<p>Katarakta i glaukom su po svom toku hronične i progresivne bolesti koji predstavljaju dva vodeća uzroka slepila u svetu. Obe bolesti su karakteristične za stariju životnu dob i često se sreću zajedno kod iste osobe. Katarakta podrazumeva hirur&scaron;ko lečenja, dok se lečenje glaukoma zasniva na snižavanju visine intraokularnog pritiska (IOP), medikamentoznim i hirur&scaron;kim sredstvima. Cilj ovog istraživanja bio je da se utvrdi da li i u kojoj meri dolazi promene IOP-a i dubine prednje komore oka (ACD) nakon operacije katarakte, da li su preoperativne vrednosti IOP-a i ACD povezane sa postoperativnom visinom IOP-a i da li postoje razlike u ovim pojavama kod osoba operisanih od katarakte sa i bez prisutnog primarnog glaukoma otvorenog ugla (POAG). Rezultati ove studije pokazuju da postoji statistički značajno sniženje IOP-a 6 meseci nakon operacije katarakte. U poređenju sa preoperativnim vrednostima, ono iznosi prosečno 1,2 mmHg (7,5%) u grupi pacijenata bez POAG i 1,24 mmHg (6,49%) u grupi pacijenata sa POAG. Između dve grupe pacijenata nije postojala razlika u stepenu sniženja (p&gt;0,05). Ustanovljen je statistički značajano veći (p&lt;0,05) porast dubine ACD u grupi pacijenata sa POAG (1,03 mm; 34,8%) u odnosu pacijente bez glaukomske bolesti (0,92 mm; 30,37%). Rezultati korelacione analize, kao i regresionih univarijantih i multivarijantnih modela, pokazali su da statistički značajna povezanost postoji između preoperativne visine IOP-a i njegovog sniženja nakon operacije katarakte. Povezanost je bila pozitivnog smera i nije se uočena značajna razlika između obe grupe pacijenata. Ustanovljena je i pozitiva korelacija, bez statistički značajne razlike u obe grupe pacijenata, između PD indeksa (odnos preoperativnog IOP-a i ACD) i promene IOP-a nakon operacije katarakte. Preoperativna dubina prednje komore oka nije ispoljila povezanost sa postoperativnom promenom IOP-a. Na&scaron;a studija je pokazala statistički značajno postoperativno sniženje IOP-a i povećanje dubine ACD nakon operacije katarakte, koja se održava &scaron;est meseci nakon operacije katarakte. Nije ustanovljena razlika u redukciji IOP-a između pacijenata sa i bez POAG. Ustanovljena je pozitivna korelacija preoperativne visine IOP-a i PD indeksa sa postoperativnom promenom IOP-a, &scaron;to može biti od koristi prilikom odluke o optimalnom lečenju katarakte kod pacijenata sa POAG.</p> / <p>Cataract and glaucoma are chronic and progressive diseases and they are two of the leading causes of blindness wold wide. Both diseases are typical for an older age and often coincide within the same person. Treatment of cataract is surgical, while glaucoma treatment is based on lowering the level of intraocular pressure (IOP) with various medical and surgical options. The aims of this research were to determine whether there is a change in IOP and in the depth of anterior chamber of the eye (ACD) after cataract surgery, whether preoperative values of IOP and ACD are related to postoperative IOP values and to determine if there are differences in these events between people operated from cataract with or without primary open angle glaucoma (POAG). Results of this study show that there is a statistically significant decrease of IOP six months after cataract surgery. Comparing with preoperative values, it was found to be 1.2 mmHg (7.5%) in group of patients without POAG, and 1.24 mmHg (6.49%) in patients with POAG. There was no statistically significant difference found between two groups of patients (p&lt;0.05). Group of patients with POAG had significantly higher (p&lt;0.05) deepening of ACD (1.03 mm; 34.8%), in comparison with patients with no glaucoma (0.92 mm; 30.37%). Results of correlation analysis, as well as univariate and multivariate regression models, have shown significant correlation of preoperative IOP and its reduction after cataract surgery. Correlation was of positive direction with no statistically significant differences among two groups of patients. There was a positive correlation found, with no statistically significant differences in both groups of patients, between PD index (ratio of preoperative IOP and ACD) and IOP change after cataract surgery. Preoperative anterior chamber depth has shown no correlation with postoperativeIOP change. Our study showed statisticallysignificant postoperative reduction ofIOP and deepening of ACD, lasting for six months aftercataract surgery. No difference inpostoperativeIOP decrease has been detected betweenpatients with or without POAG. A positivecorrelation of preoperativeIOP height and PDindex with postoperativeIOP change has beenestablished, which mayprove usefulfordecision of optimal treatmentof cataract among POAG patients.</p>

OBJETIVOS: Comparar os valores da pressão intraocular (PIO), obtidos por intermédio do tonômetro de Perkins (TPK), tonômetro de contorno dinâmico Pascal (TCD) e Tono-Pen (TNP), confrontando-os com o tonômetro de aplanação de Goldmann (TAG), e correlacionar seus valores tonométricos com parâmetros biométricos oculares em pacientes portadores de glaucoma congênito primário. MÉTODOS: Estudo prospectivo, transversal, com inclusão de 46 pacientes (46 olhos) com diagnóstico de glaucoma congênito primário, com idades entre 12 e 40 anos, após obtenção do Termo de Consentimento Livre e Esclarecido. Todos os olhos estudados foram submetidos à tonometria ocular usando os tonômetros de Goldmann, de Perkins, o Tono-Pen e o tonômetro de contorno dinâmico Pascal. A ordem das tonometrias foi aleatória e o tonômetro de Goldmann foi adotado como padrão ouro. Os parâmetros biométricos estudados foram a curvatura (medida pela ceratometria), a espessura central da córnea (paquimetria), o diâmetro corneal (medido por meio de compasso cirúrgico) e o comprimento axial do olho foi obtido pela biometria ultrassônica. As distribuições dos parâmetros biométricos, assim como das tonometrias foram plotadas e analisadas conforme teste de Kolmogorov-Smirnov para aceitação de normalidade. O teste t de Student pareado para amostras independentes foi empregado para comparar as médias tonométricas de cada tonômetro com o padrão ouro. As correlações entre os parâmetros biométricos e as tonometrias foram realizadas através do coeficiente de correlação de Pearson e gráficos de regressão linear. O mesmo procedimento foi feito entre os parâmetros biométricos e as diferenças entre as três distintas tonometrias e a TAG. A concordância entre os tonômetros Perkins, Pascal e Tono-Pen e o de Goldamnn foi realizada pelo teste de concordância de correlação (CCC) e graficamente pelo método de Bland-Altman. O valor de corte de 2 mmHg foi adotado para avaliar a empregabilidade clínica desses tonômetros em pacientes semelhantes aos da amostra. RESULTADOS: O teste de Kolmogorov-Smirnov indicou aceitação da normalidade para todas as distribuições estudadas (TAG, TPK, TCD, TNP, Diâmetros corneal e axial, ceratometria média e paquimetria). Os momentos de correlação de Pearson empregados para realizar estudo das correlações entre os parâmetros biométricos e cada tonometria foram estatisticamente não significativos. As correlações entre os parâmetros biométricos e as diferenças entre tonometrias em relação ao TAG não apresentaram significância em sua maioria, sendo a única exceção a correlação moderada entre a diferença do TAG e o Tono-Pen versus a ceratometria média. No entanto, o coeficiente de determinação evidenciou influência modesta da ceratometria nessas diferenças (r² = 0,16; p = 0,004). O teste t de Student pareado demonstrou diferença significativa entre o TAG e o TP (p < 0,001). A diferença não foi significativa entre o TAG e o Pascal (p = 0.30), ou entre o TAG e o Tono-Pen (p = 0.68). Houve excelente concordância entre o TAG e o TP (CCC = 0,98; intervalo de confiança 95% (IC95%) = 0,97 - 0,99), já entre o TAG e o Pascal (CCC = 0,89; IC95% = 0,82 - 0,94) e entre o TAG e o Tono-Pen (CCC = 0,92; IC95% = 0,87 - 0,95). O gráfico tipo Bland-Altman TAG x Perkins demonstrou diferença média de 0,47 mmHg com intervalo de 95% (I95%) situado entre -0,98 e 1,92 mmHg. A dispersão das diferenças seguiu caráter aleatório. Os outros dois tonômetros também tiveram suas dispersões em caráter aleatório. TAG em relação ao tonômetro de Pascal apresentou diferença média de -0,3 mmHg (I95% = -4,2 a 3,6 mmHg). A diferença média do TAG em relação ao Tono-Pen foi de -0,1 mmHg (I95% = -3,7 a 3,5 mmHg). Em 21% dos pacientes, o tonômetro de Pascal apresentou diferenças maiores de 2 mmHg em relação ao TAG, ao passo que no Tono- Pen essa proporção foi de 17,3%, e o tonômetro de Perkins não apresentou em nenhum dos pacientes diferenças maiores que estes limites. CONCLUSÕES: A ceratometria, paquimetria e os diâmetros axial e corneal não se correlacionaram com a PIO obtida por meio do TAG, tonômetro de Perkins, Pascal ou Tono-Pen. As diferenças tonométricas entre TAG (padrão ouro) e os outros tonômetros também não se correlacionaram com esses parâmetros biométricos, com exceção da ceratometria média, que se correlacionou positiva e moderadamente com a diferença da PIO entre TAG e Tono-Pen. O tonômetro de Perkins apresentou concordância substancial com o TAG, já o Tono-Pen e o TCD apresentaram concordâncias moderadas, sendo a concordância do Tono-Pen maior que a do TCD / OBJECTIVES: To compare the values of intraocular pressure (IOP) obtained by Perkins tonometer (PKT), Pascal dynamic contour tonometer (DCT) and Tono-Pen (TP), comparing then with Goldmann applanation tonometry (GAT), analyzing their correlations with ocular biometric parameters in patients with primary congenital glaucoma. METHODS: Prospective and cross-sectional study, including 46 patients (46 eyes) diagnosed with primary congenital glaucoma, between 12 and 40 years old, after obtaining informed consent. Keratometry was performed, followed by Goldmann applanation tonometry, Perkins tonometry, DCT and TP. The order of tonometries was randomized. The Goldmann tonometer was adopted as the gold standard. Ultrasound pachymetry, ultrasound biometry and corneal diameter measurement with surgical compass were also performed. The distributions of biometric parameters, as well as the tonometries were plotted and analyzed using Kolmogorov-Smirnov for acceptance of normality. Paired Student\'s t test for independent samples was used to compare the means of each tonometry with the gold standard. The correlations between biometric parameters and tonometries were performed by Pearson\'s product moment correlation coefficient and linear regression plots. The same procedure was done between biometric parameters and the differences between the three distinct tonometries and Goldmann tonometry. The agreement between tonometers and the GAT was performed through concordance correlation coefficient (CCC) and graphically by the Bland-Altman method. End point of 2 mmHg was adopted to evaluate clinical employability of these tonometers in patients with similar conditions. RESULTS: The Kolmogorov-Smirnov indicated acceptance of normality for all distributions studied (GAT, PKT, DCT, TP, corneal diameter, axial length, keratometry and pachymetry). All the Pearson´s product moment correlation coefficients between biometric parameters and each tonometry were not significant. The correlations between the biometric parameters and the differences between tonometries compared to the gold standard were not significant in most cases. The only exception was a positive and moderate correlation between the difference of the GAT and Tono-Pen versus the keratometry. The determintation coefficient revealed a considerable, but no large influence of K on the differences between GAT and Tono-Pen (r² = 0.16; p = 0.004). Student\'s paired t test showed a significant difference between GAT and PT (p < 0.001). The difference was not significant between the GAT and Pascal (p = 0.30), or between the GAT and Tono-Pen (p = 0.68). There was excellent agreement between GAT and PT (CCC = 0.98, 95% confidence interval (95% CI) = 0.97 to 0.99), as between GAT and Pascal (CCC = 0.90, 95% CI = 0.82 to 0.94) and between GAT and Tono-Pen (CCC = 0.92, 95% CI = .87 to .95). Bland-Altman plot GAT x Perkins showed a mean difference of 0, 47 mmHg with 95% CI located between -0.98 and 1.92 mmHg. The distribution of the IOP differences was aleatory. The other two differences` distributions also had aleatory characteristics. When comparing GAT with Pascal, the mean difference was -0.3 mmHg (95% CI = -4.2% to 3.6 mmHg). Mean difference between GAT and Tono-Pen was -0.1 mmHg (95% CI = -3,7 to 3.5 mmHg). Pascal tonometer showed a difference greater than 2 mmHg comparing to GAT in 21% of the patients, while with Tono-Pen this ratio was 17.3% and the Perkins tonometer did not present in any patient differences greater than these limits. CONCLUSIONS: The keratometry, pachymetry, corneal diameter and axial length did not correlate with IOP obtained by GAT, Perkins tonometer, Tono-Pen or Pascal. The differences between GAT (gold standard) and the other tonometers also did not correlate with these biometric parameters, with the exception of corneal curvature, which was positive and moderately correlated with the difference in IOP between GAT and Tono-Pen. GAT and Perkins tonometer showed substantial agreement, although Tono-Pen and DCT showed moderate agreement with GAT. The concordance obtained with Tono-Pen was higher than the concordance obtained with DCT

<p>Glaucoma is a common disease in the elderly population. Open-angle glaucoma (OAG) is the predominant form of glaucoma. Chronic simple glaucoma and capsular glaucoma, characterized by the occurrence of pseudoexfoliation in the anterior eye segment, are the most frequent types of OAG. The purpose of the present thesis was to study the epidemiology of OAG in the municipality of Tierp, whose population has a high exposure to pseudoexfoliation.</p><p>In a case-finding study, the prevalence of known cases of OAG by December 31, 1983 was estimated to 1.4% in people ≥45 years of age. Sixty-three percent of all cases had capsular glaucoma. Patients with advanced glaucoma were older, had had the disease for longer, had higher mean initial intraocular pressure, and had more extensive visual field defects at the time of diagnosis.</p><p>A population survey of people 65–74 years of age was conducted in 1984–86. The prevalence of OAG was 5.3%. Pseudoexfoliation was found in 17%, being more common in females. Pseudoexfoliation was associated with OAG only in people previously diagnosed with the disease (odds ratio = 16). In cases detected at the survey, an intraocular pressure ≥20 mmHg was a serious risk factor of having OAG (odds ratio = 9.7).</p><p>In a 5-year follow-up study of participants in the population survey, increased intraocular pressure and pseudoexfoliation were recognized as independent risk factors for the development of OAG (standardized risk ratios = 3.4 and 9.8, respectively). Interaction between increased intraocular pressure and pseudoexfoliation was indicated. By May 2006, the incidence of OAG was estimated to 7.1 per 1,000 person-years. The incidence of capsular glaucoma was more than twice that of chronic simple glaucoma.</p><p>The prevalence and incidence of OAG was higher than that reported from other studies conducted on Caucasian populations. The probable explanation for this finding is exposure to pseudoexfoliation.</p>

Glaucoma is a common disease in the elderly population. Open-angle glaucoma (OAG) is the predominant form of glaucoma. Chronic simple glaucoma and capsular glaucoma, characterized by the occurrence of pseudoexfoliation in the anterior eye segment, are the most frequent types of OAG. The purpose of the present thesis was to study the epidemiology of OAG in the municipality of Tierp, whose population has a high exposure to pseudoexfoliation. In a case-finding study, the prevalence of known cases of OAG by December 31, 1983 was estimated to 1.4% in people ≥45 years of age. Sixty-three percent of all cases had capsular glaucoma. Patients with advanced glaucoma were older, had had the disease for longer, had higher mean initial intraocular pressure, and had more extensive visual field defects at the time of diagnosis. A population survey of people 65–74 years of age was conducted in 1984–86. The prevalence of OAG was 5.3%. Pseudoexfoliation was found in 17%, being more common in females. Pseudoexfoliation was associated with OAG only in people previously diagnosed with the disease (odds ratio = 16). In cases detected at the survey, an intraocular pressure ≥20 mmHg was a serious risk factor of having OAG (odds ratio = 9.7). In a 5-year follow-up study of participants in the population survey, increased intraocular pressure and pseudoexfoliation were recognized as independent risk factors for the development of OAG (standardized risk ratios = 3.4 and 9.8, respectively). Interaction between increased intraocular pressure and pseudoexfoliation was indicated. By May 2006, the incidence of OAG was estimated to 7.1 per 1,000 person-years. The incidence of capsular glaucoma was more than twice that of chronic simple glaucoma. The prevalence and incidence of OAG was higher than that reported from other studies conducted on Caucasian populations. The probable explanation for this finding is exposure to pseudoexfoliation.

The inherited form of primary open angle glaucoma, a disorder characterized by increased intraocular pressure and retina degeneration, is linked to mutations in the olfactomedin (OLF) domain of the myocilin gene. Disease-causing myocilin variants accumulate within trabecular meshwork cells instead of being secreted to the trabecular extracellular matrix thought to regulate aqueous humor flow and control intraocular pressure. Like other diseases of protein misfolding, we hypothesize myocilin toxicity originates from defects in protein biophysical properties. In this thesis, the first preparative recombinant high-yield expression and purification system for the C-terminal OLF domain of myocilin (myoc-OLF) is described. To determine the relative stability of wild-type (WT) and mutant OLF domains, a fluorescence thermal stability assay was adapted to provide the first direct evidence that mutated OLF is folded but less thermally stable than WT. In addition, mutant myocilin can be stabilized by chemical chaperones. Together, this work provides the first quantitative demonstration of compromised stability among identified OLF variants and placing myocilin glaucoma in the context of other complex diseases of protein misfolding. Subsequent investigations into the biophysical properties of WT myoc-OLF provide insight into its structure and function. In particular, myoc-OLF is stable in the presence of glycosaminoglycans (GAGs), as well as over a wide pH range in buffers with functional groups reminiscent of such GAGs. Myoc-OLF contains significant â-sheet and â-turn secondary structure as revealed by circular dichroism analysis. At neutral pH, thermal melts indicate a highly cooperative transition with a melting temperature of ~55°C. A compact core structural domain of OLF was identified by limited proteolysis and consists of approximately residues 238-461, which retains the single disulfide bond and is as stable as the full myoc-OLF construct. This construct also is capable of generating 3D crystals for structure determination. This data, presented in Chapter 3, inform new testable hypotheses for interactions with specific trabecular extracellular matrix components. To gain further insight into the biological function of myoc-OLF, a facile fluorescence chemical stability assay was designed to identify possible ligands and drug candidates. In the assay described in Chapter 4, the target protein is initially destabilized with a chemical denaturant and is tested for re-stabilization upon the addition of small molecules. The assay requires no prior knowledge of the structure and/or function of the target protein, and it is amendable to high-throughput screening. Application of the assay using a library of 1,280 compounds revealed 14 possible ligands and drug candidates for myoc-OLF that may also generate insights into myoc-OLF function. Due to the high â-sheet content of monomeric myoc-OLF and presence of an aggregated species upon myoc-OLF purification, the ability of myoc-OLF to form amyloid fibrils was suspected and verified. The fibril forming region was confirmed to reside in the OLF domain of myocilin. Kinetic analyses of fibril formation reveal a self-propagating process common to amyloid. The presence of an aggregated species was confirmed in cells transfected with WT myocilin, but to a greater extent in cells transfected with P370L mutant myocilin. Both cell lines stained positive for amyloid. Taken together, these results provide further insights into the structure of myocilin and suggest a new hypothesis for glaucoma pathogenesis. Finally, in a related study, small molecule drug candidates were investigated to treat acid â-glucosidase (GCase), the deficient lysosomal enzyme in Gaucher disease, another protein conformational disorder. Three new GCase active-site directed 3,4,5,6-tetrahydroxylazepane inhibitors were synthesized that exhibit half inhibitory concentrations (IC50) in the low millimolar to low micromolar range. Although the compounds thermally stabilize GCase at pH 7.4, only one of the synthesized analogs exhibits chaperoning activity under typical assay conditions. This successful pharmacological chaperone is also one in which GCase is in its proposed active conformation as revealed by X-ray crystallography. Probing the plasticity of the active-site of GCase offers additional insight into possible molecular determinants for an effective small molecule therapy for GD.

INTRODUÇÃO: Comparar duas soluções viscoelásticas, ácido hialurônico 1,6%/sulfato de condroitina 4% (DisCoVisc®, Alcon Laboratórios, EUA) e hidroxipropilmetilcelulose 2% (HPMC, Ophthalmos, Brasil), com relação ao desempenho durante a facoemulsificação (FACO) e o implante de lente intraocular. MÉTODOS: Foi realizado um ensaio clínico randomizado, envolvendo 78 olhos (39 pacientes) submetidos à FACO bilateral, por um único cirurgião. Os pacientes foram randomizados para receber DisCoVisc ou HPMC no primeiro olho. O olho contralateral foi operado mais tarde recebendo a outra solução viscoelástica em todas as etapas da cirurgia. Examinadores mascarados realizaram as avaliações pré e pósoperatórias (5, 24 e 48 horas; 7 e 14 dias; 3 e 6 meses), incluindo a medida da pressão intraocular (PIO), espessura cornena central (ECC) e acuidade visual corrigida. A densidade endotelial foi realizada no pré-operatório e ao final do seguimento (6 meses). Variáveis intraoperatórias incluíram medidas da quantidade total de solução viscoelástica, tempo de ultrassom durante a FACO e tempo para a retirada completa da solução do olho. RESULTADOS: A densidade endotelial foi estatisticamente superior com DisCoVisc (2.214 ± 372 cel/mm2) do que com HPMC (2.032 ± 460 cel/mm2) ao final do seguimento (p = 0,001). Uma redução média de 7% e de 15%, respectivamente. Não houve diferença estatística entre as soluções viscoelásticas com relação a densidade da catarata (p = 0,363) e o tempo de ultrassom (p = 0,456). O tempo de aspiração da HPMC (0,22 ± 0,09 min) foi significativamente maior que o DisCoVisc (0,17 ± 0,06 min) (p = 0,001) e a quantidade de viscoelástico utilizada foi maior com a HPMC (1,35 ± 0,20 ml) do que com DisCoVisc (0,89 ± 0,11 ml) (p < 0,001). Não houve diferença estatisticamente significativa entre as soluções quanto a ECC e a PIO durante o seguimento. CONCLUSÕES: A densidade endotelial ao final do estudo foi significativamente maior com o uso de DisCoVisc, o que pode representar uma melhor proteção endotelial. Foi necessário uma menor quantidade de DisCoVisc e um tempo de aspiração menor durante a FACO com essa solução viscoelástica / INTRODUCTION: To compare two ophthalmic viscosurgical devices (OVDs), 1.6% hyaluronic acid/4% chondroitin sulfate (DisCoVisc®, Alcon Lab., USA) and 2% hydroxypropylmethylcellulose (HPMC, Ophthalmos, Brazil), in terms of their overall performance during phacoemulsification (PHACO) and intraocular lens implantation. METHODS: This prospective, randomized clinical trial comprised 78 eyes (39 patients) that underwent PHACO by the same surgeon. Patients were randomly assigned to receive DisCoVisc or HPMC on the first eye. The other eye was treated later and received the other OVD. Masked examiners measured intraocular pressure (IOP), central corneal thickness (CCT) and best-corrected visual acuity. The corneal endothelial cell density was measured at baseline and at 6 months postoperatively. Intraoperative variables include the total amount of the OVD, ultrasound and washout times. RESULTS: Corneal endothelial cell density was significantly higher with DisCoVisc (2.214 ± 372 cell/mm2) than HPMC (2.032 ± 460 cell/mm2) at the end of follow-up (p = 0.001). A mean reduction of 7% and 15%, respectively. There were no statistically significant differences between OVDs in terms of cataract density (p = 0.363) or ultrasound time (p = 0.456). Regarding washout time, it took longer to remove HPMC (0.22 ± 0.09 min) than DisCoVisc (0.17 ± 0.06 min) (p = 0.001), and the amount of viscoelastic material used was greater with HPMC (1.35 ± 0.20 ml) than DisCoVisc (0.89 ± 0.11 ml) (p < 0.001). There were no statistically significant differences between the two OVDs regarding CCT or IOP measurements at any point in time. CONCLUSION: The corneal endothelial cell loss was significantly less with DisCoVisc than HPMC, which can improve corneal endothelium protection. DisCoVisc was easier to remove after IOL implantation and fewer amounts were necessary during PHACO

OBJETIVOS: Comparar os valores da pressão intraocular (PIO), obtidos por intermédio do tonômetro de Perkins (TPK), tonômetro de contorno dinâmico Pascal (TCD) e Tono-Pen (TNP), confrontando-os com o tonômetro de aplanação de Goldmann (TAG), e correlacionar seus valores tonométricos com parâmetros biométricos oculares em pacientes portadores de glaucoma congênito primário. MÉTODOS: Estudo prospectivo, transversal, com inclusão de 46 pacientes (46 olhos) com diagnóstico de glaucoma congênito primário, com idades entre 12 e 40 anos, após obtenção do Termo de Consentimento Livre e Esclarecido. Todos os olhos estudados foram submetidos à tonometria ocular usando os tonômetros de Goldmann, de Perkins, o Tono-Pen e o tonômetro de contorno dinâmico Pascal. A ordem das tonometrias foi aleatória e o tonômetro de Goldmann foi adotado como padrão ouro. Os parâmetros biométricos estudados foram a curvatura (medida pela ceratometria), a espessura central da córnea (paquimetria), o diâmetro corneal (medido por meio de compasso cirúrgico) e o comprimento axial do olho foi obtido pela biometria ultrassônica. As distribuições dos parâmetros biométricos, assim como das tonometrias foram plotadas e analisadas conforme teste de Kolmogorov-Smirnov para aceitação de normalidade. O teste t de Student pareado para amostras independentes foi empregado para comparar as médias tonométricas de cada tonômetro com o padrão ouro. As correlações entre os parâmetros biométricos e as tonometrias foram realizadas através do coeficiente de correlação de Pearson e gráficos de regressão linear. O mesmo procedimento foi feito entre os parâmetros biométricos e as diferenças entre as três distintas tonometrias e a TAG. A concordância entre os tonômetros Perkins, Pascal e Tono-Pen e o de Goldamnn foi realizada pelo teste de concordância de correlação (CCC) e graficamente pelo método de Bland-Altman. O valor de corte de 2 mmHg foi adotado para avaliar a empregabilidade clínica desses tonômetros em pacientes semelhantes aos da amostra. RESULTADOS: O teste de Kolmogorov-Smirnov indicou aceitação da normalidade para todas as distribuições estudadas (TAG, TPK, TCD, TNP, Diâmetros corneal e axial, ceratometria média e paquimetria). Os momentos de correlação de Pearson empregados para realizar estudo das correlações entre os parâmetros biométricos e cada tonometria foram estatisticamente não significativos. As correlações entre os parâmetros biométricos e as diferenças entre tonometrias em relação ao TAG não apresentaram significância em sua maioria, sendo a única exceção a correlação moderada entre a diferença do TAG e o Tono-Pen versus a ceratometria média. No entanto, o coeficiente de determinação evidenciou influência modesta da ceratometria nessas diferenças (r² = 0,16; p = 0,004). O teste t de Student pareado demonstrou diferença significativa entre o TAG e o TP (p < 0,001). A diferença não foi significativa entre o TAG e o Pascal (p = 0.30), ou entre o TAG e o Tono-Pen (p = 0.68). Houve excelente concordância entre o TAG e o TP (CCC = 0,98; intervalo de confiança 95% (IC95%) = 0,97 - 0,99), já entre o TAG e o Pascal (CCC = 0,89; IC95% = 0,82 - 0,94) e entre o TAG e o Tono-Pen (CCC = 0,92; IC95% = 0,87 - 0,95). O gráfico tipo Bland-Altman TAG x Perkins demonstrou diferença média de 0,47 mmHg com intervalo de 95% (I95%) situado entre -0,98 e 1,92 mmHg. A dispersão das diferenças seguiu caráter aleatório. Os outros dois tonômetros também tiveram suas dispersões em caráter aleatório. TAG em relação ao tonômetro de Pascal apresentou diferença média de -0,3 mmHg (I95% = -4,2 a 3,6 mmHg). A diferença média do TAG em relação ao Tono-Pen foi de -0,1 mmHg (I95% = -3,7 a 3,5 mmHg). Em 21% dos pacientes, o tonômetro de Pascal apresentou diferenças maiores de 2 mmHg em relação ao TAG, ao passo que no Tono- Pen essa proporção foi de 17,3%, e o tonômetro de Perkins não apresentou em nenhum dos pacientes diferenças maiores que estes limites. CONCLUSÕES: A ceratometria, paquimetria e os diâmetros axial e corneal não se correlacionaram com a PIO obtida por meio do TAG, tonômetro de Perkins, Pascal ou Tono-Pen. As diferenças tonométricas entre TAG (padrão ouro) e os outros tonômetros também não se correlacionaram com esses parâmetros biométricos, com exceção da ceratometria média, que se correlacionou positiva e moderadamente com a diferença da PIO entre TAG e Tono-Pen. O tonômetro de Perkins apresentou concordância substancial com o TAG, já o Tono-Pen e o TCD apresentaram concordâncias moderadas, sendo a concordância do Tono-Pen maior que a do TCD / OBJECTIVES: To compare the values of intraocular pressure (IOP) obtained by Perkins tonometer (PKT), Pascal dynamic contour tonometer (DCT) and Tono-Pen (TP), comparing then with Goldmann applanation tonometry (GAT), analyzing their correlations with ocular biometric parameters in patients with primary congenital glaucoma. METHODS: Prospective and cross-sectional study, including 46 patients (46 eyes) diagnosed with primary congenital glaucoma, between 12 and 40 years old, after obtaining informed consent. Keratometry was performed, followed by Goldmann applanation tonometry, Perkins tonometry, DCT and TP. The order of tonometries was randomized. The Goldmann tonometer was adopted as the gold standard. Ultrasound pachymetry, ultrasound biometry and corneal diameter measurement with surgical compass were also performed. The distributions of biometric parameters, as well as the tonometries were plotted and analyzed using Kolmogorov-Smirnov for acceptance of normality. Paired Student\'s t test for independent samples was used to compare the means of each tonometry with the gold standard. The correlations between biometric parameters and tonometries were performed by Pearson\'s product moment correlation coefficient and linear regression plots. The same procedure was done between biometric parameters and the differences between the three distinct tonometries and Goldmann tonometry. The agreement between tonometers and the GAT was performed through concordance correlation coefficient (CCC) and graphically by the Bland-Altman method. End point of 2 mmHg was adopted to evaluate clinical employability of these tonometers in patients with similar conditions. RESULTS: The Kolmogorov-Smirnov indicated acceptance of normality for all distributions studied (GAT, PKT, DCT, TP, corneal diameter, axial length, keratometry and pachymetry). All the Pearson´s product moment correlation coefficients between biometric parameters and each tonometry were not significant. The correlations between the biometric parameters and the differences between tonometries compared to the gold standard were not significant in most cases. The only exception was a positive and moderate correlation between the difference of the GAT and Tono-Pen versus the keratometry. The determintation coefficient revealed a considerable, but no large influence of K on the differences between GAT and Tono-Pen (r² = 0.16; p = 0.004). Student\'s paired t test showed a significant difference between GAT and PT (p < 0.001). The difference was not significant between the GAT and Pascal (p = 0.30), or between the GAT and Tono-Pen (p = 0.68). There was excellent agreement between GAT and PT (CCC = 0.98, 95% confidence interval (95% CI) = 0.97 to 0.99), as between GAT and Pascal (CCC = 0.90, 95% CI = 0.82 to 0.94) and between GAT and Tono-Pen (CCC = 0.92, 95% CI = .87 to .95). Bland-Altman plot GAT x Perkins showed a mean difference of 0, 47 mmHg with 95% CI located between -0.98 and 1.92 mmHg. The distribution of the IOP differences was aleatory. The other two differences` distributions also had aleatory characteristics. When comparing GAT with Pascal, the mean difference was -0.3 mmHg (95% CI = -4.2% to 3.6 mmHg). Mean difference between GAT and Tono-Pen was -0.1 mmHg (95% CI = -3,7 to 3.5 mmHg). Pascal tonometer showed a difference greater than 2 mmHg comparing to GAT in 21% of the patients, while with Tono-Pen this ratio was 17.3% and the Perkins tonometer did not present in any patient differences greater than these limits. CONCLUSIONS: The keratometry, pachymetry, corneal diameter and axial length did not correlate with IOP obtained by GAT, Perkins tonometer, Tono-Pen or Pascal. The differences between GAT (gold standard) and the other tonometers also did not correlate with these biometric parameters, with the exception of corneal curvature, which was positive and moderately correlated with the difference in IOP between GAT and Tono-Pen. GAT and Perkins tonometer showed substantial agreement, although Tono-Pen and DCT showed moderate agreement with GAT. The concordance obtained with Tono-Pen was higher than the concordance obtained with DCT

Introdução: A hipertensão arterial sistêmica (HAS) é uma doença que pode determinar lesões em diversos órgãos inclusive nos olhos. As doenças vasculares oculares constituem a grande maioria das causas de cegueira na atualidade e a HAS tem contribuição importante nesta estatística. A variabilidade da pressão arterial tem sido implicada na gênese de uma série de lesões de órgãos-alvo. Na tentativa de compreender melhor a patogênese das doenças vasculares oculares testamos a hipótese de que não apenas os efeitos da HAS, mas também a variabilidade da pressão arterial (PA) poderia determinar lesão de órgão-alvo (ocular). Materiais e Métodos: A desnervação sino-aórtica (DSA), um modelo experimental de aumento da variabilidade da pressão arterial foi utilizado nos experimentos. Foram obtidas medidas da pressão intraocular e a partir destas medidas, a pressão de perfusão ocular. Foram analisados marcadores de estresse oxidativo (8-OHdG e nitrotirosina),VEGF e receptores AT1 na retina de animais normotensos e hipertensos com e sem DSA aguda (12 e 24 horas) e crônica (10 semanas). Resultados: Os animais desnervados apresentaram aumento da variabilidade da PA sem modificar a PA basal e redução da sensibilidade do barorreflexo. Houve aumento da modulação simpática vascular e da pressão de perfusão ocular (PPO), nos animais hipertensos, com aumento adicional da PPO nos hipertensos e desnervados crônicos.Observou-seestresse oxidativo retiniano nos animais desnervados agudos e noshipertensos desnervados crônicos, além do aumento da expressão de receptores AT1 da Angiotensina II nos animais hipertensos. Os níveis de VEGF retinianos dos animais desnervados crônicos, apresentaram comportamento inverso aos níveis de Caspase-3. Conclusão: Tais resultados indicam que só a HAS, mas também a variabilidade da PA podem determinar variações na pressão de perfusão ocular, assim como também podem induzir dano oxidativo às células retinianas. Além disso, pode-se sugerir efeito neuroprotetor retiniano do VEGF / Introduction: High blood pressure (HBP) is a disease that can determine lesions in many organs including the eyes. The ocular vascular diseases constitute the vast majority of causes of blindness and hypertension has important contribution in this statistic. Blood pressure variability has been implicated in the genesis of a series of end-organ damage. In an attempt to better understand the pathogenesis of ocular vascular diseases, we hypothesized that not only the effects of hypertension, but also the variability of blood pressure (BPV) could determine target end-organ damage (ocular). Materials and Methods: Sino-aortic denervation (SAD), an experimental model of increased blood pressure variability was used in the experiments. The intraocular pressure measurements were performed and from these measurements the ocular perfusion pressure was estimated. Oxidative stress markers (8-OHdG and nitrotyrosine), VEGF and AT1 receptor in rat retinas were analyzed inacute and chronic hypertensive and normotensiveSAD rats and in controls. Results: Denervated animals showed increased BP variability without altering the basal BP, while presenting reduced baroreflex sensitivity.There was an increase in sympatheticvascular modulation and in OPP,in hypertensive animals, that was additionally in chronic denervated hypertensive animals.Acute denervated and chronic hypertensive denervated animals showed retinal oxidative stress as well as hypertensive animals presented increased expression of AT1 receptors of angiotensin II. The levels of retinal VEGF of chronically denervated animals showed inverse behavior of levels of Caspase-3 Conclusion: These results suggest that, apart from the arterial hypertension, BP variability not only determines changes in ocular perfusion pressure, but also induces oxidative damage to retinal cells. Furthermore, one can suggest retinal neuroprotective effect of VEGF

The eyesight of birds is essential for their survival in a free environment; tiny alteration in this organ may cause loss of vision, consequently the difficulty or even the impossibility to hunt, move or protect themselves from predators; due to these particularities, the objective of this paper was to know the normal rate of intra-ocular pressure (IOP) and to identify the ocular anatomy through sonographic biometry in B-scan through transpalpebral way, so the ophthalmic examination can be complete and reliable. It was valued the IOP of 15 Toco Toucans (Ramphatos toco) and 15 Red-breasted Toucan (Ramphastos dicolorus) through applanation tonometry, using a Tono-Pen VET® tonometer and executed sonographic biometry ocular in 5 Toucans Toco and in 5 Red-breasted Toucan. The IOP from Toco Toucans, reliable in 95% got the media between 13,79 mmHg to17,61 mmHg, while the Red-breasted Toucan got the IOP between 12,05 mmHg and 16,81 mmHg. The ocular ultrasound eye was efficient as it could identify the previous segment, the lens, the posterior segment, positioning of the retina, Pecten and retrobulbar space. The Toco Toucans sonographic biometry obtained the bulbar average axial length of 1,66 cm, axial shaft of anterior segment 0,25 cm, shaft axial lens 0,35 cm axial shaft of posterior segment 1,05 cm, transverse shaft of the posterior segment 2,20 cm, transverse shaft of the lens 1,21 cm, and in Red-breasted Toucan the bulbar average axial length of 1,29 cm, axial shaft of anterior segment 0,10 cm, axial shaft lens 0,40 cm axial shaft of posterior segment 0,79 cm, shaft transverse of the posterior segment 1,39 cm, shaft transverse of the lens 0,99 cm. It follows that it is possible to measure IOP by tonometry with Tono-pen VET® tonometer and ocular sonographic biometry the B-scan transpalpebral, route is feasible for these species. / A visão das aves é fundamental para a sua sobrevivência em vida livre, pequenas alterações neste órgão, podem levar a perda da acuidade visual, consequentemente dificuldade ou mesmo impossibilidade em caçar, se locomover ou se defender de predadores. Devido a estas particularidades, o objetivo deste trabalho foi o de conhecer o valor normal da pressão intraocular (PIO) e identificar a anatomia ocular por meio da ecobiometria em modo B pela via transpalpebral, tornando o exame oftálmico mais completo e fidedigno. Foi avaliada a PIO de 15 Tucanos-toco (Ramphastos toco) e de 15 Tucanos-de-bico-verde (Ramphastos dicolorus) por meio da tonometria de aplanação, usando o tonômetro Tono-Pen VET®. Foi realizado ecobiometria ocular em 5 Tucanos-toco e 5 Tucanos-de-bico-verde. A PIO dos Tucanos-toco com 95% de confiança teve uma média entre 13,79 mmHg e 17,61 mmHg, já os Tucanos-de-bico-verde tiveram a PIO entre 12,05 mmHg e 16,81 mmHg. A ecografia ocular se mostrou eficiente pois foram identificados o segmento anterior, a lente, o segmento posterior, o posicionamento da retina, o pécten e o espaço retrobulbar. Na ecobiometria foram obtidos nos Tucanos-toco média do eixo axial bulbar de 1,66 cm, eixo axial do segmento anterior 0,25 cm, eixo axial do segmento posterior 1,05 cm, eixo transversal do segmento posterior 2,20 cm, eixo axial da lente 0,35 cm e eixo transversal da lente 1,21 cm, e nos Tucanos-de-bico-verde a média do eixo axial bulbar de 1,29 cm, eixo axial do segmento anterior 0,10 cm, eixo axial do segmento posterior 0,79 cm, eixo transversal do segmento posterior 1,39 cm, eixo axial da lente 0,40 cm e eixo transversal da lente 0,99 cm. Conclui-se que é possível mensurar a PIO por meio da tonometria de aplanação com o tonômetro Tono-pen VET® e que a ecobiometria ocular, em modo B pela via transpalpebral é viável para estas espécies.

Made available in DSpace on 2016-01-26T18:55:43Z (GMT). No. of bitstreams: 1 Claudia Lizandra Ricci.pdf: 291013 bytes, checksum: b9dccb042e091da74b7d28825ae3639d (MD5) Previous issue date: 2015-03-17 / The objective of this study was to measurement of the intraocular pressure (IOP) with Kowa HA-2 tonometer in cats analyzing the calibration, the accuracy and the validation of ambulatory clinical use. For calibration the post-mortem study was accomplished in 10 healthy eyes of 5 cats comparing the ocular manometry with the values of the IOP checked with the tonometer. For evaluation of the accuracy an in vivo study was accomplished in 20 healthy eyes of 10 anesthetized cats being compared the ocular manometry with the IOP obtained with the tonometer. For validation of the ambulatory clinical study of the IOP measurement was accomplished in 78 eyes of 39 healthy cats, in 7 eyes with clinical signs of glaucoma and in 20 eyes with clinical signs of uveitis. The correlation coefficient (r²) between the manometer and the tonometer was 0.993 and the equation of lineal regression was y=0.0915x+0.0878 in postmortem study. In the in vivo study the medium values of IOP in the manometry were 15.6±1.1 mmHg and in the tonometry were 15.5±1.2 mmHg, there was no statistics significant difference between the manometry and the tonometry. In the ambulatory clinical study with healthy cats the medium values of IOP with the tonometer were 15.0±1.5 mmHg, in the eyes with clinical signs of glaucoma were 38,4±8,1 mmHg and in the eyes with clinical signs of uveitis were of 10,4±2,0 mmHg. Therefore, there was a satisfactory correlation and accuracy between the IOP values obtained by direct ocular manometry and the tonometer in question. In the ambulatory clinical study the IOP values obtained with the tonometer were compatible for animals with healthy eyes and with clinical signs of glaucoma and uveitis. So, we can conclude that the Kowa HA-2 tonometer can be used in the routine ophthalmic examination, as it is a practical method for IOP measurement in cats. / O objetivo deste estudo foi mensurar a pressão intraocular (PIO) com o uso do tonômetro Kowa HA-2 em gatos, analisando a calibração, a acurácia e a validação do seu uso clínico ambulatorial. Para calibração foi realizado o estudo post-mortem em 10 olhos sadios de 5 gatos comparando a manometria ocular com os valores da PIO aferida com o tonômetro. Para avaliação de sua acurácia foi realizado um estudo in vivo em 20 olhos sadios de 10 gatos anestesiados comparando-se a manometria ocular com a PIO obtida com o tonômetro. Para validação do seu uso clínico ambulatorial foi realizado um estudo da mensuração da PIO em 78 olhos sadios de 39 gatos, em 7 olhos com sinais clínicos de glaucoma e em 20 olhos com sinais clínicos de uveíte. O coeficiente de correlação (r²) entre o manômetro e o tonômetro Kowa HA-2 foi de 0,993 e a equação de regressão linear foi y=0,0915x+0,0878 no estudo postmortem. No estudo in vivo, os valores médios de PIO na manometria foram de 15,6±1,1 mmHg e na tonometria foram de 15,5±1,2 mmHg não havendo diferença estatística significativa entre a manometria e a tonometria. No estudo ambulatorial com os gatos sadios, os valores médios de PIO com o tonômetro Kowa HA-2 foram 15,0±1,5 mmHg, nos olhos com sinais clínicos de glaucoma foram 38,4±8,1 mmHg e nos olhos com sinais clínicos de uveíte foram 10,4±2,0 mmHg. Houve, portanto, correlação e acurácia satisfatória entre os valores de PIO com a manometria e o tonômetro em questão. No estudo ambulatorial os valores de PIO obtidos com o tonômetro foram compatíveis para animais com olhos sadios e com sinais clínicos de glaucoma e uveíte. Desta maneira, podemos concluir que o tonômetro Kowa HA-2 pode ser empregado no exame oftálmico de rotina, pois trata-se de um método prático na aferição da PIO em gatos.