Decreased Optic Nerve Head Perfusion in Patients with Normal Tension Glaucoma and Obstructive Sleep Apnoea

Decreased Optic Nerve Head Perfusion in Patients with Normal Tension Glaucoma and Obstructive Sleep Apnoea | 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 Article Decreased Optic Nerve Head Perfusion in Patients with Normal Tension Glaucoma and Obstructive Sleep Apnoea Tin Tun, Shayne Tan, Royston Tan, Monisha Nongpiur, Leopold Schmetterer, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7473796/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: To compare optic nerve head (ONH) perfusion using laser speckle flowgraphy (LSFG) (Softcare Co., Ltd., Fukuoka, Japan) in sitting and supine positions between eyes with normal tension glaucoma and obstructive sleep apnoea (NTG-OSA) versus normal controls. Methods: Intraocular pressure (IOP), body mass index (BMI), and LSFG measurements (mean blur rate (MBR), blowout score (BOS), and blowout time (BOT)) were taken in sitting and supine positions. MBR is a quantitative index of blood cell velocity, a proxy of tissue blood flow. BOS is the blood volume maintained within a vessel during each heartbeat. BOT is the time within one heartbeat that maintains >½ average MBR. A higher BOT implies that blood flow is maintained at a sufficiently high level for a longer duration during each heartbeat for tissue perfusion. Results: 45 NTG-OSA and 29 normal eyes were recruited. The MBR of all areas, vascular areas, and tissue areas were significantly lower in the NTG-OSA group compared to the normal controls in both sitting and supine positions (all p<0.05). When changing from sitting to supine, normal eyes had significantly greater increase in BOS compared to the increase in NTG-OSA eyes (p<0.05), but only NTG-OSA eyes had significant increases in BOT (p<0.05). Conclusion: NTG-OSA eyes have significantly lower ONH perfusion, as measured by decreased MBR on LSFG, in both sitting and supine positions. The prolonged maintenance of high ONH perfusion with a change in body posture, represented by an increase in BOS may represent altered microvascular autoregulation in patients with NTG-OSA. Health sciences/Medical research Health sciences/Anatomy Figures Figure 1 Introduction Glaucoma is the leading cause of irreversible blindness, with primary open angle glaucoma (POAG) affecting more than 57.5 million people worldwide.(1) Normal tension glaucoma (NTG) forms a significant proportion of POAG patients, with an overall pooled proportion of NTG among patients with POAG in Asia estimated to be 76.3%.(2) As yet, intraocular pressure (IOP) remains the only modifiable risk factor in the treatment of glaucoma to halt or stall progression.(3–5) However, given that IOP in NTG is typically within the statistically population-normal range and tends to be equal between the eyes of an individual,(6,7) the optic nerve damage and often asymmetrical nature of NTG suggests that other non-IOP factors contribute to the pathogenesis of NTG.(8–11) One significant IOP-independent risk factor for NTG is obstructive sleep apnoea (OSA), (12,13) an upper airway breathing disorder characterised by episodes of complete (apnoea) or partial (hypopnoea) collapse of the upper airway, with associated hypoxia during sleep.(14) A meta-analysis showed that patients with OSA were 6.72 times more likely to develop NTG compared to those without OSA.(15) However, the exact pathophysiology behind this association remains unknown, although some hypothesise that it may be due to compromised ocular perfusion and reduced blood flow from nocturnal hypoxia in OSA patients.(16–18) Besides nocturnal hypoxia in OSA, it has been observed that the severity of glaucoma in NTG may also be related to preferred sleeping positions, possibly due to pressure-dependent factors.(19) IOP is known to vary with different body positions, with higher IOPs observed in the supine position compared to the upright sitting position.(20–22) This has been postulated to be due to increased episcleral venous pressure when lying down.(23,24) Since humans spend nearly one-third of their lives sleeping, some studies have suggested that fluctuations in IOP during sleep may help to explain the pathogenesis of NTG.(25–27) Some postulate that IOP-related deformations within the peripapillary sclera affect ocular perfusion, at least in part, by compressing the scleral branches of the short posterior ciliary arteries.(28) However, due to the posterior location of this anatomy in the eye and technical difficulties in assessing blood flow in the lying position, ocular perfusion at the ONH remains to be fully understood.(29) In this regard, laser speckle flowgraphy (LSFG) (Softcare Co., Ltd., Fukuoka, Japan) has been shown to be a useful tool for the quantitative measurement of blood flow at the ONH.(30,31) One of the parameters obtained with LSFG, the mean blur rate (MBR), has shown good correlation with tissue blood flow rates at the ONH using the hydrogen gas clearance technique, providing a quantitative and reproducible index of blood cell velocity.(30–32) LSFG also provides other indicators of blood flow and perfusion within the blood vessel, such as blow out score (BOS) and blow out time (BOT), where BOS refers to the blood volume maintained within the vessel during each heartbeat, while BOT refers to the time within a heartbeat waveform during which more than half of the average MBR is maintained. Taken together, these parameters provide a better understanding of blood flow and ocular perfusion. The aim of this study was to use LSFG to study changes in perfusion parameters across the optic nerve head associated with a change of position from sitting to supine in NTG patients with OSA. Methods This study had the approval of the SingHealth Centralized Institutional Review Board and adhered to the tenets of the Declaration of Helsinki, with informed consent obtained for all study participants. Healthy controls without OSA were recruited from the general population, while patients with NTG were recruited from the glaucoma clinic service at the Singapore National Eye Centre (SNEC). NTG eyes were defined as the presence of glaucomatous optic neuropathy (GON) with an IOP of 0.2 with or without focal notching, along with a compatible VF loss on static automated perimetry (SITA Standard algorithm with a 24-2 test strategy; Humphrey Visual Field Analyser II; Carl Zeiss Meditec, Dublin, CA). VF defects were considered glaucomatous if they met at least 2 Anderson’s criteria: (1) ≥ 3 continuous nonedged points in a cluster depressed to P < 5%, with at least one depressed to P < 1%; (2) Glaucoma Hemifield Test outside normal limits; or (3) pattern SD depressed to P < 5%. The VFs of all these patients were evaluated for reliability. Reliability criteria for VF testing included fixation losses of <15% and false-positives or -negatives rates of <33%. Only one eye per patient was analysed. If both eyes of one patient fulfilled the criteria for evaluation of NTG, the eye with the more severe disease based on the VF mean deviation (MD) was defined as the study eye. All NTG patients recruited had a concomitant diagnosis of OSA, which was only diagnosed by an otorhinolaryngology specialist after overnight polysomnography recording at a sleep clinic, with an apnoea-hypopnoea index (AHI) score per hour of >5. The AHI measures the cumulative number of apnoeic and hypopnoeic episodes throughout the night. All patients also had the following investigations performed: (1) measurement of body height and weight for calculation of body mass index (BMI), (2) measurement of blood pressure (BP), (3) measurement of their best-corrected visual acuity (BCVA), (4) biometry measurements using the IOL master (Carl Zeiss Meditec, Germany), (5) IOP measurements with a Tonopen AVIA® applanation tonometer (Reichert Inc., Depew, USA), and (6) LSFG measurements. BP, IOP, and LSFG measurements were performed in the sitting and supine positions, with each position maintained for 5 minutes before recordings were taken. Ocular perfusion pressure (OPP) was determined by: mean arterial pressure (MAP) – IOP. LSFG measurements were taken after pupillary dilation with 0.5% tropicamide eye drops. The LSFG machine comprises a fundus camera with a diode laser that operates at a wavelength of 830nm, and a digital charge-coupled camera with a resolution of 750 x 360 pixels. This allows a total of 118 images to be captured at a rate of 30 frames per second over 4 seconds. As mentioned above, an important output of the LSFG is the MBR, which is a parameter that measures the relative blood flow velocity in a specified area, expressed in arbitrary units (au). The LSFG-NAVI has an inbuilt software that calculates and averages all 118 images to generate a composite map of the distribution of perfusion in a single cardiac cycle. This can then be subdivided into three distinct regions of the ONH: the MBR of the vascular area (MBR-V), the MBR of the tissue area (MBR-T), and the MBR of all areas (MBR-A). (Figure 1) Other significant parameters from the LSFG include BOS and BOT, as mentioned above. A high BOT would imply that blood flow is maintained at a sufficiently high level for a long period of time during each heartbeat to ensure peripheral perfusion of tissues.(33) Statistical analysis Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) statistics for Windows (IBM Corp, Version 19.0, Armonk, New York). Continuous variables were expressed as the mean and standard deviation. The independent t -test was used to compare the difference in the distribution of continuous variables between the study NTG group and the control group. The paired t -test was also used to compare the changes between the sitting and supine position within each group. The Spearman’s correlation was used to establish the correlation coefficient between clinical and ocular parameters with all 3 regions of MBR. Statistical significance was set at p<0.05. Results A total of 45 patients with NTG-OSA and 29 healthy controls were recruited. Compared to the control group, NTG-OSA patients were older (61.51 ± 9.32 years vs 56.58 ± 7.94 years, p=0.022), predominantly males (80.0% vs 20.0%), and had a significantly higher BMI (26.22 ± 4.84 vs 22.84 ± 2.59, p<0.001). (Table 1) NTG-OSA patients were also more myopic (-2.77D ± 3.14D vs -0.39D ± 1.67D, p<0.001) with longer axial lengths (26.82 ± 1.33mm vs 23.93 ± 0.99mm, p<0.001). The NTG-OSA group had significantly lower blood saturation levels (SpO2) in the supine position compared to the normal controls (97.64% ± 1.48 vs 98.55% ± 1.09, p=0.006). (Table 2) The MBR of all areas, vascular areas, and tissue areas were also significantly lower in the NTG-OSA group compared to the normal controls in both sitting and supine positions (all p<0.05). There was a statistically significant change associated with a change in position from sitting to supine in all following parameters in both the NTG-OSA group and the normal group: IOP, SBP, DBP, OPP, and pulse rate, (all p<0.001) (Table 3) . Both NTG-OSA patients and normal controls had significant increases in BOS across all areas (tissue, vascular, and all areas) associated with a change of position from sitting to supine (all p<0.001). However, normal controls had a significantly greater increase in BOS compared to NTG-OSA patients (p<0.05). NTG-OSA patients also had significant increases in BOT in tissue and all areas (all p0.05). (Table 3) Spearman’s correlation was also calculated between clinical and ocular parameters including age, male gender, BMI, spherical equivalent, visual acuity, MD, visual field index, central corneal thickness (CCT), sitting and supine IOP, sitting and supine values of OPP, and MBRs of the ONH. Significant associations were found between MBR and the above parameters, except spherical equivalent and sitting and supine IOP. However, the Spearman’s correlation coefficients were generally poor to moderate, ranging from 0.25 to 0.527. Discussion Our study utilised the LSFG to investigate ocular perfusion of the ONH in NTG-OSA patients in different body positions and compared them to controls. We found that NTG-OSA patients had significantly longer axial lengths, higher myopia, and greater BMI compared to the controls. Using LSFG, we established that the ONH in NTG-OSA patients had significantly lower perfusion compared to that of normal controls as well, in both sitting and supine positions. A change from sitting to supine was also associated with significant increases in BOS in both normal controls and NTG-OSA patients, but only NTG-OSA patients had an associated increase in BOT. These findings support the hypothesis that NTG is a disease involving a multitude of ocular and systemic factors contributing to vascular dysfunction of the optic nerve. We found that ocular blood flow was decreased in NTG-OSA subjects compared to normal controls, with a lower MBR across all areas (p<0.05). Importantly, our results align with other studies that have also demonstrate reduced ONH blood flow using different methods such as colour Doppler ultrasound, optical coherence tomography angiography (OCTA), and laser Doppler flowmetry.(34–36) These studies were conducted only in the sitting position, but our findings extend also to the supine position, which is the primary anatomical position. The pathogenesis of NTG has been described as a complex interplay involving ocular blood flow, blood pressure, and ocular perfusion pressure, and oxidative stress.(11,37) Our findings of decreased ocular flow suggest that may be increased resistance across the optic nerve head tissues, which can be partially explained by the increased vascular resistance seen in OSA. This reduced blood flow in the optic nerve head and surrounding vessels leads to vascular dysfunction, which can result in unstable perfusion cycles and increased oxidative stress,(37) a mechanism through which GON progresses. This emphasises the importance of treating systemic risk factors in NTG, such as OSA and hypertension, which can increase vascular resistance and by extension, worsen ocular blood flow and perfusion. Normal controls showed a significantly greater increase in BOS in all areas than NTG-OSA patients during postural change from sitting to supine (p<0.05) (Table 3), indicating that there is a greater increase in the blood volume within the vascular network around the lamina cribosa. However, only NTG-OSA patients had an associated increase in BOT in tissue and all areas (p<0.05) whereas normal controls showed no significant changes in BOT with the change in body position. BOT refers to the time within a heartbeat waveform that maintains more than half of the average MBR during a single heartbeat, and a higher BOT implies that blood flow is maintained for a longer period of time during each heartbeat to ensure tissue perfusion.(33) We postulate that the increase in BOT in NTG-OSA patients may be an indicator of abnormal dynamic autoregulation in NTG-OSA optic nerves. OSA is known to have intermittent hypoxia and hypercapnia, which leads to tissue hypoxia, autonomic dysfunction, and microvascular dysfunction.(38) This theory has been supported by electrophysiological studies that demonstrate altered visual evoked potentials (VEP) in optic nerves of patients with OSA, with lower amplitude and longer latency of the P100 component compared to normal controls.(39) Our study provides posture-induced haemodynamic evidence by showing that NTG-OSA eyes exhibited significantly smaller increases in BOS in all areas, and also abnormal increases in BOT in all areas, further supporting the theory of autonomic and microvascular dysfunction in OSA. Physiologically, ocular perfusion in the ONH can also be affected by the translaminar cribosa pressure (TLCP) gradient, which is determined by the pressure difference between cerebrospinal fluid pressure (CSFP) and IOP. Pre-clinical studies have shown that a higher TLCP was associated with reduced retrograde axoplasmic flow of the optic nerve and GON.(40) Studies on CSFP and TLCP in NTG patients have reported that NTG patients have a higher TLCP and lower CSFP compared to normal controls.(41–43) However, it is also known that OSA causes transient and/or sustained increases in CSFP, and the more severe the AHI, the higher the increases in CSFP.(17,44) To our knowledge, aforementioned studies on CSFP in NTG patients have not reported if there was concomitant OSA or not. Furthermore, OSA is known to be associated with sympathetic overactivation, and intermittent hypoxia also leads to endothelial dysfunction, which contributes to increased vascular resistance.(45) Hence, the two-pressure pathogenesis theory in NTG of having a low CSFP and high TLCP(46) may not hold true in concomitant OSA, and further studies on the CSFP and TLCP in patients with NTG and concomitant OSA can be conducted to better understand this mechanism. Our study has several limitations. Firstly, we did not enforce a period to washout the effect of anti-glaucoma medications prior to the commencement of the study. The usage of certain anti-glaucoma medications has been shown to improve ocular blood flow more than others. For example, prostaglandin analogues and carbonic anhydrase inhibitors have shown improved ocular blood flow while timolol had no effect on ocular blood flow.(47,48) Also, prostaglandin analogues, but not other anti-glaucoma medications, seem to also affect IOP changes from sitting to supine.(49) Hence, the usage of different anti-glaucoma medications in different patients could have affected our results. Secondly, while all NTG patients had concomitant OSA, only 27 (60%) of OSA patients were on CPAP treatment, which is also associated with increased CSF flow and reduced CSFP.(44) CPAP use also decreases both SBP and DBP values by reducing overall sympathetic drive.(50) Lastly, although our sample size was relatively small, the significant results suggest that both the statistical power and effect size were sufficient to allow for meaningful comparisons between the two groups. In conclusion, our study has shown that the ONH perfusion dynamics of NTG patients with concomitant OSA is different from that of controls. We showed that ocular blood flow around the ONH is also reduced in NTG-OSA patients using LSFG with reduced MBR, supporting the optic nerve hypoxia theory in the pathogenesis of NTG. Additionally, we found an increase in BOT in NTG-OSA patients but not normal controls, suggesting that autonomic and microvascular dysfunctions of the optic nerve may contribute to the pathogenesis of NTG in OSA patients. These findings emphasise the importance of treating systemic comorbidities in NTG patients like OSA and also helps us understand the mechanisms of disease in NTG. Declarations Funding support: The study was supported by a SingHealth DukeNUS, Academic Medicine Research Grant (TAT: AM/SU053/2021 and AM/TP082/2024) and a STaR grant from National Medical Research Council (TA: MOH-000435). References Allison K, Patel D, Alabi O. 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Tables Table 1: Demographics and clinical data of subjects with normal tension glaucoma and obstructive sleep apnoea (n=45) and controls (n=29). Variables NTG-OSA (n=45) Controls (n=29) P-value Mean±SD or n (%) Age, year 61.51 ± 9.32 56.58 ± 7.94 0.022 Gender, male 32 (80.0%) 8 (20.0%) BMI, unit 26.22 ± 4.84 22.84 ± 2.59 <0.001 SBP at sitting, mmHg 132.84 ± 17.49 132.93 ± 21.86 0.986 DBP at sitting, mmHg 77.78 ± 8.93 72.59 ± 11.79 0.048 Pulse rate at sitting, beats/min 68.04 ± 14.17 73.76 ± 16.04 0.123 SBP at supine, mmHg 125.04 ± 15.47 122.31 ± 16.75 0.475 DBP at supine, mmHg 72.38 ± 7.81 68.03 ± 10.23 0.057 Pulse rate at supine, beats/min 63.45 ± 12.81 67.00 ± 13.14 0.256 AHI 31.83 ± 17.25 - - Sphere, D -2.77 ± 3.14 -0.39 ± 1.67 <0.001 Visual acuity, logMAR 0.17 ± 0.17 0.13 ± 0.16 0.376 Mean deviation, dB -7.86 ± 5.22 -0.76 ± 1.33 <0.001 Visual field index, dB 79.31 ± 15.96 98.62 ± 1.55 <0.001 Axial length, mm 25.82 ± 1.38 23.93 ± 0.99 <0.001 CCT, μm 542.8 ± 37.66 550.34 ± 29.65 0.365 Abbreviations: NTG-OSA, normal tension glaucoma and obstructive sleep apnoea; SD, standard deviation; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; AHI, apnoea-hypopnoea index; D, dioptre; dB, decibel; CCT, central corneal thickness. Table 2: Comparison of parameters between subjects with normal tension glaucoma and obstructive sleep apnoea versus controls. Variables NTG-OSA (n=45) Controls (n=29) P-value Mean±SD SpO2 at supine, % 97.64 ± 1.48 98.55 ± 1.09 0.006 IOP at sitting, mmHg 15.42 ± 2.82 16.07 ± 3.12 0.359 IOP at supine, mmHg 17.24 ± 2.64 17.93 ± 3.24 0.321 OPP at sitting, mmHg 53.81 ± 7.55 51.09 ± 9.14 0.168 OPP at supine, mmHg 48.46 ± 6.80 45.46 ± 7.32 0.077 MBR_V at sitting, au 33.02 ± 8.54 40.61 ± 6.80 <0.001 MBR_V at supine, au 32.81 ± 9.50 38.55 ± 7.46 0.006 MBR_T at sitting, au 9.46 ± 1.88 11.80 ± 1.59 <0.001 MBR_T at supine, au 9.53 ± 2.17 11.84 ± 1.87 <0.001 MBR_A at sitting, au 15.04 ± 3.44 19.70 ± 3.19 <0.001 MBR_A at supine, au 15.33 ± 3.62 18.82 ± 3.61 <0.001 BOS_V at sitting, au 78.93 ± 4.89 78.46 ± 5.14 0.695 BOS_V at supine, au 80.64 ± 6.95 82.93 ± 4.55 0.123 BOS_T at sitting, au 76.44 ± 5.39 73.39 ± 5.80 0.024 BOS_T at supine, au 79.85 ± 5.86 78.58 ± 4.76 0.337 BOS_A at sitting, au 77.81 ± 4.95 76.34 ± 5.44 0.233 BOS_A at supine, au 80.42 ± 6.22 80.98 ± 4.49 0.682 BOT_V at sitting, au 51.13 ± 6.32 49.73 ± 6.83 0.371 BOT_V at supine, au 55.27 ± 10.85 51.94 ± 9.29 0.183 BOT_T at sitting, au 47.56 ± 6.01 45.05 ± 5.97 0.083 BOT_T at supine, au 51.55 ± 9.88 46.70 ± 5.40 0.019 BOT_A at sitting, au 49.26 ± 5.97 47.38 ± 6.56 0.208 BOT_A at supine, au 53.41 ± 10.23 49.49 ± 7.40 0.081 Abbreviations: NTG-OSA, normal tension glaucoma and obstructive sleep apnoea; SD, standard deviation; SpO2, peripheral oxygen saturation; IOP, intraocular pressure; OPP, ocular perfusion pressure;; MBR, mean blur rate; BOS, blowout score; BOT, blowout time; V, vascular; T, tissue; A, all areas. Table 3: Change in parameters associated with a change in body position from sitting to supine. Variables NTG-OSA (n=45) Controls (n=29) NTG-OSA vs Controls Mean difference ± SD (95% CI) p-value Mean difference ± SD (95% CI) p-value Mean difference ± SD (95% CI) p-value IOP 2.06 ± 2.37 (1.48, 2.64) <0.001 1.84 ± 2.19 (1.36, 2.32) <0.001 SBP -8.31 ± 11.39 (-11.09, -5.54) <0.001 -9.40 ± 12.54 (-12.17, -6.62) <0.001 DBP -5.72 ± 6.33 (-7.26, -4.17) <0.001 -4.53 ± 4.91 (-5.62, -3.45) <0.001 OPP -5.76 ± 5.20 (-7.03, -4.49) <0.001 -5.53 ± 4.43 (-6.31, -4.35) <0.001 Pulse rate -4.36 ± 3.77 (-5.29, -3.44) <0.001 -6.10 ± 6.22 (-7.48, -4.72) <0.001 MBR_V -1.07 ± 6.22 (-3.01, 0.86) 0.27 -2.07 ± 6.67 (-4.60, 0.47) 0.106 -0.99 ± 1.55 (-4.08, 2.09) 0.523 MBR_T -0.04 ± 1.32 (-0.45, 0.38) 0.862 0.05 ± 1.11 (-0.37, 0.46) 0.828 0.08 ± 0.30 (-0.52, 0.68) 0.788 MBR_A 0.06 ± 2.22 (-0.63, 0.75) 0.857 -0.88 ± 2.79 (-1.94, 0.18) 0.101 -0.94 ± 0.60 (-2.13, 0.25) 0.119 BOS_V 1.63 ± 5.55 (-0.10, 3.36) 0.065 4.47 ± 3.38 (3.19, 5.76) <0.001 2.85 ± 1.06 (0.73, 4.97) 0.009 BOS_T 3.09 ± 4.52 (1.68, 4.49) <0.001 5.19 ± 2.92 (4.08, 6.30) <0.001 2.10 ± 0.95 (0.20, 4.00) 0.031 BOS_A 2.41 ± 4.91 (0.88, 3.94) 0.003 4.64 ± 3.01 (3.49, 5.78) <0.001 2.23 ± 0.94 (0.35, 4.10) 0.021 BOT_V 3.80 ± 12.97 (-0.24, 7.84) 0.065 2.21 ± 9.47 (-1.39, 5.81) 0.22 -1.59 ± 2.82 (-7.22, 4.03) 0.574 BOT_T 3.72 ± 10.94 (0.31, 7.13) 0.033 1.65 ± 4.77 (-0.16, 3.46) 0.073 -2.07 ± 1.91 (-5.88, 1.74) 0.282 BOT_A 3.84 ± 11.41 (0.29, 7.40) 0.035 2.10 ± 7.09 (-0.59, 4.80) 0.121 -1.74 ± 2.39 (-6.50, 3.02) 0.469 Abbreviations: NTG-OSA, normal tension glaucoma and obstructive sleep apnoea; 95% CI, 95% confidence interval; SD, standard deviation; IOP, intraocular pressure; SBP, systolic blood pressure; DBP, diastolic blood pressure; OPP, ocular perfusion pressure;; MBR, mean blur rate; BOS, blowout score; BOT, blowout time; V, vascular; T, tissue; A, all areas. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7473796","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":510599380,"identity":"be91599f-9e98-4456-b0aa-b39ce388ac95","order_by":0,"name":"Tin Tun","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAuklEQVRIiWNgGAWjYPACGyBmbDxAlFoeoNIGBoY0kJYGkrQcBnOI02LPfvz6Y94d5+3Wth8G2lJjE03YFp6cwmbeM7eTt51JBGo5lpbbQNhhOYnNvG23k80OALUwNhwmQgv/G5CWc8lm5x8Sq0Ui/SBQywE7sxtE23LjDePMuW3JCWY3gLYkEOMX9v70Bx/ettnZm51Pf/jgQ40NYS1AewxAZCJYZQJh5WB7HoBIe+IUj4JRMApGwYgEAPx5R8bIoOC8AAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0001-7649-6952","institution":"Singapore Eye Research Institute","correspondingAuthor":true,"prefix":"","firstName":"Tin","middleName":"","lastName":"Tun","suffix":""},{"id":510599381,"identity":"0b33f7ea-de0c-436e-971c-44df9fe5088e","order_by":1,"name":"Shayne Tan","email":"","orcid":"https://orcid.org/0009-0000-3557-2971","institution":"Singapore National Eye Centre","correspondingAuthor":false,"prefix":"","firstName":"Shayne","middleName":"","lastName":"Tan","suffix":""},{"id":510599382,"identity":"841b2bdb-9654-477e-9100-d25c68e27e14","order_by":2,"name":"Royston Tan","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Royston","middleName":"","lastName":"Tan","suffix":""},{"id":510599383,"identity":"c57e81fa-7c60-48b5-b7da-677b11a0bcd2","order_by":3,"name":"Monisha Nongpiur","email":"","orcid":"https://orcid.org/0000-0003-2372-8523","institution":"Singapore National Eye Center","correspondingAuthor":false,"prefix":"","firstName":"Monisha","middleName":"","lastName":"Nongpiur","suffix":""},{"id":510599384,"identity":"726f0f95-85b9-4c2d-8af3-ffa28c602e19","order_by":4,"name":"Leopold Schmetterer","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Leopold","middleName":"","lastName":"Schmetterer","suffix":""},{"id":510599385,"identity":"89e47f73-6d21-466d-988d-98d976f0dff9","order_by":5,"name":"Song Tar Toh","email":"","orcid":"","institution":"Singapore General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Song","middleName":"Tar","lastName":"Toh","suffix":""},{"id":510599386,"identity":"e3f41a07-5a96-466b-a6c0-704e27c72236","order_by":6,"name":"Tin Aung","email":"","orcid":"","institution":"Singapore National Eye Center","correspondingAuthor":false,"prefix":"","firstName":"Tin","middleName":"","lastName":"Aung","suffix":""},{"id":510599387,"identity":"96361835-2d2c-438c-a428-41512575d3d3","order_by":7,"name":"Michael Girard","email":"","orcid":"https://orcid.org/0000-0003-4408-5918","institution":"Singapore Eye Research Institute","correspondingAuthor":false,"prefix":"","firstName":"Michael","middleName":"","lastName":"Girard","suffix":""}],"badges":[],"createdAt":"2025-08-27 17:10:43","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7473796/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7473796/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":91085168,"identity":"7a211ff8-4d99-4ed5-b544-94784bdfd1b3","added_by":"auto","created_at":"2025-09-11 12:19:43","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":71510,"visible":true,"origin":"","legend":"\u003cp\u003eIllustration of laser speckle flowgraphy imaging in the sitting and supine positions\u003c/p\u003e\n\u003cp\u003eVascular and tissue perfusion in the optic nerve head is imaged using the laser speckle flowgraphy in the (A) sitting position and (B) supine position. (C) A colour-coded “composite” map depicts the distribution of blood flow in the ocular fundus.\u003c/p\u003e","description":"","filename":"NTGOSALSFGFigure300DPI.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7473796/v1/e0942e53715a54d627ee0e96.jpg"},{"id":94985728,"identity":"589550d1-7f20-4138-a4b8-e962249bb4c4","added_by":"auto","created_at":"2025-11-03 06:58:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":943906,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7473796/v1/cc9dff14-da22-49ea-9332-a637bef26390.pdf"}],"financialInterests":"There is no conflict of interest","formattedTitle":"Decreased Optic Nerve Head Perfusion in Patients with Normal Tension Glaucoma and Obstructive Sleep Apnoea","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGlaucoma is the leading cause of irreversible blindness, with primary open angle glaucoma (POAG) affecting more than 57.5 million people worldwide.(1) Normal tension glaucoma (NTG) forms a significant proportion of POAG patients, with an overall pooled proportion of NTG among patients with POAG in Asia estimated to be 76.3%.(2) As yet, intraocular pressure (IOP) remains the only modifiable risk factor in the treatment of glaucoma to halt or stall progression.(3\u0026ndash;5) However, given that IOP in NTG is typically within the statistically population-normal range and tends to be equal between the eyes of an individual,(6,7) the optic nerve damage and often asymmetrical nature of NTG suggests that other non-IOP factors contribute to the pathogenesis of NTG.(8\u0026ndash;11)\u003c/p\u003e\n\u003cp\u003eOne significant IOP-independent risk factor for NTG is obstructive sleep apnoea (OSA), (12,13) an upper airway breathing disorder characterised by episodes of complete (apnoea) or partial (hypopnoea) collapse of the upper \u0026nbsp;airway, with associated hypoxia during sleep.(14) A meta-analysis showed that patients with OSA were 6.72 times more likely to develop NTG compared to those without OSA.(15) However, the exact pathophysiology behind this association remains unknown, although some hypothesise that it may be due to compromised ocular perfusion and reduced blood flow from nocturnal hypoxia in OSA patients.(16\u0026ndash;18)\u003c/p\u003e\n\u003cp\u003eBesides nocturnal hypoxia in OSA, it has been observed that the severity of glaucoma in NTG may also be related to preferred sleeping positions, possibly due to pressure-dependent factors.(19) IOP is known to vary with different body positions, with\u0026nbsp;higher IOPs observed in the supine position compared to the upright sitting position.(20\u0026ndash;22)\u0026nbsp;This has been postulated to be due to increased episcleral venous pressure when lying down.(23,24)\u0026nbsp;Since humans spend nearly one-third of their lives sleeping, some studies have suggested that fluctuations in IOP during sleep may help to explain the pathogenesis of NTG.(25\u0026ndash;27)\u0026nbsp;Some postulate that IOP-related deformations within the peripapillary sclera affect ocular perfusion, at least in part, by compressing the scleral branches of the short posterior ciliary arteries.(28)\u0026nbsp;However, due to the posterior location of this anatomy in the eye and technical difficulties in assessing blood flow in the lying position, ocular perfusion at the ONH remains to be fully understood.(29)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn this regard, laser speckle flowgraphy (LSFG) (Softcare Co., Ltd., Fukuoka, Japan) has been shown to be a useful tool for the quantitative measurement of blood flow at the ONH.(30,31) One of the parameters obtained with LSFG, the mean blur rate (MBR), has shown good correlation with tissue blood flow rates at the ONH using the hydrogen gas clearance technique, providing a quantitative and reproducible index of blood cell velocity.(30\u0026ndash;32) LSFG also provides other indicators of blood flow and perfusion within the blood vessel, such as blow out score (BOS) and blow out time (BOT), where BOS refers to the blood volume maintained within the vessel during each heartbeat, while BOT refers to the time within a heartbeat waveform during which more than half of the average MBR is maintained. Taken together, these parameters provide a better understanding of blood flow and ocular perfusion.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe aim of this study was to use LSFG to study changes in perfusion parameters across the optic nerve head associated with a change of position from sitting to supine in NTG patients with OSA.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis study had the approval of the SingHealth Centralized Institutional Review Board and adhered to the tenets of the Declaration of Helsinki, with informed consent obtained for all study participants. Healthy controls without OSA were recruited from the general population, while patients with NTG were recruited from the glaucoma clinic service at the Singapore National Eye Centre (SNEC). NTG eyes were defined as the presence of glaucomatous optic neuropathy (GON) with an IOP of \u0026lt;21mmHg at all pre-treatment visits. GON was defined as a vertical cup-disc ratio (VCDR) \u0026ge;0.8, CDR asymmetry of \u0026gt;0.2 with or without focal notching, along with a compatible VF loss on static automated perimetry (SITA Standard algorithm with a 24-2 test strategy; Humphrey Visual Field Analyser II; Carl Zeiss Meditec, Dublin, CA). \u0026nbsp;VF defects were considered glaucomatous if they met at least 2 Anderson\u0026rsquo;s criteria: (1) \u0026ge; 3 continuous nonedged points in a cluster depressed to P \u0026lt; 5%, with at least one depressed to P \u0026lt; 1%; (2) Glaucoma Hemifield Test outside normal limits; or (3) pattern SD depressed to P \u0026lt; 5%. The VFs of all these patients were evaluated for reliability. Reliability criteria for VF testing included fixation losses of \u0026lt;15% and false-positives or -negatives rates of \u0026lt;33%. Only one eye per patient was analysed. If both eyes of one patient fulfilled the criteria for evaluation of NTG, the eye with the more severe disease based on the VF mean deviation (MD) was defined as the study eye. All NTG patients recruited had a concomitant diagnosis of OSA, which was only diagnosed by an otorhinolaryngology specialist after overnight polysomnography recording at a sleep clinic, with an apnoea-hypopnoea index (AHI) score per hour of \u0026gt;5. The AHI measures the cumulative number of apnoeic and hypopnoeic episodes throughout the night.\u003c/p\u003e\n\u003cp\u003eAll patients also had the following investigations performed: (1) measurement of body height and weight for calculation of body mass index (BMI), (2) measurement of blood pressure (BP), (3) measurement of their best-corrected visual acuity (BCVA), (4) biometry measurements using the IOL master (Carl Zeiss Meditec, Germany), (5) IOP measurements with a Tonopen AVIA\u0026reg; applanation tonometer (Reichert Inc., Depew, USA), and (6) LSFG measurements.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBP, IOP, and LSFG measurements were performed in the sitting and supine positions, with each position maintained for 5 minutes before recordings were taken. Ocular perfusion pressure (OPP) was determined by: mean arterial pressure (MAP) \u0026ndash; IOP. LSFG measurements were taken after pupillary dilation with 0.5% tropicamide eye drops. The LSFG machine comprises a fundus camera with a diode laser that operates at a wavelength of 830nm, and a digital charge-coupled camera with a resolution of 750 x 360 pixels. This allows a total of 118 images to be captured at a rate of 30 frames per second over 4 seconds. As mentioned above, an important output of the LSFG is the MBR, which is a parameter that measures the relative blood flow velocity in a specified area, expressed in arbitrary units (au). The LSFG-NAVI has an inbuilt software that calculates and averages all 118 images to generate a composite map of the distribution of perfusion in a single cardiac cycle. This can then be subdivided into three distinct regions of the ONH: the MBR of the vascular area (MBR-V), the MBR of the tissue area (MBR-T), and the MBR of all areas (MBR-A). \u003cstrong\u003e(Figure 1)\u0026nbsp;\u003c/strong\u003eOther significant parameters from the LSFG include BOS and BOT, as mentioned above. A high BOT would imply that blood flow is maintained at a sufficiently high level for a long period of time during each heartbeat to ensure peripheral perfusion of tissues.(33)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eStatistical analysis\u003c/p\u003e\n\u003cp\u003eStatistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) statistics for Windows (IBM Corp, Version 19.0, Armonk, New York). Continuous variables were expressed as the mean and standard deviation. The independent \u003cem\u003et\u003c/em\u003e-test was used to compare the difference in the distribution of continuous variables between the study NTG group and the control group. The paired \u003cem\u003et\u003c/em\u003e-test was also used to compare the changes between the sitting and supine position within each group. The Spearman\u0026rsquo;s correlation was used to establish the correlation coefficient between clinical and ocular parameters with all 3 regions of MBR. Statistical significance was set at p\u0026lt;0.05. \u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 45 patients with NTG-OSA and 29 healthy controls were recruited. Compared to the control group, NTG-OSA patients were older (61.51 \u0026plusmn; 9.32 years vs 56.58 \u0026plusmn; 7.94 years, p=0.022), predominantly males (80.0% vs 20.0%), and had a significantly higher BMI (26.22 \u0026plusmn; 4.84 vs 22.84 \u0026plusmn; 2.59, p\u0026lt;0.001). \u003cstrong\u003e(Table 1)\u003c/strong\u003e NTG-OSA patients were also more myopic (-2.77D \u0026plusmn; 3.14D vs -0.39D \u0026plusmn; 1.67D, p\u0026lt;0.001) with longer axial lengths (26.82 \u0026plusmn; 1.33mm vs 23.93 \u0026plusmn; 0.99mm, p\u0026lt;0.001).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe NTG-OSA group had significantly lower blood saturation levels (SpO2) in the supine position compared to the normal controls (97.64% \u0026plusmn; 1.48 vs 98.55% \u0026plusmn; 1.09, p=0.006). \u003cstrong\u003e(Table 2)\u0026nbsp;\u003c/strong\u003eThe MBR of all areas, vascular areas, and tissue areas were also significantly lower in the NTG-OSA group compared to the normal controls in both sitting and supine positions (all p\u0026lt;0.05).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThere was a statistically significant change associated with a change in position from sitting to supine in all following parameters in both the NTG-OSA group and the normal group: IOP, SBP, DBP, OPP, and pulse rate, (all p\u0026lt;0.001) \u003cstrong\u003e(Table 3)\u003c/strong\u003e. Both NTG-OSA patients and normal controls had significant increases in BOS across all areas (tissue, vascular, and all areas) associated with a change of position from sitting to supine (all p\u0026lt;0.001). However, normal controls had a significantly greater increase in BOS compared to NTG-OSA patients (p\u0026lt;0.05). NTG-OSA patients also had significant increases in BOT in tissue and all areas (all p\u0026lt;0.05), however, this was not observed in normal controls (p\u0026gt;0.05). \u003cstrong\u003e(Table 3)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSpearman\u0026rsquo;s correlation was also calculated between clinical and ocular parameters including age, male gender, BMI, spherical equivalent, visual acuity, MD, visual field index, central corneal thickness (CCT), sitting and supine IOP, sitting and supine values of OPP, and MBRs of the ONH. Significant associations were found between MBR and the above parameters, except spherical equivalent and sitting and supine IOP. However, the Spearman\u0026rsquo;s correlation coefficients were generally poor to moderate, ranging from 0.25 to 0.527.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study utilised the LSFG to investigate ocular perfusion of the ONH in NTG-OSA patients in different body positions and compared them to controls. We found that NTG-OSA patients had significantly longer axial lengths, higher myopia, and greater BMI compared to the controls. Using LSFG, we established that the ONH in NTG-OSA patients had significantly lower perfusion compared to that of normal controls as well, in both sitting and supine positions. A change from sitting to supine was also associated with significant increases in BOS in both normal controls and NTG-OSA patients, but only NTG-OSA patients had an associated increase in BOT. These findings support the hypothesis that NTG is a disease involving a multitude of ocular and systemic factors contributing to vascular dysfunction of the optic nerve.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe found that ocular blood flow was decreased in NTG-OSA subjects compared to normal controls, with a lower MBR across all areas (p\u0026lt;0.05). Importantly, our results align with other studies that have also demonstrate reduced ONH blood flow using different methods such as colour Doppler ultrasound, optical coherence tomography angiography (OCTA), and laser Doppler flowmetry.(34\u0026ndash;36) These studies were conducted only in the sitting position, but our findings extend also to the supine position, which is the primary anatomical position. The pathogenesis of NTG has been described as a complex interplay involving ocular blood flow, blood pressure, and ocular perfusion pressure, and oxidative stress.(11,37) Our findings of decreased ocular flow suggest that may be increased resistance across the optic nerve head tissues, which can be partially explained by the increased vascular resistance seen in OSA. This reduced blood flow in the optic nerve head and surrounding vessels leads to vascular dysfunction, which can result in unstable perfusion cycles and increased oxidative stress,(37) a mechanism through which GON progresses. This emphasises the importance of treating systemic risk factors in NTG, such as OSA and hypertension, which can increase vascular resistance and by extension, worsen ocular blood flow and perfusion.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNormal controls showed a significantly greater increase in BOS in all areas than NTG-OSA patients during postural change from sitting to supine (p\u0026lt;0.05) \u003cstrong\u003e(Table 3),\u0026nbsp;\u003c/strong\u003eindicating that there is a greater increase in the blood volume within the vascular network around the lamina cribosa. However, only NTG-OSA patients had an associated increase in BOT in tissue and all areas (p\u0026lt;0.05) whereas normal controls showed no significant changes in BOT with the change in body position. BOT refers to the time within a heartbeat waveform that maintains more than half of the average MBR during a single heartbeat, and a higher BOT implies that blood flow is maintained for a longer period of time during each heartbeat to ensure tissue perfusion.(33) We postulate that the increase in BOT in NTG-OSA patients may be an indicator of abnormal dynamic autoregulation in NTG-OSA optic nerves. OSA is known to have intermittent hypoxia and hypercapnia, which leads to tissue hypoxia, autonomic dysfunction, and microvascular dysfunction.(38) This theory has been supported by electrophysiological studies that demonstrate altered visual evoked potentials (VEP) in optic nerves of patients with OSA, with lower amplitude and longer latency of the P100 component compared to normal controls.(39) Our study provides posture-induced haemodynamic evidence by showing that NTG-OSA eyes exhibited significantly smaller increases in BOS in all areas, and also abnormal increases in BOT in all areas, further supporting the theory of autonomic and microvascular dysfunction in OSA.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePhysiologically, ocular perfusion in the ONH can also be affected by the translaminar cribosa pressure (TLCP) gradient, which is determined by the pressure difference between cerebrospinal fluid pressure (CSFP) and IOP. Pre-clinical studies have shown that a higher TLCP was associated with reduced retrograde axoplasmic flow of the optic nerve and GON.(40) Studies on CSFP and TLCP in NTG patients have reported that NTG patients have a higher TLCP and lower CSFP compared to normal controls.(41\u0026ndash;43) However, it is also known that OSA causes transient and/or sustained increases in CSFP, and the more severe the AHI, the higher the increases in CSFP.(17,44) To our knowledge, aforementioned studies on CSFP in NTG patients have not reported if there was concomitant OSA or not. Furthermore, OSA is known to be associated with sympathetic overactivation, and intermittent hypoxia also leads to endothelial dysfunction, which contributes to increased vascular resistance.(45) Hence, the two-pressure pathogenesis theory in NTG of having a low CSFP and high TLCP(46) may not hold true in concomitant OSA, and further studies on the CSFP and TLCP in patients with NTG and concomitant OSA can be conducted to better understand this mechanism.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOur study has several limitations. Firstly, we did not enforce a period to washout the effect of anti-glaucoma medications prior to the commencement of the study. The usage of certain anti-glaucoma medications has been shown to improve ocular blood flow more than others. For example, prostaglandin analogues and carbonic anhydrase inhibitors have shown improved ocular blood flow while timolol had no effect on ocular blood flow.(47,48) Also, prostaglandin analogues, but not other anti-glaucoma medications, seem to also affect IOP changes from sitting to supine.(49) Hence, the usage of different anti-glaucoma medications in different patients could have affected our results. Secondly, while all NTG patients had concomitant OSA, only 27 (60%) of OSA patients were on CPAP treatment, which is also associated with increased CSF flow and reduced CSFP.(44) CPAP use also decreases both SBP and DBP values by reducing overall sympathetic drive.(50) Lastly, although our sample size was relatively small, the significant results suggest that both the statistical power and effect size were sufficient to allow for meaningful comparisons between the two groups.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn conclusion, our study has shown that the ONH perfusion dynamics of NTG patients with concomitant OSA is different from that of controls. We showed that ocular blood flow around the ONH is also reduced in NTG-OSA patients using LSFG with reduced MBR, supporting the optic nerve hypoxia theory in the pathogenesis of NTG. Additionally, we found an increase in BOT in NTG-OSA patients but not normal controls, suggesting that autonomic and microvascular dysfunctions of the optic nerve may contribute to the pathogenesis of NTG in OSA patients. These findings emphasise the importance of treating systemic comorbidities in NTG patients like OSA and also helps us understand the mechanisms of disease in NTG.\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding support: \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was supported by a SingHealth DukeNUS, Academic Medicine Research Grant (TAT: AM/SU053/2021 and AM/TP082/2024) and a STaR grant from National Medical Research Council (TA: MOH-000435).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAllison K, Patel D, Alabi O. Epidemiology of Glaucoma: The Past, Present, and Predictions for the Future. Cureus. 2020 Nov 24;12(11):e11686. \u003c/li\u003e\n\u003cli\u003eCho H kyung, Kee C. Population-based glaucoma prevalence studies in Asians. Surv Ophthalmol. 2014 Jul;59(4):434\u0026ndash;47. \u003c/li\u003e\n\u003cli\u003eHeijl A. Reduction of Intraocular Pressure and Glaucoma Progression: Results From the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002 Oct 1;120(10):1268. \u003c/li\u003e\n\u003cli\u003eColeman AL, Kodjebacheva G. Risk factors for glaucoma needing more attention. Open Ophthalmol J. 2009 Sep 17;3:38\u0026ndash;42. \u003c/li\u003e\n\u003cli\u003eColeman AL, Miglior S. Risk Factors for Glaucoma Onset and Progression. Surv Ophthalmol. 2008 Nov;53(6):S3\u0026ndash;10. \u003c/li\u003e\n\u003cli\u003eGreenfield DS, Liebmann JM, Ritch R, Krupin T. Visual Field and Intraocular Pressure Asymmetry in the Low-Pressure Glaucoma Treatment Study. Ophthalmology. 2007 Mar;114(3):460\u0026ndash;5. \u003c/li\u003e\n\u003cli\u003eKrupin T, Liebmann JM, Greenfield DS, Rosenberg LF, Ritch R, Yang JW. The Low-pressure Glaucoma Treatment Study (LoGTS). Ophthalmology. 2005 Mar;112(3):376\u0026ndash;85. \u003c/li\u003e\n\u003cli\u003eKiller H, Pircher A. Normal tension glaucoma: review of current understanding and mechanisms of the pathogenesis. Eye. 2018 May;32(5):924\u0026ndash;30. \u003c/li\u003e\n\u003cli\u003eTrivli A, Koliarakis I, Terzidou C, Goulielmos G, Siganos C, Spandidos D, et al. Normal-tension glaucoma: Pathogenesis and genetics (Review). Exp Ther Med [Internet]. 2018 Nov 26 [cited 2025 Apr 10]; Available from: http://www.spandidos-publications.com/10.3892/etm.2018.7011\u003c/li\u003e\n\u003cli\u003eMoore D, Harris A, Wudunn D, Kheradiya N, Siesky B. Dysfunctional regulation of ocular blood flow: A risk factor for glaucoma? 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J Glaucoma. 2017 Mar;26(3):e130\u0026ndash;e130. \u003c/li\u003e\n\u003cli\u003eGharraf H, Zidan MH, ElHoffy A. Association between obstructive sleep apnea hypopnea syndrome and normal tension glaucoma. Egypt J Chest Dis Tuberc. 2016 Jan;65(1):239\u0026ndash;49. \u003c/li\u003e\n\u003cli\u003eJennum P, B\u0026oslash;rgesen SE. Intracranial Pressure and Obstructive Sleep Apnea. Chest. 1989 Feb;95(2):279\u0026ndash;83. \u003c/li\u003e\n\u003cli\u003eKim KE, Oh S, Baek SU, Ahn SJ, Park KH, Jeoung JW. Ocular Perfusion Pressure and the Risk of Open-Angle Glaucoma: Systematic Review and Meta-analysis. Sci Rep. 2020 Jun 22;10(1):10056. \u003c/li\u003e\n\u003cli\u003eKim KN, Jeoung JW, Park KH, Kim DM, Ritch R. Relationship Between Preferred Sleeping Position and Asymmetric Visual Field Loss in Open-Angle Glaucoma Patients. Am J Ophthalmol. 2014 Mar 1;157(3):739\u0026ndash;45. \u003c/li\u003e\n\u003cli\u003ePrata TS, De Moraes CGV, Kanadani FN, Ritch R, Paranhos A. 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Intracranial Pressure and Its Relationship to Glaucoma: Current Understanding and Future Directions. Med Hypothesis Discov Innov Ophthalmol J. 2015;4(3):71\u0026ndash;80. \u003c/li\u003e\n\u003cli\u003eKim KN, Jeoung JW, Park KH, Lee DS, Kim DM. Effect of Lateral Decubitus Position on Intraocular Pressure in Glaucoma Patients with Asymmetric Visual Field Loss. Ophthalmology. 2013 Apr;120(4):731\u0026ndash;5. \u003c/li\u003e\n\u003cli\u003eBaneke AJ, Aubry J, Viswanathan AC, Plant GT. The role of intracranial pressure in glaucoma and therapeutic implications. Eye Lond Engl. 2020 Jan;34(1):178\u0026ndash;91. \u003c/li\u003e\n\u003cli\u003eBurgoyne CF. A biomechanical paradigm for axonal insult within the optic nerve head in aging and glaucoma. Exp Eye Res. 2011 Aug;93(2):120\u0026ndash;32. \u003c/li\u003e\n\u003cli\u003eCherecheanu AP, Garhofer G, Schmidl D, Werkmeister R, Schmetterer L. Ocular perfusion pressure and ocular blood flow in glaucoma. Curr Opin Pharmacol. 2013 Feb;13(1):36\u0026ndash;42. \u003c/li\u003e\n\u003cli\u003eSugiyama T, Araie M, Riva CE, Schmetterer L, Orgul S. Use of laser speckle flowgraphy in ocular blood flow research. Acta Ophthalmol (Copenh). 2010 Nov;88(7):723\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eKunikata H, Nakazawa T. Recent Clinical Applications of Laser Speckle Flowgraphy in Eyes with Retinal Disease: Asia-Pac J Ophthalmol. 2016;5(2):151\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eGu C, Li A, Yu L. Diagnostic performance of laser speckle flowgraphy in glaucoma: a systematic review and meta-analysis. Int Ophthalmol. 2021 Nov;41(11):3877\u0026ndash;88. \u003c/li\u003e\n\u003cli\u003eSugiyama T. Basic Technology and Clinical Applications of the Updated Model of Laser Speckle Flowgraphy to Ocular Diseases. Photonics. 2014 Aug 12;1(3):220\u0026ndash;34. \u003c/li\u003e\n\u003cli\u003eHamard P, Hamard H, Dufaux J, Quesnot S. Optic nerve head blood flow using a laser Doppler velocimeter and haemorheology in primary open angle glaucoma and normal pressure glaucoma. Br J Ophthalmol. 1994 Jun;78(6):449\u0026ndash;53. \u003c/li\u003e\n\u003cli\u003eStalmans I, Harris A, Fieuws S, Zeyen T, Vanbellinghen V, McCranor L, et al. Color Doppler Imaging and Ocular Pulse Amplitude in Glaucomatous and Healthy Eyes. Eur J Ophthalmol. 2009 Jul;19(4):580\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eYamazaki Y, Hayamizu F. Comparison of flow velocity of ophthalmic artery between primary open angle glaucoma and normal tension glaucoma. Br J Ophthalmol. 1995 Aug;79(8):732\u0026ndash;4. \u003c/li\u003e\n\u003cli\u003eRamesh PV, Morya AK, Aradhya AK, Pannerselvam P, Gopalakrishnan ST, Ramesh SV, et al. Unveiling the silent link: Normal-tension glaucoma\u0026rsquo;s enigmatic bond with cardiac blood flow. World J Cardiol. 2024 Jan 26;16(1):10\u0026ndash;5. \u003c/li\u003e\n\u003cli\u003eAhn J, Gorin MB. The Associations of Obstructive Sleep Apnea and Eye Disorders: Potential Insights into Pathogenesis and Treatment. Curr Sleep Med Rep. 2021 Sep;7(3):65\u0026ndash;79. \u003c/li\u003e\n\u003cli\u003eLiguori C, Palmieri MG, Pierantozzi M, Cesareo M, Romigi A, Izzi F, et al. Optic Nerve Dysfunction in Obstructive Sleep Apnea: An Electrophysiological Study. Sleep. 2016 Jan 1;39(1):19\u0026ndash;23. \u003c/li\u003e\n\u003cli\u003eJonas JB, Wang N, Yang D. Translamina Cribrosa Pressure Difference as Potential Element in the Pathogenesis of Glaucomatous Optic Neuropathy. Asia-Pac J Ophthalmol. 2016;5(1):5\u0026ndash;10. \u003c/li\u003e\n\u003cli\u003eBerdahl JP, Allingham RR, Johnson DH. Cerebrospinal Fluid Pressure Is Decreased in Primary Open-angle Glaucoma. Ophthalmology. 2008 May;115(5):763\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eTailor PD, Aul BJ, Sit AJ, Fautsch MP, Chen JJ. Determination of the Trans-Lamina Cribrosa Pressure Difference in a Community-Based Population and its Association with Open-Angle Glaucoma. Ophthalmol Glaucoma. 2024 Mar;7(2):168\u0026ndash;76. \u003c/li\u003e\n\u003cli\u003eSiaudvytyte L, Januleviciene I, Daveckaite A, Ragauskas A, Siesky B, Harris A. Neuroretinal rim area and ocular haemodynamic parameters in patients with normal-tension glaucoma with differing intracranial pressures. Br J Ophthalmol. 2016 Aug;100(8):1134\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eRiedel CS, Martinez-Tejada I, Andresen M, Wilhjelm JE, Jennum P, Juhler M. Transient intracranial pressure elevations (B waves) are associated with sleep apnea. Fluids Barriers CNS. 2023 Oct 2;20(1):69. \u003c/li\u003e\n\u003cli\u003eShiina K. Obstructive sleep apnea -related hypertension: a review of the literature and clinical management strategy. Hypertens Res. 2024 Nov;47(11):3085\u0026ndash;98. \u003c/li\u003e\n\u003cli\u003eHoang TT, Anh BV, Subramanian P. Is Glaucoma a Two-Pressure-Related Optic Neuropathy? A Systematic Review and Meta-Analysis. Turk J Ophthalmol. 2024 Apr 1;54(2):83\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eFuchsj\u0026auml;ger-Mayrl G, Wally B, Rainer G, Buehl W, Aggermann T, Kolodjaschna J, et al. Effect of dorzolamide and timolol on ocular blood flow in patients with primary open angle glaucoma and ocular hypertension. Br J Ophthalmol. 2005 Oct;89(10):1293\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eZhang X, Zhou X, Zhao Y, Yang X, Zhou D, Chen B, et al. Effects of Tafluprost on Ocular Blood Flow. Ophthalmol Ther. 2022 Dec;11(6):1991\u0026ndash;2003. \u003c/li\u003e\n\u003cli\u003eMansouri K, Medeiros FA, Weinreb RN. Effect of glaucoma medications on 24-hour intraocular pressure-related patterns using a contact lens sensor. Clin Experiment Ophthalmol. 2015 Dec;43(9):787\u0026ndash;95. \u003c/li\u003e\n\u003cli\u003eRuzicka M, Knoll G, Leenen FHH, Leech J, Aaron SD, Hiremath S. Effects of CPAP on Blood Pressure and Sympathetic Activity in Patients With Diabetes Mellitus, Chronic Kidney Disease, and Resistant Hypertension. CJC Open. 2020 Jul;2(4):258\u0026ndash;64. \u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1: Demographics and clinical data of subjects with normal tension glaucoma and obstructive sleep apnoea (n=45) and controls (n=29).\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"511\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 35.5376%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.6918%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNTG-OSA (n=45)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.5007%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControls (n=29)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.8538%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 47.1924%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean\u0026plusmn;SD or n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.5654%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 35.5376%;\"\u003e\n \u003cp\u003eAge, year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.6918%;\"\u003e\n \u003cp\u003e61.51 \u0026plusmn; 9.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.5007%;\"\u003e\n \u003cp\u003e56.58 \u0026plusmn; 7.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.7118%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.022\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 35.5376%;\"\u003e\n \u003cp\u003eGender, male\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.6918%;\"\u003e\n \u003cp\u003e32 (80.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.5007%;\"\u003e\n \u003cp\u003e8 (20.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.7118%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 35.5376%;\"\u003e\n \u003cp\u003eBMI, unit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.6918%;\"\u003e\n \u003cp\u003e26.22 \u0026plusmn; 4.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.5007%;\"\u003e\n \u003cp\u003e22.84 \u0026plusmn; 2.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.7118%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 35.5376%;\"\u003e\n \u003cp\u003eSBP at sitting, mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.6918%;\"\u003e\n \u003cp\u003e132.84 \u0026plusmn; 17.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.5007%;\"\u003e\n \u003cp\u003e132.93 \u0026plusmn; 21.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.7118%;\"\u003e\n \u003cp\u003e0.986\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 35.5376%;\"\u003e\n \u003cp\u003eDBP at sitting, mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.6918%;\"\u003e\n \u003cp\u003e77.78 \u0026plusmn; 8.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.5007%;\"\u003e\n \u003cp\u003e72.59 \u0026plusmn; 11.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.7118%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.048\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 35.5376%;\"\u003e\n \u003cp\u003ePulse rate at sitting, beats/min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.6918%;\"\u003e\n \u003cp\u003e68.04 \u0026plusmn; 14.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.5007%;\"\u003e\n \u003cp\u003e73.76 \u0026plusmn; 16.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.7118%;\"\u003e\n \u003cp\u003e0.123\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 35.5376%;\"\u003e\n \u003cp\u003eSBP at supine, mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.6918%;\"\u003e\n \u003cp\u003e125.04 \u0026plusmn; 15.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.5007%;\"\u003e\n \u003cp\u003e122.31 \u0026plusmn; 16.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.7118%;\"\u003e\n \u003cp\u003e0.475\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 35.5376%;\"\u003e\n \u003cp\u003eDBP at supine, mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.6918%;\"\u003e\n \u003cp\u003e72.38 \u0026plusmn; 7.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.5007%;\"\u003e\n \u003cp\u003e68.03 \u0026plusmn; 10.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.7118%;\"\u003e\n \u003cp\u003e0.057\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 35.5376%;\"\u003e\n \u003cp\u003ePulse rate at supine, beats/min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.6918%;\"\u003e\n \u003cp\u003e63.45 \u0026plusmn; 12.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.5007%;\"\u003e\n \u003cp\u003e67.00 \u0026plusmn; 13.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.7118%;\"\u003e\n \u003cp\u003e0.256\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 35.5376%;\"\u003e\n \u003cp\u003eAHI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.6918%;\"\u003e\n \u003cp\u003e31.83 \u0026plusmn; 17.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.5007%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.7118%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 35.5376%;\"\u003e\n \u003cp\u003eSphere, D\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.6918%;\"\u003e\n \u003cp\u003e-2.77 \u0026plusmn; 3.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.5007%;\"\u003e\n \u003cp\u003e-0.39 \u0026plusmn; 1.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.7118%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 35.5376%;\"\u003e\n \u003cp\u003eVisual acuity, logMAR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.6918%;\"\u003e\n \u003cp\u003e0.17 \u0026plusmn; 0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.5007%;\"\u003e\n \u003cp\u003e0.13 \u0026plusmn; 0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.7118%;\"\u003e\n \u003cp\u003e0.376\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 35.5376%;\"\u003e\n \u003cp\u003eMean deviation, dB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.6918%;\"\u003e\n \u003cp\u003e-7.86 \u0026plusmn; 5.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.5007%;\"\u003e\n \u003cp\u003e-0.76 \u0026plusmn; 1.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.7118%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 35.5376%;\"\u003e\n \u003cp\u003eVisual field index, dB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.6918%;\"\u003e\n \u003cp\u003e79.31 \u0026plusmn; 15.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.5007%;\"\u003e\n \u003cp\u003e98.62\u0026nbsp;\u0026plusmn; 1.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.7118%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 35.5376%;\"\u003e\n \u003cp\u003eAxial length, mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.6918%;\"\u003e\n \u003cp\u003e25.82 \u0026plusmn; 1.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.5007%;\"\u003e\n \u003cp\u003e23.93 \u0026plusmn; 0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.7118%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 35.5376%;\"\u003e\n \u003cp\u003eCCT, \u0026mu;m\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.6918%;\"\u003e\n \u003cp\u003e542.8 \u0026plusmn; 37.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23.5007%;\"\u003e\n \u003cp\u003e550.34 \u0026plusmn; 29.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.7118%;\"\u003e\n \u003cp\u003e0.365\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: NTG-OSA, normal tension glaucoma and obstructive sleep apnoea; SD, standard deviation; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; AHI, apnoea-hypopnoea index; D, dioptre; dB, decibel; CCT, central corneal thickness.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2: Comparison of parameters between subjects with normal tension glaucoma and obstructive sleep apnoea versus controls.\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"511\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 189px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNTG-OSA (n=45)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControls (n=29)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 250px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean\u0026plusmn;SD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 71px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 1px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003eSpO2 at supine, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e97.64 \u0026plusmn; 1.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e98.55 \u0026plusmn; 1.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.006\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003eIOP at sitting, mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e15.42 \u0026plusmn; 2.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e16.07 \u0026plusmn; 3.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.359\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003eIOP at supine, mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e17.24 \u0026plusmn; 2.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e17.93 \u0026plusmn; 3.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.321\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003eOPP at sitting, mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e53.81 \u0026plusmn; 7.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e51.09 \u0026plusmn; 9.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.168\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003eOPP at supine, mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e48.46 \u0026plusmn; 6.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e45.46 \u0026plusmn; 7.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.077\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003eMBR_V at sitting, au\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e33.02 \u0026plusmn; 8.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e40.61 \u0026plusmn; 6.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003eMBR_V at supine, au\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e32.81 \u0026plusmn; 9.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e38.55 \u0026plusmn; 7.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.006\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003eMBR_T at sitting, au\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e9.46 \u0026plusmn; 1.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e11.80 \u0026plusmn; 1.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003eMBR_T at supine, au\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e9.53 \u0026plusmn; 2.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e11.84 \u0026plusmn; 1.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003eMBR_A at sitting, au\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e15.04 \u0026plusmn; 3.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e19.70 \u0026plusmn; 3.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003eMBR_A at supine, au\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e15.33 \u0026plusmn; 3.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e18.82 \u0026plusmn; 3.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003eBOS_V at sitting, au\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e78.93 \u0026plusmn; 4.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e78.46 \u0026plusmn; 5.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.695\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003eBOS_V at supine, au\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e80.64 \u0026plusmn; 6.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e82.93 \u0026plusmn; 4.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.123\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003eBOS_T at sitting, au\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e76.44 \u0026plusmn; 5.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e73.39 \u0026plusmn; 5.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.024\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003eBOS_T at supine, au\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e79.85 \u0026plusmn; 5.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e78.58 \u0026plusmn; 4.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.337\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003eBOS_A at sitting, au\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e77.81 \u0026plusmn; 4.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e76.34 \u0026plusmn; 5.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.233\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003eBOS_A at supine, au\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e80.42 \u0026plusmn; 6.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e80.98 \u0026plusmn; 4.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.682\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003eBOT_V at sitting, au\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e51.13 \u0026plusmn; 6.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e49.73 \u0026plusmn; 6.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.371\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003eBOT_V at supine, au\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e55.27 \u0026plusmn; 10.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e51.94 \u0026plusmn; 9.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.183\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003eBOT_T at sitting, au\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e47.56 \u0026plusmn; 6.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e45.05 \u0026plusmn; 5.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.083\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003eBOT_T at supine, au\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e51.55 \u0026plusmn; 9.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e46.70 \u0026plusmn; 5.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.019\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003eBOT_A at sitting, au\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e49.26 \u0026plusmn; 5.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e47.38 \u0026plusmn; 6.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.208\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 189px;\"\u003e\n \u003cp\u003eBOT_A at supine, au\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e53.41 \u0026plusmn; 10.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e49.49 \u0026plusmn; 7.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 72px;\"\u003e\n \u003cp\u003e0.081\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: NTG-OSA, normal tension glaucoma and obstructive sleep apnoea; SD, standard deviation; \u0026nbsp;SpO2, peripheral oxygen saturation; IOP, intraocular pressure; OPP, ocular perfusion pressure;; MBR, mean blur rate; BOS, blowout score; BOT, blowout time; V, vascular; T, tissue; A, all areas.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3: Change in parameters associated with a change in body position from sitting to supine.\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"991\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 303px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNTG-OSA (n=45)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 307px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControls (n=29)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 291px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNTG-OSA vs Controls\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 223px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean difference \u0026plusmn; SD\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 228px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean difference \u0026plusmn; SD (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 212px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean difference \u0026plusmn; SD (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eIOP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 223px;\"\u003e\n \u003cp\u003e2.06 \u0026plusmn; 2.37 (1.48, 2.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 228px;\"\u003e\n \u003cp\u003e1.84 \u0026plusmn; 2.19 (1.36, 2.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 212px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eSBP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 223px;\"\u003e\n \u003cp\u003e-8.31 \u0026plusmn; 11.39 (-11.09, -5.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 228px;\"\u003e\n \u003cp\u003e-9.40 \u0026plusmn; 12.54 (-12.17, -6.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 212px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eDBP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 223px;\"\u003e\n \u003cp\u003e-5.72 \u0026plusmn; 6.33 (-7.26, -4.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 228px;\"\u003e\n \u003cp\u003e-4.53 \u0026plusmn; 4.91 (-5.62, -3.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 212px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eOPP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 223px;\"\u003e\n \u003cp\u003e-5.76 \u0026plusmn; 5.20 (-7.03, -4.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 228px;\"\u003e\n \u003cp\u003e-5.53 \u0026plusmn; 4.43 (-6.31, -4.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 212px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003ePulse rate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 223px;\"\u003e\n \u003cp\u003e-4.36 \u0026plusmn; 3.77 (-5.29, -3.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 228px;\"\u003e\n \u003cp\u003e-6.10 \u0026plusmn; 6.22 (-7.48, -4.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 212px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eMBR_V\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 223px;\"\u003e\n \u003cp\u003e-1.07 \u0026plusmn; 6.22 (-3.01, 0.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 228px;\"\u003e\n \u003cp\u003e-2.07 \u0026plusmn; 6.67 (-4.60, 0.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e0.106\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 212px;\"\u003e\n \u003cp\u003e-0.99 \u0026plusmn; 1.55 (-4.08, 2.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e0.523\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eMBR_T\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 223px;\"\u003e\n \u003cp\u003e-0.04 \u0026plusmn; 1.32 (-0.45, 0.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e0.862\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 228px;\"\u003e\n \u003cp\u003e0.05 \u0026plusmn; 1.11 (-0.37, 0.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e0.828\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 212px;\"\u003e\n \u003cp\u003e0.08 \u0026plusmn; 0.30 (-0.52, 0.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e0.788\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eMBR_A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 223px;\"\u003e\n \u003cp\u003e0.06 \u0026plusmn; 2.22 (-0.63, 0.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e0.857\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 228px;\"\u003e\n \u003cp\u003e-0.88 \u0026plusmn; 2.79 (-1.94, 0.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e0.101\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 212px;\"\u003e\n \u003cp\u003e-0.94 \u0026plusmn; 0.60 (-2.13, 0.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e0.119\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eBOS_V\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 223px;\"\u003e\n \u003cp\u003e1.63 \u0026plusmn; 5.55 (-0.10, 3.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e0.065\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 228px;\"\u003e\n \u003cp\u003e4.47 \u0026plusmn; 3.38 (3.19, 5.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 212px;\"\u003e\n \u003cp\u003e2.85 \u0026plusmn; 1.06 (0.73, 4.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.009\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eBOS_T\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 223px;\"\u003e\n \u003cp\u003e3.09 \u0026plusmn; 4.52 (1.68, 4.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 228px;\"\u003e\n \u003cp\u003e5.19 \u0026plusmn; 2.92 (4.08, 6.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 212px;\"\u003e\n \u003cp\u003e2.10 \u0026plusmn; 0.95 (0.20, 4.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.031\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eBOS_A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 223px;\"\u003e\n \u003cp\u003e2.41 \u0026plusmn; 4.91 (0.88, 3.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.003\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 228px;\"\u003e\n \u003cp\u003e4.64 \u0026plusmn; 3.01 (3.49, 5.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 212px;\"\u003e\n \u003cp\u003e2.23 \u0026plusmn; 0.94 (0.35, 4.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.021\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eBOT_V\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 223px;\"\u003e\n \u003cp\u003e3.80 \u0026plusmn; 12.97 (-0.24, 7.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e0.065\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 228px;\"\u003e\n \u003cp\u003e2.21 \u0026plusmn; 9.47 (-1.39, 5.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 212px;\"\u003e\n \u003cp\u003e-1.59 \u0026plusmn; 2.82 (-7.22, 4.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e0.574\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eBOT_T\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 223px;\"\u003e\n \u003cp\u003e3.72 \u0026plusmn; 10.94 (0.31, 7.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.033\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 228px;\"\u003e\n \u003cp\u003e1.65 \u0026plusmn; 4.77 (-0.16, 3.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e0.073\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 212px;\"\u003e\n \u003cp\u003e-2.07 \u0026plusmn; 1.91 (-5.88, 1.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e0.282\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003eBOT_A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 223px;\"\u003e\n \u003cp\u003e3.84 \u0026plusmn; 11.41 (0.29, 7.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.035\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 228px;\"\u003e\n \u003cp\u003e2.10 \u0026plusmn; 7.09 (-0.59, 4.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e0.121\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 212px;\"\u003e\n \u003cp\u003e-1.74 \u0026plusmn; 2.39 (-6.50, 3.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e0.469\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: NTG-OSA, normal tension glaucoma and obstructive sleep apnoea; 95% CI, 95% confidence interval; SD, standard deviation; IOP, intraocular pressure; SBP, systolic blood pressure; DBP, diastolic blood pressure; OPP, ocular perfusion pressure;; MBR, mean blur rate; BOS, blowout score; BOT, blowout time; V, vascular; T, tissue; A, all areas.\u0026nbsp;\u003c/p\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":"","lastPublishedDoi":"10.21203/rs.3.rs-7473796/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7473796/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e To compare optic nerve head (ONH) perfusion using laser speckle flowgraphy (LSFG) (Softcare Co., Ltd., Fukuoka, Japan) in sitting and supine positions between eyes with normal tension glaucoma and obstructive sleep apnoea (NTG-OSA) versus normal controls.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e Intraocular pressure (IOP), body mass index (BMI), and LSFG measurements (mean blur rate (MBR), blowout score (BOS), and blowout time (BOT)) were taken in sitting and supine positions. MBR is a quantitative index of blood cell velocity, a proxy of tissue blood flow. BOS is the blood volume maintained within a vessel during each heartbeat. BOT is the time within one heartbeat that maintains \u0026gt;½ average MBR. A higher BOT implies that blood flow is maintained at a sufficiently high level for a longer duration during each heartbeat for tissue perfusion.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e 45 NTG-OSA and 29 normal eyes were recruited. The MBR of all areas, vascular areas, and tissue areas were significantly lower in the NTG-OSA group compared to the normal controls in both sitting and supine positions (all p\u0026lt;0.05). When changing from sitting to supine, normal eyes had significantly greater increase in BOS compared to the increase in NTG-OSA eyes (p\u0026lt;0.05), but only NTG-OSA eyes had significant increases in BOT (p\u0026lt;0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e NTG-OSA eyes have significantly lower ONH perfusion, as measured by decreased MBR on LSFG, in both sitting and supine positions. The prolonged maintenance of high ONH perfusion with a change in body posture, represented by an increase in BOS may represent altered microvascular autoregulation in patients with NTG-OSA.\u003c/p\u003e","manuscriptTitle":"Decreased Optic Nerve Head Perfusion in Patients with Normal Tension Glaucoma and Obstructive Sleep Apnoea","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-11 12:19:37","doi":"10.21203/rs.3.rs-7473796/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":"ffcf2f20-51a8-4c31-ad7f-5d64f5d83ee1","owner":[],"postedDate":"September 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":54238103,"name":"Health sciences/Medical research"},{"id":54238104,"name":"Health sciences/Anatomy"}],"tags":[],"updatedAt":"2025-10-31T11:17:26+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-11 12:19:37","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7473796","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7473796","identity":"rs-7473796","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}