Structure function correlation in retinal ischaemia and macular oedema

Diabetic retinopathy (DR) and retinal vein occlusion (RVO) are the two most prevalent retinal vascular diseases which affect macular perfusion, altering visual function. Firstly, healthy eyes [eyes with no structural pathology identified on Optical coherence tomography (OCT) and OCT angiogram (OCTA)] were assessed for the foveal parameters to identify the reliability of structural markers before studying pathological changes. The white ethnic group had a smaller foveal avascular zone area and perimeter compared to the Asian and Afro-Caribbean (AFC) ethnic groups, respectively in our study. Retinal capillary loss is an irreversible complication of DR. We analysed patients with advanced DR and found higher parafoveal capillary vessel density (VD) at the level of superficial capillary plexus (SCP) was associated with better best corrected visual acuity (BCVA) and low luminance visual acuity (LLVA) while for radial peripapillary capillary plexus (RPCP) only VD of temporal sector was the predictor of LLVA. Disorganization of the retinal inner layers (DRIL), a potential biomarker of focal ischaemia affects LLVA more than BCVA. In a final adjusted model, the SCP density of the parafoveal area was the only parameter that most accurately ascertained BCVA and LLVA. In the next section of this thesis, functional assessment of the effect of treatment (anti-vascular endothelial growth factor [VEGF] versus laser) on active proliferative diabetic retinopathy (PDR) showed BCVA and LLVA are well correlated before and after treatment. Our findings suggest ten letters difference between BCVA-LLVA; however, this difference becomes more remarkable for a lower level of BCVA, suggesting more advanced ischaemia affects LLVA aggressively. Next analysing, OCTA changes at the macula for PDR, and central retinal vein occlusion (CRVO), I found capillary loss was more pronounced in PDR than CRVO. The final chapter of the thesis looked at the baseline demographic and morphological changes in CRVO patients to predict vision outcomes. Baseline retinal central subfield thickness (CST) up to 900 microns can be expected to improve by 2 or more lines on Early Treatment Diabetic Retinopathy Study (ETDRS) chart or achieve >70 letters visual acuity (VA) at 100 weeks of follow up and treatment. Age of the patient and vision at the time of diagnosis of CRVO and intact ellipsoid zone can predict BCVA at 100 weeks following initiation of treatment in CRVO eyes

Advances in Ophthalmology

This book focuses on the different aspects of ophthalmology - the medical science of diagnosis and treatment of eye disorders. Ophthalmology is divided into various clinical subspecialties, such as cornea, cataract, glaucoma, uveitis, retina, neuro-ophthalmology, pediatric ophthalmology, oncology, pathology, and oculoplastics. This book incorporates new developments as well as future perspectives in ophthalmology and is a balanced product between covering a wide range of diseases and expedited publication. It is intended to be the appetizer for other books to follow. Ophthalmologists, researchers, specialists, trainees, and general practitioners with an interest in ophthalmology will find this book interesting and useful

Blindness and glaucoma: A multicenter data review from 7 academic eye clinics

Purpose To evaluate frequency, conversion rate, and risk factors for blindness in glaucoma patients treated in European Universities. Methods This multicenter retrospective study included 2402 consecutive patients with glaucoma in at least one eye. Medical charts were inspected and patients were divided into those blind and the remainder (''controls''). Blindness was defined as visual acuity-0.05 and/or visual field loss to less than 10°. Results Unilateral and bilateral blindness were respectively 11.0% and 1.6%at the beginning, and 15.5%and 3.6% at the end of the observation period (7.5±5.5 years, range:1-25 years)//conversion to blindness (at least unilateral) was 1.1%/year. 134 eyes (97 patients) developed blindness by POAG during the study. At the first access to study centre, they had mean deviation (MD) of -17.1±8.3 dB and treated intraocular pressure (IOP) of 17.1±6.6 mmHg. During follow-up the IOP decreased by 14%in these eyes but MD deteriorated by 1.1±3.5 dB/year, which was 5-fold higher than controls (0.2±1.6 dB/year). In a multivariate model, the best predictors for blindness by glaucoma were initial MD (p<0.001), initial IOP (p<0.001), older age at the beginning of follow-up (p<0.001), whereas final IOP was found to be protective (p<0.05). Conclusions In this series of patients, blindness occurred in about 20%. Blindness by glaucoma had 2 characteristics: late diagnosis and/or late referral, and progression of the disease despite in most cases IOP was within the range of normality and target IOP was achieved//it could be predicted by high initial MD, high initial IOP, and old age

Venous Thrombosis

According to Virchow's triad, venous thrombosis can occur as a result of one or more of three factors: changes in the dynamics of the blood flow, endothelial injury/dysfunction of the blood vessel and hypercoagulability. The blood in the veins is constantly forming microscopic thrombi that are routinely broken down by the body, and significant clotting can occur only when the balance of thrombus formation and resolution is altered. This book is a fresh synthesis of venous thromboembolism care and considers the opinions and studies from different fields of medicine. As venous thrombosis spectrum is wide and can affect many organ systems, from deep veins of the leg to the cerebral venous system, our intent is for this to be a comprehensive, up-to-date and readable book. We tried to present a synthesis of existing material infused with new ideas and perspectives and authors own clinical studies and even case-reports

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

Spatial and spatio-temporal statistical analyses of retinal images: a review of methods and applications.

Background: Clinical research and management of retinal diseases greatly depend on the interpretation of retinal images and often longitudinally collected images. Retinal images provide context for spatial data, namely the location of specific pathologies within the retina. Longitudinally collected images can show how clinical events at one point can affect the retina over time. In this review, we aimed to assess statistical approaches to spatial and spatio-temporal data in retinal images. We also review the spatio-temporal modelling approaches used in other medical image types. Methods: We conducted a comprehensive literature review of both spatial or spatio-temporal approaches and non-spatial approaches to the statistical analysis of retinal images. The key methodological and clinical characteristics of published papers were extracted. We also investigated whether clinical variables and spatial correlation were accounted for in the analysis. Results: Thirty-four papers that included retinal imaging data were identified for full-text information extraction. Only 11 (32.4%) papers used spatial or spatio-temporal statistical methods to analyse images, others (23 papers, 67.6%) used non-spatial methods. Twenty-eight (82.4%) papers reported images collected cross-sectionally, while 6 (17.6%) papers reported analyses on images collected longitudinally. In imaging areas outside of ophthalmology, 19 papers were identified with spatio-temporal analysis, and multiple statistical methods were recorded. Conclusions: In future statistical analyses of retinal images, it will be beneficial to clearly define and report the spatial distributions studied, report the spatial correlations, combine imaging data with clinical variables into analysis if available, and clearly state the software or packages used

Variation in Visual Outcomes and Quality of Life in Patients with Neovascular Age- Related Macular Degeneration: what does any variation mean?

Neovascular age-related macular degeneration (nAMD) represents one of the leading causes of blindness in both developed and developing countries. This thesis examines inequalities and variations in visual outcomes for people being treated for nAMD, the reasons behind any variation, and how this variation relates to self-reported quality of life. nAMD began to be treated via intraocular injections with anti-vascular endothelial growth factors (anti-VEGF) after 2006. This thesis drew on the landmark trials that first established the safety and efficacy of anti-VEGF therapy for nAMD. Using a systematic review, this thesis then investigated whether there were factors that could be identified from the literature that influenced how effective anti-VEGF therapy is in reducing visual loss in patients with nAMD. This thesis highlights the importance of being able to identify modifiable factors, such as number of anti-VEGF injections received, that could lead to better visual outcomes for these patients. This thesis then goes on to examine levels of variation in visual outcome in nAMD nationally in the UK, as well as further investigating any influencing factors that could not be identified in the systematic review. This was done using a large real-world dataset of over 26,00 patients from seven hospitals. This highlighted significant levels of variation, but struggled to identify definitively further influencing factors, such as ethnicity or social deprivation. This could be because there genuinely was not an associated relationship between these factors and visual outcomes, but certainly in the case of ethnicity, it is particularly apparent that there was an overwhelmingly white population, so there may have not been enough ethnic variation to detect any effect of ethnicity. This thesis then investigates the link between visual acuity and quality of life, in a prospective study of patients from a teaching hospital in York. However, due to a much-reduced sample size, partly due to the COVID-19 pandemic, this thesis was unable to meaningfully link the two outcomes. The focus of this thesis was that of identifying and understanding variation in patients being treated for nAMD, within a wider picture of variation and inequality in healthcare in general. It showed variation in visual outcomes, but apart from visual acuity at baseline and number of injections, it was unable to identify other influencing factors. It is therefore concluded that further work with larger sample sizes needs to be undertaken to definitively address the overall aims of this thesis. Along with this, further attention needs to be given to the role of intersectionality of possible influencing factors in visual outcomes. Some of the methodology used in this thesis also need to reconsidered, such as if further prospective work is done, considering using telephone follow-up. There also needs to be consideration of taking into account the effect of the better seeing eye on quality of life

Human retinal oximetry using spectral imaging

The principal aim of the research described in this thesis was to develop a technique of non-invasively measuring the oxygen saturation within the retinal vasculature of human subjects (retinal oximetry). The evaluation of a hyperspectral fundus camera used to acquire retinal images in different wavelengths of visible light, and the image analysis techniques used to perform retinal oximetry are described. Validation of the oximetry techniques was performed using an artificial eye containing human blood of known oxygen saturation: the calculated oxygen saturation was compared to the gold standard measurement. The mean differences between the calculated and measured oxygen saturations were small. Hyperspectral imaging/oximetry of normal subjects was performed to characterize the oximetric features of the retinal vasculature. The mean oxygen saturation (± SD) of the temporal retinal arterioles and venules were 110.8% (± 11.8%) and 27.7% (± 3.2%) respectively. The application of the retinal oximetry technique was explored in patients with retinal arterial and venous occlusion to determine whether oximetric changes in the retinal vasculature could be detected. Variation in measured oxygen saturation of the retinal arterioles and venules respectively were apparent, and corresponded with angiographic features of retinal capillary loss. The techniques were applied to patients with asymmetrical primary open angle glaucoma to determine whether oximetric changes could be detected. The mean oxygen saturation of the temporal retinal venules were significantly higher [44.8% (± 24.2%)] in the more advanced glaucomatous eyes compared to normal subjects. Hyperoxia of the retinal venules suggests reduced oxygen consumption as a consequence of inner retinal dysfunction in glaucoma. However, because of the small sample size, further research on a larger population of subjects is required to support this finding. Hyperspectral imaging could be used to detect oximetric abnormalities in the retinal vasculature in patients with retinovascular occlusion and glaucoma