Analysis of variation in retinal vascular assessment

Changes in retinal vascular parameters have been shown to be associated with systemic vascular diseases. The current assessment of retinal vascular parameters is based on a solo captured image and computer assisted measurement. The solo image assessment ignores the short term, dynamic change of the retinal vessel and its impact on the measurement. Variation in retinal vessel diameter during the cardiac cycle has been debated in the past, while other retinal vascular parameters have never been verified if affected by the cardiac cycle. There is a lack of comprehensive study on the various sources of variation. This thesis has comprehensively studied the variations from the various sources: (i) human cardiac cycle; (ii) multiple graders; (iii) different software; (iv) repeated photographs; (v) region of interest; (vi) the summary method and (vii) measurement protocol. The results showed there was significant change of retinal individual vessel diameters during the cardiac cycle while this change became non-significant after the individual vessel diameters were summarised using a summary method. Other retinal vascular parameters, such as tortuosity, branching angle, LDR and fractal dimension, had little to no variation over the cardiac cycle. Significant variations were found between graders and different measurement software. This thesis has shown that variation due to the cardiac cycle can be minimised using the ECG synchronised retinal photographs. The work has also suggested that the significant variations between different graders and the measurement software should be considered in all future studies when comparing their results. Number of strategies such as minimum length of measured vessel that reduce the variability in the measurement have also been identified, and these should be considered when developing new methodologies. To summarise, this thesis has identified variations and their sources in retinal vascular assessment that will contribute to reduce the variability of vessel measurements leading to improved clinical assessment and identified techniques to mitigate some of these

Haemodynamic studies of the eye

The study of the circulation of the eye has been taxing the imaginations of ocular investigators for 100 years, and has resulted in various and ingenious methods for its assessment. In recent decades technological advances have provided even more scope for examination. In these studies the method of colour Doppler imaging (which has considerably improved the localisation and measurement of blood flow in small blood vessels) was investigated as a means of examining the haemodynamics of the eye. The examination of 95 normal individuals showed that many orbital blood vessels could be examined but that only the Doppler recordings (blood velocities and resistive index) from the ophthalmic artery, central retinal artery and vein were reproducible. Normal ranges for the Doppler measurements from these vessels were defined. The results were influenced by the age of the patient, by systemic blood pressure and by smoking habit. The identity of individual blood vessels was confirmed by examining patients with occlusive vascular disease. According to the Hagen Poiseuille law an increase in the viscosity of a fluid reduces its flow. In a group of normal individuals the interrelationship between blood velocity (from colour Doppler imaging) and systemic blood viscosity was examined. No effect of viscosity on the blood velocities was found but a negative correlation between viscosity and resistive indices (a Doppler measure of resistance to flow) was detected. This result suggested that in normal individuals there was compensation for increased blood viscosity by a reduction in peripheral resistance thereby maintaining blood flow to the eye. The method of colour Doppler imaging was then applied to the examination of 80 patients with central retinal vein occlusion in whom significantly reduced blood velocities were found in the retinal vessels. In fact the values of the velocities (a minimum peak velocity in the central retinal vein of less than 3.0 cm/sec) could be used to predict the development of the blinding and painful complication of iris neovascularisation. Investigation of the systemic blood viscosity in these patients revealed elevated viscosity compared to population based controls and the examination of haemostatic factors demonstrated a thrombotic tendency particularly in those who developed iris neovascularisation. In contrast to normal individuals, the orbital blood velocities from the patients with central retinal vein occlusion were negatively correlated with their blood viscosities whereas resistive indices were unaffected, indicating that a reduction in peripheral resistance did not occur. In these patients therefore not only was blood viscosity elevated but there was no evidence of compensation for this by reduction of peripheral resistance. Potentially therefore retinal blood flow is reduced in eyes with central retinal vein occlusion by increased blood viscosity and poor vascular compensation to such an extent that "occlusion" of flow in the vein occurs

Detection of delay between arterial and venous pulse signal from videoophthalmoscope

Cílem této bakalářské práce je změřit rozdíl mezi tepennými a žilními pulzy na sítnici z videosekvencí získanými binokulárním videooftalmoskopem. Teoretická část obsahuje popis oka a jeho struktur, popis zobrazovací techniky používané pro zobrazení očního pozadí a rešerši metod měření a výpočtu zpoždění mezi pulzy. Praktická část se zabývá zpracováním a úprav dat z videosekvencí a změření rozdílů pulzů pomocí metody foot-to-foot a fázového rozdílu.The goal of this bachelor´s work is to measure a time difference between arterial and venous pulses on a retina from video sequences obtained from a binocular videoopthalmoscope. Theoretical part contains a description of the eye and its structures, description of the imaging devices used to display ocular background and research of methods used to measure and calculate the delay between pulses. Practical part describes the processing and adjustments of the videosequences and the measurement of time differences using foot-to-foot and phase difference method.

Development of Novel Techniques for Measuring Bulbar Conjunctival Red Blood Cell Velocity, Oximetry and Redness

Introduction The ocular surface provides a unique opportunity to study hemodynamics since the vessels can be visualized directly, without treatment and non-invasively. The availability of instruments to measure various hemodynamic parameters on the ocular surface in an objective manner are lacking. The quantification of red blood cell velocity, blood oxygen saturation and conjunctival redness on the ocular surface using novel, validated techniques has the potential of providing useful information about vascular physiology. The specific aims of each chapter are as follows: Chapter 3: The objective was to design, develop and validate a system that would non-invasively quantify the red blood cell velocity in the conjunctival vessels. A tool was developed to automatically analyze video sequences of conjunctival vessels, digitally imaged with high enough magnification to resolve movement of the blood within the vessel. Chapter 4: The objective was to: a) design and develop a method in order to non-invasively quantify the changes in blood oxygen saturation (SO2) in the conjunctival vessels and demonstrate reliability of the measures and, b) demonstrate the application of the method by showing a response to an isocapnic hyperoxic provocation and compare those values to the results from a valid instrument. Chapter 5: The aim of this experiment was to examine variations in ocular redness levels, red blood cell velocities and oxygen saturation levels over time in clinically healthy participants and also to compare differences between two age groups. Chapter 6: The aim of this experiment was to examine the ocular redness levels, red blood cell velocities and oxygen saturation levels in clinically healthy participants when a topical ophthalmic decongestant was instilled onto the eye and to demonstrate the validity of the use of two novel techniques. Chapter 7: The aim of this experiment was to examine ocular redness, red blood cell velocity and oxygen saturation in participants who were habitual soft contact lens wearers (study) compared to those that did not (control) and also to compare differences in silicone (SH) and non-silicone hydrogel wearers. Methods Chapter 3: Simulations representing moving RBCs within a vessel and the random variation of each cell in terms of speed, shape and intensity were created in order to evaluate the performance of the algorithm. For each vessel, a signal that correlated to blood cell position was extracted from each frame, and the inter-frame displacement was estimated through a modified dynamic time warping (DTW) algorithm. This provided the red blood cell velocity over time in each point of the vessels. Thus, from these estimates, the mean red blood cell velocity for each vessel was easily evaluated. The true mean velocity from the simulation with the one estimated by the algorithm was compared and the system accuracy was determined. Chapter 4: a) Conjunctival vessels were imaged with two narrow-band interference filters with O2-sensitive and O2-insensitive peak transmissions using a Zeiss slit lamp at 32x magnification. Optical densities were calculated from vascular segments using the average reflected intensities inside and outside the vessels. Optical density ratios were used to calculate relative oxygen saturation values. Video images of the bulbar conjunctiva were recorded at three times of the day. Measurement repeatability was assessed over location at each time and across consecutive frames. b) Subjects initially breathed air for 10 minutes followed by pure oxygen (O2) for 20 minutes, and then air for a final 10 minute period using a sequential re-breathing circuit. Simultaneously, SO2 values measured with a pulse oximeter ear clip and finger clip were recorded. The validity of the dual wavelength method was demonstrated by comparing the values to those from the ear clip pulse oximeter. Chapter 5: Participants attended eight separate visits over the course of a day. Levels of bulbar conjunctival redness, red blood cell velocity and blood oxygen saturation were measured on a vessel of interest. Chapter 6: Participants attended three separate visits during an allotted 60 minute session. Bulbar conjunctival redness, red blood cell velocity and blood oxygen saturation were measured on a vessel of interest, pre-insertion, just after insertion and, 10 minutes after insertion of a topical ocular decongestant. Significant differences between the three measures were assessed and correlations between the three parameters were reported. Chapter 7: Participants were measured 8 times over the course of a day with their contact lenses in place. Bulbar conjunctival redness, red blood cell velocity and blood oxygen saturation were measured. Results Chapter 3: Results for the simulated videos demonstrated a very good concordance between the estimated and actual velocities supporting its validity. The mean relative error for the modified Dynamic Time Warping (DTW) method is 6%. Chapter 4: The intraclass correlations (ICCs) between the three locations at each time point were 0.93, 0.56 and 0.86 respectively. Measurements across 5 consecutive frames showed no significant difference for all subjects (ICC = 0.96). The ICCs between the two methods at each time point were 0.45, 0.10 and 0.11 respectively. a) There was no significant difference in SO2 between the three locations measured using the dual wavelength method for all subjects. There was also no significant difference between the three locations at any of the time points for the dual wavelength method. b) In response to isocapnic hyperoxic provocation using the dual wavelength method, blood oxygen saturation was increased from control values and subsequently recovered after withdrawal of hyperoxia. Blood oxygen saturation values recorded from the ear clip and finger clip of the pulse oximeter also showed an increase from control values and subsequently recovered after withdrawal of hyperoxia. SO2 comparison between the dual wavelength method and the ear-clip pulse oximeter method did not show a significant difference. The interaction between the two methods and time on SO2 was not significant. Chapter 5: From baseline, the group mean redness and oxygen saturation did not change significantly over time. There was a significant difference in the group mean red blood cell velocity values over time. There was no significant difference between age strata for all three measures. Chapter 6: After drop instillation redness values decreased significantly. There was no change in red blood cell velocity and oxygen saturation over time. There was a moderate significant correlation between SO2 and red blood cell velocity just after drop insertion. Chapter 7: When comparing the study and control groups, no significant difference in redness or SO2 over time was found. RBC velocity over time was found to be significantly different between groups. When comparing the two study groups (SH vs. hydrogel) no significant difference across either measure over time was found. Conclusions Chapter 3: Signal displacement estimation through the DTW algorithm can be used to estimate mean red blood cell velocity. Successful application of the algorithm in the estimation of RBC velocity in conjunctival vessels was demonstrated. Chapter 4: The application of the dual wavelength method was demonstrated and optical density ratios can be used in a reliable manner for relative oxygen saturation measurements. This valid method promises to enable the study of conjunctival O2 saturation under various experimental and physiological conditions. Chapter 5: The results of this study support the theory of metabolic regulation. The lack of any significant change across time for redness and oxygen saturation along with significant changes in red blood cell velocity substantiates this notion. Chapter 6: This study supports the literature regarding metabolic regulation of the microvasculature during the use of various stimuli. The results demonstrated that oxygen saturation levels remain stable even when a significant decrease in ocular redness is measured. The novel techniques used in this experiment demonstrated the expected action of the decongestant further contributing to their application and validity. Chapter 7: In summary, the participants in the study group were habitual contact lens wearers that had lower RBC velocities when compared to the control group supporting the notion that contact lenses initiate a hypoxic response. The lack of change in SO2 in either group supports the theory of metabolic regulation

Intracranial Pressure Monitoring in Cerebrospinal Fluid Dynamics Disturbances

There are numerous gaps in the knowledge of Intracranial Pressure (ICP) physiology and Cerebrospinal Fluid (CSF) dynamics. This PhD answers some of the research questions posed by these gaps, through the use of invasive ICP monitoring in patients with suspected CSF dynamics disturbances. Research on CSF dynamics disturbances has mainly focused on conditions that cause high ICP, whilst only sparse attention has been centred on low CSF pressure/volume states. Chapter 3 and chapter 4 of this thesis are focused on Spontaneous Intracranial Hypotension (SIH). Chapter 3 is a comprehensive systematic review and meta-analysis of the clinical presentation, investigation findings and treatment outcomes of this disease. Chapter 4 is an observational study that investigated the utility of invasive ICP monitoring when there is diagnostic uncertainty for SIH. This study demonstrates that, in selected cases, ICP monitoring can be useful and confirm a low-pressure state in 8% of the patients and identify a paradoxical clinical presentation with an underlying high-pressure state in 16% of the patients. Chapters 5 and 6 provide evidence on the way that ICP and brain compliance respond to external variables, such as changes in posture and shunt setting adjustments. Chapter 5 is a retrospective observational study that describes the changes of ICP and pulse amplitude with different postures. Chapter 6 is a retrospective observational study investigating the effect of valve setting adjustments on ICP. This study demonstrates that paradoxical changes in ICP following differential pressure valves setting changes can occur. Chapters 7 and 8 investigate the possibility of replacing invasive ICP monitoring with non-invasive biomarkers of raised ICP. Chapter 7 demonstrated the association between higher ICP measurements and the absence of spontaneous retinal venous pulsations detected with infrared video recordings. Chapter 8 demonstrates the utility of integrating ophthalmic and imaging biomarkers to predict raised ICP

Retinal Haemodynamics in Primary Open Angle Glaucoma Patients with Differing Nocturnal Blood Pressure Profiles

The impairment of ocular haemodynamics has been reported in primary open angle glaucoma (POAG) patients using various blood flow measurement techniques. Studies have shown hypotension may accelerate progression in POAG and a marked nocturnal blood pressure reduction (NBPR) was reported to further expedite the neuro-degenerative disease. It has been suggested that extreme NBPR may be a form of systemic vascular dysregulation that is manifested as an ocular dysregulation, but this hypothesis has never been tested. In addition, the relationship, if any, of retinal haemodyanamics to magnitude of the NBPR is also unknown. A prototype Doppler spectral domain optical coherence tomographer (SD-OCT) together with the more established bi-directional Laser Doppler velocimetry with simultaneous vessel densitometry (BLDV-SVD) methodology (Canon Laser Blood Flowmeter, CLBF) were utilized to see if the NBPR is associated to impaired retinal haemodynamics in glaucoma patients. The specific aims of this thesis were: (1) To evaluate the association between retinal hemodynamics of healthy eyes with age, as derived by Doppler SD-OCT, (2) To evaluate retinal blood flow (RBF) in patients with early POAG and differing NBPR profiles, (3) To investigate the relationship between Doppler SD-OCT derived retinal haemodynamics and the retinal nerve fiber layer (RNFL) thickness in patients with early POAG and healthy age-matched controls, (4) To evaluate the vascular reactivity in patients with early POAG with different NBPR profiles using a normoxic hypercapnia provocation stimulus. Perfusion to the retina was not altered with increasing age among healthy people in the range of 20 to 70 years. Patients with early POAG who exhibited an exaggerated nocturnal reduction in mean arterial pressure also demonstrated lower RBF values as shown by the measurement of Doppler SD-OCT. The change in retinal circulation in early POAG was related to reduced RNFL thickness and a larger venous area may be associated with thicker RNFL among controls. Patients with early POAG who exhibited an exaggerated NBPR also demonstrated disturbance of retinal vascular reactivity

Ultrasound as a non-invasive diagnostic tool in paediatric neurosurgery : relationship between the optic nerve sheath diameter (ONSD) and intracranial pressure (ICP)

Includes bibliographical referencesBackground: Assessment of intracranial pressure (ICP) is an essential aspect in the management of most neurosurgical conditions in children. While invasive ICP monitoring is considered the criterion standard, the need for a reliable, non-invasive, easy-to-use and accurate method to detect and monitor raised ICP has inspired the development of many useful techniques. The present study examined the relationship between transorbital ultrasound measurement of the optic nerve sheath diameter (ONSD) and invasively measured ICP in children, as well as the influence of relevant physiological and demographic variables on this relationship. Methodology: ONSD measurement was performed using a high frequency, small footprint linear array probe, and prior to invasive ICP measurement. All patients were under general anaesthesia and being mechanically ventilated. Physiological variables including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), pulse rate, temperature, respiratory rate and end tidal carbon dioxide (ETCO2) level were recorded at the time of ONSD measurement. The ONSD measurements were analysed for repeatability, intra- and inter-observer variability as well for correlation between images acquired in different planes and those obtained from either eye. The diagnostic accuracy of ONSD measurement for detecting ICP at different thresholds of 20, 15, 10 and 5 mmHg was analysed. This analysis included evaluation of age-related thresholds for defining different ONSD cut-off values in children. Dynamic image acquisition was performed and analysed to evaluate the relevant pulsatile motion of the ONS as a marker of the sheath stiffness. Results: One hundred and seventy four children undergoing diagnostic or therapeutic surgical procedures were included in this study. ONSD measurement demonstrated good correlation with ICP across the entire patient cohort (r = 0.66, p 1 year or with a closed anterior fontanelle (AF) (r = 0.7, p < 0.001). Age above and below 1 year was found to be an appropriate age threshold for defining two different sets of ONSD cut-off values. The study however, supported using patency of the AF as a stronger clinical marker for describing different ONSD cut-off values in children. The second part of this work described a dynamic technique for analysing the pulsatile motion of the ONS. Analysis of the deformability index (DI) as an indirect marker of ONS stiffness, revealed a statistically significant relationship with ICP (sensitivity of 90%, specificity of 87% for detecting ICP ≥ 20 mmHg). Conclusion: Measurement of the ONSD is a sensitive surrogate marker of raised ICP, but demonstrated poorer specificity. This relationship was more reliable in older children, particularly when the AF was closed. Analysis of the dynamic characteristics of the ONS appeared to provide useful additional information as an independent marker, and may contribute to our overall understanding of ONSD measurement in raised ICP