Notre projet vise à élucider la relation complexe entre la morphologie des nerfs cornéens et la sensibilité cornéenne, afin d'améliorer la compréhension et le diagnostic des pathologies oculaires. En utilisant deux types d'esthésiomètres : l'esthésiomètre sans contact (NCCA) et le Cochet-Bonnet (CBA) pour mesurer la sensibilité, et en analysant les images de microscopie confocale (IVCM) via le logiciel CCMetrics, nous avons étudié 23 individus, y compris ceux souffrant de diabète et de kératite neurotrophique. Des corrélations négatives significatives entre certains attributs neuronaux et la sensibilité cornéenne ont été identifiées. L'utilisation d'algorithmes d'apprentissage automatique, tels que K-Plus Proches Voisins (KNN), les Réseaux de Neurones (MLP), la Régression à Vecteurs de Support (SVR) et les arbres de décision, a révélé des relations non linéaires complexes. Notre étude encourage l'utilisation de l’apprentissage automatique pour détecter ces relations complexes dans le domaine médical en général et en ophtalmologie en particulier. / Our project aims to clarify the complex relationship between the morphology of corneal nerves and corneal sensitivity, to improve understanding and diagnosis of eye pathologies. We used two types of esthesiometers: a non-contact esthesiometer (NCCA) and Cochet-Bonnet (CBA) for sensitivity measurement and analyzed confocal microscopy (IVCM) images using the software CCMetrics. We studied 23 individuals, including those with diabetes and neurotrophic keratitis. Significant negative correlations between certain neuronal attributes and corneal sensitivity were identified. The use of machine learning algorithms, such as K-Nearest Neighbors (KNN), Neural Networks (MLP), Support Vector Regression (SVR), and decision trees, revealed complex non-linear relationships. Our study advocates using machine learning to detect these complex relationships in the medical field, especially in ophthalmology.

The anterior refracting surface of the eye is the thin tear film that forms on the surface of the cornea. When a contact lens is on worn, the tear film covers the contact lens as it would a bare cornea, and is affected by the contact lens material properties. Tear film irregularity can cause both discomfort and vision quality degradation. Under normal conditions, the tear film is less than 10 microns thick and the thickness and topography change in the time between blinks. In order to both better understand the tear film, and to characterize how contact lenses affect tear film behavior, two interferometers were designed and built to separately measure tear film behavior in vitro and in vivo. An in vitro method of characterizing dynamic fluid layers applied to contact lenses mounted on mechanical substrates has been developed using a phase-shifting Twyman- Green interferometer. This interferometer continuously measures light reflected from the surface of the fluid layer, allowing precision analysis of the dynamic fluid layer. Movies showing this fluid layer behavior can be generated. The fluid behavior on the contact lens surface is measured, allowing quantitative analysis beyond what typical contact angle or visual inspection methods provide. The in vivo interferometer is a similar system, with additional modules included to provide capability for human testing. This tear film measurement allows analysis beyond capabilities of typical fluorescein visual inspection or videokeratometry and provides better sensitivity and resolution than shearing interferometry methods. The in vitro interferometer system has measured the formation and break up of fluid layers. Different fluid and contact lens material combinations have been used, and significant fluid layer properties have been observed in some cases. This dissertation discusses the design of this interferometer along with analysis methods used. Example measurement results of different contact lens are presented highlighting the capabilities of the instrument. This dissertation also provides the in vivo interferometer design, along with the considerations that must be taken when designing an interferometer for on-eye diagnostics. Discussions include accommodating eye movement, design of null optics for a range of ocular geometries, and laser emission limits for on-eye interferometry in general.

The purpose of this thesis is to describe the development of an anatomically based, young adult eye model, which includes a crystalline lens with a gradient refractive index (GRIN). This model will then be used to investigate the effect of laser refractive surgery. The first step in this process involved developing a symmetrical eye model that was found to be a better predictor of empirical longitudinal spherical aberration than any previous model. Myopia was simulated by either a purely axial or refractive technique. While these models were found to be good predictors of the spherical aberration measured in young adults, they did not predict the total amount of high-order aberrations. The techniques used to simulate a single type of myopia caused the myopic models to become anatomically inaccurate. To improve the eye models a biconic surface was used to quantify the anterior corneal shape as a function of myopia. A method to describe the refractive error and biconic shape parameters in Jackson Cross Cylinder terms was implemented to determine correlations. Results indicate that a biconic accurately models the average shape of the anterior corneal surface as a function of myopia. Adopting the biconic model for the anterior corneal surface and adding average misalignments of the ocular components transformed the models from symmetrical to asymmetrical. Refractive error was now simulated by the anatomically accurate changes in both the anterior corneal shape and axial length. The asymmetrical aberrations resulted from the misalignment of the ocular components and provided a good prediction of average empirical aberrations but underestimated the aberrations of individual subjects. Photorefractive keratectomy, a form of laser refractive surgery, was simulated by theoretically calculated and by empirically measured changes in the shape of the anterior corneal surface. Applying the change in anterior corneal shape to the asymmetrical models was used to develop postoperative models. Changes in corneal shape and model aberrations attributed to theoretical calculations do not match empirical observations. The prediction of increased high-order aberrations in postoperative models based on empirically measured changes in the anterior corneal topography was similar to clinical results. Average anatomically based, GRIN eye models have been developed that accurately predict the average aberrations of emmetropic and myopic young adults. These models underestimate the asymmetrical and total high-order aberrations that have been measured in individual subjects but are still useful for investigating the average effects of procedures like refractive surgery.

The visual quality effects from the dynamic behavior of the tear film have been determined through measurements acquired with a high resolution Twyman-Green interferometer. The base shape of the eye has been removed to isolate the aberrations induced by the tear film. The measured tear film was then combined with a typical human eye model to simulate visual performance. Fourier theory has been implemented to calculate the incoherent point spread function, the modulation transfer function, and the subjective quality factor for this system. Analysis software has been developed for ease of automation for large data sets, and outputs movies have been made that display these visual quality metrics alongside the tear film. Post processing software was written to identify and eliminate bad frames. As a whole, this software creates the potential for increased intuition about the connection between blinks, tear film dynamics and visual quality.

Background: To evaluate the toric intraocular lens (IOL) calculation considering posterior corneal astigmatism, incision-induced posterior corneal astigmatism, and effective lens position (ELP). Methods Two thousand samples of corneal parameters with keratometric astigmatism >= 1.0 D were obtained using boot-strap methods. The probability distributions for incision-induced keratometric and posterior corneal astigmatisms, as well as ELP were estimated from the literature review. The predicted residual astigmatism error using method D with an IOL add power calculator (IAPC) was compared with those derived using methods A, B, and C through Monte-Carlo simulation. Method A considered the keratometric astigmatism and incision-induced keratometric astigmatism, method B considered posterior corneal astigmatism in addition to the A method, method C considered incision-induced posterior corneal astigmatism in addition to the B method, and method D considered ELP in addition to the C method. To verify the IAPC used in this study, the predicted toric IOL cylinder power and its axis using the IAPC were compared with ray-tracing simulation results. Results The median magnitude of the predicted residual astigmatism error using method D (0.25 diopters [D]) was smaller than that derived using methods A (0.42 D), B (0.38 D), and C (0.28 D) respectively. Linear regression analysis indicated that the predicted toric IOL cylinder power and its axis had excellent goodness-of-fit between the IAPC and ray-tracing simulation. Conclusions The IAPC is a simple but accurate method for predicting the toric IOL cylinder power and its axis considering posterior corneal astigmatism, incision-induced posterior corneal astigmatism, and ELP.

Um sistema para auxílio à cirurgias oftálmicas foi desenvolvido com o objetivo de se minimizar o astigmatismo induzido devido ao formato irregular da córnea pelo ato de sutura. O sistema projeta 48 pontos de luz no filme lacrimal da córnea, provenientes de LEDs, dispostos num diâmetro precisamente circular. O deslocamento, a dimensão e a deformação da imagem refletida destes pontos luminosos são analisados proporcionando a ceratometria e a circularidade da sutura. O intervalo de medidas do sistema é de 32D - 55D (astigmatismos até 23D podem ser medidos) e um sistema para calibração do sistema foi projetado para manter o sistema calibrado. Esferas de aço de precisão foram submetidas ao sistema e uma correlação de 99% entre as medidas obtidas e os valores dos fabricantes foi obtida. O sistema foi testado em 13 voluntários para avaliação de sua aplicabilidade clínica e comparado a um ceratômetro comercial Topcon OM-4. Os fatores de correlação entre o sistema desenvolvido e o Topcon OM-4, para o astigmatismo, foi de \'R POT.2\' = 0,92, e em relação ao eixo, o fator é \'R POT.2\' = 0,99. O sistema indica que o cirurgião deve obter uma circularidade \'> OU =\' 98% para que astigmatismos acima de 3D não sejam induzidos na sutura. / A system for ophthalmic surgery support has been developed in order to minimize the residual astigmatism due to the induced irregular shape of the cornea by corneal suture. The system projects 48 light spots, from LEDs, displayed in a precise circle at the lachrymal film of the examined cornea. The displacement, the size and deformation of the reflected image of these light spots are analyzed providing the keratometry and the circularity of the suture. Measurements in the range of 32D - 55D (up to 23D of astigmatism are possible to be obtained) and a self-calibration system has been designed in order to keep the system calibrated. Steel precision spheres have been submitted to the system and the results show 99% of correlation with the fabricant\'s nominal values. The system has been tested in 13 persons in order to evaluate its clinical applicability and has been compared to a commercial keratometer Topcon OM-4. The correlation factors are 0,92 for the astigmatism and 0.99 for the associated axis. The system indicates that the surgeon should achieve circularity \'> OR =\' 98% in order to do not induce astigmatisms over 3D.

A facoemulsificação é, atualmente, considerada a técnica de eleição no tratamento da catarata, uma das principais causas de perda de visão, em cães. O procedimento demanda a realização de incisões na córnea para acesso à câmara anterior. Tais incisões, a despeito da extensão reduzida, podem lesar a inervação da córnea, comprometendo sua sensibilidade e, consequentemente, influenciar a produção lacrimal. Objetivando-se avaliar tais intercorrências, concebeu-se aferir a sensibilidade corneana e a produção lacrimal aquosa em cães submetidos à facoemulsificação. Para tanto, tais parâmetros foram investigados em 20 cães com idade, sexo, raça e peso variáveis. Os procedimentos cirúrgicos foram realizados em um único olho (OT), sendo o olho não operado utilizado como controle (OC). A sensibilidade da córnea foi mensurada com o estesiômetro de Cochet-Bonnet® e a produção lacrimal pelos testes do fenol vermelho e de Schirmer, em ambos os olhos. Os parâmetros foram aferidos previamente ao procedimento cirúrgico (M0 - valores basais) e, posteriormente, após sete dias (M1), 15 dias (M2), 30 dias (M3), 90 dias (M4) e 180 dias (M5). Os valores da produção lacrimal aferida com o teste do fenol vermelho, em M1, não diferiram dos obtidos previamente à cirurgia (M0), nos OT e OC; diferenças significativas foram observadas de M2 a M5, com valores superiores aos basais (M0), em ambos os olhos. Os resultados da mensuração lacrimal com o teste de Schirmer e da sensibilidade corneana à estesiometria (em cm e mm/g2) não diferiram dos basais (M0) em quaisquer dos períodos de avaliação (M1 a M5), em ambos os olhos. Os resultados obtidos ao estudo permitiram verificar que a realização da cirurgia de catarata por facoemulsificação, como fora proposto, não resulta em diminuição da sensibilidade corneana e produção lacrimal aquosa. / Phacoemulsification is considered the technique of choice for surgical extraction of cataracts, which is a leading cause of blindness in dogs. The procedure requires corneal incisions to enter the anterior chamber. These incisions, despite their reduced extensions, may damage the corneal innervation, compromising its sensitivity and, also, the tear production. Aiming to evaluate these consequences, this study intended to measure the corneal sensitivity and aqueous tear production in dogs undergoing phacoemulsification. These parameters were evaluated in 20 dogs, with different ages, genders, breeds and weights. Surgical procedures were performed in one eye (OT), and the fellow eye was used as a control (OC). Corneal sensitivity was measured with the Cochet-Bonnet® aesthesiometer and tear production by the phenol thread red test and Schirmer tear test, in both eyes. The parameters were measured prior to the surgery (M0 - baseline values) and after seven days (M1), 15 days (M2), 30 days (M3), 90 days (M4) and 180 days (M5). Tear production values measured with the phenol red test, in M1, were not different from the values measured prior to the surgery (M0), in OT and OC; significant differences were noticed from M2 to M5, with higher values when compared to baseline values (M0), in both eyes. Schirmer tear test and corneal sensitivity (in cm and mm/g2) values were not different from basal values (M0) in any of the evaluation times (M1 to M5), in both eyes. Our study outcomes suggest that phacoemulsification, as proposed previously, does not decrease the corneal sensitivity and aqueous tear production.

Doenças da córnea estão entre as principais causas de cegueira e os mecanismos de lesão e reparação estão em grande parte concentradas no epitélio, porém os mediadores e alvos para possíveis intervenções terapêuticas são pouco conhecidos.Nas agressões ao epitélio da córnea, a ativação dos receptores vanilóides de potencial transitório 1 (TRPV1) leva a resposta inflamatória e cicatricial. O objetivo desse trabalho é identificar os mecanismos de sinalização e resposta do TRPV1 na córnea de animais experimentais. O cultivo de células epiteliais de córnea de ratos, a identificação de mediadores por western blot, medida do influxo de cálcio, resposta de citocinas medidas por ensaio quantitativo de PCR em tempo real (RNAm) e ELISA (proteína) após estímulos nocioceptivos ou inflamatórios; e a investigação histológica e imunohistoquimica em modelos animais, sejam ratos com diabetes mellitus (DM) por 8 semanas ou expostos a cloreto de benzalcônio a 0,2% (BAC) por 7 dias. Camundongos TRPV1-/- comparados aos controles C57 foram comparados sem estimulo, ou sob estimulo único com CAP a 1µM, BAC 0,2 % por 7 dias ou após queimadura alcalina com NaOH a 1M. Os resultados mostraram a presença de TRPV1 em epitélio de córnea em cultura primária, mostraram que essas células respondem com influxo de cálcio ao estímulo com o agonista Capsaicina a 1µM e aumento de TNF? e IL-1? (sendo máximo nas combinações CAP+CPZ e Win+CAP, respectivamente). Em ratos com DM e BAC ocorre a redução da expressão do RNAm de IL-1? (p=0,0269) na córnea, entre outras alterações. Os camundongos TRPV1-/- tem fenótipo físico e ocular normal, porém reduzida sensibilidade a CAP 1µM. O tratamento com BAC leva a diminuição da secreção lacrimal (p=0,0011) e de IL-1? e TNF? na glândula lacrimal (GL) de TRPV1-/- machos (p=0,0177, p=0,0245, respectivamente). A queimadura alcalina com NaOH 1M resultou em melhor cicatrização e maior espessura epitelial no grupo TRPV1-/-. Em ix conclusão, o TRPV1 está presente na córnea e atua em resposta a agressões externas. Situações adquiridas como DM e toxicidade por BAC, reconhecidas como neuropáticas diminuem a expressão de mediadores inflamatórios. A ausência genética e TRPV1 não altera o fenótipo, mas apresenta menor sensibilidade e melhor restauração da superfície ocular após queimadura alcalina / Corneal diseases are among the leading causes of blindness.Damage and repair mechanisms are largely concentrated in the epithelium, but the mediators and targets for possible therapeutic interventions are poorly understood. The aggressions to the corneal epithelium, the activation of vanilloid receptors transient potential 1 (TRPV1) leads to inflammatory and wound healing. The aim of this study is to identify the signaling mechanisms and TRPV1 response in the cornea of experimental animals.The culture of epithelial cells from rat cornea, to identify mediators by western blot analysis, measurement of calcium influx, cytokine response measured by PCR real time (mRNA) and ELISA (protein) nocioceptivos or after inflammatory stimuli; and the histological and immunohistochemical investigation in animal models are mice with diabetes mellitus (DM) for 8 weeks, and exposed to benzalkonium chloride at 0.2% (BAC) for 7 days. Mice TRPV1-/- compared to control C57 were compared with no stimulus, or under single stimulation with 1 µM Capsaicine (CAP), BAC 0.2% for 7 days or after the alkali burn with NaOH 1 M.The results showed the presence of TRPV1 in corneal epithelium in primary culture, showed that these cells respond to calcium influx the stimulus with capsaicin agonist 1?M and increase of TNF? and IL-1? (being maximum at the CAP + CPZ combinations and Win + CAP, respectively). In rats with DM and BAC occurs reducing the expression of IL-1? mRNA (p = 0.0269) in the cornea, among other changes. The TRPV1-/- mice have physical phenotype and normal ocular but low sensitivity to CAP 1?M. Treatment with BAC leads to decreased tear secretion (p = 0.0011) and IL-1? and TNF? in the lacrimal gland (GL) of TRPV1-/- mice (p = 0.0177, p = 0.0245, respectively) . The alkaline burn with NaOH 1M resulted in better healing and greater epithelial thickness in TRPV1-/- group .In conclusion, TRPV1 is present in the cornea and operates in response to external aggressions. Situations existing as DM and xi toxicity BAC recognized as neuropathic decrease the expression of inflammatory mediators. Genetic absence and TRPV1 does not alter the phenotype, but has lower sensitivity and better restoration of the ocular surface after alkaline burn

Foi desenvolvido um sistema inédito para diagnóstico e acompanhamento de Doenças Oculares Externas, particularmente de úlceras de córnea e que foi implementado num Hospital-Escola para uso diário. As úlceras de córnea, até então, eram avaliadas de forma subjetiva e qualitativa, estimando-se a extensão da área afetada. O indicativo de evolução do quadro clínico é basicamente a alteração da área afetada. Com o intuito de se poder avaliar a evolução desta patologia de forma quantitativa e padronizada, foi desenvolvido o presente sistema. O sistema consistiu em acoplar a uma Lâmpada de Fenda (biomicroscópio ocular) um divisor de feixes e um sistema ótico, no caminho ótico onde os feixes da Lâmpada de Fenda são paralelos, de forma que a imagem proporcionada nas oculares da Lâmpada de Fenda é simultaneamente proporcionada num detector do tipo CCD. Esta câmera CCD foi acoplada a um micro computador do tipo PC, via uma interface comercial, e as imagens são disponibilizadas num monitor. Um software dedicado foi desenvolvido e possui as seguintes funções e características: reconhecimento automático e medidas das áreas de ulceração, opcionalmente, medidas interativas de áreas quaisquer, medidas lineares interativas de comprimentos quaisquer e um amplo banco de dados dedicado a este setor da Oftalmologia. Ainda, todos os comandos podem ser realizados através do teclado ou do mouse, particularmente o de capturar imagem também pode ser acionado através de um pedal desenvolvido especialmente para o sistema. O sistema apresentou uma precisão de 5% (o método convencional, para medidas de úlceras perfeitamente elípticas proporcionava uma precisão de no máximo 13%). O protótipo do sistema está em uso no Hospital das Clínicas de Ribeirão Preto (ambulatório de Oftalmologia, setor de Doenças Oculares Externas), tem demonstrado excelente desempenho e estudos clínicos, agora proporcionados pela automação do sistema, começam a ser realizados / A system for diagnostic and follow up of External Ocular Diseases has been developed, particularly for Corneal Ulcers, and has been implemented in a Hospital-School for daily use. The corneal ulcers, until then, have been evaluated in a subjective and qualitative way, just by estimating the affected area. Its clinical evolution is indicated by the increasing/decreasing of the affected area. In order to evaluate quantitatively and standardize the evolution of this pathology we have developed the present system. The system consisted in attaching to a Slit Lamp (ocular biomicroscope) a beam splitter in the parallel rays optical path and an optical system, in order to provide simultaneously the ocular images to the Slit Lamp ocular lenses and to a CCD camera. The camera has been attached to a PC, via a commercial frame grabber and the images are displayed in a monitor. A dedicated software has been developed and it has the following functions and features: corneal ulcers self recognizing and area measurements, optional interactive area and extension measurement of any image and a data bank dedicated for this sector of the Ophthalmology. Also all the commands are available for keyboard or mouse clicking. Particularly, the image capturing command can also be turned ON/OFF by clicking a pedal, which was specially developed for the system. The precision of the measurements of the system is 5% (the conventional method, for perfect elliptical ulcer areas provides a maximum precision of 13%). The system\'s prototype is being used in the Hospital das Clínicas de Ribeirão Preto and it has presented excellent performance. Clinical studies are now being able to be done due to the automation of the clinical evaluations

CIBA VISION S.A. (Barcelona)