Дисертації з теми "Ophthalmic lenses"

Fluidic lenses have been developed for ophthalmic applications. The lenses use a pressure differential to deform a membrane, which separates two fluids with different indexes of refraction. The change in membrane shape creates changes in the optical wavefront. By utilizing different boundary conditions on the membrane, the progression of the membrane shape can be controlled. Specifically, a circular restraint is used to produce optical power, whereas a rectangular restraint is used to produce a combination of power and astigmatism. These lenses are analyzed for dominant properties and wavefront quality. By combining 2 rectangular restraint lenses at 45° and a circular restraint lens, both orthogonal second order Zernike astigmatisms as well as second order power can be independently controlled. This combination can also be described as independent control of ophthalmic cylinder, cylinder axis, and power, which is required to create a basic phoropter. A fluidic phoropter is demonstrated and analyzed in this manuscript.

Las lentes progresivas (LP) para gafas es una solución muy extendida para la presbicia, ya que proporcionan una visión continua a todas las distancias debido a un cambio progresivo de potencia. En este trabajo se han medido las aberraciones de frente de onda espacialmente resueltas y la calidad visual en estas lentes. Además del astigmatismo que aumenta periféricamente, también se han encontrado pequeños valores de aberraciones de tercer orden, coma y trefoil, que producen un bajo deterioro de la calidad óptica y visual. El logaritmo de métricas sobre la PSF del sistema lente con ojo son las que mejor predicen la agudeza visual. Durante la primera semana de adaptación, no se aprecia una mejora significativa de la agudeza visual a través de distintas zonas de las LPs. Al comparar diferentes LPs, las aberraciones, principalmente el astigmatismo, se comporta como un colchón de agua, que se puede mover pero no eliminar.
Progressive lenses (PL) are designed to provide continuous vision at all distances by means a progressive change in spherical power from upper to lower zones. In this thesis, we measure the spatially resolved aberrations and the visual quality of PLs. In addition to astigmatism, third order aberrations, coma and trefoil, are also found in the PLs, but the impact of these aberrations on visual performance is limited. The logarithm of metrics on the PSF of the entire system eye plus PL are the parameters that best predict the visual acuity. There is not a significant improvement of visual acuity through the different zones of the PLs during the first week of adaptation. The current designs of PLs are somehow similar to a waterbed, with the aberrations, mainly astigmatism, being the water: they can be moved but they cannot be eliminated.

Myopia (short-sightedness) is a progressive condition often associated with near work. This research investigated the accommodation system during treatment with myopia-control multifocal spectacles. Meta-analysis of prior work showed that effectiveness of multifocal spectacles reduces with time, even after the first six months. During accommodation, the anterior ciliary muscle thickens, and its overall length reduces, in both emmetropes and myopes. Myopes have the larger lags of accommodation. Multifocal spectacles initially decrease the lags, but over-time the lags increase, and upgrading addition power by 0.50D restores the initial effect. Modifications to add power can sustain the treatment effect for longer periods.

Les technologies utilisant le CO2 supercritique sont considérées comme des alternatives vertes et éco-responsables pour la formulation de médicaments et le traitement de dispositifs médicaux. Ce travail de thèse a pour objectif de développer des dispositifs médicaux ophtalmiques innovants pour prévenir deux complications postopératoires de la chirurgie de la cataracte, l’endophtalmie et l’opacification de la capsule postérieure. Parmi d'autres procédés, l'imprégnation supercritique a été sélectionnée pour incorporer des principes actifs ophtalmiques dans des implants intraoculaires (IOLs) disponibles dans le commerce et largement utilisés pour la chirurgie de la cataracte. Une action ciblée des médicaments avec une libération prolongée directement dans les zones potentiellement affectées peut être atteinte sans nécessiter d'interventions médicales supplémentaires. L’imprégnation supercritique d’IOLs acryliques hydrophobes et souples a été étudiée en faisant varier les conditions opératoires de pression (8 à 25 MPa), de température (308 à 328 K) et de durée (30 à 240 min). L'influence de l'utilisation de l’éthanol comme co-solvant a également été évaluée. La cinétique de relargage du médicament \textit{in vitro} a été suivie pour déterminer les taux d'imprégnation. Afin de rationaliser l’influence des phénomènes concomitants gouvernant l’imprégnation, les comportements thermodynamiques des systèmes impliqués, polymère/ CO2 et médicament/CO2, ont été étudiés. L’implantation des dispositifs médicaux imprégnés dans des sacs capsulaires de donneurs humains ont montré le potentiel clinique de ces implants à libération prolongée innovants
Supercritical CO2 technologies are arisen as green and eco-responsible alternatives for drug formulation and medical device processing. The present PhD work aims to develop innovative ocular therapeutic medical devices to mitigate two post-operative complications of cataract surgery, endophthalmitis and posterior capsule opacification. Among other processes, supercritical impregnation was selected to load commercially available intraocular lenses (IOLs) commonly used in cataract surgery with ophthalmic drug components. A targeted action of drug molecules can be therefore achieved through a sustained release directly at the potential affected zones without requiring subsequent medical interventions. Supercritical impregnation of foldable hydrophobic acrylic IOLs was studied by varying the operating conditions of pressure (8 to 25 MPa), temperature (308 to 328 K) and impregnation duration (30 to 240 min). The influence of using ethanol as a co-solvent was also evaluated. In vitro drug release kinetics were studied and used to determine the impregnation yields. In order to rationalize the influence of the concomitant phenomena governing impregnation, thermodynamic behaviors of the involved systems, polymer/CO2 and drug/CO2 were studied. {Ex vivo} implantation of methotrexate impregnated IOLs on human donor capsular bags shown fibrosis reduction by inhibiting epithelial-mesenchymal transformation highlighting the potential of the innovative sustained-release drug-delivery IOLs to become of clinical relevance

Orientador: Cláudia Valéria Seullner Brandão
Resumo: Este trabalho tem como objetivo descrever valores oftalmológicos, determinar o poder dióptrico da lente intraocular (LIO), além de comparar os olhos considerando a lateralidade e sexo nesta espécie e avaliar a hipótese que os valores são similares com o cão. O lobo guará (Chrysocyon brachyurus) encontra-se na lista vermelha de espécies em extinção do The International Union for Conservation of Nature (IUCN), de animais em quase ameaça. As principais causas são a caça indiscriminada e atropelamentos. A espécie possui hábitos noturnos e crepusculares, o que torna a visão um dos seus sentidos mais importantes. Diante disso, a pesquisa avaliou 13 lobos guarás (26 olhos), hígidos, com idade superior a um ano, machos e fêmeas com peso entre 25 e 30kg. Foram realizados os seguintes testes oftalmológicos: teste lacrimal de Schirmer (TLS), estesiometria, tonometria e paquimetria. Adicionalmente, foi realizada a ultrassonografia modo A (US-A), ceratometria e a medida da distância limbo-limbo; e o calculo da dioptria lenticular. Foram obtidos os seguintes valores médios para os testes oftalmológicos: TLS 19,15±3,58mm/min; estesiometria 0,96±0,31mm; tonometria 13,96±4,75mmHg; paquimetria 528,50±55,13µm; distância limbo-limbo 18,08±1,32mm; comprimento axial 21,04±0,55mm e profundidade de câmara anterior 4,63±0,33mm; e cetarometria média 37,21±1,32D. Referente às fórmulas: SRK/T 34,04±1,66D; Hoffer Q 36,31±1,83D; Holladay I 35,42±1,88D, Haigis 42,19±2,29D e Holladay II 35,00±1,65D. Foram d... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: This study aimed to describe ophthalmologic values, to determine the dioptric power of the intraocular lens (IOL), and to evaluate the results compared to the laterality of the eyes and the sex of maned wolves and evaluate the hypothesis that the values are similar to dogs. The maned wolf (Chrysocyon brachyurus) is in the red list of endangered species of the International Union for Conservation of Nature (IUCN), a near-threatened animal. The main causes are indiscriminate hunting and trampling. The species has nocturnal and crepuscular habits, which makes the vision one of its most important senses. In this research were evaluated 13 maned wolfs (26 eyes), healthy, captive wolves, aged from 1 to 8 years, four males and nine females with weight between 25 and 30kg. The following ophthalmological tests were performed: Schirmer's lachrymal test (SLT), esthesiometry, tonometry and pachymetry. Additionally, ultrasound mode A, keratometry and measurement of limbo-limbo distance were performed; and the calculation of lenticular diopter. Values of the ophthalmological tests were obtained: SLT 19,15±3,58mm/min; esthesiometry 0,96±0,31mm; tonometry 13,96±4,75mmHg; pachymetry 528,50±55,13μm; limbo-limbo distance 18,08±1,32mm; axial length 21,04±0,55mm and anterior chamber depht 4,63±0,33mm. Cetarometry average 37,21±1,32D. The formulas: SRK/T 34,04±1,66D; Hoffer Q 36,31±1,83D; Holladay I 35,42±1,88D, Haigis 42,19±2,29D and Holladay II 35,00±1,65D. The ophthalmologic variables and diopt... (Complete abstract click electronic access below)
Doutor

Master of Science
Department of Clinical Sciences
Amy Rankin
Objective- To evaluate the use of a topical ophthalmic steroid (1% prednisolone acetate) and non-steroidal anti-inflammatory drug (0.1% diclofenac) on blood glucose concentrations, serum fructosamine concentrations, and clinical scores in diabetic dogs with cataracts using descriptive analysis. Animals- Twelve client-owned dogs with naturally-occurring, controlled (per history and physical examination), insulin-treated diabetes mellitus and cataract. A total of 40 dogs will be enrolled in the study, as determined by power analysis. Procedures- This was a prospective, randomized, double-masked, experimental study with 2 phases of data collection. Dogs were enrolled from October 2011 to March 2014 and were assigned to 1 of 2 treatments (Drug Red or Drug Blue) using blocked randomization; dogs received either 1% prednisolone acetate suspension or 0.1% diclofenac solution. Patient history, physical, and ophthalmic examinations were performed and a clinical score assigned at enrollment (Phase 1 [day 0]) and upon return (Phase 2 [day 32]). At these times, a complete blood count, serum chemistry, urinalysis, and serum fructosamine concentration were performed prior to hospitalization for up to 72 hours for continuous glucose monitoring. For 4 weeks (day 3 to 31), dogs returned home, and owners administered the dispensed ophthalmic medication 4 times daily to both eyes. Descriptive analysis of data was performed; statistical analysis will follow enrollment of 40 dogs. Results- Twelve dogs have completed the study, with 6 dogs assigned to each treatment group. Dogs received 4.44 or 0.44 mg/day of prednisolone acetate or diclofenac, respectively. Dogs assigned to Drug Red more commonly exhibited elevations in serum liver enzyme activity. Drug Red group showed a greater percent increase in fructosamine concentrations over time. Based on glucose curves alone (22 curves analyzed), an insulin dose increase was recommended for 12 curves. An insulin dose decrease and no dose change were recommended for 5 curves each. During treatment, 1 dog reportedly developed polyuria and polydipsia. Conclusions- Descriptive analysis revealed differences in some outcomes of interest among dogs treated with 2 different ophthalmic anti-inflammatory medications. Data collection is ongoing to determine if statistically significant differences exists for outcomes per group.

L'objectif est l'immobilisation reversible de medicaments (chloramphenicol, indometacine) au sein de lentilles de contact hydrophiles permettant une liberation lente et continue lors de leur adaptation sur des yeux malades

碩士
逢甲大學
視光科技碩士在職學位學程
106
Abstract In this study, we measure different blue light filters for ophthalmic lenses on the market, and use an optical spectrometer to measure the transmittance as a function of the wavelength. In order to study the effect of blue light, different kinds of blue light sources were also investigated. There are a large variety of commercially available blue-light-blocking lenses which emphasize theiranti-blue-light effects. We also studied13commercial anti-blue-light filters used as ophthalmic lenses, and analyzed the optical transmission spectrum and the contrast sensitivity test of these products to explore the issue of these blue lightfilters on the market whether has a good protective effect. The results showed that the transmittance of 30-50% can be filtered out the blue-light wavelengths. These blue-light-filteringophthalmic lenses can effectively protect the eyes from blue light hazards.

M.Phil. (Optometry)
Significant vision impairment caused by uncorrected distance or near vision (at a level defined by The World Health Organization as a disability) affects over 600 million people globally (9% of the world’s population). Over 3.5 billion people (52% of the world’s population) need some form of vision correction to see clearly. By 2020, this number is projected to reach 6.1 billion, 66% of the world’s population. Vision impairment is an important issue affecting the everyday lives of these 3.5 billion people worldwide. Two thirds of those affected live in the less developed world where the majority do not have easy access to eye care, eye examinations and affordable spectacles. Purpose If an ametrope or presbyope pricks a small hole into a leaf, piece of paper or cardboard and looks through it, he or she will usually experience improved acuity providing there is no central cataract or any ocular pathology. Rural communities, who have no access to eye-care or vision specialists, with vision problems, may benefit from looking through a pinhole while looking far and near. Many who are longsighted or presbyopic, may have problems reading their Bibles for example. They may only have candles as a source of light at night. They could improve their vision by looking through a small hole while reading. The purpose of this study is to explore the possibility of such a simple and almost cost free device contributing to solving this need. Method Uncompensated (without the pinhole) near or proximal visual acuities (VAs) were measured and recorded on one eye of 45 presbyopic subjects over the age of 50 years in photopic (250 lux) and then scotopic (20 lux) conditions. There were 36 male and 9 female subjects. Their ages ranged between 50 and 74 years with an average of 59 (SD = ±7.52) years. The ambient room illumination for photopic conditions was measured using a Sekonic Lumi Model 246 light-meter. No visual or pathological conditions or requirements were set for the subjects. The subjects were asked to read the smallest letters on the near chart by moving their head closer ...

M.Phil.
Tinted spectacle lenses have long been worn to provide ocular protection from harmful electromagnetic radiation during recreational activities. Controversy exists surrounding the colour of the spectacle tints and the environmental conditions under which these tints are worn. There is little scientific evidence to substantiate the many opinions of authors on the effects of tinted spectacle lenses on visual skills and, ultimately, on overall performance in recreational situations. This study serves to provide scientific data concerning the effects of tinted lenses on static visual acuity, contrast sensitivity, colour vision, stereopsis and visual evoked potential (VEP). These results are related to the visible spectrum transmission curve for each experimental lens. recommendations are then made concerning the environmental conditions under which each lens tint should be worn. The HOYA ULT-2000 Light Transmission Metre was used to establish the percentage of visible light being transmitted through each of the experimental lenses. The DMS 80/90 Visible Spectrophotometer was used to generate a visible spectrum transmission curve for each of the 8 experimental lenses used in this study. 30 subjects (Group A) were randomly selected from the RAU student population for the assessment of the effects of tinted lenses static visual acuity, contrast sensitivity, colour vision and stereopsis. 10 students (Group B) were then randomly selected from the RAU student population for the assessment of the effects of tinted experimental lenses on visual evoked potential (VEP). The ametropic subjects in Groups A and B all wore their habitual spectacle or contact lens corrections throughout the testing procedure. The following lens tint colours were used: clear, black, grey, yellow, green, blue, red and pink. The subjects were evaluated binocularly without any tinted lens being worn, then through each of the 8 tinted experimental lenses (randomly presented). Results of the visual skills and VEP testing were analysed as follows: Group A: An average score was calculated for the results achieved on the static visual acuity, contrast sensitivity, colour vision and stereopsis tests when no experimental lenses were worn. This average was then compared to the average static visual acuity, contrast sensitivity, colour vision and stereopsis scores for each of the 8 experimental lenses. Group B: An average score was calculated for each of the amplitude and latency components of the VEP waveforms generated when no experimental lenses are worn. This average was then compared to the average amplitude and latency components generated when each of the 8 experimental lenses (as for Group A) are worn. Static visual acuity was assessed using a Snellen visual acuity letter chart at 6m. Contrast sensitivity was assessed using a Vistech VCTS 6500 Contrast Sensitivity Chart at 3m. Colour vision assessment was performed using the lshihara Colour Vision Test and the City University Colour Vision Test. The Random Dot Near Stereo Test was used to assess stereopsis. The Nicolet Pathfinder II was used to assess visual evoked potentials (VEPs). The results of this study show that the black, grey, yellow, green, blue, red and pink tinted lenses have a statistically significant influence on visual efficiency only when subjective methods (i.e. static visual acuity, contrast sensitivity, colour -vision and stereopsis) of visual efficiency assessment are used. The tinted lenses had little effect on visual efficiency when an objective means (i.e. VEP) of assessment was used, as there were no statistically significant differences between the lenses. The results of this research project indicate that the colour of the lens tint has little real effect on visual efficiency, when measured objectively. The effect of the lens tint is shown to be highly subjective. Tinted lens selection would therefore be based on personal preference and the amount of protection that the lens provides from harmful electromagnetic radiation. It can be concluded that no single lens tint is therefore suitable for all individuals under the same environmental conditions.

SOLA International, a company which manufactures optical lenses, attended the 2000 Mathematics-in-Industry Study Group (MISG) with a wish list. Topping this list was the creation of a mathematical model of a lens, which given the lens geometry and material properties, could predict the deformation of the lens when it was subjected to an impact, such as that experienced in the fracture tests lenses must pass before being approved for sale. The first steps towards such a model were taken at MISG. At MISG, a lens was modelled simply as a thin uniform thickness plate, undergoing small, linear deformations. In the first section of my thesis I extend this model by considering variable thickness plates and larger, nonlinear deformations. For this extended model I have confirmed that the result obtained at MISG, that the contact between a plate and a spherical indentor occurs at a single point, still holds. The second part of this thesis looks at the dynamic deformation, or vibration, of plates. I have developed numerical solution methods for the large amplitude vibration equations with and without the in-plane inertia terms, based on a finite difference scheme. A comparison of these solutions confirms the often used assumption that the in-plane inertia may be neglected. I have also implemented a number of solution methods from the literature, which use separation of variables techniques. Comparing these with the numerical solutions, we find that the numerical solutions better capture the multi-modal nature of the vibration - showing multiple cycles in the approximate period. Having achieved an understanding of the types of forces involved in plate deformation and vibration I consider shell theory in the final section of my thesis. While time constraints meant no dynamic results could be obtained, general nonlinear deep shell equations have been derived. The static version of these equations has then been solved, with the development of a new solution technique which combines a Taylor expansion to approximate the behaviour at the shell centre with a numerical shooting method. Various shallow shell simplifications of the deep shell equations are then discussed and solved. By comparison of the solutions obtained for the deep and shallow, linear and nonlinear equations I have been able to determine which theories apply to which geometries. A complete model of a lens needs to take into account the shape, its thickness and curvature and the material from which it is made. From the work done in this thesis we have been able to determine that a lens model would require the nonlinear theory. Whether the deep shell theory is necessary is debatable as the geometry of a typical lens falls in the grey area, where either theory could be used depending on the accuracy required. For a very accurate model, deep shell theory would be necessary; if an approximate solution obtained quickly was more useful then I suggest the use of a particular set of shallow shell equations. A full lens model would require variable thickness shell theory and the solution of the dynamic equations, neither of which has been achieved here, but the solution techniques I have developed would be applicable to these theories.

博士
國立臺灣科技大學
材料科學與工程系
107
This thesis is aiming to investigate the effect of the composition on the physical and biological properties of silicone contact lenses. This thesis is divided into three parts to conduct the investigation. In the first part, soft lenses were synthesized by the polymerization of 3-(methacryloyloxy)propyltris(trimethylsiloxy)silane (TRIS), N,N-dimethylacrylamide (DMA), 1-vinyl-2-pyrrolidinone (NVP), and 2-hydroxyethylmethacrylate (HEMA). The physical and biochemical characterizations of silicone hydrogel lenses were measured by methods comprising equilibrium water content (EWC), oxygen permeability (Dk), optical transparency, contact angle, mechanical test, protein adsorption, and cytotoxicity. The results indicated that the TRIS concentration in all formulations enhanced Dk and decreased the EWC, whereas both DMA and NVP contributed to the hydrophilicity of the hydrogels. The maximum value of Dk was 74.9 barrer, corresponding to EWC of 44.5% as well as a contact angle of 82°. Furthermore, L929 fibroblasts grew on all these hydrogels, suggesting non-cytotoxicity. Generally, the silicone hydrogels in this study presented good oxygen permeability, stiffness, and optical transparency as well as anti-protein adsorption. Consequently, these silicone hydrogel polymers would be feasible for making contact lens. In the second part, silicone nanoparticles composites (SiNPs) were synthesized by the combination of tetraethyl orthosilicate (TEOS) and polydimethylsiloxane (PDMS) via the sol-gel reaction. Before the polymerization of hydrogel lenses, these SiNPs were blended with HEMA and NVP monomers. All samples were subject to characterization consisting of dynamic light scattering (DLS), transmission electron microscope (TEM), scanning electron microscope (SEM), EWC, Dk, optical transparency, and contact angle. SiNPs has the average diameter of SiNPs of 336 nm. The result showed that the different mixing concentrations of SiNPs composites increased Dk, but did not influence the EWC of p(HEMA-co-NVP)-SiNPs lenses. The maximum of Dk was 71 barrer for p(HEMA-co-NVP) sample containing 1.2 wt% of SiNPs whereas its highest EWC attained 73%. These results demonstrate a novel approach for producing soft lenses. In the third part, soft lenses were synthesized by the polymerization of DMA, NVP, and SiNPs. The physical and biochemical properties of all samples were analyzed based on methods such as SEM, EWC, Dk, optical transparency, contact angle, mechanical properties, protein adsorption, and cytotoxicity. The results indicated that the addition of SiNPs increased the Dk without influencing the EWC of the soft lenses. With 1.2 wt% of SiNPs, the Dk of p(DMA-co-NVP)-SiNPs was 94.8 barrer whereas its EWC remained at 85.14%. In particular, DNS12 displayed a contact angle around 39.65°. Additionally, protein adsorption primarily depended on the negatively charged SiNPs. Higher SiNPs content led to lower human serum albumin (HSA) and higher lysozyme deposition on all samples. Moreover, L929 fibroblasts grew on all hydrogel samples, suggesting non-cytotoxicity. Generally, the combination of SiNPs with hydrogels exhibited high Dk, without influencing importantly the optical transparency, moduli. These results may be applicable as ophthalmic biomaterials in for soft contact lens.

O caso prático apresentado foi desenvolvido no âmbito da realização do Mestrado de Continuidade em Gestão no Instituto Universitário de Lisboa – ISCTE. Quanto à temática, centra-se no âmbito da Gestão e do Marketing Relacional aplicados á realidade do mercado português de lentes oftálmicas. O mercado da óptica em Portugal é considerado altamente estruturado e os players existentes têm uma elevada notoriedade junto dos consumidores. Será analisado, tanto ao nível das lentes oftálmicas como das armações e óculos de sol. A marca Nikon tem já um longo percurso no que diz respeito à inovação tecnológica com uma qualidade e precisão extremas. Apesar do leque de artigos comercializados por esta marca ser muito vasto, este projecto irá incidir apenas sobre as lentes oftálmicas por si produzidas. Em 2005, este produto entra no mercado português, representado pela empresa Nikpor. Apesar do nome Nikon ter uma expressão muito forte em Portugal, este não foi suficiente para o sucesso da empresa num mercado tão competitivo e numa economia em crise. Discutir-se-á a transformação desta organização com a inserção da sua actividade na empresa Proóptica. Este caso reflecte os esforços necessários para iniciar uma nova empresa em Portugal e para a organizar num mercado muito competitivo. Espelha igualmente as dificuldades atravessadas na gestão de uma organização jovem aos níveis operacional, comercial e de direcção. Será demonstrado que o investimento deve ser cada vez mais centrado em estratégias de Marketing eficazes, que apresentem um nível de relacionamento elevado e que se foquem no cliente e na satisfação das suas necessidades específicas.
The case study presented was developed with the completion of the Master Business Continuity Management in the University Institute of Lisbon - ISCTE. Regarding the theme, focuses on Management and Relationship Marketing applied to the reality of the Portuguese market for ophthalmic lenses. The optical market in Portugal is considered highly structured and the existing players have a high reputation among consumers. It will be analyzed, both in terms of ophthalmic lenses as well as the frames and sunglasses. The Nikon brand has come a long way in terms of technological innovation with quality and extreme precision. Despite the large range of items marketed by this brand, this project will focus only on the ophthalmic lenses produced by it. In 2005, this product goes into the Portuguese market, represented by the company Nikpor. Despite the name Nikon have a very strong expression in Portugal, this was not enough for the company's success in a very competitive market and an economy in crisis. It will be discussed the transformation of this organization with the insertion of its activity in the company Prooptica. This case reflects the efforts needed to start a new company in Portugal and to arrange a very competitive market. Reflects also the difficulties in running a youth organization in the operation, business and management levels. It will be demonstrated that the investment must be increasingly focused on effective marketing strategies, which have a high level of relationship and that focus on the customer and meet their specific needs.

The utilization of in vitro tests with a tiered testing strategy for detection of mild ocular irritants can reduce the use of animals for testing, provide mechanistic data on toxic effects, and reduce the uncertainty associated with dose selection for clinical trials. The first section of this thesis describes how in vitro methods can be used to improve the prediction of the toxicity of chemicals and ophthalmic products. The proper utilization of in vitro methods can accurately predict toxic threshold levels and reduce animal use in product development. Sections two, three and four describe the development of new sensitive in vitro methods for predicting ocular toxicity. Maintaining the barrier function of the cornea is critical for the prevention of the penetration of infections microorganisms and irritating chemicals into the eye. Chapter 2 describes the development of a method for assessing the effects of chemicals on tight junctions using a human corneal epithelial and canine kidney epithelial cell line. In Chapter 3 a method that uses a primary organ culture for assessing single instillation and multiple instillation toxic effects is described. The ScanTox system was shown to be an ideal system to monitor the toxic effects over time as multiple readings can be taken of treated bovine lenses using the nondestructive method of assessing for the lens optical quality. Confirmations of toxic effects were made with the utilization of the viability dye alamarBlue. Chapter 4 describes the development of sensitive in vitro assays for detecting ocular toxicity by measuring the effects of chemicals on the mitochondrial integrity of bovine cornea, bovine lens epithelium and corneal epithelial cells, using fluorescent dyes. The goal of this research was to develop an in vitro test battery that can be used to accurately predict the ocular toxicity of new chemicals and ophthalmic formulations. By comparing the toxicity seen in vivo animals and humans with the toxicity response in these new in vitro methods, it was demonstrated that these in vitro methods can be utilized in a tiered testing strategy in the development of new chemicals and ophthalmic formulations.

Λόγω της διαφάνειας των οφθαλμικών ιστών η σκέδαση φωτός αποτελεί ιδανικό εργαλείο για την ανίχνευση των αρχικών σταδίων ορισμένων παθολογικών τους καταστάσεων. Για παράδειγμα, η θόλωση του φακού των θηλαστικών λόγω ηλικίας ή/και άλλων εξωγενών αιτίων καλείται καταρράκτης. Ο καταρράκτης δεν μπορεί να διαγνωστεί κλινικά σε πρώιμο στάδιο με αποτέλεσμα την δημιουργία σοβαρών προβλημάτων στην όραση. Το γεγονός ότι το φως έχει την ικανότητα να ανιχνεύει τις μοριακές αλλαγές οι οποίες είναι πρόδρομα συμπτώματα του καταρράκτη αναδεικνύει την σημασία της έγκαιρης διάγνωσης στην αντιμετώπιση διάφορων οφθαλμικών παθήσεων. Ο φακός θεωρείται ως ένα πυκνό διάλυμα πρωτεϊνών (κρυσταλλίνες, ~40 % wt) σε νερό και η αδιαφάνεια η οποία αποτελεί την εκδήλωση του καταρράκτη προκαλείται ουσιαστικά από την συσσωμάτωση των πρωτεϊνών. Στόχος αυτής της διατριβής είναι η διερεύνηση των μοριακών μεταβολών οι οποίες λαμβάνουν χώρα κατά την ανάπτυξη του καταρράκτη. Ιδιαίτερη σημασία δίνεται επίσης στην ανάπτυξη μιας μη-επεμβατικής μεθοδολογίας για έγκαιρη διάγνωση οφθαλμικών παθήσεων με τη βοήθεια της δυναμικής σκέδασης φωτός. Με την βοήθεια της τεχνικής αυτής, κατάλληλα τροποποιημένης για την μελέτη οφθαλμικών ιστών, μελετήθηκαν οι δυναμικές ιδιότητες των πρωτεϊνών χοίρειων φακών (π.χ. οι συντελεστές διάχυσης, η θερμοκρασιακή τους εξάρτηση σε διάφορα μέρη του φακού, κλπ.) χρησιμοποιώντας το πειραματικό μοντέλο του “ψυχρού” καταρράκτη. Στο μοντέλο αυτό η ελεγχόμενη ψύξη φακών επιφέρει βαθμιαία καταρρακτογένεση. Ιδιαίτερη έμφαση δόθηκε σε τέσσερα κυρίως είδη περαμάτων. (α) Μελέτη της εμφάνισης του ψυχρού καταρράκτη στον πυρήνα του φακού. (β) Μελέτη της επίδρασης του μήκους κύματος της ακτινοβολίας στην εμφάνιση και στην έκταση του φαινομένου του ψυχρού καταρράκτη. (γ) Μελέτη του φαινομένου του ψυχρού καταρράκτη κατά μήκος μιας διαμέτρου του φακού, δεδομένης της βαθμίδας συγκέντρωσης των πρωτεϊνών του φακού (μεγάλη συγκέντρωση στον πυρήνα και μικρή συγκέντρωση στην περιφέρεια του φακού). (δ) Μελέτη του επίδρασης της προθέρμανσης του φακού σε θερμοκρασίες υψηλότερες της φυσιολογικής στο φαινόμενο του ψυχρού καταρράκτη. Τα βασικά συμπεράσματα της παρούσας διατριβής συνοψίζονται ως εξής. Υπάρχουν σαφείς συσχετισμοί μεταξύ των φασματικών χαρακτηριστικών (συναρτήσεις αυτοσυσχέτισης) και των ιεραρχικών σταδίων ανάπτυξης του καταρράκτη. Ποιοτικές και ποσοτικές αλλαγές στην θερμοκρασιακή εξάρτηση διαφόρων παραμέτρων, οι οποίες σχετίζονται με τις μοριακές διαμορφώσεις των αρχικών σταδίων του καταρράκτη, εμφανίζονται ήδη από τους 17 oC όπου ο πυρήνας του φακού είναι ακόμα διαυγής. Η χρήση ακτινοβολίας κοντά στο υπεριώδες μέρος τους φάσματος ενισχύει την ανάπτυξη του ψυχρού καταρράκτη στον πυρήνα του φακού. Ο ψυχρός καταρράκτης δεν αναπτύσσεται στην περιφέρεια του φακού. Η προθέρμανση του φακού σε συγκεκριμένη θερμοκρασία καθώς και ο χρόνος παραμονής σε αυτήν επηρεάζει σημαντικά την ανάπτυξη του ψυχρού καταρράκτη στον πυρήνα αλλά όχι στην περιφέρεια του φακού. Όλα τα παραπάνω δείχνουν πως η δυναμική σκέδαση φωτός μπορεί να παρέχει παραμέτρους οι οποίες μπορούν να χρησιμοποιηθούν με επιτυχία ως ευαίσθητοι και αξιόπιστοι δείκτες της έγκαιρης, μη-επεμβατικής, και in vivo διάγνωσης του καταρράκτη.
On account of the transparency of ophthalmic tissues, light scattering is an ideal tool for detecting the early stages of some of their pathological conditions. For example, the opacity of the mammalian lens due to age or other external causes is called cataract. Cataract cannot be detected clinically at early stages and as a result serious vision problems appear. The fact that, light has the ability to detect molecular changes that are related to the mechanism of cataract formation draws attention to the importance of early diagnosis in ophthalmic disorders. The lens can be considered as a dense colloidal protein dispersion (crystallins, ~ 40% wt) in water where the opacity that leads to cataract formation how its basis to the aggregation of proteins. This dissertation is aimed at studying the molecular changes that take place upon cataract development. Particular emphasis is paid to the development of a non-invasive methodology for early diagnosis of ocular diseases with the aid of dynamic light scattering. By means of this technique, suitably modified for the study of ophthalmic tissues, the dynamic properties of the proteins of porcine lenses (e.g. diffusion coefficients and their temperature dependence at various parts inside the lens, etc.) were studied by using the experimental model of ‘cold’ cataract. In cold cataract the controlled cooling of the lens at temperatures below the physiological one induces gradual cataractogenesis. In particular, we focused on four kinds of experiments. (a) Detailed study on the cold cataract onset in the lens nucleus. (b) Study on the effect of the laser light wavelength in the onset and the extent development of cold cataract. (c) Study of the cold cataract effect along an equatorial diameter of the lens, considering the gradual concentration of the lens proteins (high protein concentration in the nucleus and low concentration in the cortex). (d) Study on the effect of thermal history, i.e. by warming up the lens at temperatures higher than the physiological one on the cold cataract effect. The basic conclusions of the present dissertation are summarized as follows: There are clear correlations between the spectral characteristics (autocorrelation functions) and the hierarchical stages of the onset of cataract. Qualitative and quantitative changes in the temperature dependence of several parameters, which are related with the diffusive motions of proteins at the early stages of cataract, appear already at 17 oC while the nucleus is still clear and highly transparent. The use of laser radiation close to the ultraviolet part of the spectrum seems to enhance the formation of cold cataract in the lens nucleus. Cold cataract does not develop at the cortex of the lens, in view of the low protein concentration. The lens pre-heating at a certain temperature for various time periods affects significantly cold cataract formation in the lens nucleus but not in lens cortex. The above mentioned make clear that dynamic light scattering can indeed provide useful parameters that can be successfully used as sensitive and reliable indicators for the early, non-invasive diagnosis of cataract in mammalian lenses and in vivo.