u003e\n\u003cp\u003eAltitude 4\u003c/p\u003e\n\u003cp\u003eAltitude 5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.375*\u003c/p\u003e\n\u003cp\u003e0.103\u003c/p\u003e\n\u003cp\u003e0.087\u003c/p\u003e\n\u003cp\u003e0.254\u003c/p\u003e\n\u003cp\u003e0.341*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.05*\u003c/p\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.05*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-0.031\u003c/p\u003e\n\u003cp\u003e-0.044\u003c/p\u003e\n\u003cp\u003e-0.039\u003c/p\u003e\n\u003cp\u003e0.337*\u003c/p\u003e\n\u003cp\u003e0.021\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.05*\u003c/p\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-0.069\u003c/p\u003e\n\u003cp\u003e-0.082\u003c/p\u003e\n\u003cp\u003e-0.036\u003c/p\u003e\n\u003cp\u003e0.046\u003c/p\u003e\n\u003cp\u003e-0.078\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eCorrelation analysis between AL, K, and TK.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003ealtitude\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eAL vs. K1\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eAL vs. K2\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eAL vs. TK1\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eAL vs. TK2\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003er\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003er\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ep\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003er\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003er\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAltitude 1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.04\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.182\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.057\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.192\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAltitude 2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.04\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.188\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.058\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.201\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAltitude 3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.063\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.19\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.072\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.207\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAltitude 4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.041\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.208\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.053\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.22\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAltitude 5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.045\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.206\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.054\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.228\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab4\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eCorrelation analysis between ACD, LT, CCT, and AL.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003ealtitude\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eACD vs. AL\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eACD vs. LT\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eACD vs. CCT\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003er\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003er\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003er\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAltitude 1\u003c/p\u003e\n\u003cp\u003eAltitude 2\u003c/p\u003e\n\u003cp\u003eAltitude 3\u003c/p\u003e\n\u003cp\u003eAltitude 4\u003c/p\u003e\n\u003cp\u003eAltitude 5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.224\u003c/p\u003e\n\u003cp\u003e0.357*\u003c/p\u003e\n\u003cp\u003e0.388*\u003c/p\u003e\n\u003cp\u003e0.337*\u003c/p\u003e\n\u003cp\u003e0.283\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.05*\u003c/p\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.05*\u003c/p\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.05*\u003c/p\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-0.344\u003c/p\u003e\n\u003cp\u003e-0.358\u003c/p\u003e\n\u003cp\u003e-0.32\u003c/p\u003e\n\u003cp\u003e-0.268\u003c/p\u003e\n\u003cp\u003e-0.316\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.05*\u003c/p\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.05*\u003c/p\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.05*\u003c/p\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003cp\u003e\u0026lt;\u0026thinsp;0.05*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.06\u003c/p\u003e\n\u003cp\u003e0.038\u003c/p\u003e\n\u003cp\u003e0.041\u003c/p\u003e\n\u003cp\u003e0.046\u003c/p\u003e\n\u003cp\u003e0.057\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThere are many differences between high-altitude and sea-level environments, characterized by low oxygen concentrations, low temperatures, and high UV radiation. Some studies have shown that the ocular data of people living at a high altitude for long periods of time, such as in the Tibetan Plateau, show significant differences in ocular appearance in terms of nose bridge width (NBW), inner intercanthal distance (IICD), outer intercanthal distance (IOCD), and interpupillary distance (IPD), and changes in the inner eye, such as low intraocular pressure (IOP), shorter axial length of the eye, and high prevalence of lens cloudiness, have been observed. \u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e The above suggests that there is an adaptive response to low-pressure hypoxia in the human eye at high altitudes, which results in differences from the human eye at sea level in a number of ways. The fluctuations in AL, LT, and CCT with altitude observed in the present study are similar to the physiologic changes observed in high-altitude populations. However, in the present study, we focused on the effects of acute hypoxia on the human eye by using healthy adults who lived on the plains and had never visited the plateau region before. This study was carried out in a high-altitude, low-pressure simulation chamber, which simulated the environment of low-pressure hypoxia and hypothermia in the plateau and rapidly elevated the subjects to altitudes of 3,500, 4,000, and 4,500 meters within a short period of time, to further clarify the physiological structural and functional effects of acute low-pressure hypoxia on the human eye.\u003c/p\u003e \u003cp\u003eThrough the long-term observation of high-altitude populations, one study found that Aboriginal people living at high altitudes had shorter axial lengths than white, black, and Asian people, averaging 23.05 millimeters (with a standard deviation of 0.77 millimeters). \u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e This finding is inconsistent with the results of this study, which observed that the mean axial length of the subjects' eyes increased with altitude, reached a maximum at the highest altitude, and then gradually recovered after returning to the ground again, suggesting that acute hypoxia causes reversible changes in the axial length of the eyes. The reason for the increase in mean axial length with elevation observed in the subjects in this study was considered to be possibly related to choroidal blood supply, which can be broadly classified as having two functions: the first is to provide oxygen and nutrients to the outer retina, and the second is to regulate the position of the retina through changes in the thickness of the choroid, as well being involved in vascularization and scleral remodeling, which affect the release of ocular growth regulators such as VEGF, NO, etc. In 2021, Yilin L et al. \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e reviewed the correlation between choroidal blood flow and ocular axis length in myopic patients and found that when choroidal blood flow is reduced, the choroid and sclera show ischemic and hypoxic manifestations, which appear as a reduction in the diameter of the choroidal vessels; at the same time, there is a reduction in the molecules with osmotically active molecules such as hyaluronic acid, glycosaminoglycans, and proteoglycan in the choroidal vasculature, \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e resulting in a reduction in the permeability of choroidal tubular diameters and making it not possible for more fluids to be pulled into the choroid, which leads to a further reduction in the diameter of the choroid and a thinning of the choroid, \u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e In addition, endogenous choroidal neurofactors are released by ischemic and hypoxic conditions, and they interfere with choroidal vascular and nonvascular smooth muscle, which can lead to changes in choroidal thickness, among other things. \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e In an in vitro study, 1-day-old rats were exposed to 5% oxygen and 95% nitrogen for 2 hours and recovered under normal oxygen for a time period from 3 hours to 21 days to observe the effects of acute hypoxia on retinal cellular and vascular factors in neonatal rats as well as the effects of these factors on choroidal vascular permeability. The results showed that the mRNA and protein expression of HIF-1α, VEGF, eNOS, nNOS, and iNOS, as well as the concentration of VEGF and the production of NO, significantly increased in the retina after hypoxia, which led to an increase in the permeability of the choroidal vasculature and leakage of RhIC and HRP from the vasculature, and further led to the narrowing of the vascular diameter of the choroidal vasculature and its thinning. Therefore, we speculate that when subjects are in a low-pressure hypoxic environment, blood oxygen saturation decreases, ocular choroidal blood flow decreases, ocular growth regulators and neurofactors are released, the vascular smooth muscle becomes constricted, the canaliculus narrows, the choroid thins, and the sclera thins. Studies have shown that the main area of choroidal sclera thinning is in the macular central pucker, \u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e so there is an increase in the elasticity of the wall of the eyeball, a decrease in the eyeball's tolerance to the preexisting IOP, and the emergence of a detectable increase in the eye's axial length.\u003c/p\u003e \u003cp\u003eAs an important part of the optical pathway, the transparent cornea relies on the capillary network of the corneoscleral rim for the acquisition of nutrients as well as the maintenance of its function, and thus its response to hypoxia is more pronounced. For the central corneal thickness, previous articles confirmed that a stay of 1\u0026ndash;2 weeks at a high altitude results in a decrease in the thickness of the tear film and an increase in the thickness of the corneal endothelium and the corneal mesenchymal stroma. Moreover, the central corneal thickness thickens with the increasing duration of stay at a high altitude, \u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e and gradually decreases to baseline levels when returning to sea level. The present study demonstrated the onset of acute hypoxia with a relatively rapid increase in altitude and a gradual increase in CCT from altitude 1 to altitude 3, which is consistent with the literature findings. However, in this study, after staying at 4500 meters for 40 minutes, the CCT gradually decreased to what it was at sea level, and at altitude 5, compared with the initial state, the CCT was still thicker than the corneal thickness at its initial state, meaning it was not restored. The discrepancy may be due to the fact that most of the studies in the literature were experiments of chronic hypoxia and acclimatization training was conducted on the subjects, whereas the experiments in this paper were experiments of acute hypoxia, and therefore, there was a delay in the recovery of the ocular structures. To explain why CCT thickens with altitude, the following factors were considered: Low-pressure hypoxia leads to anaerobic glycolysis and lactic acid accumulation in corneal epithelial cells, and lactic acid diffuses through the corneal stroma and endothelium and is metabolized in atrial fluid, resulting in osmolality-dependent atrial reflux and an increase in corneal edema. \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e At the same time, anaerobic glycolytic products decrease the activity of the corneal endothelial pump, leading to corneal edema and increased corneal thickness. In addition, in vitro studies showed that DNA damage and apoptosis were observed in cells of ocular surface tissues, such as those from the conjunctival and corneal epithelium, in a single episode of acute hypoxia, and that corneal epithelial cells promoted corneal edema and angiogenesis under hypoxic conditions by increasing the expression of VEGF and cytochrome p4504B1, suggesting that hypoxia may lead to corneal epithelial cells affecting its thickness and that these factors may be important corneal hypoxic regulators of corneal injury. \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn the present study, we also observed a statistically different change in lens thickness with increasing altitude, with the lens thickness being thicker at 4,000 and 4,500 meters above sea level than after returning to the ground. It is well known that the lens inherently exists in a relatively low-oxygen environment due to a lack of blood supply, with there being a gradual decrease in oxygen concentration from the surface to the core of the lens. One study measured the proliferation rate of lens epithelial cells in vitro at both high and low oxygen concentrations and found that the proliferative activity of the cells did not increase when the oxygen concentration was lower than normal. \u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e In contrast, hypoxia leads to lens maturation through the activation of hypoxia-inducible factor (HIF1a), \u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e which regulates hypoxia-responsive genes and promotes the elimination of epithelial cell organelles, enabling them to differentiate into lens fiber cells and achieve a regular arrangement. Therefore, previous studies concluded that low-pressure hypoxia does not cause changes in lens structure. However, in this experiment, an increase in the thickness of the lens alongside an increasing altitude was observed, which has not been previously reported in the literature, and so this specific mechanism needs to be further investigated.\u003c/p\u003e \u003cp\u003ePreviously, some scholars tested ACD at high altitudes for three consecutive days and observed more significant changes. \u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e Unfortunately, we did not observe significant changes in the anterior chamber depth under acute hypoxic conditions in the present study, and we assume that this may be related to the duration of hypoxia, as acute hypoxia over a short period of time could not have a statistically significant effect on anterior chamber depth. In addition, the pattern of change in the curvature of the anterior surface of the cornea and in the total surface of the cornea with altitude in the present study showed a large fluctuation in the data, which is consistent with the results of the previous literature and is also in line with the previous long-term statistical follow-up data on the anterior chamber depth of the people who stayed at high altitudes, 3,300 meters or 1,700 meters, for a short period of time or for a long period of time. \u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eA review of previous studies showed that the refractive error of the subjects changed with altitude; however, one of the possible mechanisms is that the epithelial cells of the tear film, conjunctiva, and cornea are affected by the low-oxygen environment, and the DNA in the epithelial cells of the cornea and conjunctiva breaks and undergoes apoptosis, destabilizing the tear film and conjunctiva, disrupting the regularity of the image, and disorganizing the arrangement of the corneal collagen, which leads to the clinical symptom of the subjective blurring of vision in subjects. In this present study, we found that the subjects' subjective vision was not clear. Secondly, through this study, we observed the change in the length of the ocular axis with altitude, and since the elongation of the ocular axis will change the morphology of the eyeball, affect the thickness of the ocular wall, and then affect the refractive error of the eyeball, we hope to study the correlation between the ocular axis and the refractive error in the future; regrettably, in this study we did not observe the change in the K and the TK with altitude (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), and so we could not analyze the ocular axis and the refractive error in conjunction with each other. In the future, we hope to expand the sample size, further analyze the correlation of the data from each group, and perform choroidal blood flow monitoring to clarify the causes of altered visual function after acute hypoxia and explore the pathophysiological mechanisms.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eA low-pressure hypoxic environment at a high altitude affects the ocular structure and refractive parameters in eyes, which tend to manifest themselves in the form of ocular axis elongation, increased central corneal thickness, and lens thickness, and these alterations can affect visual acuity and thus a pilot's ability to carry out information acquisition and decision making while driving. Our study provides, for the first time, more complete data on the values of refractive parameters, such as total eye axis length, central corneal thickness, and lens thickness, at different degrees of hypoxia under acute hypoxic conditions. In the future, we will expand the sample size to analyze each group of data and conduct choroidal blood flow monitoring in order to specifically study the reasons for the changes in eye physiology and pathophysiology at high altitudes, as well as the mechanisms that affect the biological parameters of the eye, so as to provide a reference basis for the design of safe aircraft.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e: We would like to thank Li Ding and Xuemin Li and their team at the Peking University Third Hospital and Beihang University. We appreciate the kindness of the volunteers for cooperating in high-altitude experiments for the advancement of science. This article is solely dedicated to them.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest:\u003c/strong\u003e The authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003ePeking University Third Hospital Key talent project, funding number: BYSYZD2021044.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e Yuchen Wang, Anqi Guo, and Xinli Yu made substantial contributions to the conception of this study; Anqi Guo processed the data; Yuchen Wang and Xinli Yu reviewed the literature and drafted the manuscript; Yihe Liu, Zesong Wang, Jiaxing Xie, Xinzuo Zhou, Haqin Xia, Jiaxi Li, Chao Sun, Jing Zhang, Zhongsheng Lv, Siru Liu, and Chengkai Zhou participated in the translation of articles; Ziyuan Liu reviewed the manuscript; Xuemin Li and Li Ding gave final approval of the version to be submitted and approved any revised versions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInstitutional Review Board Statement\u003c/strong\u003e: This study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the\u0026nbsp;Biomedical Ethics Committee of BHU.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed Consent Statement\u003c/strong\u003e: Informed consent was obtained from all subjects involved in the study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHou J, Zheng D, Wen X, Xiao W, et al. Proteomic and Morphological Profiling of Mice Ocular Tissue During High-altitude Acclimatization Process: An Animal Study at Lhasa. J Inflamm Res. 2022;15:2835-53.\u003c/li\u003e\n\u003cli\u003eDavis C, Hackett P. Advances in the Prevention and Treatment of High Altitude Illness. Emerg Med Clin North Am. May 2017;35(2):241-60.\u003c/li\u003e\n\u003cli\u003eWillmann G, Gekeler F, Schommer K, Bartsch P. Update on high altitude cerebral edema including recent work on the eye. High Alt Med Biol. Jun 2014;15(2):112-22.\u003c/li\u003e\n\u003cli\u003eWu Y, Qiong Da CR, Liu J, Yan X. Intraocular pressure and axial length changes during altitude acclimatization from Beijing to Lhasa. PLoS One. 2020;15(1):e0228267.\u003c/li\u003e\n\u003cli\u003eLi Z, Xiang Y, Wang Y, Wan W, et al. Ocular microbial diversity, community structure, and function at high altitude. Microb Pathog. Dec 2021;161(Pt A):105253.\u003c/li\u003e\n\u003cli\u003eBali J, Chaudhary KP, Thakur R. High altitude and the eye: a case controlled study in clinical ocular anthropometry of changes in the eye. High Alt Med Biol. Winter 2005;6(4):327-38.\u003c/li\u003e\n\u003cli\u003eLiu Y, Wang L, Xu Y, Pang Z, et al. The influence of the choroid on the onset and development of myopia: from perspectives of choroidal thickness and blood flow. Acta Ophthalmol. Nov 2021;99(7):730-38.\u003c/li\u003e\n\u003cli\u003eChen W, Zhang H, Zhang Y, Wang Q, et al. Relationship between Aquaporin-1 Protein Expression and Choroidal Thickness during the Recovery of Form-deprivation Myopia in Guinea Pigs. Curr Eye Res. Jun 2020;45(6):705-12.\u003c/li\u003e\n\u003cli\u003eZhang JM, Wu JF, Chen JH, Wang L, et al. Macular Choroidal Thickness in Children: The Shandong Children Eye Study. Invest Ophthalmol Vis Sci. Dec 2015;56(13):7646-52.\u003c/li\u003e\n\u003cli\u003eBrown DM, Mazade R, Clarkson-Townsend D, Hogan K, et al. Candidate pathways for retina to scleral signaling in refractive eye growth. Exp Eye Res. Jun 2022;219:109071.\u003c/li\u003e\n\u003cli\u003eMorris DS SJ, Scott KM, McCormick IJ, Aspinall P, et al. Corneal thickness at high altitude. . Cornea. 2007;26(3):308-311.\u003c/li\u003e\n\u003cli\u003eWang Y, Yu X, Liu Z, Lv Z, et al. Influence of hypobaric hypoxic conditions on ocular structure and biological function at high attitudes: a narrative review. Front Neurosci. 2023;17:1149664.\u003c/li\u003e\n\u003cli\u003eMcKay TB, Hjortdal J, Priyadarsini S, Karamichos D. Acute hypoxia influences collagen and matrix metalloproteinase expression by human keratoconus cells in vitro. PLoS One. 2017;12(4):e0176017.\u003c/li\u003e\n\u003cli\u003eAkberova SI, Markitantova YV, Ryabtseva AA, Stroeva OG. Hypoxia as pathogenic factor affecting the eye tissues: The selective apoptotic damage of the conjunctiva and anterior epithelium of the cornea. Dokl Biochem Biophys. Mar 2016;467(1):150-152.\u003c/li\u003e\n\u003cli\u003eMorris DS, Somner J, Donald MJ, McCormick IJ, et al. The eye at altitude. Adv Exp Med Biol. 2006;588:249-70.\u003c/li\u003e\n\u003cli\u003eShui YB, Beebe DC. Age-dependent control of lens growth by hypoxia. Invest Ophthalmol Vis Sci. Mar 2008;49(3):1023-29.\u003c/li\u003e\n\u003cli\u003eBrennan L, Disatham J, Kantorow M. Hypoxia regulates the degradation of non-nuclear organelles during lens differentiation through activation of HIF1a. Exp Eye Res. Sep 2020;198:108129.\u003c/li\u003e\n\u003cli\u003eWillmann G, Schatz A, Zhour A, Schommer K, et al. Impact of acute exposure to high altitude on anterior chamber geometry. Invest Ophthalmol Vis Sci. Jun 21 2013;54(6):4241-48.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"refractive values, high-altitude hypobaric hypoxia environment, axial length","lastPublishedDoi":"10.21203/rs.3.rs-4185123/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4185123/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eHigh altitude is the main area for human exploration, and human eye is an important organ for obtaining visual signals. The changes of eye structure and function caused by hypobaric hypoxia environment need to be clarified.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eMeasurements were taken at five altitudes (1: ground; 2: 3500m; 3: 4000m; 4: 4500m; and 5: end of experiment). Refractive values were measured with the IOL Master (Carl Zeiss Shanghai Co. Ltd.). Data analysis was performed using the Kolmogorov\u0026ndash;Smirnov (K-S) test, paired sample T-test, and Wilcoxon test.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eSubjects\u0026rsquo; axial length (AL) increased with altitude, peaking at 4500m, then decreased. Significant differences in AL were observed across altitudes (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), except between 2 and 5, and 3 and 5. Central corneal thickness (CCT) thickened then thinned with elevation changes, significantly thicker at altitudes 2\u0026ndash;5 compared to the baseline (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Lens thickness (LT) followed a similar pattern, increasing up to altitude 4, then decreasing at 5. Correlations were found between AL and LT at altitudes 1 (r\u0026thinsp;=\u0026thinsp;0.375, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) and 5 (r\u0026thinsp;=\u0026thinsp;0.341, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), and between AL and CCT at altitude 4 (r\u0026thinsp;=\u0026thinsp;0.337, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), but not elsewhere. No significant relationship was observed between LT and CCT.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eAs altitude increases and the degree of acute low-pressure hypoxia worsens, the refractive parameters such as AL, CCT, and LT are altered, which could potentially affect the pilot's visual function after acute hypoxia, further affecting the pilot's information acquisition and decision-making during driving and posing a threat to flight safety.\u003c/p\u003e","manuscriptTitle":"New insights into changes in ocular structural parameters in a simulated hypobaric hypoxia plateau environment","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-05 11:40:46","doi":"10.21203/rs.3.rs-4185123/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":"640c7592-6001-4130-b34e-f07c79f27416","owner":[],"postedDate":"April 5th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-06-18T12:09:28+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-05 11:40:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4185123","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4185123","identity":"rs-4185123","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}