O tratamento da catarata em cães têm passado por algumas mudanças. A facoemulsificação reduziu o tempo cirúrgico e a necessidade de incisão extensa; o implante de lentes intra-oculares (LIOs) permitiu restabelecer a emetropia após a remoção do cristalino. O processo inflamatório induzido pelas cirurgias intra-oculares leva a um estado de estresse oxidativo, com efeitos deletérios às estruturas oculares. O presente estudo teve como objetivo avaliar comparativamente o estresse oxidativo após facoemulsificação experimental em cães, com e sem implante de LIO. Doze cães (três machos e nove fêmeas), sem raça definida, com peso médio de 15,8kg, foram submetidos à facoemulsificação bilateral, sendo doze olhos sem implante de LIO (Grupo 1) e doze olhos com implante de LIO de polimetilmetacrilato no saco capsular (Grupo 2). Os animais foram medicados nos períodos pré-operatório e pós-operatório com antiinflamatórios, antibióticos e midriáticos. As amostras de humor aquoso (HA) foram obtidas por paracentese de câmara anterior, sob anestesia geral, nos períodos pré-operatório (T0) e pós-operatório com 1 dia (T1), 2 dias (T2), 3 dias (T3), 7 dias (T7) e 14 dias (T14). O estresse oxidativo foi avaliado por meio da determinação quantitativa de proteínas no HA (método de Lowry), avaliação da atividade antioxidante total do HA utilizando o AAPH, cloreto de 2,2'azobis (2-metilamidinopropano) e avaliação da concentração de ácido ascórbico no HA e no plasma (cromatografia líquida de alta eficiência). Os resultados foram submetidos à análise estatística, utilizando-se o teste t de Student, quando as variáveis apresentaram distribuição normal, e pelo teste de Wilcoxon, quando não houve distribuição normal. Os níveis de proteína total no HA aumentaram nos dois grupos, sendo de forma mais acentuada no Grupo 2 em todos os tempos pós-operatórios: T1 (p= 0,004), T2 (p= 0,002), T3 (p= 0,004), T7 (p= 0,003) e T14 (p= 0,009). A atividade antioxidante total do HA apresentou uma diminuição nos dois grupos, mais acentuada, entretanto, no Grupo 2, com diferença estatisticamente significante nos tempos T1 (p= 0,013), T2 (p= 0,016), T3 (p= 0,002) e T14 (p= 0,033). No tempo T7 (p= 0,155) essa diferença não foi observada. A concentração de ácido ascórbico no HA apresentou uma diminuição marcante no primeiro dia do pós-operatório, seguida por uma recuperação progressiva nos dois grupos. O Grupo 2 mostrou resultados mais baixos, com diferença estatisticamente significante nos tempos T1 (p= 0,003), T3 (p= 0,015), T7 (p= 0,004) e T14 (p= 0,007), exceto em T2 (p= 0,051), quando não houve diferença. A concentração de ácido ascórbico no plasma não variou em função dos procedimentos. A comparação entre os procedimentos sugere que o implante de LIO contribui para a condição de estresse oxidativo. / The cataract treatment in dogs has undergone some changes. Phacoemulsification has reduced the surgical time of cataract extraction and the need of large incision. Intraocular lens (IOL) implantation has allowed emetropic vision recovery. The inflammatory process induced by intraocular surgery leads to an oxidative stress, with ocular structures damage. The purpose of this study was to comparatively evaluate the oxidative stress following phacoemulsification in dogs with and without IOL implantation. Twelve dogs, three male and nine female, mixed breed, with an average weight of 15.8kg were submitted to bilateral phacoemulsification, being twelve eyes without IOL implantation (Group 1) and twelve eyes with polymethylmethacrylate IOL in the capsular bag (Group 2). In the pre-operative and post-operative periods, the medication consisted of anti-inflammatories, antibiotics and mydriatics. Aqueous humor (AH) samples were taken by anterior chamber paracentesis, under general anesthesia in the pre-operative (T0) and post-operative periods after 1 (T1), 2 (T2), 3 (T3), 7 (T7) and 14 (T14) days of the surgery. The oxidative stress was evaluated by quantitative protein levels in the AH (Lowry’s method), total antioxidant activity in the AH using 2,2’ azobis (2-methylpropionamidine) dihydrochloride (AAPH) and ascorbic acid concentration in the AH and plasma (high performance liquid chromatography). Results were submitted to statistical analysis using the t-student test when the variables had a normal distribution and Wilcoxon test when they did not. Aqueous humor total protein levels increased in both groups, more intensively in Group 2 in all post-operative periods: T1 (p= 0.004), T2 (p= 0.002), T3 (p= 0.004), T7 (p= 0.003) and T14 (p= 0.009). Total antioxidant activity in the AH decreased in both groups; however, it was more impressive in Group 2, with statistical significant difference in T1 (p= 0.013), T2 (p= 0.016), T3 (p= 0.002) e T14 (p= 0.033). In T7 (p= 0.155), this difference was not observed. Ascorbic acid concentration in the AH presented a remarkably decrease in the first post-operative day, then started to recover progressively in the two groups. Group 2 showed lower results with statistically significant differences in T1 (p= 0.003); T3 (p= 0.015); T7 (p= 0.004) and T14 (p= 0.007), except in T2 (p= 0.051) when there was no difference. Ascorbic acid concentration in plasma did not vary as a result of the procedures. The comparison between procedures suggests that IOL implantation contributes to an oxidative stress condition.

Objetivos: Comparar a performance visual dos pacientes submetidos ao implante das lentes intraoculares multifocais difrativas Tecnis® MF ZM900, Acrysof® Restor® SN60D3, Acrysof® SN60WF e Acrysof® SN60AT. Métodos: Estudo prospectivo comparativo, não randomizado, que incluiu 142 olhos de 71 pacientes com catarata, provenientes do ambulatório de oftalmologia do HC- FMUSP. A avaliação oftalmológica contou com medida da acuidade visual para longa, intermediária e curta distância, sem correção e com a melhor correção óptica, teste de sensibilidade ao contraste, pupilometria e análise de frente de onda por meio do aberrômetro. Um questionário de satisfação foi realizado para avaliar a acuidade visual, glare e halos. Todos os exames foram realizados com seis meses de pós-operatório. Resultados: A média de idade dos pacientes foi de 60,7 ± 6,6 anos no grupo Tecnis, 63,1 ± 4,4 anos no grupo Restor e 63,7 ± 4,2 anos no grupo monofocal (SN60AT no olho contralateral SN60WF). A acuidade visual para perto não corrigida e corrigida para longe foi estatisticamente superior nos grupos multifocal Restor e multifocal Tecnis em comparação ao grupo monofocal SN60AT/SN60WF (p<0,001). Não houve diferença estatística entre os grupos na comparação da acuidade visual para longe (p=0,56). A sensibilidade ao contraste fotópica monocular foi estatisticamente inferior nos grupos Restor e Tecnis (p<0,001). A SN60AT apresentou maior aberração esférica comparada a todas as outras lentes (p<0,001). A Tecnis se mostrou com menores valores médios de aberrações esféricas na comparação com a Restor (p<0.001). O questionário de satisfação apresentou maior independência de óculos a favor da Tecnis e Restor, mas com mais queixas de halos e glare do que no grupo monofocal SN60AT/SN60WF. Conclusão: A Restor e Tecnis apresentaram melhor acuidade visual para perto do que o grupo monofocal SN60AT/SN60WF. Todas as lentes intraoculares promoveram boa visão para longe. O grupo da Tecnis apresentou melhor sensibilidade de contraste, menos aberrações óptica e melhor visão intermediária que o grupo Restor. As lentes Restor e Tecnis apresentaram maior satisfação na visão de perto e independência do uso de óculos e glare e halos do que as lentes monofocais / Purpose: Comparison of the visual performance between patients with Tecnis® MF ZM900, Acrysof® Restor® SN60D3, Acrysof® SN60AT and Acrysof® SN60WF intraocular lenses. Patients and methods: This prospective comparative study included 142 eyes of 71 patients in Sao Paulo University. The ophthalmologic evaluation performed included near, intermediate and distance corrected and uncorrected visual acuity, contrast sensitivity measurement and wavefront analysis. All patient underwent a quality of life questionnaire related to visual acuity, glare and halos. The minimum follow-up was 6 months. Results: The mean age of patients was 60.7 ± 6.6 years in the Tecnis® MF, 63.1 ± 4.4 years in-group Restor® 63.7 ± 4.2 years in monofocal group (SN60AT in the fellow eye SN60WF). The Restor and Tecnis groups has uncorrected near and corrected distance visual acuity statistically superior compared to SN60AT/SN60WF group (p <0.001). There was no statistical difference between groups when compared uncorrected and best-corrected distance visual acuity (p = 0.56). Contrast sensitivity in photopic conditions was significantly lower in the Restor and Tecnis group (p <0.001). The SN60AT showed higher spherical aberration compared to all other lenses (p <0.001). The Tecnis showed a lower mean values of spherical aberration compared to Restor lenses (p <0.001). Quality of life questionnaire showed greater independence from glasses for the Tecnis and Restor groups, but with more complaints of halos and glare than the monofocal SN60AT/SN60WF group. Conclusion: Restor and the Tecnis had better near visual acuity than the SN60AT/SN60WF group. All intraocular lenses promoted good distance vision. The Tecnis group showed better contrast sensitivity, less aberrations and better intermediate vision than the Restor group. Restor and Tecnis lenses showed higher satisfaction with near vision and independence from glasses, glare and halos than the monofocal lens

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

Objetivos: Comparar a performance visual dos pacientes submetidos ao implante das lentes intraoculares multifocais difrativas Tecnis® MF ZM900, Acrysof® Restor® SN60D3, Acrysof® SN60WF e Acrysof® SN60AT. Métodos: Estudo prospectivo comparativo, não randomizado, que incluiu 142 olhos de 71 pacientes com catarata, provenientes do ambulatório de oftalmologia do HC- FMUSP. A avaliação oftalmológica contou com medida da acuidade visual para longa, intermediária e curta distância, sem correção e com a melhor correção óptica, teste de sensibilidade ao contraste, pupilometria e análise de frente de onda por meio do aberrômetro. Um questionário de satisfação foi realizado para avaliar a acuidade visual, glare e halos. Todos os exames foram realizados com seis meses de pós-operatório. Resultados: A média de idade dos pacientes foi de 60,7 ± 6,6 anos no grupo Tecnis, 63,1 ± 4,4 anos no grupo Restor e 63,7 ± 4,2 anos no grupo monofocal (SN60AT no olho contralateral SN60WF). A acuidade visual para perto não corrigida e corrigida para longe foi estatisticamente superior nos grupos multifocal Restor e multifocal Tecnis em comparação ao grupo monofocal SN60AT/SN60WF (p<0,001). Não houve diferença estatística entre os grupos na comparação da acuidade visual para longe (p=0,56). A sensibilidade ao contraste fotópica monocular foi estatisticamente inferior nos grupos Restor e Tecnis (p<0,001). A SN60AT apresentou maior aberração esférica comparada a todas as outras lentes (p<0,001). A Tecnis se mostrou com menores valores médios de aberrações esféricas na comparação com a Restor (p<0.001). O questionário de satisfação apresentou maior independência de óculos a favor da Tecnis e Restor, mas com mais queixas de halos e glare do que no grupo monofocal SN60AT/SN60WF. Conclusão: A Restor e Tecnis apresentaram melhor acuidade visual para perto do que o grupo monofocal SN60AT/SN60WF. Todas as lentes intraoculares promoveram boa visão para longe. O grupo da Tecnis apresentou melhor sensibilidade de contraste, menos aberrações óptica e melhor visão intermediária que o grupo Restor. As lentes Restor e Tecnis apresentaram maior satisfação na visão de perto e independência do uso de óculos e glare e halos do que as lentes monofocais / Purpose: Comparison of the visual performance between patients with Tecnis® MF ZM900, Acrysof® Restor® SN60D3, Acrysof® SN60AT and Acrysof® SN60WF intraocular lenses. Patients and methods: This prospective comparative study included 142 eyes of 71 patients in Sao Paulo University. The ophthalmologic evaluation performed included near, intermediate and distance corrected and uncorrected visual acuity, contrast sensitivity measurement and wavefront analysis. All patient underwent a quality of life questionnaire related to visual acuity, glare and halos. The minimum follow-up was 6 months. Results: The mean age of patients was 60.7 ± 6.6 years in the Tecnis® MF, 63.1 ± 4.4 years in-group Restor® 63.7 ± 4.2 years in monofocal group (SN60AT in the fellow eye SN60WF). The Restor and Tecnis groups has uncorrected near and corrected distance visual acuity statistically superior compared to SN60AT/SN60WF group (p <0.001). There was no statistical difference between groups when compared uncorrected and best-corrected distance visual acuity (p = 0.56). Contrast sensitivity in photopic conditions was significantly lower in the Restor and Tecnis group (p <0.001). The SN60AT showed higher spherical aberration compared to all other lenses (p <0.001). The Tecnis showed a lower mean values of spherical aberration compared to Restor lenses (p <0.001). Quality of life questionnaire showed greater independence from glasses for the Tecnis and Restor groups, but with more complaints of halos and glare than the monofocal SN60AT/SN60WF group. Conclusion: Restor and the Tecnis had better near visual acuity than the SN60AT/SN60WF group. All intraocular lenses promoted good distance vision. The Tecnis group showed better contrast sensitivity, less aberrations and better intermediate vision than the Restor group. Restor and Tecnis lenses showed higher satisfaction with near vision and independence from glasses, glare and halos than the monofocal lens

O tratamento da catarata em cães têm passado por algumas mudanças. A facoemulsificação reduziu o tempo cirúrgico e a necessidade de incisão extensa; o implante de lentes intra-oculares (LIOs) permitiu restabelecer a emetropia após a remoção do cristalino. O processo inflamatório induzido pelas cirurgias intra-oculares leva a um estado de estresse oxidativo, com efeitos deletérios às estruturas oculares. O presente estudo teve como objetivo avaliar comparativamente o estresse oxidativo após facoemulsificação experimental em cães, com e sem implante de LIO. Doze cães (três machos e nove fêmeas), sem raça definida, com peso médio de 15,8kg, foram submetidos à facoemulsificação bilateral, sendo doze olhos sem implante de LIO (Grupo 1) e doze olhos com implante de LIO de polimetilmetacrilato no saco capsular (Grupo 2). Os animais foram medicados nos períodos pré-operatório e pós-operatório com antiinflamatórios, antibióticos e midriáticos. As amostras de humor aquoso (HA) foram obtidas por paracentese de câmara anterior, sob anestesia geral, nos períodos pré-operatório (T0) e pós-operatório com 1 dia (T1), 2 dias (T2), 3 dias (T3), 7 dias (T7) e 14 dias (T14). O estresse oxidativo foi avaliado por meio da determinação quantitativa de proteínas no HA (método de Lowry), avaliação da atividade antioxidante total do HA utilizando o AAPH, cloreto de 2,2'azobis (2-metilamidinopropano) e avaliação da concentração de ácido ascórbico no HA e no plasma (cromatografia líquida de alta eficiência). Os resultados foram submetidos à análise estatística, utilizando-se o teste t de Student, quando as variáveis apresentaram distribuição normal, e pelo teste de Wilcoxon, quando não houve distribuição normal. Os níveis de proteína total no HA aumentaram nos dois grupos, sendo de forma mais acentuada no Grupo 2 em todos os tempos pós-operatórios: T1 (p= 0,004), T2 (p= 0,002), T3 (p= 0,004), T7 (p= 0,003) e T14 (p= 0,009). A atividade antioxidante total do HA apresentou uma diminuição nos dois grupos, mais acentuada, entretanto, no Grupo 2, com diferença estatisticamente significante nos tempos T1 (p= 0,013), T2 (p= 0,016), T3 (p= 0,002) e T14 (p= 0,033). No tempo T7 (p= 0,155) essa diferença não foi observada. A concentração de ácido ascórbico no HA apresentou uma diminuição marcante no primeiro dia do pós-operatório, seguida por uma recuperação progressiva nos dois grupos. O Grupo 2 mostrou resultados mais baixos, com diferença estatisticamente significante nos tempos T1 (p= 0,003), T3 (p= 0,015), T7 (p= 0,004) e T14 (p= 0,007), exceto em T2 (p= 0,051), quando não houve diferença. A concentração de ácido ascórbico no plasma não variou em função dos procedimentos. A comparação entre os procedimentos sugere que o implante de LIO contribui para a condição de estresse oxidativo. / The cataract treatment in dogs has undergone some changes. Phacoemulsification has reduced the surgical time of cataract extraction and the need of large incision. Intraocular lens (IOL) implantation has allowed emetropic vision recovery. The inflammatory process induced by intraocular surgery leads to an oxidative stress, with ocular structures damage. The purpose of this study was to comparatively evaluate the oxidative stress following phacoemulsification in dogs with and without IOL implantation. Twelve dogs, three male and nine female, mixed breed, with an average weight of 15.8kg were submitted to bilateral phacoemulsification, being twelve eyes without IOL implantation (Group 1) and twelve eyes with polymethylmethacrylate IOL in the capsular bag (Group 2). In the pre-operative and post-operative periods, the medication consisted of anti-inflammatories, antibiotics and mydriatics. Aqueous humor (AH) samples were taken by anterior chamber paracentesis, under general anesthesia in the pre-operative (T0) and post-operative periods after 1 (T1), 2 (T2), 3 (T3), 7 (T7) and 14 (T14) days of the surgery. The oxidative stress was evaluated by quantitative protein levels in the AH (Lowry’s method), total antioxidant activity in the AH using 2,2’ azobis (2-methylpropionamidine) dihydrochloride (AAPH) and ascorbic acid concentration in the AH and plasma (high performance liquid chromatography). Results were submitted to statistical analysis using the t-student test when the variables had a normal distribution and Wilcoxon test when they did not. Aqueous humor total protein levels increased in both groups, more intensively in Group 2 in all post-operative periods: T1 (p= 0.004), T2 (p= 0.002), T3 (p= 0.004), T7 (p= 0.003) and T14 (p= 0.009). Total antioxidant activity in the AH decreased in both groups; however, it was more impressive in Group 2, with statistical significant difference in T1 (p= 0.013), T2 (p= 0.016), T3 (p= 0.002) e T14 (p= 0.033). In T7 (p= 0.155), this difference was not observed. Ascorbic acid concentration in the AH presented a remarkably decrease in the first post-operative day, then started to recover progressively in the two groups. Group 2 showed lower results with statistically significant differences in T1 (p= 0.003); T3 (p= 0.015); T7 (p= 0.004) and T14 (p= 0.007), except in T2 (p= 0.051) when there was no difference. Ascorbic acid concentration in plasma did not vary as a result of the procedures. The comparison between procedures suggests that IOL implantation contributes to an oxidative stress condition.

<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)

Cataract is one of the leading causes of vision loss worldwide. The rate of cataract surgery has been steadily increasing. Toxic Anterior Segment Syndrome (TASS) is a sterile inflammatory response in the anterior segment of the eye that may occur following cataract surgery. When left untreated, it can lead to permanent vision loss. Corneal endothelial cells are the cells most affected by TASS. These cells are unable to reproduce in vivo and consequently once the density of these cells drops below a certain level, vision is reduced and cannot be reversed. The damage is thought to be mediated by cytokines and endotoxins, primarily through the NF-κΒ pathway. It is hypothesized that anti-inflammatory drug delivery intraocular lenses may help reduce the occurrence of TASS and consequent vision loss. In this research thesis project, an in vitro model was developed as a tool to select drug and delivery material to be used in an anti-TASS ophthalmic biomaterial. In an attempt to find a novel and more effective approach to TASS prevention, dexamethasone, a potent anti-inflammatory steroid drug, was compared to triptolide, a cytokine inhibitor; aprotinin, a general protease inhibitor; and PPM-18, a NF-κΒ inhibitor. To assess the efficacy of these drugs, an in vitro assay using human umbilical vein endothelial cells (HUVEC) and lipopolysaccharide as a stimulant was developed. Cell response to dexamethasone (10 nM), triptolide (3 nM), aprotinin (20 μM) and PPM-18 (10 μM) with or without LPS was characterized by cell viability and flow cytometry analysis of cell activation. Activation was characterized using markers for cell adhesion and activation ICAM-1, PECAM-1, VCAM-1, β1-integrin, CD44 and E-selectin. Following preliminarily testing, the efficacy of dexamethasone (10 nM) and PPM-18 (10 μM) loaded polymer (PDMS) and copolymer (PDMS/pNIPAAm) interpenetrating polymer networks were evaluated over a 4 day release period. The results from soluble drug and LPS (100 ng/mL) testing indicated no decrease in cell viability after 24 h. Dexamethasone, triptolide, aprotinin, and PPM-18 did not reduce the significant ICAM-1 upregulation seen in HUVECs after exposure to LPS for 4 days. PPM-18 in combination with LPS significantly upregulated E-selectin iv and CD44 from unstimulated HUVEC cells. The polymer materials without drug loading did not influence the cell phenotype. However, PPM-18 delivering polymer and copolymer materials significantly upregulated VCAM-1, CD44 when compared to all other treatments. Propidium iodide uptake in HUVEC exposed to PPM-18 drug delivering polymer and copolymer treatments indicated that these treatments caused cell necrosis. None of the drugs, or the drug delivering materials were shown to counteract the upregulation seen from LPS stimulation of HUVEC cells. Future work should focus on validating the in vitro model to more closely replicate the in vivo environment of the anterior segment with the use of primary bovine corneal endothelial cells.

Cataract is one of the leading causes of vision loss worldwide. The rate of cataract surgery has been steadily increasing. Toxic Anterior Segment Syndrome (TASS) is a sterile inflammatory response in the anterior segment of the eye that may occur following cataract surgery. When left untreated, it can lead to permanent vision loss. Corneal endothelial cells are the cells most affected by TASS. These cells are unable to reproduce in vivo and consequently once the density of these cells drops below a certain level, vision is reduced and cannot be reversed. The damage is thought to be mediated by cytokines and endotoxins, primarily through the NF-κΒ pathway. It is hypothesized that anti-inflammatory drug delivery intraocular lenses may help reduce the occurrence of TASS and consequent vision loss. In this research thesis project, an in vitro model was developed as a tool to select drug and delivery material to be used in an anti-TASS ophthalmic biomaterial. In an attempt to find a novel and more effective approach to TASS prevention, dexamethasone, a potent anti-inflammatory steroid drug, was compared to triptolide, a cytokine inhibitor; aprotinin, a general protease inhibitor; and PPM-18, a NF-κΒ inhibitor. To assess the efficacy of these drugs, an in vitro assay using human umbilical vein endothelial cells (HUVEC) and lipopolysaccharide as a stimulant was developed. Cell response to dexamethasone (10 nM), triptolide (3 nM), aprotinin (20 μM) and PPM-18 (10 μM) with or without LPS was characterized by cell viability and flow cytometry analysis of cell activation. Activation was characterized using markers for cell adhesion and activation ICAM-1, PECAM-1, VCAM-1, β1-integrin, CD44 and E-selectin. Following preliminarily testing, the efficacy of dexamethasone (10 nM) and PPM-18 (10 μM) loaded polymer (PDMS) and copolymer (PDMS/pNIPAAm) interpenetrating polymer networks were evaluated over a 4 day release period. The results from soluble drug and LPS (100 ng/mL) testing indicated no decrease in cell viability after 24 h. Dexamethasone, triptolide, aprotinin, and PPM-18 did not reduce the significant ICAM-1 upregulation seen in HUVECs after exposure to LPS for 4 days. PPM-18 in combination with LPS significantly upregulated E-selectin iv and CD44 from unstimulated HUVEC cells. The polymer materials without drug loading did not influence the cell phenotype. However, PPM-18 delivering polymer and copolymer materials significantly upregulated VCAM-1, CD44 when compared to all other treatments. Propidium iodide uptake in HUVEC exposed to PPM-18 drug delivering polymer and copolymer treatments indicated that these treatments caused cell necrosis. None of the drugs, or the drug delivering materials were shown to counteract the upregulation seen from LPS stimulation of HUVEC cells. Future work should focus on validating the in vitro model to more closely replicate the in vivo environment of the anterior segment with the use of primary bovine corneal endothelial cells.

Aberrations affect image quality of the eye away from the line of sight as well as along it. High amounts of lower order aberrations are found in the peripheral visual field and higher order aberrations change away from the centre of the visual field. Peripheral resolution is poorer than that in central vision, but peripheral vision is important for movement and detection tasks (for example driving) which are adversely affected by poor peripheral image quality. Any physiological process or intervention that affects axial image quality will affect peripheral image quality as well. The aim of this study was to investigate the effects of accommodation, myopia, age, and refractive interventions of orthokeratology, laser in situ keratomileusis and intraocular lens implantation on the peripheral aberrations of the eye. This is the first systematic investigation of peripheral aberrations in a variety of subject groups. Peripheral aberrations can be measured either by rotating a measuring instrument relative to the eye or rotating the eye relative to the instrument. I used the latter as it is much easier to do. To rule out effects of eye rotation on peripheral aberrations, I investigated the effects of eye rotation on axial and peripheral cycloplegic refraction using an open field autorefractor. For axial refraction, the subjects fixated at a target straight ahead, while their heads were rotated by ±30º with a compensatory eye rotation to view the target. For peripheral refraction, the subjects rotated their eyes to fixate on targets out to ±34° along the horizontal visual field, followed by measurements in which they rotated their heads such that the eyes stayed in the primary position relative to the head while fixating at the peripheral targets. Oblique viewing did not affect axial or peripheral refraction. Therefore it is not critical, within the range of viewing angles studied, if axial and peripheral refractions are measured with rotation of the eye relative to the instrument or rotation of the instrument relative to the eye. Peripheral aberrations were measured using a commercial Hartmann-Shack aberrometer. A number of hardware and software changes were made. The 1.4 mm range limiting aperture was replaced by a larger aperture (2.5 mm) to ensure all the light from peripheral parts of the pupil reached the instrument detector even when aberrations were high such as those occur in peripheral vision. The power of the super luminescent diode source was increased to improve detection of spots passing through the peripheral pupil. A beam splitter was placed between the subjects and the aberrometer, through which they viewed an array of targets on a wall or projected on a screen in a 6 row x 7 column matrix of points covering a visual field of 42 x 32. In peripheral vision, the pupil of the eye appears elliptical rather than circular; data were analysed off-line using custom software to determine peripheral aberrations. All analyses in the study were conducted for 5.0 mm pupils. Influence of accommodation on peripheral aberrations was investigated in young emmetropic subjects by presenting fixation targets at 25 cm and 3 m (4.0 D and 0.3 D accommodative demands, respectively). Increase in accommodation did not affect the patterns of any aberrations across the field, but there was overall negative shift in spherical aberration across the visual field of 0.10 ± 0.01m. Subsequent studies were conducted with the targets at a 1.2 m distance. Young emmetropes, young myopes and older emmetropes exhibited similar patterns of astigmatism and coma across the visual field. However, the rate of change of coma across the field was higher in young myopes than young emmetropes and was highest in older emmetropes amongst the three groups. Spherical aberration showed an overall decrease in myopes and increase in older emmetropes across the field, as compared to young emmetropes. Orthokeratology, spherical IOL implantation and LASIK altered peripheral higher order aberrations considerably, especially spherical aberration. Spherical IOL implantation resulted in an overall increase in spherical aberration across the field. Orthokeratology and LASIK reversed the direction of change in coma across the field. Orthokeratology corrected peripheral relative hypermetropia through correcting myopia in the central visual field. Theoretical ray tracing demonstrated that changes in aberrations due to orthokeratology and LASIK can be explained by the induced changes in radius of curvature and asphericity of the cornea. This investigation has shown that peripheral aberrations can be measured with reasonable accuracy with eye rotation relative to the instrument. Peripheral aberrations are affected by accommodation, myopia, age, orthokeratology, spherical intraocular lens implantation and laser in situ keratomileusis. These factors affect the magnitudes and patterns of most aberrations considerably (especially coma and spherical aberration) across the studied visual field. The changes in aberrations across the field may influence peripheral detection and motion perception. However, further research is required to investigate how the changes in aberrations influence peripheral detection and motion perception and consequently peripheral vision task performance.

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No. of bitstreams: 1 queiroz_mfn_me_bot.pdf: 2835298 bytes, checksum: ec7c94dadce775ba947336b5608bc560 (MD5) Previous issue date: 2018-02-22 / RESUMO Objetivo: o presente estudo teve como objetivo geral avaliar os resultados visuais, satisfação e qualidade de vida de pacientes submetidos a implante bilateral de LIO multifocal e como objetivos específicos, a avaliação da acuidade visual (AV) para longe, perto e intermediária, do teste de sensibilidade ao contraste e da qualidade de vida destes pacientes por meio de questionário (NEI-VFQ 25). Métodos: foi realizado um estudo prospectivo e intervencionista que incluiu 20 pacientes portadores de catarata senil bilateral, em acompanhamento no setor de Catarata dos Hospital das Clínicas da Faculdade de Medicina de Botucatu. Os critérios de exclusão foram astigmatismo corneano maior que 1,5 D, olho único, história de cirurgia intraocular prévia ou doença ocular que cause redução da AV, falta de motivação do paciente em realizar o procedimento cirúrgico bilateralmente, complicações intra-operatórias e recusa em assinar o TCLE. Os pacientes foram submetidos a implante bilateral da LIO multifocal EyeDiff®, da Eyeol UK®, e foram avaliados no 1o, 3o e 6o mês de pós-operatório com medidas da AV (longe, intermediária e perto, monocular e binocular, sob condições fotópicas e mesópicas), qualidade de visão (avaliação da sensibilidade ao contraste) e qualidade de vida através de um questionário de satisfação. Resultados: todos os olhos apresentaram AV monocular e binocular de 0,3 LogMAR ou melhor para longe e J3 ou melhor para perto com a melhor correção para longe, sob condições fotópicas. A curva de defocus mostrou adição de +2,50 no plano dos óculos. A sensibilidade ao contrate esteve no nível inferior da normalidade para frequências espaciais baixas e altas e abaixo do nível mínimo em frequências intermediárias. A media geral das avaliações no questionário de qualidade de vida foi de 91. Conclusão: conclui-se que o implante da LIO multifocal proporcionou bons resultados no que se refere à AV pós-operatória, além de maior independência dos óculos e melhora da qualidade de vida. / ABSTRACT Purpose: the present study had as main goal to evaluate visual outcomes, satisfaction and quality of life of patients submitted to bilateral implant of multifocal intraocular lens (IOL), and as specific aims, evaluation of distance, intermediate and near visual acuity (VA), contrast sensitivity and quality of life of these patients using a questionnaire (NEI-VFQ 25). Methods: this was a prospective and interventionist study, that included 20 patients with bilateral senil cataract, followed at Botucatu Medicine School. Exclusion criteria were corneal astigmatism superior to 1,50 D, single eye, previous intraocular surgery or ocular disease, intra-operatory complications and refuse in signing the consent form. Patients were submitted to bilateral implant of multifocal IOL EyeDiff® Eyeol UK® and were evaluated at 1o, 3o and 6o month, postoperatively, with VA testing (for distance, intermediate and near, monocular and binocular, under fotopic and mesopic conditions), eyesight quality (contrast sensitivity evaluation) and quality of life through a satisfaction questionnaire. Results: all eyes presented monocular and binocular CDVA of 0,3 LogMar or better and DCNVA of J3 or better, under photopic and mesopic conditions. Defocus curve showed best performance at +2,50 D. Contrast sensitivity were in the minimum level of normality for low and high special frequencies and under normal limits for intermediate special frequency. The quality of life questionnaire had average score of 91. Conclusion: in conclusion, multifocal IOL implant provided good results for post-operative VA, in addition to greater spectacle independence and quality of life improvement.