A diabetes mellitus (DM) causa alterações em todas as camadas da córnea. Córneas de pacientes diabéticos têm controle de sua hidratação prejudicado e são mais propensas à descompensação após injúria. A uveíte faco-induzida (UFI) ocorre em grandes proporções associada à catarata hipermatura em cães. A UFI também acarreta danos ao endotélio da córnea e pode levar ao edema estromal, usualmente transitório. Cães diabéticos são particularmente predispostos ao desenvolvimento de catarata e UFI associada. Os efeitos da DM e UFI podem potencialmente vir a se somar em córneas de cães com catarata diabética. A pressão intra-ocular (PIO) e paquimetria podem ser ferramentas úteis na determinação dessas alterações. O objetivo deste estudo foi determinar a relação entre pressão intra-ocular e paquimetria nos diferentes estágios de desenvolvimento das cataratas diabéticas e não diabéticas em cães da raça Poodle. Cento e vinte e dois cães adultos da raça Poodle, 134 fêmeas e 99 machos, com idades de 2 a 16 anos, foram admitidos no Serviço de Oftalmologia do Hospital Veterinário da Universidade de São Paulo e incluídos no trabalho. Afecções oculares concomitantes, ou doenças sistêmicas com manifestação ocular, foram consideradas fatores de exclusão. Após exame clínico oftalmológico, coletou-se dados referentes ao tempo de leucocoria e tempo de desenvolvimento da DM. Os cães tiveram a PIO mensurada por meio do TonoPen-XL® e a paquimetria mensurada com o uso do PachPen®. Para isso realizou-se anestesia tópica (colírio de Proximetacaína a 0,5% - Anestalcon®, Alcon). As comparações estatísticas entre as variáveis foram realizadas utilizando os testes de Spearman, Mc-Nemar e Mann-Whitney quando apropriados. As distribuições das variáveis entre os grupos foram avaliadas pelo test de Kruskal-Wallis, e quando significantes, o teste de Dunn foi utilizado para descriminar as diferenças encontradas. O nível de significância foi estabelecido em p<0,05. Dos 122 cães, 233 olhos foram incluídos e classificados em grupo controle (n=39), catarata incipiente (n=20), imatura (n=29), matura (n=20), hipermatura (n=80), catarata diabética imatura (n=9), diabética matura (n=11) e diabética hipermatura (n=25). As distribuições das variáveis (sexo, idade, peso, presença de uveíte, tempo de leucocoria, PIO e paquimetria) foram estatisticamente diferentes entre os diversos grupos. Fêmeas apresentaram-se mais acometidas por catarata diabética. A idade média dos animais variou de 7,03 a 10,73 anos entre os grupos, e os animais diabéticos foram estatisticamente mais velhos. A PIO foi estatisticamente menor e os sinais clínicos de UFI mais prevalentes nos grupos de cataratas hipermaturas, tanto diabéticas, quanto não diabéticas. A PIO correlacionou-se negativamente com a idade e a paquimetria. Houve correlação positiva da paquimetria com a idade e o peso; e correlação negativa com o tempo de leucocoria e a PIO. Olhos acometidos por UFI tiveram PIO estatisticamente menor e paquimetria maior, com diferença de 2 mmHg e 60 µm, respectivamente. Nos cães acometidos por catarata diabética, a paquimetria encontrou-se particularmente aumentada, e a UFI particularmente presente. Esse aumento possivelmente reflete a somatória dos efeitos da DM e UFI sobre a córnea. A hipermaturidade foi correlacionada à presença da UFI. A PIO e paquimetria mostraram-se instrumentos valiosos na determinação da UFI, principalmente se forem negativamente correlacionadas entre si. / Diabetes mellitus (DM) causes different alterations in all corneal layers, such as deficient control of hydration, what makes them prone to decompensate after injury. Lens induced uveitis (LIU) occurs mainly in dogs presenting hypermature cataracts, what causes irreversible damages to the corneal endothelium and may lead to stromal edema, usually transient. DM dogs are particularly predisposed to cataract with LIU associated. Intraocular pressure (IOP) and pachymetry measurements may be useful procedures capable to detect such alterations. The aim of this study was to determinate the relationship between intraocular pressure and pachymetry on diabetic and nondiabetic Poodles, presenting different stages of cataracts. One hundred twenty-two Poodles, 134 females and 99 males, with ages varying from 2 to 16 years, were admitted at the Ophthalmology Service, of the Veterinary Hospital, of the University of São Paulo. After complete identification of the animals, anamnese (time of DM and cataract formation) and ophthalmological exam, dogs were included in the study. Dogs affected by other systemic diseases inducing ocular manifestation or other primary ocular alteration were excluded. LIU was diagnosed by observation of congestion of the episcleral vases and resistence to midriasis after induction with Mydriacyl®. IOP was measured by TonoPen-XL® and pachymetry by PachPen® after instillation of anesthetic eyedrop (Proximetacaine 0,5% - Anestalcon, Alcon). Statistical comparison between factors were made using Spearman, Mc-Nemar and Mann-Whitney tests when appropriated. The distributions of the factors among the groups were compared by Krusskal-Walliss test, and when significant, Dunns test was used to describe the differences found. The level of significance was set at p<0,05. Two hundred thirty-three eyes of 122 Poodles were evaluated. Eyes were classified in different groups: healthy dogs without cataracts (n=39); dogs presenting incipient cataract (n=20); with immature cataracts (n=29); mature cataracts (n=20); or hypermature cataracts (n=80); DM dogs presenting immature cataract (n=9); DM with mature cataracts (n=11); and DM with hypermature cataracts (n=25). Distribution of factors, such as age, sex, weight, time of DM and cataract, presence of LIU, IOP and pachymetry were statistically different between groups. Female Poodles were more affected by diabetic cataract and diabetic dogs were older than the other ones. IOP was statistically lower and LIU alterations more prevalent in the hypermature cataract groups (diabetic and no diabetics). IOP was negatively correlated to age and pachymetry measures. Pachymetry was positively correlated to age and weight. Negative correlation was observed between pachymetry and time of cataracts formation. LIU eyes presented lower IOP and higher pachymetry. The difference found at pachymetry and IOP measurements in LIU and non LIU eyes were 60 µm and 2 mmHg respectively. In diabetic dogs, pachymetry was particularly higher and LIU particularly present. The higher corneal thickness may possible be related to the sum of alterations caused by DM and LIU to those corneas. Hypermaturity was directly related to LIU. We concluded that pachymetry and IOP measurements are important procedures to the LIU diagnosis, mainly when negatively correlated.

A selective a2-adrenergic agonist, lofexidine, significantly reduced intraocular pressure (lOP) in intact ocular normotensive NZW rabbits, producing a differential dose-dependent decrease in IOP in'the ipsilateral and contralateral eye. Contralateral IOP reduction was most observable at low doses. Unilateral superior cervical ganglionectomy and extraocular muscle excision studies were undertaken to elucidate the factors influencing differential IOP reduction by lofexidine. Similar significant contralateral decreases in IOP were noted when the agent was applied to either the intact or operated eye. Biochemical studies demonstrated that lofexidine inhibited isoproterenol-stimulated adenylcyclase in isolated iris-ciliary body preparations. Yohimbine, an α2-adrenergic antagonist, blocked this inhibitory response. Hence, these observations suggested that lofexidine's site of IOP reduction was probably at the cellular level.

Purpose: The aim of the study was to quantify the isolated tear film adhesion error in a Goldmann applanation tonometer (GAT) prism and in a correcting applanation tonometry surface (CATS) prism. Methods: The separation force of a tonometer prism adhered by a tear film to a simulated cornea was measured to quantify an isolated tear film adhesion force. Acrylic hemispheres (7.8 mm radius) used as corneas were lathed over the apical 3.06 mm diameter to simulate full applanation contact with the prism surface for both GAT and CATS prisms. Tear film separation measurements were completed with both an artificial tear and fluorescein solutions as a fluid bridge. The applanation mire thicknesses were measured and correlated with the tear film separation measurements. Human cadaver eyes were used to validate simulated cornea tear film separation measurement differences between the GAT and CATS prisms. Results: The CATS prism tear film adhesion error (2.74 +/- 0.21 mmHg) was significantly less than the GAT prism (4.57 +/- 0.18 mmHg, p<0.001). Tear film adhesion error was independent of applanation mire thickness (R-2=0.09, p=0.04). Fluorescein produces more tear film error than artificial tears (+0.51 +/- 0.04 mmHg; p<0.001). Cadaver eye validation indicated the CATS prism's tear film adhesion error (1.40 +/- 0.51 mmHg) was significantly less than that of the GAT prism (3.30 +/- 0.38 mmHg; p=0.002). Conclusion: Measured GAT tear film adhesion error is more than previously predicted. A CATS prism significantly reduced tear film adhesion error by similar to 41%. Fluorescein solution increases the tear film adhesion compared to artificial tears, while mire thickness has a negligible effect.

Abstract This study was undertaken to identify mechanisms of adhesion of intraocular lenses (IOLs) to the capsular bag after cataract surgery and IOL implantation. It was also done to challenge the sandwich theory presented for posterior capsular opacification (PCO): If the IOL is made of a bioactive material it would allow a single lens epithelial cell layer to bond both to the IOL and the posterior capsule at the same time. This would produce a sandwich pattern including the IOL, the cell monolayer and the posterior capsule. The sealed sandwich structure would prevent further epithelial ingrowth. The degree of bioactivity of the IOL could explain the basic difference in the incidence of PCO and capsulotomy rates with different IOL materials. The sandwich theory was put forward on the basis of a search for a keratoprosthesis material, which would allow maximal adhesion of the prosthesis to corneal tissue. Titanium and glass-ceramic coated titanium were found to develop better adhesion than poly (methyl methacrylate) (PMMA). The adhesion of PMMA to the corneal stromal tissue was loose, and down growth of corneal epithelial cells was seen around the prosthesis. The differences between various IOL materials were first tested with rabbit corneal tissue cultures. There was better adhesion of corneal tissue to soft, hydrophobic acrylate than to PMMA, heparin surface modified (HSM)-PMMA, silicone or hydrogel IOLs. To assess differences in protein adhesion to IOL surfaces, different IOLs were incubated for 24 hours with radioactive iodine labeled fibronectin. Soft hydrophobic acrylate (AcrySof®) showed the highest binding of fibronectin, and the differences relative to all the other materials were significant (p &lt; 0.01-0.001), except to PMMA (p = 0.31). The sandwich theory and the results with rabbit corneal tissue cultures and the protein adhesion study in vitro were evaluated against the results found in pseudophakic autopsy eyes. Altogether, 70 autopsy eyes were analyzed. From 38 autopsy eyes containing PMMA, silicone, soft hydrophobic acrylate or hydrogel IOLs histological sections were prepared from the capsular bag and immunohistochemical analyses were performed for fibronectin, vitronectin, laminin and collagen type IV. A total of 152 specimens were analyzed. From 32 autopsy eyes containing IOLs made of PMMA, silicone, acrylate or hydrogel, IOLs were explanted from the capsular bag and immunohistochemical analysis was done on both sides of the IOLs for fibronectin, vitronectin, laminin or collagen type IV. Soft hydrophobic acrylate IOLs had significantly more adhesion of fibronectin to their surfaces than PMMA or silicone IOLs. Also, more vitronectin was attached to acrylate IOLs than to the other IOL materials. Silicone IOLs had more collagen type IV adhesion in comparison to the other IOL materials studied. In histologic sections a sandwich-like structure (anterior or posterior capsule-fibronectin-one cell layer-fibronectin-IOL surface) was seen significantly more often in eyes with acrylate IOLs than in PMMA, silicone or hydrogel IOL eyes. These studies support the sandwich theory for posterior capsule opacification after cataract surgery with IOLs. The results suggest that fibronectin may be the major extracellular protein responsible for the attachment of acrylate IOLs to the capsular bag. This may represent a true bioactive bond between the IOL and the lens epithelial cells, and between the IOL and the capsular bag. This may explain the reason for clinical observations of less posterior capsular opacification and lower capsulotomy rates with the soft hydrophobic acrylate material of AcrySof® IOLs compared to the other IOL materials studied.

It is widely known that Central Corneal Thickness (CCT) and Radius of Curvature (RoC) in uence the estimated IntraOcular Pressure (IOP) obtained from Goldmann Applanation Tonometry (GAT). However, not much is known about the in uence of corneal material properties, especially in a clinical setting. Several numerical studies have been conducted in an attempt to quantify the in uence of corneal material properties on the IOP. These studies agree that corneal material properties do in uence the estimated IOP, which contradict the initial premise on which GAT was designed, namely that material properties do not in uence the obtained GAT readings. Also, there is no consensus among these studies with respect to corneal material properties, thus a wide range of proposed properties exist. A possible explanation for this range of available corneal properties is the numerical modi elling assumptions used, which seem to be quite different. Different sets of experimental in ation test data were used to calibrate the constitutive models and different limbal boundary conditions were applied to simulate the experimental setup as well as in vivo conditions during GAT simulations. Therefore the purpose of this study is to determine whether these modelling assumptions in uence the obtained IOP and ultimately the overall conclusions. A Finite Element (FE) model of the human cornea is developed, implementing a constitutive model to represent the complex corneal structure and two limbal boundary conditions. This model is then calibrated using two different sets of experimental in ation test data. During calibration of the fibre reinforced elastic constitutive model it is found that independent of the assumptions made regarding the material coe cients, that the numerical in ation data compare well with the experimental data for all cases. Using this model a GAT simulation is conducted to estimate the IOP and the in uence of the modelling assumptions, cornea geometry and material properties are then investigated. The results indicate that the modelling assumptions, cornea geometry and material properties do infuence the estimated IOP. However, when assuming the cornea ground substance stiffness to be constant, it is found that the in uence on IOP due to material properties is not as significant. A correction equation is also proposed to account for the corneal geometric properties by calibrating the numerical model for a numerically normal cornea. This is done by utilising the various data sets which are obtained during the calibration of the constitutive model with the experimental inflation test data. It is concluded that using only inflation data to calibrate the constitutive model is not sufficient to uniquely describe the corneal material. This is evident as different material data sets are obtained, even though the experimental inflation data is matched well for a variety of considered cases. Each of these material data sets, in conjunction with geometric properties, yield different estimates for IOP during GAT simulations. This study therefore recommends the use of additional experimental data, such as strip extensometry, along with inflation test data to adequately calibrate a numerical model. It should also be noted that when modelling GAT care should be taken when considering the choice of limbal boundary condition, experimental data for calibration and assumptions made with regards to material coe cients, as these choices could potentially influence the outcomes and conclusions of a study. / Dissertation (MEng)--University of Pretoria, 2014. / gm2014 / Mechanical and Aeronautical Engineering / unrestricted

Le glaucome est une neuropathie optique associée à une augmentation de la pression intraoculaire (PIO). L’élévation de la PIO est due à la dégénérescence progressive du trabéculum. Les traitements antiglaucomateux vise à réduire la PIO, cependant il n’existe aucun traitement ciblant la dégénérescence du trabéculum. Les cellules souches mésenchymateuses (CSMs) sont utilisées comme outils thérapeutiques dans différentes pathologies dégénératives. Elles sécrètent un panel de molécules qui sont décrit comme atténuant les processus dégénératifs. L’objectif de ce travail a été d’évaluer l’intérêt des CSMs dans la prise en charge du glaucome. La caractérisation des CSMs ont été mis au point à partir de culture primaire de moelle osseuse de rat. En parallèle, un modèle expérimental de glaucome par cautérisation des veines épisclérales (EVC) a été réalisé. Nous nous sommes intéressés à l’effet de l’injection intracamérulaire des CSMs dans ce modèle. Les CSMs sont retrouvées incorporées aux tissus autour et dans le trabéculum. Les résultats obtenus in vivo montrent une diminution de la PIO par l’injection des CSMs préservant ainsi les cellules ganglionnaires périphériques de la rétine (CGRs). Par une approche in vitro, nous avons également caractérisé les effets du sécrétome des CSMs sur les cellules impliquées dans la pathologie glaucomateuse: les cellules trabéculaires et les cellules ganglionnaires de la rétine. Ces résultats ont permis de montrer que l’injection intracamérulaire de CSMs permettrait de protéger la fonction de régulation de la PIO et de protéger les CGRs dont la mort est responsable de la diminution de l’acuité visuelle chez le patient glaucomateux. / Glaucoma is a sight-threatening retinal neuropathy associated with elevated intraocular pressure (IOP) due to degeneration and fibrosis of the trabecular meshwork (TM). Glaucoma medications aim to reduce IOP without targeting the specific TM pathology, which could explain treatment failure observed in some cases. Bone-marrow mesenchymal stem cells (MSCs) are used today in various clinical studies to treat various degenerative processes. Here, we investigated the potential of MSC therapy in an ocular hypertension model. We demonstrated a rapid and long-lasting in vivo effect of MSC transplantation that significantly reduced IOP in hypertensive eyes induced by episcleral vein cauterization (EVC). MSCs were found located to the ciliary processes and the TM and are able to survive at these places. Enumeration of retinal ganglion cells (RGCs) on whole flat-mounted retina highlighted a protective effect of MSCs on RGC death. In vitro, the effect of MSC-conditioned medium (MSC-CM) on both the primary human trabecular meshwork (hTM) and RGCs showed that MSC-CM promotes: (i) hTM survival by activating the antiapoptotic pathway, Akt, (ii) hTM decontractibility as analyzed by the decrease in myosin phosphorylation and (iii) inhibition of TGF-β2-dependent profibrotic phenotype acquisition in hTM, (iiii) RGC survival and neuritic outgrowth in vitro. Finally, MSCs injection in the ocular anterior chamber in a rat model of ocular hypertension provides a neuroprotective effect in the glaucoma pathophysiology directly on RGC and indirectly via TM protection. These results originally demonstrate that MSCs represent promising tool for treating ocular hypertension and retinal cell degeneration.

Orientador: Vital Paulino Costa / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-24T05:19:20Z (GMT). No. of bitstreams: 1 Santana_AlanaMendonca_M.pdf: 2805390 bytes, checksum: 9512111e988de78a1ffde9d9f877658b (MD5) Previous issue date: 2014 / Resumo: O objetivo deste trabalho foi investigar os efeitos das combinações fixas dos análogos de prostaglandinas com timolol sobre a barreira hematoaquosa, a espessura macular central e a pressão intraocular (PIO), em pacientes pseudofácicos com glaucoma primário de ângulo aberto. Neste ensaio clínico randomizado, com observador mascarado e duração de 6 meses, os pacientes foram tratados uma vez por dia (20:00 horas) com lubrificante (grupo controle) ou com a combinação fixa de maleato de timolol 0,5% e latanoprosta 0,005% (CFLT), maleato de timolol 0,5% e bimatoprosta 0,03% (CFBT) ou maleato de timolol 0,5% e travoprosta 0,004% (CFTT). Foi incluído no estudo apenas um olho de 61 pacientes: CFLT (n=16), CFBT (n=15), CFTT (n=15) e grupo controle (n=15). A barreira hematoaquosa foi avaliada por meio do &quot;laser flare meter¿ antes do início do uso das medicações e após 15 dias, 1,2,3,4,5 e 6 meses de tratamento. A PIO foi medida sempre às 9:00 horas, nas mesmas ocasiões. A espessura macular central foi avaliada por meio da tomografia de coerência óptica antes do uso das medicações, após 1 e 6 meses de tratamento ou na hipótese de piora da acuidade visual. Não houve aumento estatisticamente significante nos valores médios de &quot;flare¿ em comparação aos valores iniciais em todos os grupos (p>0,05) em todas as visitas, exceto no grupo CFTT no primeiro mês (p=0,0476) e no grupo CFLT (p=0,0129) no terceiro mês de seguimento. Não houve diferença estatisticamente significativante entre os valores médios de &quot;flare¿ entre os grupos durante o estudo (p>0,05). A média dos valores da espessura macular central aumentou significativamente nos grupos CFLT (p=0,012) e CFTT (p=0,0419) no primeiro mês de tratamento em relação aos valores iniciais. Não houve aumento estatisticamente significante nos valores médios da espessura macular central em relação aos valores iniciais em todos os grupos após 6 meses de tratamento (p>0,05) e não ocorreu diferença estatisticamente significante entre os grupos durante o estudo (p>0,05). A PIO média inicial foi significativamente menor no grupo controle (p=0,0000). Todas as combinações fixas reduziram significativamente a PIO em todas as visitas (P<0,0001), com efeito hipotensor semelhante entre si (p=0,816). Estes resultados indicam que o uso das combinações fixas de análogos de prostaglandinas com timolol não aumentou significativamente a média dos valores de &quot;flare¿ ou a média da espessura macular após 6 meses de tratamento nesta população / Abstract: The aim of this study was to investigate the effects of prostaglandin analogues and timolol fixed-combinations on the blood-aqueous barrier, central macular thickness and intraocular pressure (IOP) in pseudophakic patients with primary open angle glaucoma. In this randomized, masked-observer, 6-month clinical trial, patients were treated once daily (8 pm) with lubricant eye drops (control group), 0,5% timolol and 0,005% latanoprost fixed-combination (LTFC), 0,5% timolol and 0,03% bimatoprost fixed-combination (BTFC) or 0,5% timolol and 0,004% travoprost fixed-combination (TTFC). One eye of 61 patients were included in the study: LTFC (n=16), BTFC (n=15), TTFC (n=15) and control group (n=15). The blood-aqueous barrier status was assessed using the laser flare meter before the medications were started and after 15 days, 1, 2, 3, 4, 5 and 6 months of treatment. The IOP was measured always at 9 am, at the same intervals. The central macular thickness was evaluated with optical coherence tomography before medications were started, after 1 and 6 months of follow-up or if a patient showed decreased visual acuity at any time during follow-up. There was no significant increase in mean flare measurements from baseline in all groups (p>0.05) in all visits, except TTFC group at 1 month (p=0,0476) and LTFC group at 3 months (p=0,0129). There were no significant differences in mean flare values among the groups (p>0.05). Mean central macular thickness values were significantly higher in LTFC (p=0,012) and TTFC groups (p=0,0419) at 1 month of follow-up. There was no significant increase in mean central macular thickness values from baseline in all groups (p>0.05) after 6 months and no significant differences among the groups (p>0.05) during follow-up. At baseline, mean IOP was significantly lower in control group (p=0,0000). All fixed-combinations significantly reduced IOP in all follow-up visits, with similar lowering effect (p=0,816). These findings indicate that the use of prostaglandin analogues and timolol fixed-combinations didn't significantly increased mean flare values or mean central macular thicknes measurements after 6 months of follow-up in this population / Mestrado / Oftalmologia / Mestra em Ciências Médicas

Tesis por compendio / [ES] La presbicia es el error refractivo con mayor incidencia en la población debido al envejecimiento de la misma. Existen múltiples medidas para corregirla, desde lentes oftálmicas, lentes de contacto, lentes intraoculares etc¿ Actualmente, los implantes intracorneales (corneal inlays) se encuentran entre las soluciones más novedosas. Estos dispositivos se sitúan en el estroma corneal mediante una cirugía mínimamente invasiva. Existen tres implantes intracorneales comerciales cuyos mecanismos difieren entre sí. El más estudiado es el KAMRA inlay® y utiliza el efecto estenopeico para aumentar la profundad de foco. Por otra parte, Flexivue Microlens® se basa en una estructura multifocal donde el centro focaliza en lejos mientras que la periferia focaliza en cerca. Por último, Raindrop Near Vision® modifica la estructura de la córnea para aumentar el radio de curvatura de la parte central de ésta y permitir enfocar a distancias próximas. Todos ellos deben permitir el paso de nutrientes y oxígeno a través de la córnea, ya sea mediante aperturas o siendo permeables. Existe un cuarto tipo de implante intracorneal no comercial desarrollado por el Diffractive Optics Group (DiOG), el cual distribuye los micro-agujeros, que permiten el paso de nutrientes y oxígeno, en las zonas transparentes de una placa zonal de Fresnel. Además, contiene un agujero central, que actúa como estenopeico. Este dispositivo tiene como nombre Diffractive Corneal Inlay (DCI). Esta Tesis pretende modificar y optimizar los parámetros de diseño del DCI y comparar sus propiedades ópticas con otros implantes intracorneales comerciales. / [EN] Presbyopia is the refractive error with the highest incidence in the population due to the aging of the population. There are many solutions to correct it, from ophthalmic lenses, contact lenses, intraocular lenses, etc... Currently the corneal inlays are among the newest solutions. These devices are placed in the corneal stroma by means of minimally invasive surgery. There are three commercial corneal inlays whose mechanisms differ from each other. The most studied is KAMRA inlay® which uses the pinhole effect to increase the depth of focus. On the other hand, Flexivue Microlens® is based on a multi-focal structure where the center focuses at distance vision while the periphery focuses at near vision. Finally, Raindrop Near Vision® modifies the structure of the cornea to increase the radius of curvature of the central part of it and allow focusing at near vision. All of them must all allow pass through to the cornea nutrients and oxygen, either by holes or being permeable. There is a fourth type of non-commercial corneal inlay developed by the Diffractive Optics Group (DiOG), which distributes micro-holes, allow the passage of nutrients and oxygen, in the transparent zones of a Fresnel zone plate. In addition, it contains a central hole, which acts as a pinhole. This device is called Diffractive Corneal Inlay (DCI). This Thesis aims to modify and optimize the design parameters of the DCI and to compare its optical properties with other commercial corneal inlays. / [CA] La presbícia es l'error refractiu amb major incidència en la població degut a l'envelliment d'aquesta. Hi existeixen múltiples solucions per corregir-la, des de lents oftàlmiques, lents de contacte, lents intraoculars, etc... Actualment, els implants intracorneales comercials es troben entre les solucions mes noves. Aquests dispositius es situen a l'estroma corneal mitjançant uns cirurgia mínimament invasiva. Hi existeixen tres tipus d'implants intracorneals amb diferents mecanismes. El mes estudiat es el KAMRA inlay® i utilitza l'efecte estenopeic per augmentar la profunditat de focus. Per altra banda, Flexivue Microlens® es basa en una estructura multifocal on el centre de la lent focalitza en el focus llunyà mentre que la perifèria focalitza prop. Per últim Raindrop Near Vision® modifica l'estructura de la còrnia per augmentar el radi de curvatura de la part central d'aquesta i permetre enfocar a distàncies pròximes. Tots ells deuen permetre el pas de nutrients i oxigen a través de la còrnia, ja siga mitjançant obertures o sent permeables. Existeix un quart tipus d'implant intracorneal no comercial desenvolupat pel Diffractive Optics Group (DiOG), el qual distribueix els micro-forats, que permeten el flux de nutrients i oxigen, en les zones transparents d'una placa zonal de Fresnel. A més, contenen un forat central, que actua com estenopeic. Aquest dispositiu rep el nom Diffractive Corneal Inlay (DCI). Aquesta tesi pretén modificar i optimitzar els paràmetres de disseny del DCI i comparar les seues propietats òptiques amb altres implantes intracorneals comercials. / Funding: Ministerio de Economía y Competitividad (DPI2015-71256-R); Generalitat Valenciana (PROMETEO/2019/048). D. Montagud-Martínez and V. Ferrando acknowledge the financial support from the Universitat Politècnica de València, Spain (fellowships FPI-2016 and PAID10-18, respectively). / Montagud Martínez, D. (2020). Diseño, realización y evaluación de implantes intracorneales difractivos multifocales [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/153474 / TESIS / Compendio

<p>Improved materials for implantation as intraocular lens (IOL) devices are needed to minimize the occurrence of posterior capsule opacification (PCO). In this work, novel polydimethylsiloxane (PDMS) loaded with matrix metalloprotease inhibitors (MMPI) were developed as model IOL materials.</p> <p>PDMS was chosen as silicones are currently used successfully as IOLs. Inhibitor release rates and amount of initial burst of drug-loaded PDMS could be controlled by changing solvent when loading into elastomer base, as well as drug loading method, and release buffer.</p> <p>Two lens epithelial cell lines were characterized for in vitro tests: FHL124 and HLE B3. These cell lines produce different combinations of extracellular matrix proteins when grown on various biomaterial surfaces. Significant differences between the two cell lines were observed both in collagen VIII and α-smooth muscle actin levels, both when cells were unstimulated, and as a result of epithelial to mesenchymal transition induced by treatment with transforming growth factor β2. FHL124 cells were selected in further tests due to their consistent expression of extracellular matrix components when exposed to different materials.</p> <p>Solutions of synthetic MMPI GM6001 and MMP 2/9 Inhibitor II, known to mitigate anterior subcataract formation, were released from PDMS and found to protect in a modest but significant way against protein profile changes and to delay migration. Due to the Zn²⁺ dependence of MMPs, chelators, including EDTA, TPEN and 1-10 phenanthroline were examined as alternative inhibitors. Only the latter was found to have a significant effect on cell migration rates in vitro. Sulfadiazine, due to its chemical resemblance to synthetic MMPI was determined to be the most efficient at reducing migration rates as well as to have the lowest toxicity.</p> <p>Overall, sulfadiazine was determined in this work to be a potentially effective solution to mitigating PCO. These results indicate that releasing MMPI molecules from PDMS as a model IOL is a promising way to mitigate aspects of PCO.</p> / Thesis / Doctor of Philosophy (PhD)

Purpose: The purpose of this study was to investigate the role of the vasculature and immune system in models of glaucoma. Vascular changes have been implicated in glaucoma. As well there is mounting evidence that the immune system plays a role in the disease. It is my hypothesis that the vasculature and immune system play a role in the retinal response to injury in models of glaucoma. Methods: Immunohistochemistry, in vivo retinal imaging (Bright field, fluorescent, optical coherence tomography), Slit2 injections and Evan’s blue labeling were used to investigate vascular and immune changes associated with retinal ganglion cell death after optic nerve crush up to 28 days after injury. Histology, immunohistochemistry, and intravascular labeling were utilized to investigate the role of the vascular degeneration and the systemic immune response to elevated intraocular pressure in 8-16 week old AP-2β Neural Crest Cell Knockout (AP-2β NCC KO) mice. Results: The vascular and immune responses to optic nerve crush were not found to play a significant role in the response to retinal ganglion cell death. Conversely the role of vascular degeneration and immune cell recruitment to the retinas of AP-2β NCC KO mice demonstrated that these factors played a significant role in the retinal response to injury. Conclusion: The vasculature and immune system play a varied role in the response to retinal injury and neurodegeneration depending on the model being studied. The vascular and immune changes were of minimal significance in acute optic nerve crush injury. On the other hand, the chronic injury associated with elevated intraocular pressure in AP-2β NCC KO mice was associated with significant vascular degeneration and systemic immune cell infiltration. / Thesis / Doctor of Philosophy (PhD)