Purpose: We evaluate solutions for an applanating surface modification to the Goldmann tonometer prism, which substantially negates the errors due to patient variability in biomechanics. Methods: A modified Goldmann or correcting applanation tonometry surface (CATS) prism is presented which was optimized to minimize the intraocular pressure (lOP) error due to corneal thickness, stiffness, curvature, and tear film. Mathematical modeling with finite element analysis (FEA) and manometric lOP referenced cadaver eyes were used to optimize and validate the design. Results: Mathematical modeling of the optimized CATS prism indicates an approximate 50% reduction in each of the corneal biomechanical and tear film errors. Manometric lOP referenced pressure in cadaveric eyes demonstrates substantial equivalence to GAT in nominal eyes with the CATS prism as predicted by modeling theory. Conclusion: A CATS modified Goldmann prism is theoretically able to significantly improve the accuracy of lOP measurement without changing Goldmann measurement technique or interpretation. Clinical validation is needed but the analysis indicates a reduction in CCT error alone to less than +/- 2 mm Hg using the CATS prism in 100% of a standard population compared to only 54% less than +/- 2 mm Hg error with the present Goldmann prism. Translational Relevance: This article presents an easily adopted novel approach and critical design parameters to improve the accuracy of a Goldmann applanating tonometer.

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This study aimed to create computer models to aid the diagnosis of keratoconus using an edge segmentation algorithm, wavelet transforms and machine-learning techniques based on biomechanical parameters of the cornea derived from Corvis ST. 102 normal eyes, and 73 eyes with keratoconus grade I and II for training and validation of the models were included. Initially the 31 original equipment parameters were studied to assess its power in separating the control groups and research group. Then, it was used the Canny algorithm for edges segmentation of the selected images, so that 400 central points of these images could be processed with the wavelet transforms and later with machine learning techniques. The best result was achieved using the Haar wavelet transform and a Multilayer Perceptron Neural Network, reaching the sensitivity of 84.93%, a specificity of 89.22% and an Area Under the ROC Curve (AUC) of 0932. It concludes that the developed models can help make the diagnosis of early keratoconus. / O presente trabalho objetivou criar modelos computacionais de auxílio ao diagnóstico de ceratocone, utilizando um algoritmo de segmentação de borda, transformadas de wavelet e técnicas de aprendizagem de máquina, baseados em parâmetros biomecânicos da córnea derivados do CorVis ST. Foram incluídos 102 olhos normais, e 73 olhos com ceratocone grau I e II para o treinamento e validação dos modelos criados. Inicialmente foram estudados os 31 parâmetros originais do equipamento, para avaliar seu poder em separar os grupos de controle e pesquisa. Foi então utilizado o algoritmo Canny para segmentação das bordas das imagens selecionadas, para que 400 pontos centrais extraídos dessas imagens pudessem ser processados com as transformadas de wavelet e posteriormente com técnicas de aprendizado de máquina. O melhor resultado foi alcançado utilizando a transformada de Wavelet do tipo Haar e uma Rede Neural Multilayer Perceptron, alcançando a sensibilidade de 84.93%, uma especificidade de 89.22% e uma Area Under de ROC Curve (AUC) de 0.932. Conclui-se que os modelos desenvolvidos podem contribuir para tornar o diagnóstico de ceratocone mais precoce.

Purpose: Clinically evaluate a modified applanating surface Goldmann tonometer prism designed to substantially negate errors due to patient variability in biomechanics. Methods: A modified Goldmann prism with a correcting applanation tonometry surface (CATS) was mathematically optimized to minimize the intraocular pressure (IOP) measurement error due to patient variability in corneal thickness, stiffness, curvature, and tear film adhesion force. A comparative clinical study of 109 eyes measured IOP with CATS and Goldmann prisms. The IOP measurement differences between the CATS and Goldmann prisms were correlated to corneal thickness, hysteresis, and curvature. Results: The CATS tonometer prism in correcting for Goldmann central corneal thickness (CCT) error demonstrated a reduction to <+/- 2 mmHg in 97% of a standard CCT population. This compares to only 54% with CCT error <+/- 2 mmHg using the Goldmann prism. Equal reductions of similar to 50% in errors due to corneal rigidity and curvature were also demonstrated. Conclusion: The results validate the CATS prism's improved accuracy and expected reduced sensitivity to Goldmann errors without IOP bias as predicted by mathematical modeling. The CATS replacement for the Goldmann prism does not change Goldmann measurement technique or interpretation.

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Le glaucome est une maladie neurodégénérative qui se définit par une perte progressive en fibres nerveuses rétiniennes et un rétrécissement du champ visuel. Il s’agit de la première cause de cécité irréversible dans le monde et le principal facteur de risque est la pression intraoculaire (PIO). L’étude ALIENOR (Antioxydants, Lipides Essentiels, Nutrition et maladies OculaiRes) est une étude épidémiologique qui a pour but de déterminer l’incidence des différentes pathologies oculaires liées à l’âge avec les facteurs nutritionnels, démographiques ou environnementaux dans une population représentative de la région de Bordeaux. En 2009-2010, 624 sujets âgés de plus de 74 ans ont bénéficié d’un examen ophtalmologique complet incluant un examen du nerf optique en rétinophotographie et en tomographie à cohérence optique spectral-domain (SD-OCT), d’une mesure la PIO au tonomètre à air et d’une évaluation des propriétés biomécaniques de la cornée. Une mesure de l’accumulation cutanée de produits de glycation avancée a été réalisée par autofluorescence. Le diagnostic de glaucome a été réalisé en utilisant les critères de la classification ISGEO (International Society for Epidemiologic and Geographical Ophthalmology). Les paramètres biomécaniques de la cornée étaient modifiés avec l’âge et chez les sujets ayant une histoire résidentielle à des latitudes plus exposées aux ultraviolets ambiants. L’épaisseur de cornée était plus élevée chez les sujets anciennement fumeurs. L’autofluorescence cutanée ≥ 2.7 UA (Unité Arbitraire) était indépendamment associée au glaucome. Les paramètres d’épaisseur en fibres nerveuses rétiniennes du SD-OCT présentaient de bonnes performances diagnostiques pour discriminer les sujets glaucomateux des témoins et la base normative présentait de bonnes performances discriminatives lorsqu’au moins un des paramètres était considéré comme anormal. Notre étude apporte des résultats originaux en termes de facteurs de risque de glaucome ou de déterminants des facteurs de risque de glaucome. De plus les performances diagnostiques du SD-OCT pourraient fournir des informations utiles pour optimiser les stratégies de dépistage du glaucome dans une population générale âgée. / Glaucoma is a neurodegenerative disease defined by a progressive loss of optic nerve axons and retinal ganglion cells resulting in a characteristic enlargement of the optic nerve head cup and associated visual field defects. It remains the first cause of irreversible blindness worldwide and intraocular pressure (IOP) is the main risk factor. The ALIENOR (Antioxydants, Lipides Essentiels, Nutrition et maladies OculaiRes) study is a population-based study. It aims to assess the associations of age-related eye diseases with nutritional, demographic and environmental factors in a representative population of the Bordeaux area. In 2009-2010, 624 subjects, aged 74 years or more, underwent a complete eye examination, including an optic nerve head evaluation using retinophotography and a spectral-domain optical coherence tomography (SD-OCT), an IOP measurement using air-puff tonometry and an evaluation of biomechanical properties of the cornea. A measurement of skin accumulation of advanced glycation end-products was performed using an autofluorescence reader. Glaucoma diagnosis was made using ISGEO (International Society for Epidemiologic and Geographical Ophthalmology) criteria. Biomechanical properties of the cornea were modified by increasing age and in subjects having a higher lifetime ambient ultraviolet exposure. Central corneal thickness was thicker in former smokers. Skin autofluorescence values ≥ 2.7 AU (Arbitrary Unit) were independently associated with glaucoma. SD-OCT retinal nerve fiber layer thickness parameters had good diagnostic performances for discriminating glaucoma and control subjects and the normative database had good diagnostic performances if at least one parameter was considered abnormal by the machine. Our study provides new insights on glaucoma risk factors and determinants of glaucoma risk factors. Furthermore diagnostic performances of SD-OCT may provide valuable information in a screening strategy to optimize glaucoma detection in a general population of elderly people.

The thesis investigates methods of examining corneal biomechanics using non-contact tonometry and introduces novel techniques to investigate corneal material properties in vivo. A comprehensive systems analysis of the CorvisST (CST) and Ocular Response Analyser (ORA) was performed. Pressure sensors were used to characterisation the airflow produced by the CST and the ORA. Distinct differences were observed between the central airflow pressures between the two devices: the CST pressure was higher and of shorter duration. Scheimpflug high-speed imaging via the CST allowed components of the corneal deformation to be investigated and the development of a 3D deformation matrix (time, depth and spatial resolution) through tracing of the anterior and posterior corneal surface. Measures of whole eye movement (WEM) with CST were found to be robust. WEM demonstrated an asymmetric profile and a correction method was developed to address the corneal deformation matrix for this asymmetry. Novel methods for characterisation of intrinsic material characteristics of the cornea were developed using numerical and graphical analytical procedures. Application of these parameters was tested on enucleated porcine eyes across a wide range of manometry internal ocular pressure (MIOP). The dynamic E-Modulus was found to be most affected by MIOP change. To investigate the in vivo distribution and heterogeneity of the corneal biomechanics, a novel set-up allowed the mapping of corneal biomechanics across the cornea using the CST (central, paracentral, peripheral) and ORA (central, peripheral). Biometric and demographic grouping of subjects allowed detection of discriminating factors between individuals. The results suggest that the in vivo cornea of healthy human adults can be characterised as a viscoelastic, damped system for longitudinal strain and a highly oscillating system for lateral strain. The cornea is approximately homogenous for measures of rigidity and dynamic E-Modulus but other corneal material characteristics (longitudinal and lateral strain, hysteresis, damping and compressibility) demonstrated regional differences. The experimental design employed allowed for strict control of biometric and biomechanical intersubject variables, based on gold-standard techniques as well as newly-developed methods, thereby creating a normative database for future use.

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