Optimizing riboflavin/ultraviolet-a corneal collagen cross-linking for the treatment of progressive keratoconus

Patients with keratoconus exhibit a biomechanically weakened cornea which loses its proper shape and thereby loses its refractive power. It is usually progressive, beginning with poor visual acuity and eventually necessitating corneal transplant. The cause is likely multifactorial, but involves the weakening of the collagen structure of the corneal stroma, resulting in characteristic thinning and conical distortion. Collagen cross-linking is the first treatment to demonstrate efficacy in halting the progression of the disease. UVA radiation is used to activate riboflavin and photochemically induce cross-linking reactions among collagen and proteoglycans within the stroma, thereby stiffening and strengthening the tissue, and preventing further loss of shape. The current standard treatment, which gained FDA approval less than one year ago, has proven to be efficacious, but has been modified very little since pioneering experiments. Optimization aims to maximize clinical effect while maintaining safety and reducing total treatment time. Major procedural modifications involve increasing light intensity over a reduced exposure duration, and varying the method of delivering riboflavin to the stroma. Theoretical modeling, informed by and scaled to experimental results, has the potential to predict clinical effect as a function of treatment parameters, enabling tailoring of individual treatments to the specific needs of each patient

Optical designs and image processing algorithms for optical coherence tomography detection of glaucoma

textOptical Coherence Tomography (OCT) is an optical tomography technique which provides high resolution non-invasive three-dimensional (3D) structural images of the sample based on coherent properties of light. The dissertation focuses on the use of OCT systems for detecting glaucoma, which is the second leading cause of blindness worldwide. First, as a prerequisite of analyzing ophthalmologic OCT images, a retinal sublayer segmentation algorithm is presented and implemented with GPU assisted computation. Then, a polarization-sensitive optical coherence tomography (PS-OCT) system was constructed for the study of glaucoma. Three closely related clinical and animal studies on early-stage glaucoma detection using either OCT or PS-OCT were performed. Statistical analysis of the study results indicates that the scattering property of retinal nerve fiber layer (RNFL) is the earliest indicator for glaucoma. Finally, to investigate the scattering properties of RNFL, a pathlength-multiplexed scattering-angle-diverse optical coherence tomography (PM-SAD-OCT) system was designed and built. PM-SAD-OCT images were collected from human and rodent retina as well as earthworm nerve cord. PM-SAD-OCT system shows promising potentials to detect neurodegenerative diseases including glaucoma.Biomedical Engineerin

Ganglion cell complex analysis in glaucoma patients: what can it tell us?

Glaucoma is a group of optic neuropathies characterized by a progressive degeneration of retina ganglion cells (RGCs) and their axons that precedes functional changes detected on the visual field. The macular ganglion cell complex (GCC), available in commercial Fourier-domain optical coherence tomography, allows the quantification of the innermost retinal layers that are potentially involved in the glaucomatous damage, including the retinal nerve fiber (RNFL), ganglion cell and inner plexiform layers. The average GCC thickness and its related parameters represent a reliable biomarker in detecting preperimetric glaucomatous damage. The most accurate GCC parameters are represented by average and inferior GCC thicknesses, and they can be associated with progressive visual field loss. Although the diagnostic accuracy increases with more severe glaucomatous damage and higher signal strength values, it is not affected by increasing axial length, resulting in a more accurate discrimination of glaucomatous damage in myopic eyes with respect to the traditional RNFL thickness. The analysis of the structure-function relationship revealed a good agreement between the loss in retinal sensitivity and GCC thickness. The use of a 10-2° visual field grid, adjusted for the anatomical RGCs displacement, describes more accurately the relationship between RGCs thickness and visual field sensitivity loss

Uso da microscopia digital para comparação de espessura entre córneas normais e rejeitadas ex-vivo: ênfase na Membrana de Descemet

Objective: To analyze and compare thickness measurements of corneal layers, especially the Descemet membrane (DM), in normal corneas and in failed grafts due to rejection (FGRs) using a digital microscopy method. Methods: An experimental, cross-sectional, and analytical study was performed at the Henry C. Witelson Ocular Pathology Laboratory (McGill University Health Center and Research Institute, Montreal/Canada). Slides of 25 normal human corneas and 40 FGRs were examined using a Philips Ultra Fast Scanner® and the associated software. The inclusion criteria adopted were samples diagnosed as normal corneas or FGRs, all specimens were from patients older than 18 years of age. Slides with corneal structures that could not be adequately visualized and/or whose donor epidemiological information could not be obtained were excluded from the study. On each slide, the thickness of the corneal layers was measured, with 2 central measurements, 2 measurements at the nasal periphery, and 2 measurements at the temporal periphery using perpendicular planes as reference. Results: There were differences between the normal and FGR groups in the means of the central thickness of the epithelium (p<0.001), the nasal and temporal stroma regions (p<0.001), and the DM in the nasal and temporal regions (p<0.001). Comparing the mean thicknesses of the different regions (central, nasal and temporal) of the DM in the same group, the central region of the DM in the normal corneas had a lower mean thickness than the two peripheral regions (p<0.001), a difference that did not occur in the FGR group. Conclusions: Normal corneas had a lower epithelium thickness in the central region than did corneas in the FGR group. In addition, the stroma and DM thickness of the nasal and temporal periphery was significantly higher in normal corneas than in those from the FGR group.Objetivo: Analisar e comparar as medidas de espessura das camadas corneanas, especialmente a membrana de Descemet (MD), em córneas normais e provenientes de enxertos apresentando falência por rejeição (EFR) através do método de microscopia digital. Métodos: Estudo experimental, transversal e analítico, realizado no laboratório de patologia ocular Henry C. Witelson (McGill University Health Centre and Research Institute/Canadá). Foram examinadas lâminas de 25 córneas humanas normais e 40 provenientes de EFR utilizando scanner e software Philips Ultra Fast Scanner®. Os critérios de inclusão adotados foram amostras diagnosticadas como córneas normais ou EFR e advindos de pacientes acima dos 18 anos de idade. Foram excluídas da pesquisa as lâminas cujas estruturas corneanas não pudessem ser visibilizadas de forma adequada e/ou cujas informações epidemiológicas do doador não pudessem ser obtidas. De cada lâmina foram aferidas as espessuras das camadas corneanas, sendo realizadas 2 medidas centrais, 2 medidas na periferia nasal e 2 medidas na periferia temporal, utilizando planos perpendiculares como referência. Resultados: Houve diferença entre os grupos normais e com EFR nas médias da espessura central do epitélio (p<0,001), na região estromal nasal e temporal (p<0,001) e na MD nas regiões nasal e temporal (p<0,001). Quando efetuada comparação entre a média da espessura das diferentes regiões (central, nasal e temporal) da MD entre um mesmo grupo, nas córneas normais a região central da MD apresenta média de espessura mais fina em relação às duas regiões periféricas (p<0,001), diferença esta que não se verifica no grupo de EFR. Conclusões: Córneas normais apresentavam medidas de espessura centrais epiteliais menores em relação ao grupo EFR. Ainda, nas córneas normais as espessuras do estroma e MD da periferia nasal e temporal eram significativamente maiores em comparação com o grupo EFR.Dados abertos - Sucupira - Teses e dissertações (2019

An in vivo investigation of choroidal vasculature in age-related macular degeneration

Age-related macular degeneration (AMD) is the leading cause of visual impairment in the developed world. Whilst the pathogenesis is complex and not fully understood, changes to the choroidal vasculature in AMD have been demonstrated using histology. Advances in imaging technology, particularly long-wavelength optical coherence tomography (OCT), allow in vivo visualisation and investigation of this structure. The aim of this work is to determine whether changes to the choroidal vasculature are detectable in AMD using in vivo imaging. This was achieved through the evaluation of parameters for quantifying the structure, and the application of a machine learning approach to automated disease severity classification, based on choroidal appearance. Participants with early AMD (n=25), neovascular AMD (nAMD; n=25), and healthy controls (n=25) underwent imaging with a non-commercial long-wavelength (λc=1040 nm) OCT device. Subfoveal choroidal thickness, choroidal area, and luminal area were significantly lower in the nAMD group than the healthy and early AMD groups, whilst vessel ratio was significantly greater (P<0.05 in all cases). There was no significant difference in visible vessel diameter, choroidal vascularity index, luminal area ratio, or luminal perimeter ratio between the groups. No significant differences were found between the healthy and early AMD groups for any of the eight vascular parameters assessed. Classification of the disease groups based on choroidal OCT images was demonstrated using machine learning techniques. Textural features within the images were extracted using Gabor filters, and K-nearest neighbour, support vector machine, and random forest classifiers were assessed for this classification task. Textural changes were most pronounced in late-stage disease, although attribution to pathology or pharmacological intervention (anti-VEGF treatment) was not possible. Changes were also discernible in the early AMD group, suggesting sensitivity of this approach to detecting vascular involvement in early disease. In conclusion, structural changes to the choroidal vasculature in AMD are detectable in vivo using OCT imaging, demonstrated with both manual and automated analysis techniques. Whilst changes were most prominent in late-stage disease, subtle structural changes in early AMD were identified with texture analysis, warranting further investigation to improve our understanding of choroidal involvement in the pathogenesis of early AMD

Microscopy and Analysis

Microscopes represent tools of the utmost importance for a wide range of disciplines. Without them, it would have been impossible to stand where we stand today in terms of understanding the structure and functions of organelles and cells, tissue composition and metabolism, or the causes behind various pathologies and their progression. Our knowledge on basic and advanced materials is also intimately intertwined to the realm of microscopy, and progress in key fields of micro- and nanotechnologies critically depends on high-resolution imaging systems. This volume includes a series of chapters that address highly significant scientific subjects from diverse areas of microscopy and analysis. Authoritative voices in their fields present in this volume their work or review recent trends, concepts, and applications, in a manner that is accessible to a broad readership audience from both within and outside their specialist area

Retinal structure and function in age-related maculopathy

Age-related macular degeneration (AMD) is the principle cause of visual loss and blindness in the developed world. As new treatments and therapies are developed the need to better diagnose and then monitor outcomes of treatment has become more important. This thesis evaluates both structural and functional changes that occur in the early stage of AMD, known as age-related maculopathy (ARM), with the aim of determining their diagnostic potential. This thesis also explores the relationship between structural and functional parameters. Twenty four participants with ARM and 26 control participants were recruited. Retinal function was probed using four focal electroretinography (ERG) techniques: the focal cone ERG, focal flicker ERG, ERG photostress test and focal rod ERG. Long wavelength optical coherence tomography (OCT) was used to assess retinal structure, specifically retinal, choroidal and four intra-retinal layer thicknesses at 21 macular locations. These techniques were initially developed and optimised for the detection of AMD related changes. The ability of each parameter to diagnose ARM was assessed. Correlation and linear regression analyses were carried out to identify any relationships between retinal structure and function in healthy controls. Retinal thickness was reduced in participants with ARM at parafoveal locations (~2° eccentricity), but choroid thickness was unaffected. Diagnostically, focal ERG parameters provided better sensitivity and specificity to ARM than OCT measures, with the ERG photostress test providing the best diagnostic potential. No strong relationships were shown between any ERG parameter and any retinal or choroidal layer volume in control participants. Three ERG parameters were shown to be related to specific retinal features of ARM, but the strongest associations were between ERG photostress test recovery and focal cone ERG b-wave implicit time and a diagnosis of wet AMD in the contralateral eye. In conclusion the structural and functional parameters assessed appeared to provide independent information regarding disease status and severity. ERG parameters showed better diagnostic potential than OCT measures. The single most diagnostic parameter was the recovery time constant of the ERG photostress test

Retinal structure and function in age-related maculopathy

Age-related macular degeneration (AMD) is the principle cause of visual loss and blindness in the developed world. As new treatments and therapies are developed the need to better diagnose and then monitor outcomes of treatment has become more important. This thesis evaluates both structural and functional changes that occur in the early stage of AMD, known as age-related maculopathy (ARM), with the aim of determining their diagnostic potential. This thesis also explores the relationship between structural and functional parameters. Twenty four participants with ARM and 26 control participants were recruited. Retinal function was probed using four focal electroretinography (ERG) techniques: the focal cone ERG, focal flicker ERG, ERG photostress test and focal rod ERG. Long wavelength optical coherence tomography (OCT) was used to assess retinal structure, specifically retinal, choroidal and four intra-retinal layer thicknesses at 21 macular locations. These techniques were initially developed and optimised for the detection of AMD related changes. The ability of each parameter to diagnose ARM was assessed. Correlation and linear regression analyses were carried out to identify any relationships between retinal structure and function in healthy controls. Retinal thickness was reduced in participants with ARM at parafoveal locations (~2° eccentricity), but choroid thickness was unaffected. Diagnostically, focal ERG parameters provided better sensitivity and specificity to ARM than OCT measures, with the ERG photostress test providing the best diagnostic potential. No strong relationships were shown between any ERG parameter and any retinal or choroidal layer volume in control participants. Three ERG parameters were shown to be related to specific retinal features of ARM, but the strongest associations were between ERG photostress test recovery and focal cone ERG b-wave implicit time and a diagnosis of wet AMD in the contralateral eye. In conclusion the structural and functional parameters assessed appeared to provide independent information regarding disease status and severity. ERG parameters showed better diagnostic potential than OCT measures. The single most diagnostic parameter was the recovery time constant of the ERG photostress test.EThOS - Electronic Theses Online ServiceGBUnited Kingdo