Direct crosstalk between adult human retinas as suggested by interocular transfer of neurovascular coupling through photic stimulation

Direct crosstalk between adult human retinas as suggested by interocular transfer of neurovascular coupling through photic stimulation | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Direct crosstalk between adult human retinas as suggested by interocular transfer of neurovascular coupling through photic stimulation João Jordão, João Figueira, Miguel Morgado, Pedro Guimarães, Pedro Serranho, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5661001/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 21 Apr, 2025 Read the published version in Scientific Reports → Version 1 posted 11 You are reading this latest preprint version Abstract Crosstalk mechanisms between retinas were never documented in humans despite being documented for several other species, including non-human primates. Here, we report the results of the first-in-human study that documents the crosstalk between retinas by measuring the vascular response in one retina to the photic stimulation of the contralateral eye in health and disease. We developed a stimulation apparatus and integrated it into an adaptive-optics fundus camera to image 32 healthy control (HC) subjects and 20 type 1 diabetes mellitus (DM) patients. We documented both the ipsilateral and the contralateral neurovascular coupling effect and established criteria to consider an actual response to find positive and negative responses. Ten (31.2%) and two (6.2%) subjects of the HC group presented contralateral positive and negative responses, respectively, and three (15.0%) positive and four (20.0%) negative responses were found for the DM group. Also, statistically significant differences in the ipsilateral and contralateral responses were found for the HC group, rejecting the null (non-response) hypothesis. This finding raises the need to revisit the current knowledge of neurovascular coupling mechanisms and the association between its dysregulation and neurological disorders. Further studies involving distinct populations and imaging centers are necessary to validate the findings herein. Biological sciences/Physiology/Circulation/Vasodilation Health sciences/Anatomy/Nervous system/Central nervous system Health sciences/Biomarkers Physical sciences/Engineering/Biomedical engineering Neurovascular Coupling Circulation Central Nervous System Retina Functional Imaging Flicker-induced hyperemia Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Introduction The complexity of the human central nervous system (CNS) is undisputable and broadly recognized. Also, any change in it has a potentially massive impact on people's daily lives. Therefore, specific knowledge of the CNS function and arrangement is paramount and attracts a substantial research focus. Unveiling new communication channels across its different parts will bring additional insight into this fundamental system. Neurovascular coupling (NVC) is a well-established effect in which the CNS reacts to stimuli by increasing the local blood flow to satisfy the elevated demand for oxygen due to the increased activity, a fundamental task as the CNS lacks a fuel reservoir to suppress energy needs [ 1 ]. Roy and Sherrington [ 2 ] initially noted this effect, which has been further demonstrated in the brain and the retina across species [ 3; 4 ]. Despite its fundamental role and the fact that its impairment has been associated with a variety of disorders, including glaucoma, macular degeneration, Alzheimer's disease, cognitive dysfunction, and diabetes [ 1 ], the complete NVC mechanism is still not fully understood. In this work, we aim to demonstrate the existence of a functional crosstalk mechanism between human retinas in the adult and in vivo. Demonstrating a vascular response in the retina to stimuli of the contralateral eye and the distinct responses in health and disease support the crosstalk mechanism and add to current knowledge on the NVC mechanism. Moreover, it paves the way for further discoveries and the use of NVC to detect, assess, and monitor vascular-associated diseases. However, the distant modulation of the vascular network, particularly concerning the communication between retinas, implies a long communication channel yet to be documented. While the extensive innervation of the vascular network [ 5 ] did not raise any questions on the NVC existence in the brain, mechanisms of autoregulation control in the retina are still poorly understood [ 6; 7; 8; 9 ]. Also, the support for local neural control came from the comparison with the brain [ 10 ]. The demonstration of the NVC coupling did not come without discussion. In [ 11 ], the authors stated that all techniques measure distinct parts of the complex nature of the blood flow and, therefore, reaction to metabolic demands depends on the region observed. Moreover, the numerous mechanisms involved in vessel diameter regulation represent a complex closed-loop biological control system. The limits of innervation of the vascular network in the eye [ 7 ] are still based on the works of Ehinger and Laties [ 12; 13 ]. The innervation of the central retinal artery (CRA) is dense along its course within the optic disc, but vessels in the retina "almost completely lack extrinsic innervation" [ 14 ]. On the other hand, the concept of intrinsic innervation has been proposed repeatedly [ 15 ]. Whether arterioles are the primary site of blood flow regulation remains to be determined in the brain. During neurovascular coupling, the local dilation of arterioles in an activation area will not substantially increase blood flow unless upstream vessels also dilate. How vasodilator and vasoconstrictor responses are conveyed to upstream locations is unclear [ 16 ]. The same question can be raised for the retina, and the answer may rely on coupling and communication between cells within the vessel wall. Indeed, through gap junctions between adjacent vascular smooth muscle cells, the brain's intramural propagation of vascular signals produces remote vasodilatation of upstream pial arterioles [ 17; 18 ]. The retinal crosstalk in the mammalian visual system is demonstrated in [ 19 ]. In this work, the authors illustrate the presence of direct communication between the eyes of adult mammals (rats) able to change retinal activity and leave the door open for this effect in other species. While anatomical evidence for cortico-retinal and retino-retinal projections is substantial [ 19 ], there is a lack of physiological evidence for the human species. The standard view of the adult visual system stipulates that the axons of retinal ganglion cells (RGC) exit the eye to form the optic nerve, with nasal fibers projecting along the contralateral optic tract and temporal fibers along the ipsilateral optic tract to the lateral geniculate nucleus (LGN) and other brain areas. Nevertheless, a diversity of connections exists during embryogenesis and early development but are pruned to form the mature pathway [ 20; 21; 22 ]. Anatomical studies that have started with the work of Santiago Ramón y Cajal have shown that the optic nerves of adult mammals, including humans [ 23 , 24 ], contain sparse populations of efferent fibers. These originate from multiple locations, including the brain stem and hypothalamus [ 25 , 26 , 27 , 28 ] and the contralateral eye in young mice [ 29 ]. As a matter of fact, "the existence of neurons extending from one retina to the other has been reported during the perinatal development in different vertebrates" [ 29 ]. Although initially believed to be artifacts or misprojections, their presence was unequivocally demonstrated for a small subset of RGC in mice [ 29 ]. The efferent fibers branch in the eye covers approximately a quarter of the retinal surface [ 27 ]. Their branches terminate in the inner and outer plexiform layers (IPL, OPL), inner nuclear layer (INL), and ganglion cell layer (GCL) depending on fiber type [ 24 , 30 , 31 , 32 ]. Hence, even few, there may be retinal efferent fibers in adult mammals with potential impact on several mechanisms, control, and function. While the efferent innervation of the retina has now been widely documented in rodents and other animals [ 33 ], the existence and function of an efferent system in humans and non-human primates remains to be definitively established. Yet, their presence (efferent innervation, not retina-retina fibers) is strongly suggested based on non-tracing and tracer methods/immunohistochemistry for Chimpanzees, Macaca mulatta, Saimiri sciureus, Macaca fascicularis, Macaca nemestrina, Papio anubis, and Cebus paella [ 33 ]. Concerning humans, all anatomical evidence was generated from autopsy cases or eyes removed during surgery. Morphological studies of an enucleated eye, ten days after complete occlusion of the CRA, showed that all ganglion cells and afferent neurites had degenerated. In contrast, all of the presumed efferent nerves with their cell bodies in the brain were still present in the optic disc [ 33 ]. In the present study, an adaptive-optics (AO) fundus camera (rtx1) from Imagine Eyes (Imagine Eyes, Orsay, France) was used to scan the retinas of a group of healthy controls and a group of type 1 diabetes mellitus (T1DM) patients. The camera was equipped with an in-house built apparatus to stimulate the non-imaged eye synchronously with the acquisition of fundus images to document the contralateral response. The gathered data show the vascular response in the imaged eye to the stimulus of the contralateral eye and a distinct response pattern of the diabetic group from that of the healthy group, therefore supporting the presence of a functional crosstalk mechanism between retinas never documented in the human species. Methods Neurovascular coupling is the alteration in local perfusion in response to changes in energy demands due to neuronal activity. To quantify it, the variation in vessel lumen at the same vessel section, before and after stimulation, is measured and then expressed as a percentage (% var). This method disregards differences in vessel calibers, facilitating comparisons across various subjects. Instrumentation: An rtx1 adaptive-optics fundus camera from Imagine Eyes was used to gather data in this work. The camera system utilizes an en-face reflectance imaging method. It captures images in the near-infrared spectrum (850 nm) using a charge-coupled device (CCD) sensor with low noise and an exposure time of less than 10 ms. It allows for the acquisition of 4x4 degree field-of-view (FOV) images of the ocular fundus (1.2x1.2 mm 2 FOV, 1500x1500 pixels image) with high resolution (2 microns, 250-line pairs per millimeter) [ 34 , 35 ]. The rtx1 acquires images with or without stimulating the imaged retina. It allows for different acquisition timings: temporarily overlapping the stimulation, after the end of stimulation, or with a defined delay after stimulation. The adaptive optics control is fully automatic and corrects for blinking and saccades. The camera can compensate for refractive errors ranging from − 12 D to + 6 D, making it suitable for most individuals. Additionally, as an add-on for this study, the rtx1 outputs two 3.3 V digital trigger signals, one enabled during fundus acquisition and the other triggering the flicker stimulation. The rtx1 light flicker stimulus is based on an internal OLED micro-display panel configured to deliver yellow light with a peak wavelength of 570 nm. Henceforth, the flicker of the rtx1 system will be referred to as the " internal flicker. " To establish the presence of a crosstalk mechanism, the NVC effect is assessed in the imaged eye in response to the stimulation of the contralateral one. Custom in-house developed hardware composed of a light source and control system was fully integrated into the rtx1. It synchronizes with the acquisition through the rtx1-trigger signals mentioned above. The apparatus and its parts can be seen in Fig. 1 . The prototype developed for stimulating the non-imaged retina will be referred to as the " external flicker. " This prototype consists of two modules, one for inputting trigger signals and the other for controlling the light flickers (Fig. 1 ). For details, see [ 36 ]. The external stimulation was set up with two arrays of seven individually addressable red, green, and blue light-emitting diodes (RGB LED), one for each eye, to allow studying the contralateral effect in the left or right eyes. The irradiance of the external device was measured using a calibrated SR900 spectrometer (Opsytec Dr. Gröbel, Ettlingen, Germany) to ensure it meets the International Commission on Non-Ionizing Radiation Protection (ICNIRP) guidelines concerning eye exposure limits in conditions of ophthalmic examination [ 37 ]. Nevertheless, the LEDs' maximum irradiance was limited in firmware to ensure that a possible communication error would not override settings and exceed exposure limits. The RGB LEDs were configured to achieve a perceived dark yellow color matching the rtx1 internal one. The external device and the rtx1 are controlled using a custom-developed software application written in C++. The control software integrates with the existing rtx1 software and allows the user to specify the settings for both the rtx1 camera and the external flicker module, namely the duration, flickering frequency, and intensity parameters of the stimuli. Study design and participants: All subjects were instructed not to drink coffee on the day of the examination, and all subjects fulfilled the inclusion and exclusion criteria defined as: - Inclusion criteria: • aged 18 to 60, inclusive; • best corrected visual acuity equal to or over 69 letters (20/40 Snellen scale); • refractive spherical equivalent between − 6 and + 5 diopters; • type I Diabetes Mellitus (for the patient group); • level 10 of the ETDRS-DRSS scale (for the patient group); • demographic matching with the patient group (for the healthy group). - Exclusion criteria: • any ocular diseases that may interfere with the examination of the study eye; • presence of a history of glaucoma; • pupillary dilation below 5 mm in the study eye; • ocular inflammation, conjunctivitis, or any history of uveitis in the study eye; • signs or history of diabetic macular edema (for the patient group); • signs or history of retinal vascular disease or neurodegenerative disease, including hypertensive retinopathy in the study eye; • only one functional eye; • any previous intravitreous treatment; • any previous laser treatment in the retina; • any ocular surgery in the past 6 months before enrollment in the study; • any signs of arterial obstructive disease; • any history of thromboembolic events; • history of central nervous system disorders, neurodevelopment disorders, psychiatric disorders, or auditory or visual deficits; • pregnant or breastfeeding women; • history of alcohol or drug abuse. The dataset used in this cross-sectional study consists of 32 healthy control subjects (19 females and 13 males, 17 left/15 right eyes, age range: 19–55 years, median 28.5 years, m(sd): 32.7(10.5) years), and 20 type 1 diabetic patients with no signs of diabetic retinopathy (10 females and 10 males, 10 left/10 right eyes, age range: 20–57 years, median 32.0 years, m(sd): 35.0(12.3) years, HbA 1C range: 5.8–7.9%, median 6.8%, m(sd): 6.9(0.5)%). All subjects presented a best-corrected visual acuity (BCVA) of 0.00 (logMAR) and an intraocular pressure (IOP) of the imaged eye ranging from 10 to 23 mmHg (m(sd): 15.8(3.6) mmHg) and an IOP of the contralateral eye ranging from 10 to 23 mmHg (m(sd): 15.8(3.6) mmHg). Blood pressure (BP) ranges from 90 to 139 mmHg (m(sd): 116.0(11.3) mmHg) and from 59 to 93 mmHg (m(sd): 73.0(8.1) mmHg), respectively for the systolic and diastolic BP, and was measured for all but the initial 12 healthy controls (HC01 to HC12). All participants provided written informed consent for the study, which was conducted in accordance with the Declaration of Helsinki and its subsequent revisions. Additionally, ethical approval (CE-039/2023) was obtained from the ethics committee of the Faculty of Medicine of the University of Coimbra. All patients are regularly followed at the ophthalmology department following the standard protocol for type I diabetic patients and underwent a complete ophthalmic examination at the ophthalmology department of the Coimbra University Hospital before enrollment in the study, which included a slit lamp exam, widefield fundus photography, OCT (Optical Coherence Tomography)(macular and optic disc protocols), OCT-A (OCT – Angiography), and best corrected visual acuity. Besides these data, all patients were checked for the inclusion and exclusion criteria and collection of demographics and anthropometric data, heart blood pressure and metabolic status, hormonal status, relevant family history, medication, and life habits prior to the enrollment in the study. Only one eye per subject was considered (imaged), selected per group alternatively between the right and left eye at the study enrollment. The experimental procedure begins with measuring the intraocular pressure and applying tropicamide-based mydriatic eye drops to promote mydriasis and cycloplegia. Two acquisition modes were used: the baseline mode, in which image acquisitions were performed without being preceded by any stimulation, and the stimulation mode, in which image acquisitions immediately follow a stimulation of 20 seconds of flicker light at 15 Hz. For both modes, image acquisition lasted 2 seconds. After the full dilation, following the application of mydriatic eye drops and keeping subjects in the imaging room in dark conditions, the selected subject's eye was imaged three times without stimulation ( Basal 1 ) and immediately imaged three times following the contralateral stimulation ( Contra ) using the external stimulator. A waiting time of 5 minutes before the next sequence was set to allow the neurovascular coupling to return to a stable state. After that, three acquisitions were performed without any stimulation ( Basal 2 ) immediately followed by three acquisitions following the ipsilateral stimulation ( Ipsi ) using the rtx1 internal flicker (Fig. 2 ). All acquisitions were performed at an artery as close as possible to the subject's fovea, and all acquisitions of the same subject were performed at the same location where the selected artery presents a well-defined lumen and walls. The imaging room was kept in dark conditions for the entire duration of the subject’s study. Data analysis: All acquired images were exported for further processing. A grader manually segmented a vessel portion using custom-made software allowing to zoom in and out, image panning, and mouse pointing at rtx1 images to define the vessel lumen. All 12 images (three images per acquisition type: Basal 1, Contra, Basal 2, and Ipsi) were individually segmented by the same grader. Image examples and respective segmentation can be seen in Fig. 3. One independent grader assessed all segmentations, and another assessed segmentation by sampling the dataset. A binary mask was defined based on the lumen segmentation, and the vessel centerline was determined from the mask. The same vessel segment limits were used across all images per eye. Per image, the lumen width was defined as the ratio of the area to the length of the segment (length of the centerline), obtaining an estimate of its average in pixels. The lumen width for each acquisition type was defined as the maximum of the respective three consecutive scans. Each subject has, therefore, four measures of the vessel lumen at the same location. The respective NVC response is defined as the percentage of the relative variation between the lumen values for the baseline and the ones following the stimulation, therefore allowing the comparison of the responses for the different subjects/eyes. The contralateral and the ipsilateral responses are computed as %var contra = 100*(lw contra – lw basal1 )/lw basal1 and %var ipsi = 100*(lw ipsi – lw basal2 )/lw basal2 , respectively, where lw stands for lumen width. A non-parametric Wilcoxon test for pairwise samples was performed to test whether significant contralateral and ipsilateral responses were found in the healthy group. Also, for both groups, a set of criteria was established to define an individual relevant contralateral response: C1 only cases where the lumen's width following a contralateral stimulation was either both over basal1 and basal2 lumens (positive response) or under basal1 and basal2 lumens (negative response); C2: the minimum variation to any of the basal1 or basal2 should be over 10% of the maximum variation to any of these; C3: the contralateral response should exceed 50% of the minimum ipsilateral response for the entire group; C4: the contralateral response should be over 1% or exceed 50% of the respective ipsilateral response. Results Raw data can be seen in Table 1 and Figs. 4 and 5 . Table 1 Raw data and subject characterization. HC – healthy controls; T1DM – type 1 diabetes mellitus; M/F – male/female; OD/OS – right/left eye; BP – blood pressure; IOP – intraocular pressure; Basal 1/2 – acquisitions without stimulation; Contra/Ipsi – acquisition after contralateral/ipsilateral stimulation; NA – not available. ID Type Sex Age (years) BP (mmHg) HbA 1C (%) Menopause Imaged Eye IOP [mmHg] Lumen width (pixels) Imaged Eye Contralateral Eye Basal 1 Contra Basal 2 Ipsi HC01 HC F 39 NA NA No OS 15 16 119.8 119.1 119.0 120.1 HC02 HC F 33 NA NA No OD 11 11 49.4 49.9 50.3 51.0 HC03 HC F 27 NA NA No OS 21 21 86.9 84.5 86.7 92.9 HC04 HC M 22 NA NA -- OD 20 20 104.4 105.0 106.3 109.3 HC05 HC M 26 NA NA -- OS 22 22 78.7 79.9 77.2 80.2 HC06 HC F 33 NA NA No OD 15 16 89.0 89.9 89.1 91.5 HC07 HC F 30 NA NA No OS 10 13 105.6 108.2 104.9 108.8 HC08 HC F 24 NA NA No OD 15 15 80.9 85.6 84.7 88.1 HC09 HC F 35 NA NA No OS 15 13 51.8 51.9 52.4 55.1 HC10 HC F 25 NA NA No OD 19 19 84.0 85.2 84.6 86.0 HC11 HC F 23 NA NA No OS 18 15 93.8 93.3 90.1 98.8 HC12 HC M 35 NA NA -- OD 20 20 70.9 73.7 71.7 75.8 HC13 HC F 19 122/59 NA No OS 18 18 75.7 76.4 75.2 78.4 HC14 HC M 24 123/80 NA -- OD 16 16 96.6 97.4 95.7 98.3 HC15 HC F 24 110/80 NA No OS 20 20 94.1 95.2 93.6 94.9 HC16 HC M 24 128/65 NA -- OD 18 20 96.9 96.0 99.1 99.4 HC17 HC F 24 116/73 NA No OD 23 23 76.0 76.2 76.6 77.9 HC18 HC M 52 120/88 NA -- OS 20 20 72.4 73.3 71.4 77.0 HC19 HC F 24 116/73 NA No OD 20 20 75.3 74.2 74.3 78.0 HC20 HC F 52 103/68 NA No OD 10 10 82.8 83.4 82.8 84.4 HC21 HC F 54 130/79 NA No OS 14 13 71.9 74.2 75.4 78.2 HC22 HC M 25 98/63 NA -- OD 15 15 53.7 54.2 55.1 56.9 HC23 HC M 41 121/73 NA -- OS 10 11 102.8 104.3 95.6 104.5 HC24 HC M 21 124/80 NA -- OD 12 12 83.6 83.5 84.6 90.0 HC25 HC F 44 126/73 NA No OS 12 12 63.0 63.6 64.4 64.0 HC26 HC F 45 102/65 NA No OD 11 10 104.0 104.1 103.2 104.0 HC27 HC F 39 108/68 NA No OS 15 15 82.2 82.4 81.2 82.9 HC28 HC F 24 114/62 NA No OS 13 13 102.5 101.6 102.0 105.7 HC29 HC M 40 110/73 NA -- OS 11 11 64.5 65.1 65.1 66.1 HC30 HC M 55 110/70 NA -- OS 12 12 82.6 82.9 82.4 83.3 HC31 HC M 24 120/88 NA -- OS 12 13 88.8 86.1 85.6 91.8 HC32 HC M 38 102/63 NA -- OD 10 10 89.7 90.2 88.4 89.6 DM01 T1DM F 45 90/66 6.7 Yes OD 17 17 66.3 66.1 66.0 66.1 DM02 T1DM M 24 120/75 6.4 -- OS 16 16 84.7 87.4 86.3 88.3 DM03 T1DM M 51 116/76 5.8 -- OD 14 14 120.5 122.6 122.7 122.9 DM04 T1DM M 42 120/60 5.8 -- OS 16 16 80.1 76.7 79.6 81.6 DM05 T1DM M 57 118/74 6.6 -- OD 14 14 78.7 78.4 79.0 81.9 DM06 T1DM M 57 127/79 7.4 -- OS 16 14 72.0 70.7 70.5 72.5 DM07 T1DM M 22 122/74 6.7 -- OD 18 18 90.8 90.7 92.0 91.6 DM08 T1DM F 42 123/93 6.8 No OS 12 12 72.0 72.3 70.1 76.0 DM09 T1DM F 28 96/71 6.9 No OD 15 14 85.7 85.0 83.8 85.7 DM10 T1DM F 22 112/67 7.4 No OS 20 20 82.7 82.3 83.3 85.2 DM11 T1DM F 21 105/86 6.7 No OD 20 20 111.7 110.7 112.3 112.5 DM12 T1DM F 47 121/73 7.9 No OD 19 19 77.7 78.0 78.1 79.6 DM13 T1DM M 25 117/68 6.8 -- OS 20 20 55.7 56.9 56.1 56.5 DM14 T1DM M 25 132/63 7.6 -- OD 21 21 82.9 82.4 82.7 82.5 DM15 T1DM M 27 139/72 6.8 -- OS 16 16 103.4 102.8 103.9 106.7 DM16 T1DM M 44 136/86 7.6 -- OD 16 15 92.5 92.3 91.3 92.6 DM17 T1DM F 36 98/76 6.7 No OS 15 18 60.1 60.4 59.4 61.3 DM18 T1DM F 42 131/80 6.8 No OS 14 14 82.9 83.8 83.3 83.8 DM19 T1DM F 20 113/68 7.3 No OD 21 20 108.6 107.8 107.2 106.0 DM20 T1DM F 24 103/69 7.2 No OS 10 10 101.5 99.2 100.1 101.1 For the healthy control group, a statistically significant difference is found between the contralateral and ipsilateral NVC and the previous basal state, respectively, p = 0.027 and p < 0.001 (Wilcoxon test), rejecting the null hypothesis of no response in both cases. Of the 32 healthy controls, 24 (75.0%) presented a contralateral positive response (please note the marginal positive response of the HC09 subject). Twenty subjects (62.5%) verified criteria C#1 to C#3 (Fig. 6 ). Twelve healthy controls (37.5%) verified criteria C#1 to C#4, ten subjects (83.3%) presented positive contralateral responses, and two individuals (16.7%) presented negative contralateral responses (Fig. 7 ). For the diabetic group, 13 individuals (65.0%) presented a negative contralateral response (Fig. 5 ). Twelve subjects (60.0%) verified criteria C#1 to C#3 (Fig. 8 ). Seven subjects (35.0%) verified criteria C#1 to C#4, three with a positive and four with a negative contralateral response (Fig. 9 ). These results support the NVC reflex in response to the stimulation of the contralateral eye, with 12/32 (37.5%) healthy controls and 7/20 (35.0%) type 1 diabetes mellitus patients fulfilling the established criteria, implying a response followed by a return to the baseline condition. Discussion For the first time, we have imaged the human retina with an adaptive-optics fundus camera equipped with an external stimulation apparatus to allow the photic stimulation of the contralateral eye. The same eye of each subject was imaged first without being stimulated (basal measurement) and after the stimulation of the contralateral eye. After a period of 5 minutes, the same eye was imaged again, without being stimulated (new basal) and after its ipsilateral stimulation. The same vessel portion was analyzed by segmenting the vessel's lumen. The average lumen width for each of the four scenarios was computed, and the response to the stimulus was determined as the percentage of variation in the lumen width in relation to the respective basal value to account for temporal variations in the basal lumen. We have shown that there is a response to the contralateral stimulation by demonstrating that the computed variation in lumen obeys several criteria (for the healthy and patient groups) and has a statistically significant difference from the null hypothesis (no response) for the healthy control group. How the information propagates from one eye to the other is still unknown. However, a mechanism similar to the one in the brain, where through gap junctions between adjacent vascular smooth muscle cells the brain's intramural propagation of vascular signals produces remote vasodilatation of upstream pial arterioles [ 17 ; 18 ], associated with the dense innervation of the CRA and the local propagation of vasodilatory signals, suggest this as a potential mechanism for the contralateral NVC effect in the retina. In addition to demonstrating the crosstalk between adult human retinas, we have shown the mechanism is present both in health and disease (type 1 diabetes). Our results also suggest a different response pattern in the patient group. The main strengths of this study were the use of detailed ophthalmic imaging and the demonstration of the statistically significant difference for the contralateral stimulation in the adult healthy population, in vivo and non-invasively, through the direct evaluations of the change in the vessels' lumen. Nevertheless, there are some limitations to our study. First, this cross-sectional study has a limited sample size. Second, the study sample might not adequately represent other populations where different response patterns can exist. Additionally, a different set of operating parameters, e.g., stimulation period, a time gap between the stimulation and acquisition, or the acquisition while still stimulating, different stimulation intensities, may show an increased contralateral response. However, for the sake of demonstration of a working mechanism in the adult human retina, the system configuration used proved to be adequate, and the novel findings shed new light on the NVC mechanism, a significant breakthrough because existing NVC models do not consider the demonstrated effect and may need to be revisited. Demonstrating these effects in a larger population and across different imaging centers is paramount, as well as assessing the pattern of response for several disorders, particularly those known to be associated with vascular changes, including Alzheimer's disease, cognitive dysfunction, and diabetes. This study's findings are still far from an immediate application in clinical practice, and further studies involving several distinct populations are necessary. However, the prospects for new biomarkers of disease onset, progression, or staging seem to be waiting to be discovered. Conclusion We present evidence on the crosstalk between adult human retinas through the modulation of vessels' width in response to the photic stimulation of the contralateral eye. Our results also suggest that this crosstalk mechanism may be modified in type 1 diabetes mellitus patients and may be a biomarker of initial changes not identified by current methods. Declarations Conflict of interest: The authors declare that the research was conducted without commercial or financial relationships that could be interpreted as a potential conflict of interest. Supplementary material: The Supplementary Material for this article can be found online at: xxxx Funding: This study was supported by The Portuguese Foundation for Science and Technology (FCT) through the 2022.07585.PTDC project (DOI: 10.54499/2022.07585.PTDC ), UI/BD/154285/2022 (Ph.D. grant), FCT/UIDB/4950/Base/2020 (DOI: 10.54499/UIDB/04950/2020 ) and FCT/UIDP/4950/Programatico/2020 (DOI: 10.54499/UIDP/04950/2020 ). Author Contribution JJ: Software, Hardware, Formal analysis, Validation, Writing – first draft & review. JF: Subjects inclusion/exclusion criteria, Methodology, Formal analysis, Validation, Writing – review. MM: Methodology, Hardware, Formal analysis, Validation, Writing – review & editing. PG: Formal analysis, Validation, Writing – review & editing. PS: Formal analysis, Validation, Writing – review & editing. DCF: Subjects inclusion/exclusion criteria, Methodology, Formal analysis, Validation, Writing – review. DCD: Methodology, Formal analysis, Validation, Writing – review & editing. MC-B: Subjects inclusion/exclusion criteria, Methodology, Formal analysis, Investigation, Validation, Writing – review & editing, Funding acquisition, Resources. MP: Subjects inclusion/exclusion criteria, Methodology, Formal analysis, Validation, Writing – review & editing. RB: Conceptualization, Project administration, Supervision, Subjects inclusion/exclusion criteria, Methodology, Software, Hardware, Formal analysis, Validation, Writing – review & editing, Funding acquisition, Resources. Acknowledgement We are grateful to Nuno Gouveia and Ana Luís Carreira for identifying patients, Hugo Quental and Sílvia Simão for all data acquisitions, Joana Domingues for handling all subjects and segmenting all images, and Sérgio Rodrigues for his collaboration in developing the segmentation tool used in this work. Data Availability The raw data supporting the conclusions of this article will be made available by the authors upon formal and reasonable request. References Iadecola, C. The Neurovascular Unit Coming of Age: A Journey through Neurovascular Coupling in Health and Disease. Neuron 96 (1), 17–42. https://doi.org/10.1016/j.neuron.2017.07.030 (2017). Roy, C. S. & Sherrington, C. S. On the Regulation of the Blood-supply of the Brain. J. Physiol. 11 (1–2), 85–158. https://doi.org/10.1113/jphysiol.1890.sp000321 (1890). Lecleire-Collet, A. et al. 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Inaccuracies in initial growth and arborization of chick retinotectal axons followed by course corrections and axon remodeling to develop topographic order. J. Neurosci. 9 (11), 3776–3795. https://doi.org/10.1523/jneurosci.09-11-03776.1989 (1989). Honrubia, F. M. & Elliott, J. H. Efferent Innervation of the Retina: I. Morphologic Study of the Human Retina. Arch. Ophthalmol. 80 (1), 98–103. https://doi.org/10.1001/archopht.1968.00980050100017 (1968). Honrubia, F. M. & Elliott, J. H. Efferent innervation of the retina. II. Morphologic study of the monkey retina. Invest. Ophthalmol. 9 (12), 971–976 (1970). Terubayashi, H., Fujisawa, H., Itoi, M. & Ibata, Y. Hypothalamo-retinal centrifugal projection in the dog. Neurosci. Lett. 40 (1), 1–6. https://doi.org/10.1016/0304-3940(83)90082-4 (1983). Labandeira-Garcia, J. L., Guerra-Seijas, M. J., Gonzalez, F., Perez, R. & Acuña, C. Location of neurons projecting to the retina in mammals. Neurosci. 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Neurosci. 12 (6), 1083–1092. https://doi.org/10.1017/s0952523800006738 (1995). Gastinger, M. J. et al. Abnormal centrifugal axons in streptozotocin-diabetic rat retinas. Investig. Ophthalmol. Vis. Sci. 42 (11), 2679–2685 (2001). Ortiz, G., Odom, J. V., Passaglia, C. L. & Tzekov, R. T. Efferent influences on the bioelectrical activity of the retina in primates. Doc. Ophthalmol. 134 (1), 57–73. https://doi.org/10.1007/s10633-016-9567-5 (2017). Koch, E. et al. Morphometric analysis of small arteries in the human retina using adaptive optics imaging: relationship with blood pressure and focal vascular changes. J. Hypertens. 32 (4), 890–898. https://doi.org/10.1097/hjh.0000000000000095 (2014). Zacharria, M., Lamory, B. & Chateau, N. New view of the eye. Nat. Photonics . 5 (1), 24–26. https://doi.org/10.1038/nphoton.2010.298 (2011). Jordão, J. et al. Neurovascular coupling reflex - Contralateral stimulation apparatus and setup. 2023 IEEE 7th Portuguese Meeting on Bioengineering (ENBENG), 00 , 28–31. (2023). https://doi.org/10.1109/enbeng58165.2023.10175365 Sliney, D. et al. Adjustment of guidelines for exposure of the eye to optical radiation from ocular instruments: statement from a task group of the International Commission on Non-Ionizing Radiation Protection (ICNIRP). Appl. Opt. 44 (11), 2162–2176. https://doi.org/10.1364/ao.44.002162 (2005). Additional Declarations No competing interests reported. Supplementary Files SupplementaryMaterial.docx Cite Share Download PDF Status: Published Journal Publication published 21 Apr, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 06 Mar, 2025 Reviews received at journal 25 Feb, 2025 Reviews received at journal 19 Feb, 2025 Reviewers agreed at journal 10 Feb, 2025 Reviewers agreed at journal 06 Feb, 2025 Reviewers agreed at journal 06 Feb, 2025 Reviewers invited by journal 05 Feb, 2025 Editor assigned by journal 04 Feb, 2025 Editor invited by journal 31 Dec, 2024 Submission checks completed at journal 30 Dec, 2024 First submitted to journal 17 Dec, 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-5661001","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":396129798,"identity":"9c0fd606-8956-4bf4-abc1-78711aca265f","order_by":0,"name":"João Jordão","email":"","orcid":"","institution":"University of Coimbra, Institute for Nuclear Sciences Applied to Health (ICNAS), Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), Coimbra","correspondingAuthor":false,"prefix":"","firstName":"João","middleName":"","lastName":"Jordão","suffix":""},{"id":396129799,"identity":"da8a5cbc-619c-4339-8e88-1e75b414149d","order_by":1,"name":"João Figueira","email":"","orcid":"","institution":"University of Coimbra, Faculty of Medicine, Clinical and Academic Centre of Coimbra (CACC), Coimbra","correspondingAuthor":false,"prefix":"","firstName":"João","middleName":"","lastName":"Figueira","suffix":""},{"id":396129800,"identity":"d4d25a34-0151-4b41-8931-99be520d1dde","order_by":2,"name":"Miguel Morgado","email":"","orcid":"","institution":"University of Coimbra, Institute for Nuclear Sciences Applied to Health (ICNAS), Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), Coimbra","correspondingAuthor":false,"prefix":"","firstName":"Miguel","middleName":"","lastName":"Morgado","suffix":""},{"id":396129801,"identity":"0fcb4355-7a74-42f0-85dd-f08d269db2ff","order_by":3,"name":"Pedro 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Coimbra","correspondingAuthor":true,"prefix":"","firstName":"Rui","middleName":"","lastName":"Bernardes","suffix":""}],"badges":[],"createdAt":"2024-12-17 10:53:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5661001/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5661001/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-025-98631-7","type":"published","date":"2025-04-21T15:56:58+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":72754680,"identity":"5a9aa72d-3371-46c9-a8b5-01f0b0133fd3","added_by":"auto","created_at":"2025-01-01 16:51:48","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":160714,"visible":true,"origin":"","legend":"\u003cp\u003eLeft: apparatus installed on the rtx1 (Imagine Eyes). Right: Apparatus parts. The external light sources are fixed to a pair of custom supports covered by foam pads to prevent flicker light from propagating to the imaged retina during contralateral stimulation and provide comfort.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-5661001/v1/8d9e3b2f62761dddf1a4ac32.jpeg"},{"id":72754678,"identity":"2b409fcd-dfaa-46a2-b6e1-2839acdac4ed","added_by":"auto","created_at":"2025-01-01 16:51:48","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":102312,"visible":true,"origin":"","legend":"\u003cp\u003eSequence and time duration (not-to-scale) of eye fundus acquisition protocol. Each acquisition takes 2 seconds, preceded or not by a photic stimulation of 20 seconds. A five-minute interval takes place between the top and bottom sequences.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-5661001/v1/e1bec05fbd82ac655472a905.png"},{"id":72754691,"identity":"1ff612d1-c6c5-4f89-8235-42e911f905c2","added_by":"auto","created_at":"2025-01-01 16:51:49","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":904802,"visible":true,"origin":"","legend":"\u003cp\u003eTwo healthy control (top) and two diabetic patients (bottom) examples. From top \u0026nbsp;\u0026nbsp;to bottom: cases HC03, HC08, D02 and D04. Left: color fundus photography with \u0026nbsp;\u0026nbsp;the rtx1 shown overlapped in grayscale. Middle/Right: full-size rtx1 images (4x4 \u0026nbsp;\u0026nbsp;degree field-of-view) after the contralateral/ipsilateral stimulation. \u0026nbsp;\u0026nbsp;Analyzed vessel segment in blue.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-5661001/v1/935a2e4ffd1f147e64c4ae22.png"},{"id":72754689,"identity":"2929f087-446d-43b3-866a-2bab42ad6c58","added_by":"auto","created_at":"2025-01-01 16:51:48","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":63197,"visible":true,"origin":"","legend":"\u003cp\u003eLumen width data (in pixels) for all cases in the study (32 healthy controls (HC01-HC32) and 20 type 1 diabetic patients (D01-D20)). Color bars, from left to right: \"Basal 1\" (blue), \"Contra\" (green - contralateral stimulation), \"Basal 2\" (blue), and \"Ipsi\" (red - ipsilateral stimulation).\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5661001/v1/1ee954c1e3b84b3ea424ca0e.jpg"},{"id":72754706,"identity":"1c538837-6258-494d-a149-acae0fb67d45","added_by":"auto","created_at":"2025-01-01 16:51:49","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":54078,"visible":true,"origin":"","legend":"\u003cp\u003eNeurovascular response data for the health control (top) and the diabetic patient (bottom) groups. Response to the photic stimuli is shown as a percentage of lumen width variation from the basal lumen width. Left: contralateral stimulation response. Right: ipsilateral stimulation response.\u003c/p\u003e","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5661001/v1/edecc6b3e4a4882a9b85f343.jpg"},{"id":72754683,"identity":"28ec61d5-0c91-4ea7-a8bf-acd219150f98","added_by":"auto","created_at":"2025-01-01 16:51:48","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":27297,"visible":true,"origin":"","legend":"\u003cp\u003eHealthy control cases (20/32 (62.5%)) for whom the response to the contralateral stimulation recovered totally or partially to the basal lumen value and for whom the response (absolute value) is over half the minimum of the ipsilateral response for the entire set.\u003c/p\u003e","description":"","filename":"6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5661001/v1/5de8d47df4c407efeeec091f.jpg"},{"id":72754693,"identity":"f3c499f2-b5ca-484d-b906-8755882ac346","added_by":"auto","created_at":"2025-01-01 16:51:49","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":24664,"visible":true,"origin":"","legend":"\u003cp\u003eHealthy control cases (12/32 (37.5%)) for whom the response to the contralateral stimulation recovered totally or partially to the basal lumen value and for which the response (absolute value) is over half the minimum of the ipsilateral response for the entire set, and for whom the contralateral response is over 1% or over half of the ipsilateral response for the same subject.\u003c/p\u003e","description":"","filename":"7.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5661001/v1/ee483fd2b82e33b47a6ca804.jpg"},{"id":72755934,"identity":"c2a7ecdd-5b34-422f-b91f-72fa5f352a32","added_by":"auto","created_at":"2025-01-01 16:59:49","extension":"jpg","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":24446,"visible":true,"origin":"","legend":"\u003cp\u003eType I diabetic patient cases (12/20 (60.0%)) for whom the response to the contralateral stimulation recovered totally or partially to the basal lumen value and for whom the response (absolute value) is over half the minimum of the ipsilateral response for the entire set.\u003c/p\u003e","description":"","filename":"8.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5661001/v1/253cec3be25ac97733da2981.jpg"},{"id":72754687,"identity":"9b529dc9-6a79-426c-988d-5f61bbafa1a6","added_by":"auto","created_at":"2025-01-01 16:51:48","extension":"jpg","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":21737,"visible":true,"origin":"","legend":"\u003cp\u003eType 1 diabetic patient cases (7/20 (35.0%)) for whom the response to the contralateral stimulation recovered totally or partially to the basal lumen value and for which the response (absolute value) is over half the minimum of the ipsilateral response for the entire set, and for whom the contralateral response is over 1% or over half of the ipsilateral response for the same subject.\u003c/p\u003e","description":"","filename":"9.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5661001/v1/2479e8873f04aafe9cd5c6bc.jpg"},{"id":81569608,"identity":"14344c91-1537-4f81-bea7-6da537e99445","added_by":"auto","created_at":"2025-04-28 16:07:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2511934,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5661001/v1/3cc5e91c-5b77-47d7-bb7d-bcb6e291d258.pdf"},{"id":72754682,"identity":"8b7f6683-272b-4170-8227-911405a97d02","added_by":"auto","created_at":"2025-01-01 16:51:48","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":1770776,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-5661001/v1/94d5bbf32b20a59e5a89e735.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Direct crosstalk between adult human retinas as suggested by interocular transfer of neurovascular coupling through photic stimulation","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe complexity of the human central nervous system (CNS) is undisputable and broadly recognized. Also, any change in it has a potentially massive impact on people's daily lives. Therefore, specific knowledge of the CNS function and arrangement is paramount and attracts a substantial research focus. Unveiling new communication channels across its different parts will bring additional insight into this fundamental system.\u003c/p\u003e \u003cp\u003eNeurovascular coupling (NVC) is a well-established effect in which the CNS reacts to stimuli by increasing the local blood flow to satisfy the elevated demand for oxygen due to the increased activity, a fundamental task as the CNS lacks a fuel reservoir to suppress energy needs [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Roy and Sherrington [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] initially noted this effect, which has been further demonstrated in the brain and the retina across species [\u003cb\u003e3; 4\u003c/b\u003e]. Despite its fundamental role and the fact that its impairment has been associated with a variety of disorders, including glaucoma, macular degeneration, Alzheimer's disease, cognitive dysfunction, and diabetes [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], the complete NVC mechanism is still not fully understood.\u003c/p\u003e \u003cp\u003eIn this work, we aim to demonstrate the existence of a functional crosstalk mechanism between human retinas in the adult and in vivo.\u003c/p\u003e \u003cp\u003eDemonstrating a vascular response in the retina to stimuli of the contralateral eye and the distinct responses in health and disease support the crosstalk mechanism and add to current knowledge on the NVC mechanism. Moreover, it paves the way for further discoveries and the use of NVC to detect, assess, and monitor vascular-associated diseases.\u003c/p\u003e \u003cp\u003eHowever, the distant modulation of the vascular network, particularly concerning the communication between retinas, implies a long communication channel yet to be documented.\u003c/p\u003e \u003cp\u003eWhile the extensive innervation of the vascular network [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] did not raise any questions on the NVC existence in the brain, mechanisms of autoregulation control in the retina are still poorly understood [\u003cb\u003e6; 7; 8; 9\u003c/b\u003e]. Also, the support for local neural control came from the comparison with the brain [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe demonstration of the NVC coupling did not come without discussion. In [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], the authors stated that all techniques measure distinct parts of the complex nature of the blood flow and, therefore, reaction to metabolic demands depends on the region observed. Moreover, the numerous mechanisms involved in vessel diameter regulation represent a complex closed-loop biological control system.\u003c/p\u003e \u003cp\u003eThe limits of innervation of the vascular network in the eye [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] are still based on the works of Ehinger and Laties [\u003cb\u003e12; 13\u003c/b\u003e]. The innervation of the central retinal artery (CRA) is dense along its course within the optic disc, but vessels in the retina \"almost completely lack extrinsic innervation\" [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. On the other hand, the concept of intrinsic innervation has been proposed repeatedly [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWhether arterioles are the primary site of blood flow regulation remains to be determined in the brain. During neurovascular coupling, the local dilation of arterioles in an activation area will not substantially increase blood flow unless upstream vessels also dilate. How vasodilator and vasoconstrictor responses are conveyed to upstream locations is unclear [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The same question can be raised for the retina, and the answer may rely on coupling and communication between cells within the vessel wall. Indeed, through gap junctions between adjacent vascular smooth muscle cells, the brain's intramural propagation of vascular signals produces remote vasodilatation of upstream pial arterioles [\u003cb\u003e17; 18\u003c/b\u003e].\u003c/p\u003e \u003cp\u003eThe retinal crosstalk in the mammalian visual system is demonstrated in [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. In this work, the authors illustrate the presence of direct communication between the eyes of adult mammals (rats) able to change retinal activity and leave the door open for this effect in other species.\u003c/p\u003e \u003cp\u003eWhile anatomical evidence for cortico-retinal and retino-retinal projections is substantial [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], there is a lack of physiological evidence for the human species.\u003c/p\u003e \u003cp\u003eThe standard view of the adult visual system stipulates that the axons of retinal ganglion cells (RGC) exit the eye to form the optic nerve, with nasal fibers projecting along the contralateral optic tract and temporal fibers along the ipsilateral optic tract to the lateral geniculate nucleus (LGN) and other brain areas. Nevertheless, a diversity of connections exists during embryogenesis and early development but are pruned to form the mature pathway [\u003cb\u003e20; 21; 22\u003c/b\u003e].\u003c/p\u003e \u003cp\u003eAnatomical studies that have started with the work of Santiago Ram\u0026oacute;n y Cajal have shown that the optic nerves of adult mammals, including humans [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], contain sparse populations of efferent fibers. These originate from multiple locations, including the brain stem and hypothalamus [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] and the contralateral eye in young mice [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. As a matter of fact, \"the existence of neurons extending from one retina to the other has been reported during the perinatal development in different vertebrates\" [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Although initially believed to be artifacts or misprojections, their presence was unequivocally demonstrated for a small subset of RGC in mice [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe efferent fibers branch in the eye covers approximately a quarter of the retinal surface [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Their branches terminate in the inner and outer plexiform layers (IPL, OPL), inner nuclear layer (INL), and ganglion cell layer (GCL) depending on fiber type [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Hence, even few, there may be retinal efferent fibers in adult mammals with potential impact on several mechanisms, control, and function.\u003c/p\u003e \u003cp\u003eWhile the efferent innervation of the retina has now been widely documented in rodents and other animals [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e], the existence and function of an efferent system in humans and non-human primates remains to be definitively established. Yet, their presence (efferent innervation, not retina-retina fibers) is strongly suggested based on non-tracing and tracer methods/immunohistochemistry for Chimpanzees, Macaca mulatta, Saimiri sciureus, Macaca fascicularis, Macaca nemestrina, Papio anubis, and Cebus paella [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eConcerning humans, all anatomical evidence was generated from autopsy cases or eyes removed during surgery. Morphological studies of an enucleated eye, ten days after complete occlusion of the CRA, showed that all ganglion cells and afferent neurites had degenerated. In contrast, all of the presumed efferent nerves with their cell bodies in the brain were still present in the optic disc [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the present study, an adaptive-optics (AO) fundus camera (rtx1) from Imagine Eyes (Imagine Eyes, Orsay, France) was used to scan the retinas of a group of healthy controls and a group of type 1 diabetes mellitus (T1DM) patients. The camera was equipped with an in-house built apparatus to stimulate the non-imaged eye synchronously with the acquisition of fundus images to document the contralateral response. The gathered data show the vascular response in the imaged eye to the stimulus of the contralateral eye and a distinct response pattern of the diabetic group from that of the healthy group, therefore supporting the presence of a functional crosstalk mechanism between retinas never documented in the human species.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eNeurovascular coupling is the alteration in local perfusion in response to changes in energy demands due to neuronal activity. To quantify it, the variation in vessel lumen at the same vessel section, before and after stimulation, is measured and then expressed as a percentage (% var). This method disregards differences in vessel calibers, facilitating comparisons across various subjects.\u003c/p\u003e\n\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003ch2\u003eInstrumentation:\u003c/h2\u003e\n \u003cp\u003eAn rtx1 adaptive-optics fundus camera from Imagine Eyes was used to gather data in this work. The camera system utilizes an \u003cem\u003een-face\u003c/em\u003e reflectance imaging method. It captures images in the near-infrared spectrum (850 nm) using a charge-coupled device (CCD) sensor with low noise and an exposure time of less than 10 ms. It allows for the acquisition of 4x4 degree field-of-view (FOV) images of the ocular fundus (1.2x1.2 mm\u003csup\u003e2\u003c/sup\u003e FOV, 1500x1500 pixels image) with high resolution (2 microns, 250-line pairs per millimeter) [\u003cspan class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e35\u003c/span\u003e]. The rtx1 acquires images with or without stimulating the imaged retina. It allows for different acquisition timings: temporarily overlapping the stimulation, after the end of stimulation, or with a defined delay after stimulation.\u003c/p\u003e\n \u003cp\u003eThe adaptive optics control is fully automatic and corrects for blinking and saccades. The camera can compensate for refractive errors ranging from \u0026minus;\u0026thinsp;12 D to +\u0026thinsp;6 D, making it suitable for most individuals. Additionally, as an add-on for this study, the rtx1 outputs two 3.3 V digital trigger signals, one enabled during fundus acquisition and the other triggering the flicker stimulation. The rtx1 light flicker stimulus is based on an internal OLED micro-display panel configured to deliver yellow light with a peak wavelength of 570 nm. Henceforth, the flicker of the rtx1 system will be referred to as the \u0026quot;\u003cem\u003einternal flicker.\u003c/em\u003e\u0026quot;\u003c/p\u003e\n \u003cp\u003eTo establish the presence of a crosstalk mechanism, the NVC effect is assessed in the imaged eye in response to the stimulation of the contralateral one. Custom in-house developed hardware composed of a light source and control system was fully integrated into the rtx1. It synchronizes with the acquisition through the rtx1-trigger signals mentioned above. The apparatus and its parts can be seen in Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n \u003cp\u003eThe prototype developed for stimulating the non-imaged retina will be referred to as the \u0026quot;\u003cem\u003eexternal flicker.\u003c/em\u003e\u0026quot; This prototype consists of two modules, one for inputting trigger signals and the other for controlling the light flickers (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). For details, see [\u003cspan class=\"CitationRef\"\u003e36\u003c/span\u003e]. The external stimulation was set up with two arrays of seven individually addressable red, green, and blue light-emitting diodes (RGB LED), one for each eye, to allow studying the contralateral effect in the left or right eyes.\u003c/p\u003e\n \u003cp\u003eThe irradiance of the external device was measured using a calibrated SR900 spectrometer (Opsytec Dr. Gr\u0026ouml;bel, Ettlingen, Germany) to ensure it meets the International Commission on Non-Ionizing Radiation Protection (ICNIRP) guidelines concerning eye exposure limits in conditions of ophthalmic examination [\u003cspan class=\"CitationRef\"\u003e37\u003c/span\u003e]. Nevertheless, the LEDs\u0026apos; maximum irradiance was limited in firmware to ensure that a possible communication error would not override settings and exceed exposure limits. The RGB LEDs were configured to achieve a perceived dark yellow color matching the rtx1 internal one.\u003c/p\u003e\n \u003cp\u003eThe external device and the rtx1 are controlled using a custom-developed software application written in C++. The control software integrates with the existing rtx1 software and allows the user to specify the settings for both the rtx1 camera and the external flicker module, namely the duration, flickering frequency, and intensity parameters of the stimuli.\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eStudy design and participants:\u003c/h3\u003e\n\u003cp\u003eAll subjects were instructed not to drink coffee on the day of the examination, and all subjects fulfilled the inclusion and exclusion criteria defined as:\u003c/p\u003e\n\u003cp\u003e- Inclusion criteria:\u003c/p\u003e\n\u003cp\u003e\u0026bull; aged 18 to 60, inclusive;\u003c/p\u003e\n\u003cp\u003e\u0026bull; best corrected visual acuity equal to or over 69 letters (20/40 Snellen scale);\u003c/p\u003e\n\u003cp\u003e\u0026bull; refractive spherical equivalent between \u0026minus;\u0026thinsp;6 and +\u0026thinsp;5 diopters;\u003c/p\u003e\n\u003cp\u003e\u0026bull; type I Diabetes Mellitus (for the patient group);\u003c/p\u003e\n\u003cp\u003e\u0026bull; level 10 of the ETDRS-DRSS scale (for the patient group);\u003c/p\u003e\n\u003cp\u003e\u0026bull; demographic matching with the patient group (for the healthy group).\u003c/p\u003e\n\u003cp\u003e- Exclusion criteria:\u003c/p\u003e\n\u003cp\u003e\u0026bull; any ocular diseases that may interfere with the examination of the study eye;\u003c/p\u003e\n\u003cp\u003e\u0026bull; presence of a history of glaucoma;\u003c/p\u003e\n\u003cp\u003e\u0026bull; pupillary dilation below 5 mm in the study eye;\u003c/p\u003e\n\u003cp\u003e\u0026bull; ocular inflammation, conjunctivitis, or any history of uveitis in the study eye;\u003c/p\u003e\n\u003cp\u003e\u0026bull; signs or history of diabetic macular edema (for the patient group);\u003c/p\u003e\n\u003cp\u003e\u0026bull; signs or history of retinal vascular disease or neurodegenerative disease, including hypertensive retinopathy in the study eye;\u003c/p\u003e\n\u003cp\u003e\u0026bull; only one functional eye;\u003c/p\u003e\n\u003cp\u003e\u0026bull; any previous intravitreous treatment;\u003c/p\u003e\n\u003cp\u003e\u0026bull; any previous laser treatment in the retina;\u003c/p\u003e\n\u003cp\u003e\u0026bull; any ocular surgery in the past 6 months before enrollment in the study;\u003c/p\u003e\n\u003cp\u003e\u0026bull; any signs of arterial obstructive disease;\u003c/p\u003e\n\u003cp\u003e\u0026bull; any history of thromboembolic events;\u003c/p\u003e\n\u003cp\u003e\u0026bull; history of central nervous system disorders, neurodevelopment disorders, psychiatric disorders, or auditory or visual deficits;\u003c/p\u003e\n\u003cp\u003e\u0026bull; pregnant or breastfeeding women;\u003c/p\u003e\n\u003cp\u003e\u0026bull; history of alcohol or drug abuse.\u003c/p\u003e\n\u003cp\u003eThe dataset used in this cross-sectional study consists of 32 healthy control subjects (19 females and 13 males, 17 left/15 right eyes, age range: 19\u0026ndash;55 years, median 28.5 years, m(sd): 32.7(10.5) years), and 20 type 1 diabetic patients with no signs of diabetic retinopathy (10 females and 10 males, 10 left/10 right eyes, age range: 20\u0026ndash;57 years, median 32.0 years, m(sd): 35.0(12.3) years, HbA\u003csub\u003e1C\u003c/sub\u003e range: 5.8\u0026ndash;7.9%, median 6.8%, m(sd): 6.9(0.5)%). All subjects presented a best-corrected visual acuity (BCVA) of 0.00 (logMAR) and an intraocular pressure (IOP) of the imaged eye ranging from 10 to 23 mmHg (m(sd): 15.8(3.6) mmHg) and an IOP of the contralateral eye ranging from 10 to 23 mmHg (m(sd): 15.8(3.6) mmHg). Blood pressure (BP) ranges from 90 to 139 mmHg (m(sd): 116.0(11.3) mmHg) and from 59 to 93 mmHg (m(sd): 73.0(8.1) mmHg), respectively for the systolic and diastolic BP, and was measured for all but the initial 12 healthy controls (HC01 to HC12).\u003c/p\u003e\n\u003cp\u003eAll participants provided written informed consent for the study, which was conducted in accordance with the Declaration of Helsinki and its subsequent revisions. Additionally, ethical approval (CE-039/2023) was obtained from the ethics committee of the Faculty of Medicine of the University of Coimbra.\u003c/p\u003e\n\u003cp\u003eAll patients are regularly followed at the ophthalmology department following the standard protocol for type I diabetic patients and underwent a complete ophthalmic examination at the ophthalmology department of the Coimbra University Hospital before enrollment in the study, which included a slit lamp exam, widefield fundus photography, OCT (Optical Coherence Tomography)(macular and optic disc protocols), OCT-A (OCT \u0026ndash; Angiography), and best corrected visual acuity. Besides these data, all patients were checked for the inclusion and exclusion criteria and collection of demographics and anthropometric data, heart blood pressure and metabolic status, hormonal status, relevant family history, medication, and life habits prior to the enrollment in the study.\u003c/p\u003e\n\u003cp\u003eOnly one eye per subject was considered (imaged), selected per group alternatively between the right and left eye at the study enrollment. The experimental procedure begins with measuring the intraocular pressure and applying tropicamide-based mydriatic eye drops to promote mydriasis and cycloplegia.\u003c/p\u003e\n\u003cp\u003eTwo acquisition modes were used: the baseline mode, in which image acquisitions were performed without being preceded by any stimulation, and the stimulation mode, in which image acquisitions immediately follow a stimulation of 20 seconds of flicker light at 15 Hz. For both modes, image acquisition lasted 2 seconds.\u003c/p\u003e\n\u003cp\u003eAfter the full dilation, following the application of mydriatic eye drops and keeping subjects in the imaging room in dark conditions, the selected subject\u0026apos;s eye was imaged three times without stimulation (\u003cem\u003eBasal 1\u003c/em\u003e) and immediately imaged three times following the contralateral stimulation (\u003cem\u003eContra\u003c/em\u003e) using the external stimulator. A waiting time of 5 minutes before the next sequence was set to allow the neurovascular coupling to return to a stable state. After that, three acquisitions were performed without any stimulation (\u003cem\u003eBasal 2\u003c/em\u003e) immediately followed by three acquisitions following the ipsilateral stimulation (\u003cem\u003eIpsi\u003c/em\u003e) using the rtx1 internal flicker (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). All acquisitions were performed at an artery as close as possible to the subject\u0026apos;s fovea, and all acquisitions of the same subject were performed at the same location where the selected artery presents a well-defined lumen and walls. The imaging room was kept in dark conditions for the entire duration of the subject\u0026rsquo;s study.\u003c/p\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n \u003ch2\u003eData analysis:\u003c/h2\u003e\n \u003cp\u003eAll acquired images were exported for further processing. A grader manually segmented a vessel portion using custom-made software allowing to zoom in and out, image panning, and mouse pointing at rtx1 images to define the vessel lumen. All 12 images (three images per acquisition type: Basal 1, Contra, Basal 2, and Ipsi) were individually segmented by the same grader. Image examples and respective segmentation can be seen in Fig. 3. One independent grader assessed all segmentations, and another assessed segmentation by sampling the dataset.\u003c/p\u003e\n \u003cp\u003eA binary mask was defined based on the lumen segmentation, and the vessel centerline was determined from the mask. The same vessel segment limits were used across all images per eye. Per image, the lumen width was defined as the ratio of the area to the length of the segment (length of the centerline), obtaining an estimate of its average in pixels. The lumen width for each acquisition type was defined as the maximum of the respective three consecutive scans. Each subject has, therefore, four measures of the vessel lumen at the same location. The respective NVC response is defined as the percentage of the relative variation between the lumen values for the baseline and the ones following the stimulation, therefore allowing the comparison of the responses for the different subjects/eyes. The contralateral and the ipsilateral responses are computed as %var\u003csub\u003econtra\u003c/sub\u003e = 100*(lw\u003csub\u003econtra\u003c/sub\u003e \u0026ndash; lw\u003csub\u003ebasal1\u003c/sub\u003e)/lw\u003csub\u003ebasal1\u003c/sub\u003e and\u003c/p\u003e\n \u003cp\u003e%var\u003csub\u003eipsi\u003c/sub\u003e = 100*(lw\u003csub\u003eipsi\u003c/sub\u003e \u0026ndash; lw\u003csub\u003ebasal2\u003c/sub\u003e)/lw\u003csub\u003ebasal2\u003c/sub\u003e, respectively, where lw stands for lumen width.\u003c/p\u003e\n \u003cp\u003eA non-parametric Wilcoxon test for pairwise samples was performed to test whether significant contralateral and ipsilateral responses were found in the healthy group. Also, for both groups, a set of criteria was established to define an individual relevant contralateral response:\u003c/p\u003e\n \u003cp\u003eC1 only cases where the lumen\u0026apos;s width following a contralateral stimulation was either both over basal1 and basal2 lumens (positive response) or under basal1 and basal2 lumens (negative response);\u003c/p\u003e\n \u003cp\u003eC2: the minimum variation to any of the basal1 or basal2 should be over 10% of the maximum variation to any of these;\u003c/p\u003e\n \u003cp\u003eC3: the contralateral response should exceed 50% of the minimum ipsilateral response for the entire group;\u003c/p\u003e\n \u003cp\u003eC4: the contralateral response should be over 1% or exceed 50% of the respective ipsilateral response.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eRaw data can be seen in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Figs.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e4\u003c/span\u003e and \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e5\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\u003eRaw data and subject characterization. HC \u0026ndash; healthy controls; T1DM \u0026ndash; type 1 diabetes mellitus; M/F \u0026ndash; male/female; OD/OS \u0026ndash; right/left eye; BP \u0026ndash; blood pressure; IOP \u0026ndash; intraocular pressure; Basal 1/2 \u0026ndash; acquisitions without stimulation; Contra/Ipsi \u0026ndash; acquisition after contralateral/ipsilateral stimulation; NA \u0026ndash; not available.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"14\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eID\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eType\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003cp\u003e(years)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eBP\u003c/p\u003e \u003cp\u003e(mmHg)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eHbA\u003csub\u003e1C\u003c/sub\u003e\u003c/p\u003e \u003cp\u003e(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMenopause\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eImaged\u003c/p\u003e \u003cp\u003eEye\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003eIOP [mmHg]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c14\" namest=\"c11\"\u003e \u003cp\u003eLumen width (pixels)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eImaged\u003c/p\u003e \u003cp\u003eEye\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eContralateral\u003c/p\u003e \u003cp\u003eEye\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eBasal 1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003eContra\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003eBasal 2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c14\"\u003e \u003cp\u003eIpsi\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e119.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e119.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e119.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e120.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e49.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e49.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e50.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e51.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e86.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e84.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e86.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e92.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e104.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e105.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e106.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e109.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e78.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e79.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e77.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e80.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e89.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e89.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e89.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e91.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e105.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e108.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e104.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e108.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e80.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e85.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e84.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e88.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e51.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e51.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e52.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e55.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e84.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e85.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e84.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e86.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e93.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e93.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e90.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e98.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e70.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e73.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e71.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e75.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e122/59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e75.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e76.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e75.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e78.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e123/80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e96.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e97.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e95.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e98.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e110/80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e94.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e95.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e93.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e94.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e128/65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e96.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e96.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e99.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e99.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e116/73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e76.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e76.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e76.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e77.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e120/88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e72.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e73.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e71.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e77.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e116/73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e75.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e74.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e74.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e78.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e103/68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e82.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e83.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e82.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e84.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e130/79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e71.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e74.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e75.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e78.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e98/63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e53.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e54.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e55.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e56.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e121/73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e102.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e104.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e95.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e104.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e124/80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e83.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e83.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e84.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e90.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e126/73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e63.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e63.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e64.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e64.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e102/65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e104.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e104.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e103.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e104.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e108/68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e82.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e82.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e81.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e82.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e114/62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e102.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e101.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e102.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e105.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e110/73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e64.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e65.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e65.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e66.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e110/70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e82.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e82.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e82.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e83.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e120/88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e88.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e86.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e85.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e91.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHC32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e102/63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e89.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e90.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e88.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e89.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDM01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT1DM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e90/66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e66.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e66.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e66.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e66.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDM02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT1DM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e120/75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e84.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e87.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e86.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e88.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDM03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT1DM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e116/76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e120.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e122.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e122.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e122.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDM04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT1DM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e120/60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e80.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e76.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e79.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e81.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDM05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT1DM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e118/74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e78.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e78.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e79.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e81.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDM06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT1DM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e127/79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e72.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e70.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e70.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e72.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDM07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT1DM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e122/74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e90.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e90.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e92.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e91.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDM08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT1DM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e123/93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e72.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e72.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e70.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e76.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDM09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT1DM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e96/71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e85.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e85.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e83.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e85.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDM10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT1DM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e112/67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e82.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e82.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e83.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e85.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDM11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT1DM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e105/86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e111.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e110.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e112.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e112.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDM12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT1DM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e121/73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e77.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e78.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e78.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e79.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDM13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT1DM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e117/68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e55.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e56.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e56.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e56.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDM14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT1DM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e132/63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e82.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e82.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e82.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e82.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDM15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT1DM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e139/72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e103.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e102.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e103.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e106.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDM16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT1DM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e136/86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e--\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e92.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e92.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e91.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e92.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDM17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT1DM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e98/76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e60.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e60.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e59.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e61.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDM18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT1DM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e131/80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e82.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e83.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e83.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e83.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDM19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT1DM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e113/68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e108.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e107.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e107.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e106.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDM20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eT1DM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e103/69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c11\"\u003e \u003cp\u003e101.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e99.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c13\"\u003e \u003cp\u003e100.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e \u003cp\u003e101.1\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\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFor the healthy control group, a statistically significant difference is found between the contralateral and ipsilateral NVC and the previous basal state, respectively, p\u0026thinsp;=\u0026thinsp;0.027 and p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 (Wilcoxon test), rejecting the null hypothesis of no response in both cases.\u003c/p\u003e \u003cp\u003eOf the 32 healthy controls, 24 (75.0%) presented a contralateral positive response (please note the marginal positive response of the HC09 subject). Twenty subjects (62.5%) verified criteria C#1 to C#3 (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e6\u003c/span\u003e). Twelve healthy controls (37.5%) verified criteria C#1 to C#4, ten subjects (83.3%) presented positive contralateral responses, and two individuals (16.7%) presented negative contralateral responses (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFor the diabetic group, 13 individuals (65.0%) presented a negative contralateral response (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e5\u003c/span\u003e). Twelve subjects (60.0%) verified criteria C#1 to C#3 (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e8\u003c/span\u003e). Seven subjects (35.0%) verified criteria C#1 to C#4, three with a positive and four with a negative contralateral response (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThese results support the NVC reflex in response to the stimulation of the contralateral eye, with 12/32 (37.5%) healthy controls and 7/20 (35.0%) type 1 diabetes mellitus patients fulfilling the established criteria, implying a response followed by a return to the baseline condition.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eFor the first time, we have imaged the human retina with an adaptive-optics fundus camera equipped with an external stimulation apparatus to allow the photic stimulation of the contralateral eye.\u003c/p\u003e \u003cp\u003eThe same eye of each subject was imaged first without being stimulated (basal measurement) and after the stimulation of the contralateral eye. After a period of 5 minutes, the same eye was imaged again, without being stimulated (new basal) and after its ipsilateral stimulation. The same vessel portion was analyzed by segmenting the vessel's lumen. The average lumen width for each of the four scenarios was computed, and the response to the stimulus was determined as the percentage of variation in the lumen width in relation to the respective basal value to account for temporal variations in the basal lumen. We have shown that there is a response to the contralateral stimulation by demonstrating that the computed variation in lumen obeys several criteria (for the healthy and patient groups) and has a statistically significant difference from the null hypothesis (no response) for the healthy control group.\u003c/p\u003e \u003cp\u003eHow the information propagates from one eye to the other is still unknown. However, a mechanism similar to the one in the brain, where through gap junctions between adjacent vascular smooth muscle cells the brain's intramural propagation of vascular signals produces remote vasodilatation of upstream pial arterioles [\u003cb\u003e17\u003c/b\u003e; \u003cb\u003e18\u003c/b\u003e], associated with the dense innervation of the CRA and the local propagation of vasodilatory signals, suggest this as a potential mechanism for the contralateral NVC effect in the retina.\u003c/p\u003e \u003cp\u003eIn addition to demonstrating the crosstalk between adult human retinas, we have shown the mechanism is present both in health and disease (type 1 diabetes). Our results also suggest a different response pattern in the patient group.\u003c/p\u003e \u003cp\u003eThe main strengths of this study were the use of detailed ophthalmic imaging and the demonstration of the statistically significant difference for the contralateral stimulation in the adult healthy population, in vivo and non-invasively, through the direct evaluations of the change in the vessels' lumen.\u003c/p\u003e \u003cp\u003eNevertheless, there are some limitations to our study. First, this cross-sectional study has a limited sample size. Second, the study sample might not adequately represent other populations where different response patterns can exist. Additionally, a different set of operating parameters, e.g., stimulation period, a time gap between the stimulation and acquisition, or the acquisition while still stimulating, different stimulation intensities, may show an increased contralateral response. However, for the sake of demonstration of a working mechanism in the adult human retina, the system configuration used proved to be adequate, and the novel findings shed new light on the NVC mechanism, a significant breakthrough because existing NVC models do not consider the demonstrated effect and may need to be revisited.\u003c/p\u003e \u003cp\u003eDemonstrating these effects in a larger population and across different imaging centers is paramount, as well as assessing the pattern of response for several disorders, particularly those known to be associated with vascular changes, including Alzheimer's disease, cognitive dysfunction, and diabetes.\u003c/p\u003e \u003cp\u003eThis study's findings are still far from an immediate application in clinical practice, and further studies involving several distinct populations are necessary. However, the prospects for new biomarkers of disease onset, progression, or staging seem to be waiting to be discovered.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eWe present evidence on the crosstalk between adult human retinas through the modulation of vessels' width in response to the photic stimulation of the contralateral eye. Our results also suggest that this crosstalk mechanism may be modified in type 1 diabetes mellitus patients and may be a biomarker of initial changes not identified by current methods.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eConflict of interest:\u003c/h2\u003e \u003cp\u003eThe authors declare that the research was conducted without commercial or financial relationships that could be interpreted as a potential conflict of interest.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eSupplementary material:\u003c/h2\u003e \u003cp\u003eThe Supplementary Material for this article can be found online at: \u003cb\u003exxxx\u003c/b\u003e\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eThis study was supported by The Portuguese Foundation for Science and Technology (FCT) through the 2022.07585.PTDC project (DOI:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.54499/2022.07585.PTDC\u003c/span\u003e\u003cspan address=\"10.54499/2022.07585.PTDC\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e), UI/BD/154285/2022 (Ph.D. grant), FCT/UIDB/4950/Base/2020 (DOI:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.54499/UIDB/04950/2020\u003c/span\u003e\u003cspan address=\"10.54499/UIDB/04950/2020\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) and FCT/UIDP/4950/Programatico/2020 (DOI:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.54499/UIDP/04950/2020\u003c/span\u003e\u003cspan address=\"10.54499/UIDP/04950/2020\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eJJ: Software, Hardware, Formal analysis, Validation, Writing \u0026ndash; first draft \u0026amp; review. JF: Subjects inclusion/exclusion criteria, Methodology, Formal analysis, Validation, Writing \u0026ndash; review. MM: Methodology, Hardware, Formal analysis, Validation, Writing \u0026ndash; review \u0026amp; editing. PG: Formal analysis, Validation, Writing \u0026ndash; review \u0026amp; editing. PS: Formal analysis, Validation, Writing \u0026ndash; review \u0026amp; editing. DCF: Subjects inclusion/exclusion criteria, Methodology, Formal analysis, Validation, Writing \u0026ndash; review. DCD: Methodology, Formal analysis, Validation, Writing \u0026ndash; review \u0026amp; editing. MC-B: Subjects inclusion/exclusion criteria, Methodology, Formal analysis, Investigation, Validation, Writing \u0026ndash; review \u0026amp; editing, Funding acquisition, Resources. MP: Subjects inclusion/exclusion criteria, Methodology, Formal analysis, Validation, Writing \u0026ndash; review \u0026amp; editing. RB: Conceptualization, Project administration, Supervision, Subjects inclusion/exclusion criteria, Methodology, Software, Hardware, Formal analysis, Validation, Writing \u0026ndash; review \u0026amp; editing, Funding acquisition, Resources.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe are grateful to Nuno Gouveia and Ana Lu\u0026iacute;s Carreira for identifying patients, Hugo Quental and S\u0026iacute;lvia Sim\u0026atilde;o for all data acquisitions, Joana Domingues for handling all subjects and segmenting all images, and S\u0026eacute;rgio Rodrigues for his collaboration in developing the segmentation tool used in this work.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe raw data supporting the conclusions of this article will be made available by the authors upon formal and reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eIadecola, C. 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Opt.\u003c/em\u003e \u003cb\u003e44\u003c/b\u003e (11), 2162\u0026ndash;2176. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1364/ao.44.002162\u003c/span\u003e\u003cspan address=\"10.1364/ao.44.002162\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2005).\u003c/span\u003e\u003c/li\u003e\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":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Neurovascular Coupling, Circulation, Central Nervous System, Retina, Functional Imaging, Flicker-induced hyperemia","lastPublishedDoi":"10.21203/rs.3.rs-5661001/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5661001/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eCrosstalk mechanisms between retinas were never documented in humans despite being documented for several other species, including non-human primates. Here, we report the results of the first-in-human study that documents the crosstalk between retinas by measuring the vascular response in one retina to the photic stimulation of the contralateral eye in health and disease. We developed a stimulation apparatus and integrated it into an adaptive-optics fundus camera to image 32 healthy control (HC) subjects and 20 type 1 diabetes mellitus (DM) patients. We documented both the ipsilateral and the contralateral neurovascular coupling effect and established criteria to consider an actual response to find positive and negative responses. Ten (31.2%) and two (6.2%) subjects of the HC group presented contralateral positive and negative responses, respectively, and three (15.0%) positive and four (20.0%) negative responses were found for the DM group. Also, statistically significant differences in the ipsilateral and contralateral responses were found for the HC group, rejecting the null (non-response) hypothesis. This finding raises the need to revisit the current knowledge of neurovascular coupling mechanisms and the association between its dysregulation and neurological disorders. Further studies involving distinct populations and imaging centers are necessary to validate the findings herein.\u003c/p\u003e","manuscriptTitle":"Direct crosstalk between adult human retinas as suggested by interocular transfer of neurovascular coupling through photic stimulation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-01 16:51:43","doi":"10.21203/rs.3.rs-5661001/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-03-06T06:58:20+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-02-26T02:50:38+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-02-20T01:46:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"144062744985088782573168206378987156464","date":"2025-02-10T14:49:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"263221097272047889480616163964010351421","date":"2025-02-06T17:43:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"18316914122280585662480881880794081090","date":"2025-02-06T06:29:38+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-02-05T06:11:44+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-02-04T12:25:33+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-12-31T09:35:44+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-12-30T12:18:46+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-12-17T10:40:38+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b89d2a9f-664a-4f3f-8148-a89362d0e3e7","owner":[],"postedDate":"January 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":42202031,"name":"Biological sciences/Physiology/Circulation/Vasodilation"},{"id":42202032,"name":"Health sciences/Anatomy/Nervous system/Central nervous system"},{"id":42202033,"name":"Health sciences/Biomarkers"},{"id":42202034,"name":"Physical sciences/Engineering/Biomedical engineering"}],"tags":[{"value":"featured","date":"2025-01-02 18:49:13"}],"updatedAt":"2025-04-28T16:01:06+00:00","versionOfRecord":{"articleIdentity":"rs-5661001","link":"https://doi.org/10.1038/s41598-025-98631-7","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-04-21 15:56:58","publishedOnDateReadable":"April 21st, 2025"},"versionCreatedAt":"2025-01-01 16:51:43","video":"","vorDoi":"10.1038/s41598-025-98631-7","vorDoiUrl":"https://doi.org/10.1038/s41598-025-98631-7","workflowStages":[]},"version":"v1","identity":"rs-5661001","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5661001","identity":"rs-5661001","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}