Eye Yoga for Glaucoma: Recovery of Vascular Dysregulation and Visual Field Loss - A Randomized Controlled Trial

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Sabel This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5053793/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 19 Dec, 2024 Read the published version in EPMA Journal → Version 1 posted 10 You are reading this latest preprint version Abstract Purpose Because stress can aggravate primary open angle glaucoma (POAG) progress, we studied if stress reduction by eye muscle exercises and meditation (Eye Yoga, EY) and can normalize VD, intraocular pressure (IOP) and visual field (VF) function as a complementary, personalized approach of eye care. Patients and Methods: POAG patients were randomized 1:1 to an EY (n = 15) or control group (n = 12). While EY was practiced daily for one hours for one month at home using an iPod-audio guide, control patients read daily relaxing books. Outcome criteria were IOP, retinal vessel dynamics and VF recovery. Results After intervention, EY patients, but not controls, showed a 6.4% IOP reduction (p = 0.027). This was associated with VF improvement (mean deviation) which were greater in EY than controls (p < 0.001). Furthermore, in EY, but not controls, pattern deviation recovered in VF regions where microvessel (third order-branch) vasoconstriction improved (artery: p = 0.012; vein: p = 0.042) and EY mean artery diameter recovered significantly (p = 0.015). When pooling data of both groups, recovered VF regions, but not non-recovered fields, showed significantly larger arterial diameter gains (2.4 [-0.3-5.3] MU). Neither treatment had any adverse events. Conclusions Because EY is able to reduce vasoconstriction and improve VF function in POAG confirms the hypothesis that mental stress is a contributing, or even key mechanism of POAG, and improved blood flow a fundamental mechanism of vision recovery and restoration. Daily eye yoga home-exercises are a safe and effective complementary PPPM method which can be easily adopted for POAG care. Trial Registration clinicaltrials.gov (NCT04037384) Eye yoga glaucoma vision restoration vision loss retinal vascular dysregulation Figures Figure 1 Figure 2 Figure 3 Introduction Vision loss in glaucoma results from central nervous system damage of the retina, optic nerve and brain, but the prognosis is pessimistic as the associated visual field (VF) loss is considered irreversible and progressive 1 , 2 . Though vision can recover to some extent following IOP reduction 3 – 12 , vision training 13 – 15 or microcurrent stimulation 16 , 17 , the mechanisms of recovery are still unclear. According to the “residual vision activation theory” 18 , vision recovery is explained by synaptic plasticity in the retina and reorganization of brain functional connectivity networks 18 – 24 which are thought to enhance visual/perceptual processing. But besides neuronal reorganization we should also consider vascular mechanisms because their role in vision recovery is still unknown. Conventional glaucoma treatment focuses solely on controlling IOP through drugs or surgery. But many patients do not respond well to the treatment, because vision loss progresses despite well-controlled IOP. In line with the principles of Predictive, Preventive, and Personalized Medicine (PPPM), consideration of other individual risk factors such as mental stress versus relaxation is vital for stopping progression and/or inducing restoration and repair. It is well known that the vascular state is a key component of glaucoma pathology and other eye and brain disorders 25 , 26 . Especially normal tension glaucoma patients suffer from vascular dysregulation (VD) with typically signs or symptoms, collectively termed the “Flammer-Syndrome (FS)” 27 – 34 . The symptoms include cold hands or feet, prolonged sleep onset time, prolonged blood flow cessation in finger capillaries after cooling, autoregulation problems of ocular blood flow (OBF), increased retinal venous pressure with increased vessel stiffness, and altered activity of the autonomic nervous system (heart beat-to-beat variation 19 ). It is expected that the resulting microvessel perfusion problems deprive energy-hungry neurons of oxygen and nutrients, disturbing neuronal activity and brain network synchronization which is tightly intertwined with blood flow by “neurovascular coupling” (NVC) 35 – 37 . This energy deprivation impairs neuronal signaling (propagation of action potentials), and visual processing in the retina and/or brain is disturbed or lost. We propose that this “hypo-metabolic” state may be a primary “root cause” of neuronal dysfunction in primary open angle glaucoma (POAG) which may either kill neurons in case of no energy supply or only “silence” neurons which are hypo-metabolic 38 . Stress may be one major cause of vasoconstriction. Patients showing Flammer-symptoms of VD tend to have stress prone personality dispositions with low stress resilience, as they are particularly vulnerable to receive bad news that their vision loss progresses which creates even more stress by anxiety and fear of going blind in a down-ward vicious cycle as follows: Stress ->eye muscle tension/vasoconstriction ->silencing neurons ->low vision -> more stress -> ….. -> more vision loss … and so on To evaluate if mental stress may be a root cause of POAG 38 , we countered stress by relaxation to learn if this improves vascular health and VF function. Indeed, meditation is already known to reduce IOP, lower stress hormone levels, alter gene expression, and improve quality of life 39 – 41 . Even short-term ocular exercises and yoga-based lifestyle intervention lower IOP 42 , 43 . If we gain a better understanding of how IOP, blood flow, and mental stress factors are related we submit that it will help predict and prevent disease progression and develop more personalized treatment plans. As we now show, one-month of stress-reducing relaxation with daily Eye Yoga exercise (EY) (the independent variable) can improve vascular health and restore VF function (the dependent variables). Materials and Methods Experimental design To participate in our prospective, randomized, double-blind, placebo-controlled clinical trial (flow diagram and study design in Fig. 1 ), participants gave written informed consent followed by 1:1 randomized by lot to either EY or “active” placebo group by the unblinded project manager (L.F.). The local ethics committees approved the study plan in compliance with the Declaration of Helsinki (registered at ClinicalTrials.gov: NCT04037384). Patient recruitment and follow-up were carried out from 8/2019 to 12/2022 with diagnostic evaluations at BASELINE and after the 30-day treatment (POST) by study nurses blinded regarding group identities in Institute of Medical Psychology, Faculty of Medicine, University of Magdeburg, Germany. Figure 1 Flow diagram of patient selection and DVA analysis. Of 49 eligible patients, 4 did not meet all inclusion criterion (1 no visual field defect, 2 angle closure glaucoma, 1 unable to read), 1 withdrew during baseline evaluation. During the treatment phase, 4 subjects discontinued for personal problems, therapy change or health problem, 1 subjects lost for Covid-19 and 2 lost contact. In the analysis stage, 8 had poor DVA image quality at baseline or post treatment (7 poor refractive pathway, 1 had sick feeling), 2 excluded for temporarily high BP. Inclusion criteria: residual vision, ability to read, and POAG known for at least 6 months. Exclusion criteria: Cataract, narrow-angle glaucoma, acute autoimmune disease, neurological or mental disease (e.g. epilepsy, schizophrenia, depression), addiction, hypertension > 160/100 mmHg, other ocular diseases affecting nerve tissue, pathological nystagmus, unoperated tumors or tumor recurrence, known history of abnormalities in EEG, or signs of photosensitivity, and pregnancy. Patient Sample Description Because there have been no detailed reports on visual field results after EY, we used short-term IOP change after yoga ocular exercise to estimate sample size (IOP decreased from 16.25 ± 2.48 mmHg to 14.50 ± 2.58 mmHg) 43 . The required sample size was 20 per group (95% confidence level and 90% power). Assuming a 10% drop-out rate we recruited 44 patients (22 per group). Patients were asked to continue their prescribed drugs (no “wash-out”). Outcome Measures Retinal vessel regulation and VF function analyses reported here were secondary outcome measures. The primary outcome criterion (results to be reported elsewhere) was microsaccade dysfunction improvement. Eye Yoga Intervention EY is known for thousands of years in Indian Ayurveda traditional medicine, and Chinese “ocular gymnastics” are still popular today and compulsory for schoolchildren in some Asian cultures. Our patients learned EY before baseline evaluation and were asked to practice daily for 30 days at home (15 min. morning and evening) using an iPod-based audio app which systematically guided them (i) to perform systematic eye movements to stretch their ocular muscles in all directions, (ii) periorbital and facial massage, (iii) iris relaxation in darkness (“palming”), and (iv) controlled breathing meditation (“Pranayama”) 44 . Meditation is a well-accepted mind relaxation technique which normalizes stress hormone levels and inflammation markers 41 . Controls were asked to daily read relaxing/entertaining books for 30 min (“active placebo”). Visual field and intraocular pressure examinations VF testing pre- (baseline) and post-intervention was done with Twinfield-2 Perimetry (Oculus/Germany) using 8-pattern setting (0–30°/66 points; fast threshold strategy; size III/white stimuli). It quantifies age-adjusted global (mean deviation, MD) and local VF defects at each test position (pattern deviation, PD). IOP was measured pre/post intervention (averaged triplicates) with iCare HOME Tonometer (Icare, Vantaa, Finland). To reduce test-retest variability, all VF and IOP measurements were made in the morning, in the same place and in the same sequence. All subjects had a POAG history and experience with repeated IOP and visual field measurement which limits any learning effect confounds. Dynamic vessel analysis Retinal vessels were imaged 45 , 46 in a darkened room with a dynamic vessel analyzer (DVA) (Imedos, Jena, Germany) with blood pressure (BP) before and after DVA and IOP-tests prior and after pupil dilation and after completing DVA. Following the first pupil dilation (Mydriatics 1 ml solution containing 5.0 mg tropicamide, Pharma Stulln GmbH, Germany), the fundus of the central 30 degrees of visual angle was video-recorded with the DVA in each eye compriseing three phases: (i) a 30-s pre-flicker baseline (PFB), (ii) three 20-s stimulation periods of diffuse luminance 12.5 Hz light flickers, and (iii) three 80-s post-flicker periods. Using DVA-software, vessels were analyzed regarding absolute vessel diameters (measuring unit: MU = micrometers in Gullstrand’s eye) and dilation dynamics. To establish PFB diameter (100%), the pre-flicker 50-s recordings (including 20s from last post-flicker periods) were pooled and averaged. Based on the diameter response to flickering light, expressed in percentage change over PFB, different parameters were calculated (see Fig. 2 a for details). DVA measurement was also conducted in the morning to reduce test-retest variability. Figure 2 Part A: Parameters of retinal vascular response to flickering light stimulation: “maximal dilation” (dila%): peak dilatation during a 20 sec. flickering period compared to PFB; “time to maximal dilation”(tdila): time to peak dilatation after flickering onset; “maximal constriction” (constr%): peak constriction after flicker onset compared to PFB; “time to maximal constriction” (tconstr): time to reach peak constriction. Part B and C: compound analysis of retinal vessel tree, visual field function (in dB), determination of branch order for arteries (A1-3) and veins (V1-3). B is an example of a retinal image with a superimposed 8 (0–30°/66 points) visual field test pattern (retina image resolution: 2,452 ×2,056 pixels; visual field size: 50°×42°). The linear scaling was 2,45/50 = 49 pixel/degree. The 8 (0–30°/66 points) visual field pattern (same linear scaling) was centered on the macula and vessel segments were assigned to a nearest PD (vertically flipped to match orientation). This example shows two vessel segments (A1, V1) that were assigned to their nearest PD value (-18dB). Part C: Illustration of branch order analysis showing how branch levels 1–3 were matched with the visual field defect values: A1 (branch order 1; [BO-1]) was located in the mild defect, A2 (BO-2) in a moderate and A3 (BO-3) in a severely damaged visual field sector. Vessel dynamics was measured in multiple retinal locations to differentiate branch hierarchies (smaller vs. larger vessels) and different VF areas of the intact and damaged eye for mild, moderate, or severe defect depth. Vessel segments were only analyzed if (i) the image had sufficient contrast for artefact free recording, (ii) no crossing, bend, or vessel bifurcation, (iii) located outside a circular area of one disc diameter from the optic disc center, and (iv) > 1 vessel diameter distance to neighboring vessels. Retinal vessel topography To match VFs with vessels, retina photographs were obtained by fundus camera (50°, Zeiss, Jena, Germany) digitized at 2,452×2,056 pixel resolution in a linear scaling of 49 pixels/degree (reference: emmetropic eye). This image was superimposed on the 8-pattern VF-plots of identical scaling (49 pixels/degree) using Photoshop so the VF center could be aligned to the fovea. After vertical flip of the VF chart, the retina fundus image could be matched with the specific PD value (VF depth) and the nearest PD value was selected (Fig. 2 b). Only vessel branch segments were chosen where both baseline and post-treatment PD values were available. We next combined the data of the EY and reading group to calculate the average parameters of three PD sub-groups according to their baseline perimeter results (mild defect < -6 dB, moderate defect − 6 to -12 dB and severe defect ≤ -12 dB). Retinal vessel branch level analysis All vessel segments were classified by branch order (BO): BO-1 are the largest vessels emerging from the papilla; BO-2 those branching off first from BO-1, and BO-3 all those beyond the next bifurcation, i.e. higher-up branches (Fig. 2 c). Of note, many BO-3 branches were too small (faint) for DVA-detection. To determine how vessel morphology and dynamics relate to VF recovery, we also pooled the data of both study groups and calculated the absolute difference (Δ, pre–post) of all vessel parameters as a function of PD recovery defined as improvement > 3 dB, ie. irrespective of intervention. Statistical analysis Data were analyzed with SPSS 26 (IBM, New York, USA) and Matlab (MathWorks, Natick, USA). Chi-square test was applied for gender analysis, independent-samples T-test for two-group comparisons, and paired-samples T-test for pre- and post-treatment comparison for samples normally distributed. Otherwise, we used Mann–Whitney U-test for two-group comparisons and Wilcoxon test for pre- and post-treatment comparison. Because our study was of exploratory nature, alpha was not adjusted for multiple comparisons to avoid type-1 errors and vessels were treated as independent samples. MD, IOP and vessel diameter were tested hypothesis-wise (one-sided p-value). Results Demographic parameters, blood pressure, IOP and visual field function Nineteen patients each in the EY and reading group completed baseline evaluation, but some either did not completed the trial, and in others the DVA-analysis was not possible (see Fig. 1 ). Finally, 15 EY and 12 control patients had complete data sets with comparable mean age, gender ratios and BP of both groups (Table 1 ). Both group´s baseline parameters were similar to those of the lost subjects, except that IOP of lost patients (16.3 [13.8,18.9] mmHg) was significantly higher than those retained (13.6 [12.4,14.7] mmHg), though both were still in the normal range. While after intervention BP was unchanged in both groups, hypothesis-wise testing revealed a significant IOP reduction and improved VF function (MD) only in the EY group but not in the reading group (pre/post 12.8 [10.8, 14.9]/12.8 [10.7, 14.9] mmHg, p = 0.465), i.e. 6.4% IOP reduction after EY (pre: 14.1 [12.7, 15.5]; post 13.2 [11.8, 14.7] mmHg; p = 0.027). Regarding VF function controls showed a non-significant 4% MD improvement (pre/post 4.7 [2.7, 6.7]/ 4.5 [2.3, 6.7] dB, p = 0.217) and EY a significant 24% improvement from 3.3dB [1.3, 5.4] to 2.5 dB [0.4, 4.6] (p < 0.001) (Fig. 3 c) (Table 1 ). Table 1 BP, IOP, MD and BO-3 vessel responses normal a reading eye yoga p b number of subjects 22 12 15 number of eyes 43 21 29 age (SD), year 66.4(8.8) 67.1(8.3) 62.8(12.7) 0.331 gender(female:male) 14:8 4:8 9:6 0.168 systolic pressure (SD), mmHg pre 132.1(12.7) 130.8(14.9) 131.7(14.5) 0.864 post - 128.9(17.4) 132.9(14.3) 0.516 p c - 0.618 0.654 diastolic pressure (SD), mmHg pre 82.6(8.7) 76.3(12.7) 80.7(5.7) 0.284 post - 73.3(11.4) 80.5(6.1) 0.067 p c - 0.135 0.872 IOP (SD), mmHg pre 14.3(3.7) 12.8(4.6) 14.1(3.7) 0.281 post - 12.8(4.6) 13.2(3.8) 0.733 p c - 0.465 0.027 Mean Deviation (SD) d , dB pre - 4.7(4.4) 3.3(5.4) 0.201 post - 4.2(5.1) 2.5(5.4) 0.178 p c - 0.217 < 0.001 BO-3 Artery vessel number 87 23 29 Pattern Deviation(SD), dB pre - -1(2) -2.7(2.9) 0.033 post - -0.8(2.6) -1.2(4) 0.296 p c - 0.386 0.012 Diameter(SD), MU pre 83.7(12.4) 79.7(13.9) 79.9(10.5) 0.530 post - 80.4(14.1) 82.5(12.1) 0.596 p c - 0.273 0.015 dila%(SD), % over baseline pre 3.6(2.4) 3.2(2.4) 4.5(4.2) 0.473 post - 3.9(5.2) 4(3.1) 0.106 p c - 0.808 0.820 constr%(SD), %over baseline pre -3.0(2.0) -3.4(2) -3.2(2.2) 0.473 post - -3.6(3.6) -3.2(1.8) 0.615 p c - 0.26 0.854 tdila(SD), s pre 13.3(5.3) 39(5.6) 42.9(5.6) 0.032 post - 42.4(5.7) 42.1(6.9) 0.950 p c - 0.011 0.809 tconstr(SD), s pre 46.4(26.0) 88.2(30) 84.5(26.8) 0.451 post - 84(30.7) 81.4(28.3) 0.733 p c - 0.7 0.746 BO-3 Vein vessel number 71 23 21 Pattern Deviation(SD), dB pre - -1.9(3.3) -2(2.7) 0.961 post - -2(6.3) -0.7(3.8) 0.902 p c - 0.188 0.042 Diameter(SD), MU pre 88.1(20.7) 84.8(14.1) 83.7(12.1) 0.743 post - 82.5(14.1) 84(11) 0.568 p c - 0.065 0.379 dila%(SD), % over baseline pre 3.7(2.0) 3.6(2.7) 5.7(5.9) 0.215 post - 2.4(1.4) 5.4(4.4) 0.027 p c - 0.181 0.848 constr%(SD), %over baseline pre -2.4(2.3) -2.8(1.8) -2.8(1.4) 0.528 post - -2.2(1.6) -3(1.8) 0.089 p c - 0.23 0.694 tdila(SD), s pre 15.1(5.2) 41.3(6.4) 46.5(4.2) 0.002 post - 43.4(5.3) 41.8(7.1) 0.442 p c - 0.337 0.007 tconstr(SD), s pre 47.1(35.2) 93(29.9) 89.4(32) 0.894 post - 86.8(33.1) 83.8(36.9) 0.697 p c - 0.315 0.639 a Quoted from our last publication. b Chi-square test for gender analysis, Mann-Whitney U-test or independent-samples T test for other comparisons between reading and eye yoga groups. c Wilcoxon test or paired T test for pre- and post-treatment comparison. d Absolute value. Vessel results reported here are only from the smallest measurable microvessels of branch order level 3 (BO-3). MU = measuring unit. 1 MU is approx. 1 µm Figure 3 Part A: Elements of the eye yoga exercises (meditation not shown); Part B: Average of BO-3 artery diameter and its response to flicker light in the eye yoga or reading (control) group; Part C: example of visual field recovery in all four quadrants of an excellent eye yoga responder. Vascular morphology and dynamics We already reported our baseline data showing vessel diameter shrinkage in glaucoma patients compared to healthy controls 38 . But unexpectedly, there was no significant difference between those healthy controls and our EY patients (suppl.Table 1 ). This could possibly be explained by a sampling bias caused by the limited DVA-optics resolution or loss of small (BO-2/ BO-3) microvessels in the patients. BO-3 microvessels were of special interest because they are the smallest microvessels still visible and they have the largest surface:volume ratios. This makes them particularly vulnerable to vasoconstriction with the greatest (4th -power) impact on OBF. Hence, subtle microvessel diameter changes (decline or recovery) have the greatest impact on local OBF and neuronal function. Indeed, our analysis revealed no consistent signs of recovery of vessel morphology or dynamics in larger BO-1/BO-2-branches. But post-intervention the tiniest BO-3 EY vessels had significantly increased arterial diameters and faster venous dilation, whereas controls had slower arterial dilation (Table 1 ). When matching visual dysfunction (PD) with vascular status, EY patients had significantly improved visual sensitivity in locations where signs of arterial and venous (BO-3) microvessels diameter recovery was observed. The respective visual sensitivity improvement for retinal regions showing recovered arteries was − 2.7 [1.6, 3.8] to -1.2 [0.3,2.8] dB (p = 0.012) and for veins − 2.0 [0.8,3.2] to -0.7,[-1.0, 2.5] dB, p = 0.042). While arterial diameter significantly increased after EY from 79.9 [75.9,83.9] to 82.5 [77.9,87.1] MU (p = 0.015), the reading group showed no such changes (Table 1 , Fig. 3 a). Furthermore, after intervention, time-to-peak dilation was significantly slower in arteries of controls and significantly faster in veins after EY (Table 1 ). Vascular state and visual field defect depth We also studied if vessel state or dynamics vary as a function of VF dysfunction (defect depth) at baseline. When data of both groups was combined there was no apparent recovery in regions of mild impairment (ceiling effect?), but significant VF recovery was observed in regions of moderate and severe of damage (see Suppl.-Table 2). Unexpectedly, the vessel parameters were comparable across different VF severity levels. Comparing vessels in recovered vs. non-recovered visual field sectors To gain insight into vascular mechanisms of vision restoration/recovery, we explored how vascular changes relate to VF recovery of > 3 dB gain when the data of all patients were pooled, i.e. irrespective of invention (Table 2 ). In retinal areas with arterial recovery the respective PD recovery was 6.2 [4.8, 7.6] dB in controls, 7.7 [6.1, 9.2] dB in EY and 7.1 [6.0, 8.1] dB in both groups combined. No such change was noted in regions without arterial recovery (PD values: 0.0 [-0.4,0.4], -1.5 [-2.1, -0.9], and − 0.9 [-1.3, -0.5] dB, respectively). VF regions of recovered veins showed similar results (p < 0.001). Recovered VF sectors in EY patients, but not controls, had increased arterial vessel diameters (2.4 [-0.3, 5.3] MU gain) but no change in non-recovered VFs (-0.1 [-0.9,0.7] MU) (p = 0.014). Venous vessel diameters in controls showed a trend of smaller diameters (p = 0.053) in recovered fields, whereas EY veins had a trend of enlarged diameters of 1.0 [-1.1,3.0] MU (p = 0.076, Fig. 3 b). Adverse events Both treatments were well tolerated without treatment-associated adverse events. Table 2 Vessel response in recovered vs. non-recovered visual field sector ( = post–pre) Δ recovered non-recovered p* Artery Vessel number reading 16 108 yoga 23 152 pooled 39 260 ΔPattern Deviation(SD), dB reading 6.2(2.6) 0(2.2) < 0.001 yoga 7.7(3.6) -1.5(4) < 0.001 pooled 7.1(3.3) -0.9(3.5) < 0.001 ΔDiameter(SD), MU reading -2.2(4) -1(5.2) 0.188 yoga 2.4(6.5) -0.1(4.9) 0.014 pooled 0.5(6) -0.5(5.1) 0.142 Δdila%(SD), % over baseline reading -1.2(3.3) 0.1(3.3) 0.365 yoga 0.3(3.5) -0.3(3) 0.236 pooled -0.3(3.5) -0.2(3.1) 0.685 Δconstr%(SD), %over baseline reading 0(1.6) 0.1(2.8) 0.964 yoga -0.6(2.1) 0.5(2.2) 0.092 pooled -0.4(1.9) 0.3(2.5) 0.179 Δtdila(SD), s reading -0.3(5.4) 1.5(7.6) 0.282 yoga -0.2(7.9) 0.3(7.9) 0.791 pooled -0.2(6.9) 0.8(7.8) 0.45 Δtconstr(SD), s reading 0.4(38.1) -0.6(40.1) 0.928 yoga -2.8(40.6) -3.8(35.1) 0.901 pooled -1.5(39.1) -2.5(37.2) 0.571 Vein Vessel number reading 16 105 yoga 30 139 pooled 46 244 Pattern Deviation(SD), dB reading 7.8(3.3) 0.1(2.7) < 0.001 yoga 6.8(2.9) -1.2(3.5) < 0.001 pooled 7.1(3.1) -0.6(3.3) < 0.001 Diameter(SD), MU reading -2.9(3.5) -1.1(7.1) 0.053 yoga 1(5.4) -1.2(5.2) 0.076 pooled -0.4(5.2) -1.1(6.1) 0.432 dila%(SD), % over baseline reading 0.1(2) 0.2(2.8) 0.603 yoga -0.3(2.7) 0(3.7) 0.57 pooled -0.2(2.5) 0.1(3.3) 0.345 constr%(SD), %over baseline reading 0.2(1.6) 0.1(1.9) 0.973 yoga -0.8(2.6) 0.1(2.5) 0.113 pooled -0.5(2.3) 0.1(2.2) 0.198 tdila(SD), s reading 0.3(5.7) 0.7(6.8) 0.794 yoga -2.7(6.5) -1.2(6.4) 0.497 pooled -1.7(6.4) -0.4(6.6) 0.616 tconstr(SD), s reading -5.5(47.3) -3.5(46) 0.777 yoga -1.4(44.8) -5(44.3) 0.939 pooled -2.8(45.2) -4.3(45) 0.902 Δ = post–pre. Recovered vessel are those located in visual field sector where Δ Pattern Deviation > 3 dB. Non-recovered vessel ≤ 3 dB. *Mann-Whitney U-test or independent-samples T test for comparisons between reading and eye yoga group. Discussion Though there are only three pubmed -listed EY-studies in glaucoma, there is growing interest in relaxation techniques to lower IOP 47 . Following our earlier demonstration that vessel diameters are reduced in POAG-patients which compromises OBF, our study is the first controlled trial showing that EY is safe and effective to lower IOP, normalize VD in microvessels and improve VF function. Though a 3% diameter recovery seems small, according to Poiseuille’s law vessel diameter has a 4th -power influence on blood flow. Therefore, an EY-induced 2.5 MU increase in recovered vessels translates to a 12.6% OBF restoration [(100%+3%) 4 -100%=12.6%], i.e. an increase reaching almost the 15% that POAG patient lost compared to healthy controls 38 . We hypothesize that this normalization of vasoconstriction has a (secondary) down-stream effect of reactivating hypo-metabolic (“silent”) neurons and provides the biological mechanism of vision restoration. From a basic science perspective, our results confirm the hypothesis that stress should be considered a key cause , not only an effect , of glaucoma and that relaxation is a complementary technique to improve vision. This causality is justified because the independent variable (treatment using relaxation altered the dependend variable IOP, vessel diameter and visual field function. Therefore, the widespread opinion that stress is a “non-issue” in glaucoma care needs revision for two reasons: firstly, glaucoma patients with VD tend to have personality dispositions of low stress resilience,being worrisome, perfectionistic, ambitious, compulsive and/or neglecting their own needs 48 – 50 . This, in turn, creates sudden or long-term mental stress triggering a psychosomatic response 51 . Secondly, the diagnosis of progressing vision loss triggers a pessimistic life perspective because the continuous anxiety and fear of going blind possibly accelerates progression (“dark thoughts - cloudy vision”), a downward spiraling (vicious) cycle 52 , 53 . That stress negatively impacts all bodily organs is the basis of psychosomatic medicine, and, as we confirm, the eyes are no exception: firstly, stress increases stress hormones such as glucocorticoids 54 , pro-inflammatory cytokines 55 , and endothelin-1 30,56–58 , and it reduced nitric oxide (NO) 59 , 60 , a vasodilatory neuropeptide lining rich in peri-vascular neurons and in the endothelium. Secondly, stress triggers sympathetic activation, increasing muscle tone (tension/constriction) not only of the perivascular muscles but possibly also of the oculomotor muscles. We submit that chronic vasoconstriction in POAG therefore continuously deprives retinal and brain neurons of oxygen and nutrients, lowering neuronal energy states and reducing visual processing 38 , 52 . The most effective, long-known remedy for stress is relaxation. It is not only used for thousands of years in traditional medicine, but many relaxation programs are standard care in psychosomatic medicine, psychotherapy, psychiatry and neuro-rehabilitation. But so far they are not used in standard care of low vision rehabilitation. Our study results confirm the benefits of relaxation techniques (here: eye exercises and meditation) and it provides the biological explanation why vision can be improved or restored: improved vascular regulation and blood flow. This is in line with others showing that yogic ocular exercises lower IOP in the short- 43 and long-term 42 as does breathing (mindfulness) meditation. Indeed, meditation reduces stress- and inflammation biomarkers (cortisol, IL6, TNF-α, ROS), elevates β-endorphins, BDNF, TAC and even alters gene expression 40 , 41 . Based on our observations we propose the following two-pronged theory of glaucoma which will require further study: firstly, increased (sympathetic) muscle tension shortens oculomotor muscles, pulling the eyes slightly backward against the eye socket of the skull which, in turn, couldincreases IOP and constricts OBF in the optic nerve head (paling) and choroid, especially when intracranial and optic nerve subarachnoid space pressure is low 61 , 62 . Secondly, stress may increase retinal perivascular smooth muscle tension, adding to the eye pressure-induced vasoconstriction. This “eyeball-retraction-theory” could explain why relaxation by EY is a remedy for glaucoma: stretching the oculomotor muscles during eye movement exercises lowers their tension which has the advantage of lifting the pressure against the choroid, possibly reducing IOP 40 , 41 , normalizing the eye globe´s shape and/or enhances aqueous outflow. Relaxation of the perivascular smooth muscles on the other hand increases vessel diameter, normalizing OBF. This lead us to the proposition that the mechanism of vision restoration after eye yoga is primarily due to vascular recovery. If true, neuronal recovery (neuroplasticity) would only be a secondary effect. Overall, although further study is needed for confirm the proposed mechanism and long term effect of EY, our study offers a potential avenues for personalized POAG therapy within the framework of PPPM: in contrast to an IOP-centric focus to explain glaucoma, we agree with the proposal of Josef Flammer 27 , 29 that vascular dysregulation or dysfunction is a key mechanism which, according to our own suggestion that mental stress may be the underlying cause 52 . We hope that in the future glaucoma treatment will be more tailored to the patients´individual characteristics (blood flow, mental stress, whole body status, lifestyle, environmental factors, etc.) rather than focusing on the one and only risk factor, IOP. It would open the door for a more personalized, holistic approach of preventing progression of vision loss and optimization of restoration and recovery in low vision rehabilitation. Limitations and recommendations: Though our study sample is small, yet significant benefits of EY were observed which argues for a strong effect. Furthermore, some of our “active control” patients showed some vision recovery as well, possibly due to either normal variation, placebo effects, or the (non-specific) benefit of daily “time-out” relaxation. Whatever the mechanism, relaxation by EY is “complementary” (not an alternative) to standard IOP management. Future studies could test if EY can increase efficacy of drug therapies and/or improve a more optimistic mental state of mind. Conclusion Stress-reducing relaxation by Eye yoga (combined eye exercises and meditation) can normalize vasoconstriction and improve VF in POAG. Though a study with larger sample size is desirable, we recommend that EY (including meditation) can already be adopted in low vision rehabilitation. It is safe and effective to improve visual field dysfunction, possibly slowing down progression. And it may be a useful solution for patients who fail to respond to standard eye care and help achieving PPPM in the management of glaucoma. Declarations Competing interest W.Z. and L.F. have no relevant financial or non-financial interests to disclose. B.S. is shareholder of a low vision rehabilitation center offering Eye Yoga and neuromodulation (www.SAVIR-Center.com) Ethics approval The study was approved by the Ethical Committee of Otto-von-Guericke University of Magdeburg, Medical Faculty, Magdeburg, Germany. Consent to participate Participants have given their written informed consent to participate in this study. Consent for publication All authors approved its final version. Availability of data and material The data in the present study is available from the corresponding author on reasonable request. Authors contributions W.Z. contributed with study design, data collection, data analysis and manuscript drafting. L.F. contributed to the study design and data collection and data analysis. BS directed the study design, data analysis and interpretation, and obtained funding for the study and helped with manuscript drafting. Funding/Support We appreciate the generous funding support by the Velux Foundation (#1359). The author Wanshu Zhou was supported by a scholarship from China Scholarship Council (201908080281) and a scholarship from LOM program of the University of Magdeburg (#485). Role of the Sponsor The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Additional Contributions Sandra Heinrich and Eileen Johnsen assisted in recruiting and some of the testing of the patients. References Chen PP. Blindness in patients with treated open-angle glaucoma. Ophthalmology. 2003;110(4):726-733. Group CN-TGS. 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Retinal neurovascular coupling in patients with glaucoma and ocular hypertension and its association with the level of glaucomatous damage. Graefes Arch Clin Exp Ophthalmol. 2013;251(6):1577-1585. Flammer J, Pache M, Resink T. Vasospasm, its role in the pathogenesis of diseases with particular reference to the eye. Prog Retin Eye Res. 2001;20(3):319-349. Kim 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;10(1):10056. Abegão Pinto L, Willekens K, Van Keer K, et al. Ocular blood flow in glaucoma - the Leuven Eye Study. Acta Ophthalmol. 2016;94(6):592-598. Iadecola C. The Neurovascular Unit Coming of Age: A Journey through Neurovascular Coupling in Health and Disease. Neuron. 2017;96(1):17-42. Kaplan L, Chow BW, Gu C. Neuronal regulation of the blood-brain barrier and neurovascular coupling. Nat Rev Neurosci. 2020;21(8):416-432. Segarra M, Aburto MR, Hefendehl J, Acker-Palmer A. Neurovascular Interactions in the Nervous System. Annu Rev Cell Dev Biol. 2019;35:615-635. Zhou W, Sabel BA. Vascular dysregulation in glaucoma: retinal vasoconstriction and normal neurovascular coupling in altitudinal visual field defects. EPMA J. 2023;14(1):87-99. Tolahunase MR, Sagar R, Faiq M, Dada R. Yoga- and meditation-based lifestyle intervention increases neuroplasticity and reduces severity of major depressive disorder: A randomized controlled trial. Restor Neurol Neurosci. 2018;36(3):423-442. Dada T, Bhai N, Midha N, et al. Effect of mindfulness meditation on intraocular pressure and trabecular meshwork gene expression: a randomized controlled trial. Am J Ophthalmol. 2021;223:308-321. Dada T, Mittal D, Mohanty K, et al. Mindfulness meditation reduces intraocular pressure, lowers stress biomarkers and modulates gene expression in glaucoma: a randomized controlled trial. J Glaucoma. 2018;27(12):1061-1067. Sankalp, Dada T, Yadav RK, Sharma HB, Netam RK, Kochhar KP. Effect of Tratak (Yogic Ocular Exercises) on Intraocular Pressure in Glaucoma: An RCT. Int J Yoga. 2022;15(1):59-69. Dimitrova G, Trenceva A. The short-term effect of yoga ocular exercise on intra-ocular pressure. Acta Ophthalmol. 2017;95(1):e81-e82. Sabel BA. Restoring Low Vision: How to Strengthen Your Potentials in Low Vision an Blindness. Monograph, Amazon Book Store; 2016. Garhofer G, Bek T, Boehm AG, et al. Use of the retinal vessel analyzer in ocular blood flow research. Acta Ophthalmol. 2010;88(7):717-722. Seifertl BU, Vilser W. Retinal Vessel Analyzer (RVA)--design and function. Biomed Tech (Berl). 2002;47 Suppl 1 Pt 2:678-681. Wu ACL, Choy BNK. Psychological interventions to reduce intraocular pressure (IOP) in glaucoma patients: a review. Graefes Arch Clin Exp Ophthalmol. 2023;261(5):1215-1227. Tan Z, Tung TH, Xu SQ, Chen PE, Chien CW, Jiang B. Personality types of patients with glaucoma: A systematic review of observational studies. Medicine (Baltimore). 2021;100(23):e25914. Mabuchi F, Yoshimura K, Kashiwagi K, et al. Personality assessment based on the five-factor model of personality structure in patients with primary open-angle glaucoma. Jpn J Ophthalmol. 2005;49(1):31-35. Lim MC, Shiba DR, Clark IJ, et al. Personality type of the glaucoma patient. J Glaucoma. 2007;16(8):649-654. Gillmann K, Hoskens K, Mansouri K. Acute emotional stress as a trigger for intraocular pressure elevation in Glaucoma. BMC Ophthalmol. 2019;19(1):69. Sabel BA, Wang J, Cárdenas-Morales L, Faiq M, Heim C. Mental stress as consequence and cause of vision loss: the dawn of psychosomatic ophthalmology for preventive and personalized medicine. EPMA J. 2018;9(2):133-160. Akuffo KO, Sewpaul R, Darrah S, et al. Vision loss, vision difficulty and psychological distress in South Africa: results from SANHANES-1. BMC Psychol. 2021;9(1):66. Schwartz B, McCarty G, Rosner B. Increased plasma free cortisol in ocular hypertension and open angle glaucoma. Arch Ophthalmol. 1987;105(8):1060-1065. Vidal-Villegas B, Burgos-Blasco B, Santiago Alvarez JL, et al. Proinflammatory Cytokine Profile Differences between Primary Open-Angle and Pseudoexfoliative Glaucoma. Ophthalmic Res. 2022;65(1):111-120. Lommatzsch C, Rothaus K, Schopmeyer L, et al. Elevated endothelin-1 levels as risk factor for an impaired ocular blood flow measured by OCT-A in glaucoma. Sci Rep. 2022;12(1):11801. Chen HY, Chang YC, Chen WC, Lane HY. Association between plasma endothelin-1 and severity of different types of glaucoma. J Glaucoma. 2013;22(2):117-122. Nicolela MT, Ferrier SN, Morrison CA, et al. Effects of cold-induced vasospasm in glaucoma: the role of endothelin-1. Invest Ophthalmol Vis Sci. 2003;44(6):2565-2572. Cavet ME, Vittitow JL, Impagnatiello F, Ongini E, Bastia E. Nitric oxide (NO): an emerging target for the treatment of glaucoma. Invest Ophthalmol Vis Sci. 2014;55(8):5005-5015. Bahr-Hosseini M, Bikson M. Neurovascular-modulation: A review of primary vascular responses to transcranial electrical stimulation as a mechanism of action. Brain Stimul. 2021;14(4):837-847. Hou R, Zhang Z, Yang D, et al. Intracranial pressure (ICP) and optic nerve subarachnoid space pressure (ONSP) correlation in the optic nerve chamber: the Beijing Intracranial and Intraocular Pressure (iCOP) study. Brain Res. 2016;1635:201-208. Hou R, Zhang Z, Yang D, et al. Pressure balance and imbalance in the optic nerve chamber: The Beijing Intracranial and Intraocular Pressure (iCOP) Study. Sci China Life Sci. 2016;59(5):495-503. Additional Declarations No competing interests reported. Supplementary Files Supptable1.docx Supp. Table 1 Vessel parameters per vessel (all vessel branch orders) a Quoted from our earlier publication reference 38 . b Mann-Whitney U-test or independent-samples T test for comparisons between reading and eye yoga groups. c Wilcoxon test or paired T test for pre- and post-treatment comparison. Supptable2.docx Supp. Table 2 Vessel parameters as a function of visual field defect depth a Wilcoxon test or paired T test for pre- and post-treatment comparison. Mild defect > − 6 dB, − 6–12 dB moderate defect and severe defect ≤ − 12 dB. Cite Share Download PDF Status: Published Journal Publication published 19 Dec, 2024 Read the published version in EPMA Journal → Version 1 posted Editorial decision: Revision requested 26 Sep, 2024 Reviews received at journal 25 Sep, 2024 Reviews received at journal 23 Sep, 2024 Reviewers agreed at journal 15 Sep, 2024 Reviewers agreed at journal 15 Sep, 2024 Reviewers agreed at journal 14 Sep, 2024 Reviewers invited by journal 13 Sep, 2024 Editor assigned by journal 13 Sep, 2024 Submission checks completed at journal 09 Sep, 2024 First submitted to journal 08 Sep, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5053793","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":359372124,"identity":"6addb463-3395-410e-a653-028c874560a5","order_by":0,"name":"Wanshu Zhou","email":"","orcid":"","institution":"Otto-von-Guericke University of Magdeburg","correspondingAuthor":false,"prefix":"","firstName":"Wanshu","middleName":"","lastName":"Zhou","suffix":""},{"id":359372125,"identity":"e85261d3-f9ec-4092-914e-7b16ea8a2d5d","order_by":1,"name":"Luisa Fricke","email":"","orcid":"","institution":"Otto-von-Guericke University of Magdeburg","correspondingAuthor":false,"prefix":"","firstName":"Luisa","middleName":"","lastName":"Fricke","suffix":""},{"id":359372126,"identity":"a8857626-be2b-4725-a128-560a41d46a39","order_by":2,"name":"Bernhard A. Sabel","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABG0lEQVRIiWNgGAWjYBACAyBmBmLGBgYGNgaGAhsgOwEqd4AoLQZppGs5TFiLOXvvs8cFNfdkG/gPP3vwweB8ND97AuNjnl+HGfiON2DVYtlz3Nx4xrFi4waJNHPDGQa3c2f2PGA25u07zCB5Brs1BjfS2KR52BISGyQYzKR5gFo23Ehgk5zZcxgolYBdy/1nQC3/gFr4j3+T/mNwLnc/XMv9BzhsYWOT5m0DamHIMZNmMDiQu0EigU3iww+QLdi9b9kDdBhvX4Jxm0ROuWGPQXLujDMPmw0+NqTzSJ7B7jBz9mNAh31LkO3nP77twY8Ku9z+9uSDDxL+WMvxHcfufThgQzCBccTYxsCDXz0m+EOqhlEwCkbBKBjGAADkE2GsbjXVBAAAAABJRU5ErkJggg==","orcid":"","institution":"Otto-von-Guericke University of Magdeburg","correspondingAuthor":true,"prefix":"","firstName":"Bernhard","middleName":"A.","lastName":"Sabel","suffix":""}],"badges":[],"createdAt":"2024-09-08 17:57:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5053793/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5053793/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s13167-024-00389-x","type":"published","date":"2024-12-19T15:58:30+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":69507136,"identity":"63a668c8-e5b5-481e-bdf0-03df21f80bee","added_by":"auto","created_at":"2024-11-21 06:47:49","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":189743,"visible":true,"origin":"","legend":"\u003cp\u003eFlow diagram of patient selection and DVA analysis. Of 49 eligible patients, 4 did not meet all inclusion criterion (1 no visual field defect, 2 angle closure glaucoma, 1 unable to read), 1 withdrew during baseline evaluation. During the treatment phase, 4 subjects discontinued for personal problems, therapy change or health problem, 1 subjects lost for Covid-19 and 2 lost contact. In the analysis stage, 8 had poor DVA image quality at baseline or post treatment (7 poor refractive pathway, 1 had sick feeling), 2 excluded for temporarily high BP.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-5053793/v1/7927eaa4ec8c157860b774fc.png"},{"id":69505856,"identity":"b41365c1-45de-45db-80d9-8191b0a406ff","added_by":"auto","created_at":"2024-11-21 06:31:49","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":107529,"visible":true,"origin":"","legend":"\u003cp\u003ePart A: Parameters of retinal vascular response to flickering light stimulation: “maximal dilation” (dila%): peak dilatation during a 20 sec. flickering period compared to PFB; “time to maximal dilation”(tdila): time to peak dilatation after flickering onset; “maximal constriction” (constr%): peak constriction after flicker onset compared to PFB; “time to maximal constriction” (tconstr): time to reach peak constriction. Part B and C: compound analysis of retinal vessel tree, visual field function (in dB), determination of branch order for arteries (A1-3) and veins (V1-3). B is an example of a retinal image with a superimposed 8 (0-30°/66 points) visual field test pattern (retina image resolution: 2,452 ×2,056 pixels; visual field size: 50°×42°). The linear scaling was 2,45/50 = 49 pixel/degree. The 8 (0-30°/66 points) visual field pattern (same linear scaling) was centered on the macula and vessel segments were assigned to a nearest PD (vertically flipped to match orientation). This example shows two vessel segments (A1, V1) that were assigned to their nearest PD value (-18dB). Part C: Illustration of branch order analysis showing how branch levels 1-3 were matched with the visual field defect values: A1 (branch order 1; [BO-1]) was located in the mild defect, A2 (BO-2) in a moderate and A3 (BO-3) in a severely damaged visual field sector.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-5053793/v1/54ae05b6dd518bb42fbe63b8.png"},{"id":69505854,"identity":"7f369476-ff2a-4930-8811-a7bf0be97d05","added_by":"auto","created_at":"2024-11-21 06:31:49","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":160863,"visible":true,"origin":"","legend":"\u003cp\u003ePart A: Elements of the eye yoga exercises (meditation not shown); Part B: Average of BO-3 artery diameter and its response to flicker light in the eye yoga or reading (control) group; Part C: example of visual field recovery in all four quadrants of an excellent eye yoga responder.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-5053793/v1/16788e4bd1384bce21291697.png"},{"id":72202012,"identity":"b46404e3-e887-496e-905f-7e6cf3ba4cea","added_by":"auto","created_at":"2024-12-23 16:13:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1402570,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5053793/v1/9d551406-992c-4ebc-bdf8-1cdf1831f042.pdf"},{"id":69506790,"identity":"3917baac-943e-4b99-bd37-f41794dabbf4","added_by":"auto","created_at":"2024-11-21 06:39:49","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":19936,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupp. Table 1 Vessel parameters per vessel (all vessel branch orders)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ea\u003c/sup\u003eQuoted from our earlier publication reference\u003csup\u003e38\u003c/sup\u003e. \u003csup\u003eb\u003c/sup\u003eMann-Whitney U-test or independent-samples T test for comparisons between reading and eye yoga groups. \u003csup\u003ec\u003c/sup\u003eWilcoxon test or paired T test for pre- and post-treatment comparison.\u003c/p\u003e","description":"","filename":"Supptable1.docx","url":"https://assets-eu.researchsquare.com/files/rs-5053793/v1/74ecd300b5dcbaaab6500f55.docx"},{"id":69506792,"identity":"252f7eb5-fc26-4932-9600-ece7d9d76257","added_by":"auto","created_at":"2024-11-21 06:39:49","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":18871,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupp. Table 2 Vessel parameters as a function of visual field defect depth\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ea\u003c/sup\u003eWilcoxon test or paired T test for pre- and post-treatment comparison. Mild defect \u0026gt; − 6 dB, − 6–12 dB moderate defect and severe defect ≤ − 12 dB.\u003c/p\u003e","description":"","filename":"Supptable2.docx","url":"https://assets-eu.researchsquare.com/files/rs-5053793/v1/c4713043f4d11536da66f13a.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Eye Yoga for Glaucoma: Recovery of Vascular Dysregulation and Visual Field Loss - A Randomized Controlled Trial","fulltext":[{"header":"Introduction","content":"\u003cp\u003eVision loss in glaucoma results from central nervous system damage of the retina, optic nerve and brain, but the prognosis is pessimistic as the associated visual field (VF) loss is considered irreversible and progressive\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Though vision can recover to some extent following IOP reduction\u003csup\u003e\u003cspan additionalcitationids=\"CR4 CR5 CR6 CR7 CR8 CR9 CR10 CR11\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e, vision training\u003csup\u003e\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e or microcurrent stimulation\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e, the mechanisms of recovery are still unclear.\u003c/p\u003e \u003cp\u003eAccording to the \u0026ldquo;residual vision activation theory\u0026rdquo;\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e, vision recovery is explained by synaptic plasticity in the retina and reorganization of brain functional connectivity networks\u003csup\u003e\u003cspan additionalcitationids=\"CR19 CR20 CR21 CR22 CR23\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e which are thought to enhance visual/perceptual processing. But besides \u003cem\u003eneuronal\u003c/em\u003e reorganization we should also consider \u003cem\u003evascular\u003c/em\u003e mechanisms because their role in vision recovery is still unknown.\u003c/p\u003e \u003cp\u003eConventional glaucoma treatment focuses solely on controlling IOP through drugs or surgery. But many patients do not respond well to the treatment, because vision loss progresses despite well-controlled IOP. In line with the principles of Predictive, Preventive, and Personalized Medicine (PPPM), consideration of other individual risk factors such as mental stress versus relaxation is vital for stopping progression and/or inducing restoration and repair.\u003c/p\u003e \u003cp\u003eIt is well known that the vascular state is a key component of glaucoma pathology and other eye and brain disorders\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e,\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. Especially normal tension glaucoma patients suffer from vascular dysregulation (VD) with typically signs or symptoms, collectively termed the \u0026ldquo;Flammer-Syndrome (FS)\u0026rdquo;\u003csup\u003e\u003cspan additionalcitationids=\"CR28 CR29 CR30 CR31 CR32 CR33\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e. The symptoms include cold hands or feet, prolonged sleep onset time, prolonged blood flow cessation in finger capillaries after cooling, autoregulation problems of ocular blood flow (OBF), increased retinal venous pressure with increased vessel stiffness, and altered activity of the autonomic nervous system (heart beat-to-beat variation\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e). It is expected that the resulting microvessel perfusion problems deprive energy-hungry neurons of oxygen and nutrients, disturbing neuronal activity and brain network synchronization which is tightly intertwined with blood flow by \u0026ldquo;neurovascular coupling\u0026rdquo; (NVC)\u003csup\u003e\u003cspan additionalcitationids=\"CR36\" citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e. This energy deprivation impairs neuronal signaling (propagation of action potentials), and visual processing in the retina and/or brain is disturbed or lost. We propose that this \u0026ldquo;hypo-metabolic\u0026rdquo; state may be a primary \u0026ldquo;root cause\u0026rdquo; of neuronal dysfunction in primary open angle glaucoma (POAG) which may either kill neurons in case of no energy supply or only \u0026ldquo;silence\u0026rdquo; neurons which are hypo-metabolic \u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eStress may be one major cause of vasoconstriction. Patients showing Flammer-symptoms of VD tend to have stress prone personality dispositions with low stress resilience, as they are particularly vulnerable to receive bad news that their vision loss progresses which creates even more stress by anxiety and fear of going blind in a down-ward vicious cycle as follows:\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003e \u003cb\u003eStress -\u0026gt;eye muscle tension/vasoconstriction -\u0026gt;silencing neurons -\u0026gt;low vision -\u0026gt; more stress -\u0026gt; \u0026hellip;.. -\u0026gt; more vision loss\u003c/b\u003e\u0026hellip; and so on\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eTo evaluate if mental stress may be a root cause of POAG\u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e, we countered stress by relaxation to learn if this improves vascular health and VF function. Indeed, meditation is already known to reduce IOP, lower stress hormone levels, alter gene expression, and improve quality of life\u003csup\u003e\u003cspan additionalcitationids=\"CR40\" citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e. Even short-term ocular exercises and yoga-based lifestyle intervention lower IOP\u003csup\u003e\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e,\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e. If we gain a better understanding of how IOP, blood flow, and mental stress factors are related we submit that it will help predict and prevent disease progression and develop more personalized treatment plans. As we now show, one-month of stress-reducing relaxation with daily Eye Yoga exercise (EY) (the \u003cem\u003eindependent\u003c/em\u003e variable) can improve vascular health and restore VF function (the \u003cem\u003edependent\u003c/em\u003e variables).\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eExperimental design\u003c/h2\u003e \u003cp\u003eTo participate in our prospective, randomized, double-blind, placebo-controlled clinical trial (flow diagram and study design in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), participants gave written informed consent followed by 1:1 randomized by lot to either EY or \u0026ldquo;active\u0026rdquo; placebo group by the unblinded project manager (L.F.). The local ethics committees approved the study plan in compliance with the Declaration of Helsinki (registered at ClinicalTrials.gov: NCT04037384). Patient recruitment and follow-up were carried out from 8/2019 to 12/2022 with diagnostic evaluations at BASELINE and after the 30-day treatment (POST) by study nurses blinded regarding group identities in Institute of Medical Psychology, Faculty of Medicine, University of Magdeburg, Germany.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e Flow diagram of patient selection and DVA analysis. Of 49 eligible patients, 4 did not meet all inclusion criterion (1 no visual field defect, 2 angle closure glaucoma, 1 unable to read), 1 withdrew during baseline evaluation. During the treatment phase, 4 subjects discontinued for personal problems, therapy change or health problem, 1 subjects lost for Covid-19 and 2 lost contact. In the analysis stage, 8 had poor DVA image quality at baseline or post treatment (7 poor refractive pathway, 1 had sick feeling), 2 excluded for temporarily high BP.\u003c/p\u003e \u003cp\u003eInclusion criteria: residual vision, ability to read, and POAG known for at least 6 months. Exclusion criteria: Cataract, narrow-angle glaucoma, acute autoimmune disease, neurological or mental disease (e.g. epilepsy, schizophrenia, depression), addiction, hypertension\u0026thinsp;\u0026gt;\u0026thinsp;160/100 mmHg, other ocular diseases affecting nerve tissue, pathological nystagmus, unoperated tumors or tumor recurrence, known history of abnormalities in EEG, or signs of photosensitivity, and pregnancy.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003ePatient Sample Description\u003c/h2\u003e \u003cp\u003eBecause there have been no detailed reports on visual field results after EY, we used short-term IOP change after yoga ocular exercise to estimate sample size (IOP decreased from 16.25\u0026thinsp;\u0026plusmn;\u0026thinsp;2.48 mmHg to 14.50\u0026thinsp;\u0026plusmn;\u0026thinsp;2.58 mmHg)\u003csup\u003e\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e. The required sample size was 20 per group (95% confidence level and 90% power). Assuming a 10% drop-out rate we recruited 44 patients (22 per group). Patients were asked to continue their prescribed drugs (no \u0026ldquo;wash-out\u0026rdquo;).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eOutcome Measures\u003c/h2\u003e \u003cp\u003eRetinal vessel regulation and VF function analyses reported here were \u003cem\u003esecondary\u003c/em\u003e outcome measures. The primary outcome criterion (results to be reported elsewhere) was microsaccade dysfunction improvement.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section3\"\u003e \u003ch2\u003eEye Yoga Intervention\u003c/h2\u003e \u003cp\u003eEY is known for thousands of years in Indian Ayurveda traditional medicine, and Chinese \u0026ldquo;ocular gymnastics\u0026rdquo; are still popular today and compulsory for schoolchildren in some Asian cultures. Our patients learned EY before baseline evaluation and were asked to practice daily for 30 days at home (15 min. morning and evening) using an iPod-based audio app which systematically guided them (i) to perform systematic eye movements to stretch their ocular muscles in all directions, (ii) periorbital and facial massage, (iii) iris relaxation in darkness (\u0026ldquo;palming\u0026rdquo;), and (iv) controlled breathing meditation (\u0026ldquo;Pranayama\u0026rdquo;)\u003csup\u003e\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u003c/sup\u003e. Meditation is a well-accepted mind relaxation technique which normalizes stress hormone levels and inflammation markers\u003csup\u003e\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e. Controls were asked to daily read relaxing/entertaining books for 30 min (\u0026ldquo;active placebo\u0026rdquo;).\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eVisual field and intraocular pressure examinations\u003c/h2\u003e \u003cp\u003eVF testing pre- (baseline) and post-intervention was done with Twinfield-2 Perimetry (Oculus/Germany) using 8-pattern setting (0\u0026ndash;30\u0026deg;/66 points; fast threshold strategy; size III/white stimuli). It quantifies age-adjusted global (mean deviation, MD) and local VF defects at each test position (pattern deviation, PD). IOP was measured pre/post intervention (averaged triplicates) with iCare HOME Tonometer (Icare, Vantaa, Finland). To reduce test-retest variability, all VF and IOP measurements were made in the morning, in the same place and in the same sequence. All subjects had a POAG history and experience with repeated IOP and visual field measurement which limits any learning effect confounds.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eDynamic vessel analysis\u003c/h2\u003e \u003cp\u003eRetinal vessels were imaged\u003csup\u003e\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e,\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u003c/sup\u003e in a darkened room with a dynamic vessel analyzer (DVA) (Imedos, Jena, Germany) with blood pressure (BP) before and after DVA and IOP-tests prior and after pupil dilation and after completing DVA. Following the first pupil dilation (Mydriatics 1 ml solution containing 5.0 mg tropicamide, Pharma Stulln GmbH, Germany), the fundus of the central 30 degrees of visual angle was video-recorded with the DVA in each eye compriseing three phases: (i) a 30-s pre-flicker baseline (PFB), (ii) three 20-s stimulation periods of diffuse luminance 12.5 Hz light flickers, and (iii) three 80-s post-flicker periods. Using DVA-software, vessels were analyzed regarding absolute vessel diameters (measuring unit: MU\u0026thinsp;=\u0026thinsp;micrometers in Gullstrand\u0026rsquo;s eye) and dilation dynamics. To establish PFB diameter (100%), the pre-flicker 50-s recordings (including 20s from last post-flicker periods) were pooled and averaged. Based on the diameter response to flickering light, expressed in percentage change over PFB, different parameters were calculated (see Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea for details). DVA measurement was also conducted in the morning to reduce test-retest variability.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e Part A: Parameters of retinal vascular response to flickering light stimulation: \u0026ldquo;maximal dilation\u0026rdquo; (dila%): peak dilatation during a 20 sec. flickering period compared to PFB; \u0026ldquo;time to maximal dilation\u0026rdquo;(tdila): time to peak dilatation after flickering onset; \u0026ldquo;maximal constriction\u0026rdquo; (constr%): peak constriction after flicker onset compared to PFB; \u0026ldquo;time to maximal constriction\u0026rdquo; (tconstr): time to reach peak constriction. Part B and C: compound analysis of retinal vessel tree, visual field function (in dB), determination of branch order for arteries (A1-3) and veins (V1-3). B is an example of a retinal image with a superimposed 8 (0\u0026ndash;30\u0026deg;/66 points) visual field test pattern (retina image resolution: 2,452 \u0026times;2,056 pixels; visual field size: 50\u0026deg;\u0026times;42\u0026deg;). The linear scaling was 2,45/50\u0026thinsp;=\u0026thinsp;49 pixel/degree. The 8 (0\u0026ndash;30\u0026deg;/66 points) visual field pattern (same linear scaling) was centered on the macula and vessel segments were assigned to a nearest PD (vertically flipped to match orientation). This example shows two vessel segments (A1, V1) that were assigned to their nearest PD value (-18dB). Part C: Illustration of branch order analysis showing how branch levels 1\u0026ndash;3 were matched with the visual field defect values: A1 (branch order 1; [BO-1]) was located in the mild defect, A2 (BO-2) in a moderate and A3 (BO-3) in a severely damaged visual field sector.\u003c/p\u003e \u003cp\u003eVessel dynamics was measured in multiple retinal locations to differentiate branch hierarchies (smaller vs. larger vessels) and different VF areas of the intact and damaged eye for mild, moderate, or severe defect depth. Vessel segments were only analyzed if (i) the image had sufficient contrast for artefact free recording, (ii) no crossing, bend, or vessel bifurcation, (iii) located outside a circular area of one disc diameter from the optic disc center, and (iv)\u0026thinsp;\u0026gt;\u0026thinsp;1 vessel diameter distance to neighboring vessels.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eRetinal vessel topography\u003c/h2\u003e \u003cp\u003eTo match VFs with vessels, retina photographs were obtained by fundus camera (50\u0026deg;, Zeiss, Jena, Germany) digitized at 2,452\u0026times;2,056 pixel resolution in a linear scaling of 49 pixels/degree (reference: emmetropic eye). This image was superimposed on the 8-pattern VF-plots of identical scaling (49 pixels/degree) using Photoshop so the VF center could be aligned to the fovea. After vertical flip of the VF chart, the retina fundus image could be matched with the specific PD value (VF depth) and the nearest PD value was selected (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb). Only vessel branch segments were chosen where both baseline and post-treatment PD values were available. We next combined the data of the EY and reading group to calculate the average parameters of three PD sub-groups according to their baseline perimeter results (mild defect \u0026lt; -6 dB, moderate defect \u0026minus;\u0026thinsp;6 to -12 dB and severe defect \u0026le; -12 dB).\u003c/p\u003e \u003cdiv id=\"Sec10\" class=\"Section3\"\u003e \u003ch2\u003eRetinal vessel branch level analysis\u003c/h2\u003e \u003cp\u003eAll vessel segments were classified by branch order (BO): BO-1 are the largest vessels emerging from the papilla; BO-2 those branching off first from BO-1, and BO-3 all those beyond the next bifurcation, i.e. higher-up branches (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ec). Of note, many BO-3 branches were too small (faint) for DVA-detection. To determine how vessel morphology and dynamics relate to VF recovery, we also pooled the data of both study groups and calculated the absolute difference (Δ, pre\u0026ndash;post) of all vessel parameters as a function of PD recovery defined as improvement\u0026thinsp;\u0026gt;\u0026thinsp;3 dB, ie. irrespective of intervention.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eData were analyzed with SPSS 26 (IBM, New York, USA) and Matlab (MathWorks, Natick, USA). Chi-square test was applied for gender analysis, independent-samples T-test for two-group comparisons, and paired-samples T-test for pre- and post-treatment comparison for samples normally distributed. Otherwise, we used Mann\u0026ndash;Whitney U-test for two-group comparisons and Wilcoxon test for pre- and post-treatment comparison. Because our study was of exploratory nature, alpha was not adjusted for multiple comparisons to avoid type-1 errors and vessels were treated as independent samples. MD, IOP and vessel diameter were tested hypothesis-wise (one-sided p-value).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eDemographic parameters, blood pressure, IOP and visual field function\u003c/h2\u003e \u003cp\u003eNineteen patients each in the EY and reading group completed baseline evaluation, but some either did not completed the trial, and in others the DVA-analysis was not possible (see Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Finally, 15 EY and 12 control patients had complete data sets with comparable mean age, gender ratios and BP of both groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Both group\u0026acute;s baseline parameters were similar to those of the lost subjects, except that IOP of lost patients (16.3 [13.8,18.9] mmHg) was significantly higher than those retained (13.6 [12.4,14.7] mmHg), though both were still in the normal range. While after intervention BP was unchanged in both groups, hypothesis-wise testing revealed a significant IOP reduction and improved VF function (MD) only in the EY group but not in the reading group (pre/post 12.8 [10.8, 14.9]/12.8 [10.7, 14.9] mmHg, p\u0026thinsp;=\u0026thinsp;0.465), i.e. 6.4% IOP reduction after EY (pre: 14.1 [12.7, 15.5]; post 13.2 [11.8, 14.7] mmHg; p\u0026thinsp;=\u0026thinsp;0.027). Regarding VF function controls showed a non-significant 4% MD improvement (pre/post 4.7 [2.7, 6.7]/ 4.5 [2.3, 6.7] dB, p\u0026thinsp;=\u0026thinsp;0.217) and EY a significant 24% improvement from 3.3dB [1.3, 5.4] to 2.5 dB [0.4, 4.6] (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ec) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBP, IOP, MD and BO-3 vessel responses\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003enormal\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ereading\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eeye yoga\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003enumber of subjects\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003enumber of eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eage (SD), year\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66.4(8.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e67.1(8.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e62.8(12.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.331\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003egender(female:male)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14:8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4:8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9:6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.168\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003esystolic pressure (SD), mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epre\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e132.1(12.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e130.8(14.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e131.7(14.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.864\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epost\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e128.9(17.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e132.9(14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.516\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ep\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.618\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.654\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003ediastolic pressure (SD), mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epre\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e82.6(8.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e76.3(12.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e80.7(5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.284\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epost\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e73.3(11.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e80.5(6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.067\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ep\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.135\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.872\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eIOP (SD), mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epre\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.3(3.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.8(4.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14.1(3.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.281\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epost\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.8(4.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13.2(3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.733\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ep\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.465\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan type=\"ItalicUnderline\" class=\"ItalicUnderline\" name=\"Emphasis\"\u003e0.027\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eMean Deviation (SD)\u003csup\u003ed\u003c/sup\u003e, dB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epre\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.7(4.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.3(5.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.201\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epost\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.2(5.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.5(5.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.178\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ep\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.217\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan type=\"ItalicUnderline\" class=\"ItalicUnderline\" name=\"Emphasis\"\u003e\u0026lt;\u0026thinsp;0.001\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBO-3 Artery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003evessel number\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003ePattern Deviation(SD), dB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epre\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-2.7(2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan type=\"ItalicUnderline\" class=\"ItalicUnderline\" name=\"Emphasis\"\u003e0.033\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epost\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.8(2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-1.2(4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.296\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ep\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.386\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan type=\"ItalicUnderline\" class=\"ItalicUnderline\" name=\"Emphasis\"\u003e0.012\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eDiameter(SD), MU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epre\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e83.7(12.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e79.7(13.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e79.9(10.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.530\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epost\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e80.4(14.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e82.5(12.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.596\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ep\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.273\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan type=\"ItalicUnderline\" class=\"ItalicUnderline\" name=\"Emphasis\"\u003e0.015\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003edila%(SD), % over baseline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epre\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.6(2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.2(2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.5(4.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.473\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epost\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.9(5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4(3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.106\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ep\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.808\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.820\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003econstr%(SD), %over baseline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epre\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-3.0(2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-3.4(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-3.2(2.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.473\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epost\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-3.6(3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-3.2(1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.615\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ep\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.854\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003etdila(SD), s\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epre\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.3(5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39(5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e42.9(5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan type=\"ItalicUnderline\" class=\"ItalicUnderline\" name=\"Emphasis\"\u003e0.032\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epost\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42.4(5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e42.1(6.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.950\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ep\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan type=\"ItalicUnderline\" class=\"ItalicUnderline\" name=\"Emphasis\"\u003e0.011\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.809\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003etconstr(SD), s\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epre\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46.4(26.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e88.2(30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e84.5(26.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.451\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epost\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e84(30.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e81.4(28.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.733\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ep\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.746\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBO-3 Vein\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003evessel number\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003ePattern Deviation(SD), dB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epre\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.9(3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-2(2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.961\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epost\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-2(6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.7(3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.902\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ep\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.188\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.042\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eDiameter(SD), MU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epre\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e88.1(20.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e84.8(14.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e83.7(12.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.743\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epost\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e82.5(14.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e84(11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.568\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ep\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.065\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.379\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003edila%(SD), % over baseline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epre\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.7(2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.6(2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.7(5.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.215\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epost\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.4(1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.4(4.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan type=\"ItalicUnderline\" class=\"ItalicUnderline\" name=\"Emphasis\"\u003e0.027\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ep\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.181\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.848\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003econstr%(SD), %over baseline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epre\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-2.4(2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-2.8(1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-2.8(1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.528\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epost\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-2.2(1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-3(1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.089\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ep\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.694\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003etdila(SD), s\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epre\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.1(5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41.3(6.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e46.5(4.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan type=\"ItalicUnderline\" class=\"ItalicUnderline\" name=\"Emphasis\"\u003e0.002\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epost\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e43.4(5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e41.8(7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.442\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ep\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.337\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan type=\"ItalicUnderline\" class=\"ItalicUnderline\" name=\"Emphasis\"\u003e0.007\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003etconstr(SD), s\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epre\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47.1(35.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e93(29.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e89.4(32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.894\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epost\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e86.8(33.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e83.8(36.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.697\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ep\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.315\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.639\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003csup\u003ea\u003c/sup\u003eQuoted from our last publication. \u003csup\u003eb\u003c/sup\u003eChi-square test for gender analysis, Mann-Whitney U-test or independent-samples T test for other comparisons between reading and eye yoga groups. \u003csup\u003ec\u003c/sup\u003eWilcoxon test or paired T test for pre- and post-treatment comparison. \u003csup\u003ed\u003c/sup\u003eAbsolute value. Vessel results reported here are only from the smallest measurable microvessels of branch order level 3 (BO-3). MU\u0026thinsp;=\u0026thinsp;measuring unit. 1 MU is approx. 1 \u0026micro;m\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e Part A: Elements of the eye yoga exercises (meditation not shown); Part B: Average of BO-3 artery diameter and its response to flicker light in the eye yoga or reading (control) group; Part C: example of visual field recovery in all four quadrants of an excellent eye yoga responder.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eVascular morphology and dynamics\u003c/h2\u003e \u003cp\u003eWe already reported our baseline data showing vessel diameter shrinkage in glaucoma patients compared to healthy controls\u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e. But unexpectedly, there was no significant difference between those healthy controls and our EY patients (suppl.Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). This could possibly be explained by a sampling bias caused by the limited DVA-optics resolution or loss of small (BO-2/ BO-3) microvessels in the patients.\u003c/p\u003e \u003cp\u003eBO-3 microvessels were of special interest because they are the smallest microvessels still visible and they have the largest surface:volume ratios. This makes them particularly vulnerable to vasoconstriction with the greatest (4th -power) impact on OBF. Hence, subtle microvessel diameter changes (decline or recovery) have the greatest impact on local OBF and neuronal function. Indeed, our analysis revealed no consistent signs of recovery of vessel morphology or dynamics in larger BO-1/BO-2-branches. But post-intervention the tiniest BO-3 EY vessels had significantly increased arterial diameters and faster venous dilation, whereas controls had slower arterial dilation (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWhen matching visual dysfunction (PD) with vascular status, EY patients had significantly improved visual sensitivity in locations where signs of arterial and venous (BO-3) microvessels diameter recovery was observed. The respective visual sensitivity improvement for retinal regions showing recovered arteries was \u0026minus;\u0026thinsp;2.7 [1.6, 3.8] to -1.2 [0.3,2.8] dB (p\u0026thinsp;=\u0026thinsp;0.012) and for veins \u0026minus;\u0026thinsp;2.0 [0.8,3.2] to -0.7,[-1.0, 2.5] dB, p\u0026thinsp;=\u0026thinsp;0.042). While arterial diameter significantly increased after EY from 79.9 [75.9,83.9] to 82.5 [77.9,87.1] MU (p\u0026thinsp;=\u0026thinsp;0.015), the reading group showed no such changes (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003ea). Furthermore, after intervention, time-to-peak dilation was significantly slower in arteries of controls and significantly faster in veins after EY (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eVascular state and visual field defect depth\u003c/h2\u003e \u003cp\u003eWe also studied if vessel state or dynamics vary as a function of VF dysfunction (defect depth) at baseline. When data of both groups was combined there was no apparent recovery in regions of mild impairment (ceiling effect?), but significant VF recovery was observed in regions of moderate and severe of damage (see Suppl.-Table\u0026nbsp;2). Unexpectedly, the vessel parameters were comparable across different VF severity levels.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eComparing vessels in recovered vs. non-recovered visual field sectors\u003c/h2\u003e \u003cp\u003eTo gain insight into vascular mechanisms of vision restoration/recovery, we explored how vascular changes relate to VF recovery of \u0026gt;\u0026thinsp;3 dB gain when the data of all patients were pooled, i.e. irrespective of invention (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). In retinal areas with arterial recovery the respective PD recovery was 6.2 [4.8, 7.6] dB in controls, 7.7 [6.1, 9.2] dB in EY and 7.1 [6.0, 8.1] dB in both groups combined. No such change was noted in regions without arterial recovery (PD values: 0.0 [-0.4,0.4], -1.5 [-2.1, -0.9], and \u0026minus;\u0026thinsp;0.9 [-1.3, -0.5] dB, respectively). VF regions of recovered veins showed similar results (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Recovered VF sectors in EY patients, but not controls, had increased \u003cem\u003earterial\u003c/em\u003e vessel diameters (2.4 [-0.3, 5.3] MU gain) but no change in non-recovered VFs (-0.1 [-0.9,0.7] MU) (p\u0026thinsp;=\u0026thinsp;0.014). \u003cem\u003eVenous\u003c/em\u003e vessel diameters in controls showed a trend of smaller diameters (p\u0026thinsp;=\u0026thinsp;0.053) in recovered fields, whereas EY veins had a trend of enlarged diameters of 1.0 [-1.1,3.0] MU (p\u0026thinsp;=\u0026thinsp;0.076, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eb).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eAdverse events\u003c/h2\u003e \u003cp\u003eBoth treatments were well tolerated without treatment-associated adverse events.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eVessel response in recovered vs. non-recovered visual field sector (\u0026thinsp;=\u0026thinsp;post\u0026ndash;pre)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eΔ\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003erecovered\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003enon-recovered\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArtery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eVessel number\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ereading\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e108\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eyoga\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e152\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epooled\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e260\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eΔPattern Deviation(SD), dB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ereading\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.2(2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(2.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan type=\"ItalicUnderline\" class=\"ItalicUnderline\" name=\"Emphasis\"\u003e\u0026lt;\u0026thinsp;0.001\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eyoga\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.7(3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.5(4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan type=\"ItalicUnderline\" class=\"ItalicUnderline\" name=\"Emphasis\"\u003e\u0026lt;\u0026thinsp;0.001\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epooled\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.1(3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.9(3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan type=\"ItalicUnderline\" class=\"ItalicUnderline\" name=\"Emphasis\"\u003e\u0026lt;\u0026thinsp;0.001\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eΔDiameter(SD), MU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ereading\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-2.2(4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1(5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.188\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eyoga\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.4(6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.1(4.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan type=\"ItalicUnderline\" class=\"ItalicUnderline\" name=\"Emphasis\"\u003e0.014\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epooled\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5(6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.5(5.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.142\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eΔdila%(SD), % over baseline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ereading\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-1.2(3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.1(3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.365\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eyoga\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.3(3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.3(3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.236\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epooled\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.3(3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.2(3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.685\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eΔconstr%(SD), %over baseline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ereading\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.1(2.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.964\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eyoga\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.6(2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.5(2.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.092\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epooled\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.4(1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.3(2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.179\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eΔtdila(SD), s\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ereading\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.3(5.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.5(7.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.282\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eyoga\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.2(7.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.3(7.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.791\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epooled\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.2(6.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.8(7.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.45\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eΔtconstr(SD), s\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ereading\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.4(38.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.6(40.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.928\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eyoga\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-2.8(40.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-3.8(35.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.901\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epooled\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-1.5(39.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-2.5(37.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.571\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVein\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eVessel number\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ereading\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e105\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eyoga\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e139\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epooled\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e244\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003ePattern Deviation(SD), dB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ereading\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.8(3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.1(2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan type=\"ItalicUnderline\" class=\"ItalicUnderline\" name=\"Emphasis\"\u003e\u0026lt;\u0026thinsp;0.001\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eyoga\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.8(2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.2(3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan type=\"ItalicUnderline\" class=\"ItalicUnderline\" name=\"Emphasis\"\u003e\u0026lt;\u0026thinsp;0.001\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epooled\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.1(3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.6(3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan type=\"ItalicUnderline\" class=\"ItalicUnderline\" name=\"Emphasis\"\u003e\u0026lt;\u0026thinsp;0.001\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eDiameter(SD), MU\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ereading\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-2.9(3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.1(7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.053\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eyoga\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(5.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.2(5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.076\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epooled\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.4(5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.1(6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.432\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003edila%(SD), % over baseline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ereading\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.1(2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.2(2.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.603\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eyoga\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.3(2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(3.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.57\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epooled\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.2(2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.1(3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.345\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003econstr%(SD), %over baseline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ereading\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.2(1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.1(1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.973\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eyoga\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.8(2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.1(2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.113\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epooled\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.5(2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.1(2.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.198\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003etdila(SD), s\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ereading\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.3(5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.7(6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.794\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eyoga\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-2.7(6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.2(6.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.497\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epooled\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-1.7(6.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.4(6.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.616\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003etconstr(SD), s\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ereading\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-5.5(47.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-3.5(46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.777\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eyoga\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-1.4(44.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-5(44.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.939\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epooled\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-2.8(45.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-4.3(45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.902\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eΔ\u0026thinsp;=\u0026thinsp;post\u0026ndash;pre. Recovered vessel are those located in visual field sector where Δ Pattern Deviation\u0026thinsp;\u0026gt;\u0026thinsp;3 dB. Non-recovered vessel\u0026thinsp;\u0026le;\u0026thinsp;3 dB. *Mann-Whitney U-test or independent-samples T test for comparisons between reading and eye yoga group.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThough there are only three \u003cem\u003epubmed\u003c/em\u003e-listed EY-studies in glaucoma, there is growing interest in relaxation techniques to lower IOP\u003csup\u003e\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e\u003c/sup\u003e. Following our earlier demonstration that vessel diameters are reduced in POAG-patients which compromises OBF, our study is the first controlled trial showing that EY is safe and effective to lower IOP, normalize VD in microvessels and improve VF function. Though a 3% diameter recovery seems small, according to Poiseuille\u0026rsquo;s law vessel diameter has a 4th -power influence on blood flow. Therefore, an EY-induced 2.5 MU increase in recovered vessels translates to a 12.6% OBF restoration [(100%+3%)\u003csup\u003e4\u003c/sup\u003e-100%=12.6%], i.e. an increase reaching almost the 15% that POAG patient lost compared to healthy controls\u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e. We hypothesize that this normalization of vasoconstriction has a (secondary) down-stream effect of reactivating hypo-metabolic (\u0026ldquo;silent\u0026rdquo;) neurons and provides the biological mechanism of vision restoration.\u003c/p\u003e \u003cp\u003eFrom a basic science perspective, our results confirm the hypothesis that stress should be considered a key \u003cem\u003ecause\u003c/em\u003e, not only an \u003cem\u003eeffect\u003c/em\u003e, of glaucoma and that relaxation is a complementary technique to improve vision. This causality is justified because the independent variable (treatment using relaxation altered the dependend variable IOP, vessel diameter and visual field function. Therefore, the widespread opinion that stress is a \u0026ldquo;non-issue\u0026rdquo; in glaucoma care needs revision for two reasons: firstly, glaucoma patients with VD tend to have personality dispositions of low stress resilience,being worrisome, perfectionistic, ambitious, compulsive and/or neglecting their own needs\u003csup\u003e\u003cspan additionalcitationids=\"CR49\" citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e\u003c/sup\u003e. This, in turn, creates sudden or long-term mental stress triggering a psychosomatic response\u003csup\u003e\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e\u003c/sup\u003e. Secondly, the diagnosis of progressing vision loss triggers a pessimistic life perspective because the continuous anxiety and fear of going blind possibly accelerates progression (\u0026ldquo;dark thoughts - cloudy vision\u0026rdquo;), a downward spiraling (vicious) cycle\u003csup\u003e\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e,\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThat stress negatively impacts all bodily organs is the basis of psychosomatic medicine, and, as we confirm, the eyes are no exception: firstly, stress increases stress hormones such as glucocorticoids\u003csup\u003e\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e\u003c/sup\u003e, pro-inflammatory cytokines\u003csup\u003e\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e\u003c/sup\u003e, and endothelin-1\u003csup\u003e30,56\u0026ndash;58\u003c/sup\u003e, and it reduced nitric oxide (NO)\u003csup\u003e\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e,\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e\u003c/sup\u003e, a vasodilatory neuropeptide lining rich in peri-vascular neurons and in the endothelium. Secondly, stress triggers sympathetic activation, increasing muscle tone (tension/constriction) not only of the perivascular muscles but possibly also of the oculomotor muscles. We submit that chronic vasoconstriction in POAG therefore continuously deprives retinal and brain neurons of oxygen and nutrients, lowering neuronal energy states and reducing visual processing\u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e,\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe most effective, long-known remedy for stress is relaxation. It is not only used for thousands of years in traditional medicine, but many relaxation programs are standard care in psychosomatic medicine, psychotherapy, psychiatry and neuro-rehabilitation. But so far they are not used in standard care of low vision rehabilitation. Our study results confirm the benefits of relaxation techniques (here: eye exercises and meditation) and it provides the biological explanation why vision can be improved or restored: improved vascular regulation and blood flow. This is in line with others showing that yogic ocular exercises lower IOP in the short-\u003csup\u003e\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e and long-term\u003csup\u003e\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e as does breathing (mindfulness) meditation. Indeed, meditation reduces stress- and inflammation biomarkers (cortisol, IL6, TNF-α, ROS), elevates β-endorphins, BDNF, TAC and even alters gene expression\u003csup\u003e\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e,\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eBased on our observations we propose the following two-pronged theory of glaucoma which will require further study: firstly, increased (sympathetic) muscle tension shortens oculomotor muscles, pulling the eyes slightly backward against the eye socket of the skull which, in turn, couldincreases IOP and constricts OBF in the optic nerve head (paling) and choroid, especially when intracranial and optic nerve subarachnoid space pressure is low\u003csup\u003e\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e,\u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e\u003c/sup\u003e. Secondly, stress may increase retinal perivascular smooth muscle tension, adding to the eye pressure-induced vasoconstriction.\u003c/p\u003e \u003cp\u003eThis \u0026ldquo;eyeball-retraction-theory\u0026rdquo; could explain why relaxation by EY is a remedy for glaucoma: stretching the oculomotor muscles during eye movement exercises lowers their tension which has the advantage of lifting the pressure against the choroid, possibly reducing IOP\u003csup\u003e\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e,\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e, normalizing the eye globe\u0026acute;s shape and/or enhances aqueous outflow. Relaxation of the perivascular smooth muscles on the other hand increases vessel diameter, normalizing OBF. This lead us to the proposition that the mechanism of vision restoration after eye yoga is primarily due to vascular recovery. If true, neuronal recovery (neuroplasticity) would only be a secondary effect.\u003c/p\u003e \u003cp\u003eOverall, although further study is needed for confirm the proposed mechanism and long term effect of EY, our study offers a potential avenues for personalized POAG therapy within the framework of PPPM: in contrast to an IOP-centric focus to explain glaucoma, we agree with the proposal of Josef Flammer\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e,\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e that vascular dysregulation or dysfunction is a key mechanism which, according to our own suggestion that mental stress may be the underlying cause\u003csup\u003e\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e\u003c/sup\u003e. We hope that in the future glaucoma treatment will be more tailored to the patients\u0026acute;individual characteristics (blood flow, mental stress, whole body status, lifestyle, environmental factors, etc.) rather than focusing on the one and only risk factor, IOP. It would open the door for a more personalized, holistic approach of preventing progression of vision loss and optimization of restoration and recovery in low vision rehabilitation.\u003c/p\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eLimitations and recommendations:\u003c/h2\u003e \u003cp\u003eThough our study sample is small, yet significant benefits of EY were observed which argues for a strong effect. Furthermore, some of our \u0026ldquo;active control\u0026rdquo; patients showed some vision recovery as well, possibly due to either normal variation, placebo effects, or the (non-specific) benefit of daily \u0026ldquo;time-out\u0026rdquo; relaxation. Whatever the mechanism, relaxation by EY is \u0026ldquo;complementary\u0026rdquo; (not an alternative) to standard IOP management. Future studies could test if EY can increase efficacy of drug therapies and/or improve a more optimistic mental state of mind.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eStress-reducing relaxation by Eye yoga (combined eye exercises and meditation) can normalize vasoconstriction and improve VF in POAG. Though a study with larger sample size is desirable, we recommend that EY (including meditation) can already be adopted in low vision rehabilitation. It is safe and effective to improve visual field dysfunction, possibly slowing down progression. And it may be a useful solution for patients who fail to respond to standard eye care and help achieving PPPM in the management of glaucoma.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCompeting interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eW.Z. and L.F. have no relevant financial or non-financial interests to disclose. B.S. is shareholder of a low vision rehabilitation center offering Eye Yoga and neuromodulation (www.SAVIR-Center.com)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Ethical Committee of Otto-von-Guericke University of Magdeburg, Medical Faculty, Magdeburg, Germany.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants have given their written informed consent to participate in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors approved its final version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data in the present study is available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eW.Z. contributed with study design, data collection, data analysis and manuscript drafting. L.F. contributed to the study design and data collection and data analysis. BS directed the study design, data analysis and interpretation, and obtained funding for the study and helped with manuscript drafting.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding/Support\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe appreciate the generous funding support \u0026nbsp; by the Velux Foundation (#1359). The author Wanshu Zhou was supported by a scholarship from China Scholarship Council (201908080281) and a scholarship from LOM program of the University of Magdeburg (#485).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRole of the Sponsor\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdditional Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSandra Heinrich and Eileen Johnsen assisted in recruiting and some of the testing of the patients.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eChen PP. 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Pressure balance and imbalance in the optic nerve chamber: The Beijing Intracranial and Intraocular Pressure (iCOP) Study. \u003cem\u003eSci China Life Sci. \u003c/em\u003e2016;59(5):495-503.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"epma-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"epmj","sideBox":"Learn more about [EPMA Journal](https://www.springer.com/journal/13167)","snPcode":"13167","submissionUrl":"https://submission.nature.com/new-submission/13167/3","title":"EPMA Journal","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Eye yoga, glaucoma, vision restoration, vision loss, retinal vascular dysregulation","lastPublishedDoi":"10.21203/rs.3.rs-5053793/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5053793/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBecause stress can aggravate primary open angle glaucoma (POAG) progress, we studied if stress reduction by eye muscle exercises and meditation (Eye Yoga, EY) and can normalize VD, intraocular pressure (IOP) and visual field (VF) function as a complementary, personalized approach of eye care.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatients and Methods:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePOAG patients were randomized 1:1 to an EY (n = 15) or control group (n = 12). While EY was practiced daily for one hours for one month at home using an iPod-audio guide, control patients read daily relaxing books. Outcome criteria were IOP, retinal vessel dynamics and VF recovery.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter intervention, EY patients, but not controls, showed a 6.4% IOP reduction (p = 0.027). This was associated with VF improvement (mean deviation) which were greater in EY than controls (p \u0026lt; 0.001). Furthermore, in EY, but not controls, pattern deviation recovered in VF regions where microvessel (third order-branch) vasoconstriction improved (artery: p = 0.012; vein: p = 0.042) and EY mean artery diameter recovered significantly (p = 0.015). When pooling data of both groups, recovered VF regions, but not non-recovered fields, showed significantly larger arterial diameter gains (2.4 [-0.3-5.3] MU). Neither treatment had any adverse events.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBecause EY is able to reduce vasoconstriction and improve VF function in POAG confirms the hypothesis that mental stress is a contributing, or even key mechanism of POAG, and improved blood flow a fundamental mechanism of vision recovery and restoration. Daily eye yoga home-exercises are a safe and effective complementary PPPM method which can be easily adopted for POAG care.\u003c/p\u003e\n\u003cp\u003eTrial Registration clinicaltrials.gov (NCT04037384)\u003c/p\u003e","manuscriptTitle":"Eye Yoga for Glaucoma: Recovery of Vascular Dysregulation and Visual Field Loss - A Randomized Controlled Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-21 06:31:45","doi":"10.21203/rs.3.rs-5053793/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-09-26T12:47:30+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-25T15:56:09+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-23T19:27:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"254307472282160722287832697759764655166","date":"2024-09-15T17:04:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"126311983822038300652820154672697829227","date":"2024-09-15T16:47:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"129428685699567905889449358691623955847","date":"2024-09-14T12:49:49+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-09-13T15:05:09+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-09-13T14:58:01+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-09-09T14:01:53+00:00","index":"","fulltext":""},{"type":"submitted","content":"EPMA Journal","date":"2024-09-08T17:55:51+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"epma-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"epmj","sideBox":"Learn more about [EPMA Journal](https://www.springer.com/journal/13167)","snPcode":"13167","submissionUrl":"https://submission.nature.com/new-submission/13167/3","title":"EPMA Journal","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"79774538-e7db-43ad-b5ed-b2d2f3d270e0","owner":[],"postedDate":"November 21st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-12-23T16:05:48+00:00","versionOfRecord":{"articleIdentity":"rs-5053793","link":"https://doi.org/10.1007/s13167-024-00389-x","journal":{"identity":"epma-journal","isVorOnly":false,"title":"EPMA Journal"},"publishedOn":"2024-12-19 15:58:30","publishedOnDateReadable":"December 19th, 2024"},"versionCreatedAt":"2024-11-21 06:31:45","video":"","vorDoi":"10.1007/s13167-024-00389-x","vorDoiUrl":"https://doi.org/10.1007/s13167-024-00389-x","workflowStages":[]},"version":"v1","identity":"rs-5053793","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5053793","identity":"rs-5053793","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}