INTRODUÇÃO: O edema macular difuso é uma importante causa de baixa visual em portadores de diabetes mellitus. O tratamento clássico deste tipo de retinopatia consiste na fotocoagulação, entretanto, esta terapêutica é ineficaz em muitos casos. Neste trabalho, avaliou-se a eficácia do uso intravítreo da triancinolona acetonida associada à fotocoagulação com laser de argônio no tratamento do edema macular difuso diabético. Esta associação terapêutica foi comparada com o uso isolado de cada tratamento. MÉTODOS: Neste estudo, realizado entre junho de 2005 e setembro de 2006, foram estudados 30 pacientes diabéticos clinicamente controlados e portadores de edema macular difuso. Estes pacientes foram alocados de forma aleatória e proporcional em um dos seguintes grupos de tratamento: (1) fotocoagulação macular em grade com laser de argônio; (2) aplicação intravítrea de 4 mg de triancinolona acetonida; (3) associação dos itens anteriores. O seguimento foi realizado em intervalos pré-determinados de um dia, uma semana e mensalmente, até completar 6 meses. Foram analisados os parâmetros: acuidade visual corrigida LogMAR; espessura macular central e volume macular total medido pela tomografia de coerência óptica; e pressão intra-ocular aferida pelo tonômetro de Goldmann. RESULTADOS: A fotocoagulação com laser não reduziu de forma estatisticamente significativa a espessura macular central (p=0,0862) e o volume macular total (p=0,11). Esta redução foi significativa e estatisticamente semelhante nos outros dois grupos (p<0,001). Todos os grupos apresentaram melhora da acuidade visual (p=0,003), entretanto, o grupo que recebeu a associação do laser com a triancinolona intravítrea, obteve maior percentagem de pacientes com ganho de 10 ou mais letras de visão no quarto e quinto mês de seguimento (p=0,026; p=0,034). A pressão intra-ocular elevou-se em 5 mmHg ou mais em 12 pacientes, sendo seis no grupo submetido apenas a triancinolona e os outros seis no grupo que recebeu a associação de tratamento (p<0,001).Todos estes casos foram bem controlados com colírio de maleato de timolol 0,5%. CONCLUSÕES: O uso simultâneo da fotocoagulação com a triancinolona intravítrea proporcionou maior ganho de linhas de visão do que o uso isolado de cada tratamento. A fotocoagulação com laser foi a única terapia que não reduziu de forma significativa a espessura e o volume macular total e, também, foi a única que não apresentou casos de hipertensão ocular durante o seguimento. / INTRODUCTION: The diffuse macular edema is an important cause of visual impairment in diabetic subjects. Laser photocoagulation is the main treatment for this disorder, however, it is not effective in a large number of patients. In this study, we evaluated the efficacy of intravitreal use of triamcinolone acetonide combined with laser photocoagulation for the treatment of diffuse diabetic macular edema and we compare it with either laser alone or intra-vitreal triancinolone. METHODS: In this study, performed between june 2005 and september 2006, we studied 30 well controlled diabetic patients with diffuse macular edema. These patients were randomly divided into the following treatment groups: (1) macular grid photocoagulation; (2) intravitreal injection of 4 mg of triamcinolone acetonide; (3) combination of the two previous therapies. Follow up was scheduled at predetermined intervals of one day, one week and monthly until completion of six months. The following parameters were analyzed: LogMAR best corrected visual acuity; central macular thickness and total macular volume measured by ocular coherence tomography; and intraocular pressure assessed by Goldman\'s tonometer. RESULTS: Grid photocoagulation did not significantly reduce the central macular thickness (p=0,0862) or the total macular volume (p=0,11). On the other side, this reduction was significant and statistically similar in the others two groups (p<0,001). All groups improved the mean visual acuity (p=0,003), however, the group that received the association treatment had a higher percentage of patients gaining 10 or more letters at the fourth and fifth month of follow up (p=0,026; p=0,034). A rise in 5 or more mmHg in intraocular pressure was observed in 12 patients; half of them was in the triamcinolone group and the other half was in the group that received combined therapies (p<0,001). These cases with elevated intraocular pressure were well controlled with timolol maleate 0,5% drops. CONCLUSION: The simultaneous use of photocoagulation and intravitreal triamcinolone provided a higher gain of visual lines than the isolated use of each treatment. The laser photocoagulation was the only therapy that did not significantly reduce the macular volume and the macular thickness, however, it was also the only one that did not present cases of ocular hypertension during follow up.

Introdução: As neuropatias periférica (NP) e autonômica cardiovascular (NAC) são complicações prevalentes do diabetes mellitus (DM). Há indícios de que seu desenvolvimento se deve não somente ao controle metabólico. Neste sentido, a busca por preditores genéticos faz-se imperativa. Diversos genes relacionados às vias bioquímicas que levam ao dano celular induzido pela hiperglicemia têm sido investigados, destacando-se os genes relacionados às vias do extresse oxidativo. O balanço entre os sistemas antioxidantes (como glutationa e tiorredoxina) e pró-oxidantes (como o NADPH-oxidase) é um importante fator na defesa celular contra o estresse oxidativo. Objetivo primário: avaliar a associação entre os polimorfismos de um único nucleotídeo (SNP) pertencentes às vias anti- e pró-oxidantes mencionadas e a NP e NAC em pacientes DM tipo 1: 718C/T na região 3\' UTR (untranslated region) (rs713041) no gene da glutationa peroxidase 4 (GPX4); -129 C/T (rs1788390) no gene da glutamato cisteína ligase (GLCL); -1365 C/T (rs7211) no gene da proteína de interação com a tiorredoxina (TXNIP); -2810 A/G (rs6610650) no gene do CYBB; - 675 T/A (não registrado) no gene do CYBA. Objetivo secundário: avaliar a relação entre as diferentes complicações microvasculares entre si (neuropatia, doença renal diabética [DRD] e retinopatia diabética [RD]). Material e métodos: foram selecionados 378 pacientes com DM tipo 1 do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo e do Hospital das Clínicas da Universidade Estadual de Campinas com mais de 10 anos de doença e controle inadequado (HbA1c >8% em algum período da vida), e examinados para NP e NAC. A genotipagem dos polimorfismos foi realizada pela técnica de reação em cadeia da polimerase em tempo real (Sistema Taqman ®). Foram avaliadas variáveis clínicas, laboratoriais do metabolismo glicêmico e lipídico e a presença de DRD e de RD. Foram avaliados 257 pacientes retrospectivamente quanto à evolução da taxa de filtração glomerular estimada (TFGe) em relação à NP e NAC. O teste de Pearson foi usado para comparar as frequências dos genótipos e a magnitude de associação foi estimada pelo cálculo do odds ratios (OR), com respectivo intervalo de confiança (IC) ajustada por regressão logística para possíveis fatores de confusão. Resultados: A presença de pelo menos um alelo T do SNP +718C/T no gene GPX4 conferiu proteção para NAC (OR=0,39; IC 95% 0,17 - 0,84; P = 0,0165). Na análise de associação entre as complicações, observou-se que: (1) na presença de NP há aumento na probabilidade de NAC (OR = 3,38; IC95% 2,01 - 5,73; P < 0,0001), de albuminúria A3 (OR = 7,17; IC95% 3,68 - 14,53; P < 0,0001) e de RD proliferativa (OR = 9,58; IC95% 5,04 - 19,09; P < 0,0001) e (2) na presença de NAC há aumento na probabilidade de NP (OR = 3,72; IC95% 2,14 - 6,53; P < 0,0001), de albuminuria A3 (OR = 9,37; IC95% 4,68 - 19,65; P < 0,0001) e de RD proliferativa (OR = 3,30; IC95% 1,81 - 6,18, P < 0,0001). No subgrupo avaliado retrospectivamente, a presença de NP e de NAC associou-se com queda de TFGe anual maior (-4,74 mL/min/ano vs. -1,22 mL/min/ano; P < 0,0001 e -3,74 mL/min/ano vs. -1,54 mL/min/ano; P = 0,04, respectivamente). Conclusões: (1) a presença do alelo T no SNP +718C/T (rs713041) no gene GPX4 confere proteção para NAC na população com DM tipo 1 estudada e (2) existe associação de risco para NP e NAC entre si e para as formas graves de DRD e RD / Introduction: Peripheral (PN) and cardiovascular autonomic neuropathies (CAN) are prevalent complications of diabetes mellitus (DM). There are indications that their development occurs not only secondary to metabolic control. Thus, search for genetic predictors is very important. Several genes related to the biochemical pathways that lead to cellular damage induced by hyperglycemia have been investigated, emphasizing the genes related to the pathways of oxidative stress. The balance between antioxidant systems (such as glutathione and thioredoxin) and pro-oxidants (such as NADPH oxidase) is an important factor in cell defense against oxidative stress. Primary objective: to evaluate the association between the single nucleotide polymorphisms (SNP) of the mentioned anti-and pro-oxidant pathways and NP and NAC in type 1 DM patients: 718C / T in the 3 \'UTR (untranslated region) (rs713041) of the glutathione peroxidase 4 gene (GPX4); -129 C / T (rs1788390) in the glutamate cysteine ligase gene (GLCL); -1365 C / T (rs7211) in the thioredoxin interaction protein gene (TXNIP); -2810 A / G (rs6610650) in the CYBB gene; - 675 T / A (unregistered) in the CYBA gene. Secondary objective: to evaluate the relationship between different microvascular complications (neuropathy, diabetic renal disease [DRD] and diabetic retinopathy [DR]). Material and methods: 378 type 1 patients DM were selected from the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo and from Hospital das Clínicas da Universidade Estadual de Campinas; they had more than 10 years of disease and inadequate control (HbA1c > 8% at some period of life), and were examined for NP and NAC. Polymorphism genotyping was performed by real-time polymerase chain reaction (Taqman System®). Clinical, glycemic and lipid metabolism laboratorial variables and the presence of DRD and DR were evaluated. Also 257 patients were retrospectively evaluated regarding the evolution of the estimated glomerular filtration rate (eGFR) in relation to PN and CAN. The Pearson test was used to compare the frequencies of the genotypes and the magnitude of association was estimated by the odds ratios (OR), with the respective confidence interval (CI) adjusted by logistic regression for possible confounding factors. Results: The presence of at least one T allele at the SNP + 718C / T of the GPX4 gene protected for CAN (OR = 0.39; 95% CI 0.17-0.84; P = 0.0165). In the analysis of the association between complications, it was observed that: (1) in the presence of NP, there was an increase in risk of NAC (OR = 3.38; 95% CI 2.01 - 5.73; P < 0.0001), of albuminuria A3 (OR = 7.17; 95% CI 3.68 - 14.53; P < 0.0001) and of proliferative DR (OR = 9.58; 95% CI, 5.04 - 19.09; P < 0.0001) (2) in the presence of CAN, there was an increase in risk of PN (OR = 3.72; 95% CI 2.14 - 6.53; P < 0.0001), albuminuria A3 (OR = 9.37; CI95% 4.68 - 19.65; P<0,0001) and proliferative DR (OR = 3.30; CI95% 1.81 - 6.18; P < 0,0001).) In the subgroup evaluated retrospectively, the presence of PN and CAN was associated with a greater annual decrease of eGFR (-4.74 mL / min / year vs. -1.22 mL / min / year, P < 0.0001 and - 3.74 mL / min / yr vs. -1.54 mL / min / yr, P < 0.04, respectively). Conclusions: (1) the presence of the T allele at the SNP + 718C / T (rs713041) in the GPX4 gene confers protection for the presence of CAN in the studied type 1 DM population and (2) there is a risk association for PN and CAN among themselves and for severe forms of DRD and RD

INTRODUÇÃO: A retinopatia diabética (RD) é uma das complicações mais frequentes dos diabetes mellitus tipo 1 (DM1). Durante a hiperglicemia, as células endoteliais da retina são expostas a altas concentrações de glicose e são incapazes de conter seu influxo. Isso resulta na ativação de vias deletérias intracelulares que culminam com o aumento de espécies reativas de oxigênio (ROS) e lesão neuronal e vascular. O estado pró inflamatório e pró trombótico ativa vias pró-oxidantes como a da NADPH oxidase. O excesso de ROS não é devidamente tamponado pelas vias antioxidantes (tais como as vias da glutationa e da tiorredoxina) em situações de hiperglicemia crônica, o que contribui para perpetuar o dano. OBJETIVO: Caracterizar uma população de pacientes DM1 quanto ao grau de RD e analisar a associação desta complicação microvascular com cinco polimorfismo de um único nucleotídeo (SNP) em genes pertencentes a vias pró- e antioxidantes. MÉTODOS: Pacientes acompanhados no ambulatório de diabetes de dois hospitais terciários do estado de São Paulo foram submetidos a fotos digitais do fundo de olho que incluíam os sete campos padronizados no estudo Early Treatment Diabetic Retinopathy Study (ETDRS) ou a uma oftalmoscopia binocular indireta; ambos foram avaliados por um único oftalmologista em cada um dos hospitais. A genotipagem dos SNPs foi feita por reação em cadeia de polimerase após transcrição reversa com duas sondas marcadas para cada reação. Os seguintes SNPs foram estudados: rs713041 (gene GPX4), rs17883901 (gene GCLC), rs6610650 (gene CYBB), -675 T/A (gene CYBA) e rs7211 (gene TXNIP). Os dados clínicos foram coletados por consulta ao prontuário médico ou questionário. Foi utilizado o modelo de regressão logística nominal politômica, tendo como categoria de referência a ausência de RD (ARD) ou dicotômica, tendo como categorias de referência a ausência de RD proliferativa (RDP) ou ARD. Após correção de Bonferroni, um valor de p <= 0,02 foi considerado significante. RESULTADOS: Um total de 341 pacientes (62% mulheres; idade média de 35 [±11] anos; com 22 [±9] anos de duração do DM1 e HbA1c de 8,6% [±1,6]) foi incluído. A prevalência de RDP foi de 30%, enquanto 42% dos pacientes apresentavam RD não proliferativa (RDNP). Somente os SNPs cuja distribuição dos genótipos respeitou o equilíbrio de Hardy-Weinberg foram analisados. Após ajuste para potenciais fatores de confusão, a presença do alelo T no SNP rs713041 (+718 C/T) no GPX4 foi inversamente associada à prevalência de RDP em pacientes do sexo feminino, com um odds ratio (OR) de 0,36 (intervalo de confiança [IC] de 95% de 0,17 a 0,75; p = 0,007) na análise dicotômica de RDP versus ausência de RDP. A presença do alelo T no SNP rs17883901 (-129 C/T) no GCLC conferiu risco para RDP na análise politômica (OR de 4,23; IC 95% de 1,38 a 12,93; p=0,01) e conferiu risco para a presença de qualquer grau de RD na análise dicotômica (ARD versus RDNP + RDP; OR de 3,07; IC 95% de 1,22 a 8,95; p=0,02). Não houve associação entre o SNP rs6610650 (gene CYBB) e RD nessa população. CONCLUSÃO: Os SNPs funcionais rs713041 no GPX4 e rs17883901 no GCLC modularam a susceptibilidade a RD na população de pacientes com DM1 estudada / INTRODUCTION: Diabetic retinopathy (DR) is one of the most frequent complications of type 1 diabetes mellitus (T1D). During hyperglycemia, retinal endothelial cells are exposed to high glucose concentrations and are unable to contain their influx. This results in the activation of deleterious intracellular pathways that culminate with the increase of reactive oxygen species (ROS) and neuronal and vascular injury. The pro-inflammatory and prothrombotic state activates pro-oxidant pathways such as NADPH oxidase. The excess of ROS is not adequately buffered by the antioxidant pathways (such as glutathione and thioredoxin pathways) in situations of chronic hyperglycemia, which contributes to perpetuate the damage. OBJECTIVE: To characterize a population of T1D patients regarding DR degree and to analyze the association of this microvascular complication with five single nucleotide polymorphisms (SNP) in genes belonging to pro- and antioxidant pathways. METHODS: Patients followed at the diabetes outpatient clinic of two tertiary hospitals in the state of São Paulo were submitted to digital photos of the eye fundus that included the seven fields standardized in the Early Treatment Diabetic Retinopathy Study (ETDRS) or to binocular indirect ophthalmoscopy; both were evaluated by a single ophthalmologist in each one of the hospitals. SNP genotyping was performed by polymerase chain reaction after reverse transcription with two labeled probes for each reaction. The following SNPs were studied: rs713041 (GPX4 gene), rs17883901 (GCLC gene), rs6610650 (CYBB gene), -675 T/A (CYBA gene) and rs7211 (TXNIP gene). The clinical data were collected by consulting the medical chart or by questionnaire. The polytomous nominal logistic regression model was used, having as reference category the absence of DR (ADR) or the dichotomous nominal logistic regression model was used, having as reference categories the absence of proliferative DR (PDR) or ADR. After Bonferroni correction, a p value <= 0.02 was considered significant. RESULTS: A total of 341 patients (62% female; mean age of 35 [± 11] years-old; diabetes duration of 22 [± 9] years and HbA1c of 8.6% [± 1.6]) was included. The prevalence of PDR was 30%, while 42% of the patients had non-proliferative DR (NPDR). Only SNPs whose distribution of genotypes respected the Hardy-Weinberg equilibrium were analyzed. After adjusting for potential confounding factors, the presence of the T allele at rs713041 (+718 C/T) in GPX4 was inversely associated with the prevalence of PDR in female patients, with an odds ratio (OR) of 0.36 (95% confidence interval [CI] 0.17-0.75; p = 0.007) in the dichotomous analysis of PDR versus absence of PDR. The presence of the T allele at rs17883901 (-129 C/T) in GCLC conferred risk for PDR in the polytomous analysis (OR of 4.23; 95% CI 1.38 to 12.93; p = 0.01) and for any degree of DR in the dichotomous analysis (ADR versus NPDR + PDR; OR of 3.07; 95% CI 1.22-8.95; p = 0.02). There was no association between the SNP rs6610650 (CYBB gene) and DR in this population. CONCLUSION: The functional SNPs rs713041 in GPX4 and rs17883901 in GCLC modulated the susceptibility to DR in the studied population of patients with T1D

Fok, Tsz Nam = 香港二型糖尿病併發症風險評估模型 / 霍梓楠. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (p. 71-72). / Abstracts in English and Chinese. / Fok, Tsz Nam = Xianggang er xing tang niao bing bing fa zheng feng xian ping gu mo xing / Huo Zinan. / Abstract --- p.i / 概要 --- p.iii / Acknowledgements --- p.iv / Chapter 1 --- Introduction --- p.1 / Chapter 2 --- Dataset Information --- p.3 / Chapter 3 --- Background and Literature Review --- p.9 / Chapter 3.1 --- The Idea of Risk Model --- p.9 / Chapter 3.2 --- Discrimination Problem --- p.10 / Chapter 3.3 --- Receiver Operating Characteristic (ROC) Curve --- p.11 / Chapter 3.4 --- Summary Indices of the ROC Curve --- p.13 / Chapter 3.4.1 --- Area Under ROC Curve (AROC) --- p.14 / Chapter 3.4.2 --- Maximum Vertical Distance --- p.16 / Chapter 3.5 --- Discrimination Performance in Prognostic Model --- p.18 / Chapter 3.5.1 --- Survival Data --- p.18 / Chapter 3.5.2 --- Survival Function --- p.20 / Chapter 3.5.3 --- Time-dependent ROC Curve for Censored Data --- p.21 / Chapter 3.6 --- Earlier Work on Diabetic Complications Risk Models --- p.22 / Chapter 3.6.1 --- Maximization of the AROC --- p.28 / Chapter 4 --- Model Development --- p.29 / Chapter 4.1 --- Overview --- p.29 / Chapter 4.2 --- Estimating the ROC curve and the AROC --- p.29 / Chapter 4.3 --- Choosing Suitable Risk Factors --- p.30 / Chapter 4.4 --- Mixing Risk Factors and Optimizing Coefficients --- p.31 / Chapter 4.5 --- Validation of Risk Equations Using Test Set --- p.33 / Chapter 5 --- Results and Validation --- p.34 / Chapter 5.1 --- Performance of the Risk Factor Candidates --- p.34 / Chapter 5.2 --- Estimation of the Coefficients --- p.37 / Chapter 5.3 --- Checking the Uniqueness of the Solution --- p.41 / Chapter 5.4 --- Validation Using Test Set --- p.46 / Chapter 5.5 --- Comparison of AROC-optimized and MVD-optimized Risk Equations --- p.56 / Chapter 6 --- Comparison of our Results with Earlier Work --- p.58 / Chapter 7 --- "Discussion, Outstanding Issues and Future Works" --- p.66 / Chapter 7.1 --- Comparison Between the AROC and the MVD --- p.66 / Chapter 7.2 --- Applications of Risk Models --- p.68 / Chapter 7.3 --- Limitations of the study --- p.69 / Chapter 7.4 --- Outstanding Issues and Future Works --- p.69 / Chapter 7.4.1 --- The Estimation of Error Due to Sampling Variance --- p.69 / Chapter 7.4.2 --- Time-dependent Coefficients --- p.69 / Chapter 7.4.3 --- Extending the Idea to other Datasets --- p.70 / Chapter 7.5 --- Conclusion --- p.70 / Bibliography --- p.71

INTRODUÇÃO: O tratamento padrão estabelecido pelo Early Treatment Diabetic Retinopathy Study (ETDRS) para retinopatia diabética proliferativa (RDP), com ou sem edema macular clinicamente significativo (EMCS), é a panfotocoagulação com laser. Essa forma de tratamento reduz o risco de perda visual, mas não proporciona ganho de visão. O objetivo deste estudo é avaliar os efeitos do acetonido de triancinolona associado à panfotocoagulação na RDP. MÉTODOS: Realizou-se um ensaio clínico randomizado, prospectivo e aberto com portadores de RDP bilateral e simétrica, submetidos à panfotocoagulação com laser em ambos os olhos. Portadores de EMCS foram tratados com fotocoagulação focal na região macular no primeiro episódio da panfotocoagulação. A injeção intravítrea de acetonido de triancinolona (4 mg/0,1 ml) foi administrada aleatoriamente em um dos olhos (grupo estudo), após último episódio da laserterapia, e o contralateral foi adotado para comparação (grupo controle), sendo seguidos por 6 meses. Os parâmetros adotados para avaliar os efeitos terapêuticos foram: acuidade visual com melhor correção óptica (tabela do ETDRS), medidas de espessura central e de volume macular por meio da tomografia de coerência óptica e taxa de sangramento (hemorragia pré-retiniana ou vítrea). As potenciais complicações da droga foram avaliadas durante o seguimento (pressão intra-ocular, catarata, endoftalmite e pseudo-endoftalmite). RESULTADOS: Foram incluídos 28 (vinte e oito) indivíduos com diabetes melito tipo 2. Quanto ao EMCS, 22 olhos apresentaram no grupo estudo e 23, no grupo controle (p= 0,317). A média de idade foi de 61,36 ± 5,77 anos, com predominância do sexo ferminino (57,1%). A maioria era portadora de hipertensão arterial sistêmica (82,1%) e usuária de insulina (75,0%). Não houve diferença significante nas médias de número de disparos da panfotocoagulação e da fotocoagulação na região macular entre os grupos. Quanto à acuidade visual, o grupo estudo apresentou pior acuidade antes do tratamento em relação ao grupo controle (p= 0,040), não havendo diferença significativa na primeira semana do tratamento. Durante o seguimento, o grupo estudo evoluiu com melhora na acuidade visual no primeiro (p< 0,001), no terceiro (p< 0,001) e no sexto meses (p< 0,001) em relação ao controle. Em relação às medidas de espessura central e de volume macular, os grupos não apresentaram diferença significativa antes do tratamento, no entanto, o grupo estudo apresentou medidas significativamente menores na primeira semana, no primeiro, no terceiro e no sexto meses em relação ao controle. Quanto à taxa de sangramento, 9 olhos (32,1%) do grupo controle evoluíram com sangramento e nenhum do grupo estudo (p< 0,001). Os grupos apresentaram diferença na pressão intra-ocular apenas na primeira semana do tratamento, quando as medidas do grupo estudo foram maiores que as do controle (p< 0,05). Nenhum dos olhos apresentou catarata com indicação cirúrgica, endoftalmite ou pseudo-endoftalmite. CONCLUSÃO: Os resultados deste estudo sugerem que a injeção intravítrea de triancinolona é um procedimento seguro e pode melhorar o prognóstico funcional e estrutural da mácula em olhos com RDP submetidos a panfotocoagulação com laser. / INTRODUCTION: The gold standard treatment for proliferative diabetic retinopahty (PDR) with and without clinically significant macular edema (CSME), as stablished by the Early Treatment Diabetic Retinopathy Study (ETDRS), is panretinal photocoagulation (PRP). This treatment lowers the rate of severe vision loss, but does not increase vision. The aim of this study is to evaluate the efficacy and safety of triamcinolone acetonide associated to PRP for the management of PDR. METHOD: This is a prospective, randomized clinical trial for patients with bilateral and symmetrical PDR who had undergone PRP in both eyes. Patients who had CSME were treated with macular focal photocoagulation on the first episode of the PRP. Intravitreal injection of triamcinolone acetonide (4 mg/0.1 ml) was given to the study eye after the last episode of PRP and the fellow eye was used as control. Follow up was 6 months long. Best-corrected visual acuity (BCVA) using ETDRS charts, central macular thickness and macular volume as measured by the optical coherence tomography software, and the amount of bleeding (both preretinal and vitreous) were the parameters chosen to analyse outcome. Side effects of triamcinolone acetonide such as intraocular pressure, cataracts and severe inflammation, were also followed during the study. RESULTS: Twenty eight diabetes type 2 patients were included. Twenty two study eyes and 23 fellow eyes (controls) presented with CSME (p= 0.317). Mean age was 61.36 ± 5.77 years, with 57.1% females. Many patients had hypertension (82.1%) and used insulin (75.0%). There was no significant difference on the number of spots used for PRP or macular photocoagulation in between the groups. The study eyes had lower BCVA on baseline than the control eyes (p= 0.040). One week after the treatment, there was no difference on BCVA between the study and control eyes. During the follow up, the study group increased their BCVA on the first (p< 0.001), third (p< 0.001) and sixth month (p< 0.001) compared to control. Even thought there was no significant difference on central macular thickness and macular volume between groups on baseline, the study eyes had significant lower measurements on the first week and first, third and sixth months in comparison to controls. Nine control eyes (32.1%) had hemorrhages and none study eyes (p< 0.001). Injected eyes had higher intraocular pressure than controls on the first week of treatment (p< 0.05). None of the eyes developed cataracts that needed surgery, endophthalmits or severe inflammation. CONCLUSION: This study suggests intravitreal injection of triamcinolone is a safe procedure that increases funcional and anatomical prognosis of the macula in PDR eyes that underwent PRP.

Cardiovascular disease secondary to atherosclerosis is the most common cause of human morbidity and mortality. An early and fundamental event in the development of atherosclerosis is abnormal vascular endothelial and smooth muscle function. This can be measured by flow mediated dilatation and glyceryl trinitrate mediated dilatation in children at risk of atherosclerosis. Folic acid improves endothelial function (flow mediated dilatation) in adults with coronary artery disease. No studies have previously investigated the effects of folic acid on vascular function in at risk children with diabetes or obesity. In a cross sectional study an evaluation of vascular endothelial and smooth muscle function and their determinants was performed in 159 children with type 1 diabetes, 58 children with obesity, and 53 healthy children. Children with type 1 diabetes and children with mild to moderate obesity had comparable and severe vascular dysfunction but different determinants. Vascular function in healthy and obese children related to both body mass index and weight (adjusted for age and sex), and blood glucose. Children with obesity had lower folate levels and higher homocysteine levels than children with type 1 diabetes, an abnormal lipid profile and raised inflammatory markers. A randomised double blind placebo controlled cross over trial of 8 weeks of folic acid supplementation was performed in 38 children with type 1 diabetes. In these children, folic acid improved endothelial function with a sustained increase in folate levels but independent of homocysteine levels. Folic acid did not improve smooth muscle function. A randomised double blind placebo controlled parallel trial of 8 weeks folic acid supplementation was performed including 53 obese children. Folic acid did not improve vascular function in obese children in spite of sustained increase in folate levels, and a decrease in homocysteine levels. It was concluded that children with type 1 diabetes and obesity have comparable and severe endothelial and smooth muscle function. Determinants of vascular function in children, including weight and glucose, represent a continuum effect. Folic acid supplementation improved endothelial function in children with type 1 diabetes but not in children with obesity, whose metabolic changes causing endothelial dysfunction differ from children with diabetes. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1317003 / Thesis (Ph.D.) -- University of Adelaide, School of Paediatrics and Reproductive Health, 2008

University of Macau / Institute of Chinese Medical Sciences

University of Macau / Institute of Chinese Medical Sciences

Diss. (sammanfattning) Umeå : Umeå universitet, 2010. / Härtill 4 uppsatser.

Cardiovascular disease secondary to atherosclerosis is the most common cause of human morbidity and mortality. An early and fundamental event in the development of atherosclerosis is abnormal vascular endothelial and smooth muscle function. This can be measured by flow mediated dilatation and glyceryl trinitrate mediated dilatation in children at risk of atherosclerosis. Folic acid improves endothelial function (flow mediated dilatation) in adults with coronary artery disease. No studies have previously investigated the effects of folic acid on vascular function in at risk children with diabetes or obesity. In a cross sectional study an evaluation of vascular endothelial and smooth muscle function and their determinants was performed in 159 children with type 1 diabetes, 58 children with obesity, and 53 healthy children. Children with type 1 diabetes and children with mild to moderate obesity had comparable and severe vascular dysfunction but different determinants. Vascular function in healthy and obese children related to both body mass index and weight (adjusted for age and sex), and blood glucose. Children with obesity had lower folate levels and higher homocysteine levels than children with type 1 diabetes, an abnormal lipid profile and raised inflammatory markers. A randomised double blind placebo controlled cross over trial of 8 weeks of folic acid supplementation was performed in 38 children with type 1 diabetes. In these children, folic acid improved endothelial function with a sustained increase in folate levels but independent of homocysteine levels. Folic acid did not improve smooth muscle function. A randomised double blind placebo controlled parallel trial of 8 weeks folic acid supplementation was performed including 53 obese children. Folic acid did not improve vascular function in obese children in spite of sustained increase in folate levels, and a decrease in homocysteine levels. It was concluded that children with type 1 diabetes and obesity have comparable and severe endothelial and smooth muscle function. Determinants of vascular function in children, including weight and glucose, represent a continuum effect. Folic acid supplementation improved endothelial function in children with type 1 diabetes but not in children with obesity, whose metabolic changes causing endothelial dysfunction differ from children with diabetes. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1317003 / Thesis (Ph.D.) -- University of Adelaide, School of Paediatrics and Reproductive Health, 2008