Indiana University-Purdue University Indianapolis (IUPUI) / Background: Erosive tooth wear (ETW) is the loss of tooth substance due to chemo-mechanical action unrelated to bacteria. ETW affects approximately 46 percent of children/adolescents and 80 percent of adults in the U.S. Visual examination indices are available for the clinical assessment of ETW. Although useful, they are subjective and heavily based on the clinical experience of the examiner. Some quantitative techniques have been proposed and used for clinically assessing erosive tooth wear, including quantitative light-induced fluorescence, ultrasonic measurement, and more recently, polarization-sensitive optical coherence tomography (PS-OCT). Objective: The objective of this study was to explore the ability of PS-OCT to objectively measure erosive tooth wear on occlusal surfaces. Method: This study was conducted in two phases. In the first phase, 10 sound extracted human lower first premolars were selected and then exposed to tooth wear simulation gradually. PS-OCT and micro computed tomography (μ-CT) were used to evaluate enamel thickness of those premolars at the buccal cusp tip during the simulation. In phase 2, 40 extracted human lower first premolars with different severity levels of ETW on occlusal surfaces were selected based on the Basic Erosive Wear Examination (BEWE) index. A total of 10 teeth (n =10) were selected for each BEWE score (0/1/2/3). PS-OCT and μ-CT were used to evaluate the enamel thickness at the highest point on the occlusal surface. Results: There was good agreement between PS-OCT and μ-CT in both phases (phase 1: 0.89 and phase 2: 0.97) with no significant difference between PS-OCT and μ-CT. Conclusion: This result shows the potential of PS-OCT as reliable method for measuring enamel thickness and monitoring tooth wear progression on the occlusal surface

青光眼作為一種慢性進展性視神經病變，已經成為世界眼科病變中導致不可逆盲的首要原因。青光眼的早期診斷和治療對於降低疾病進展的風險至關重要。光學相干斷層掃描（OCT）可以提供在體視網膜橫斷面的視圖，從而實現了對視網膜神經纖維層（RNFL）改變的客觀測量，這些改變已經被證明了與青光眼引起的視神經損害相關，並已成為診斷青光眼的重要參考依據。 / 頻域OCT是最新一代的光學相干斷層掃描，它具有比時域OCT更快的掃描速度和更高的圖像解析度，因此，頻域OCT可以提供更可靠的RNFL厚度測量和RNFL缺損評估。本文的研究目的在於評估頻域OCT對RNFL厚度的重測再現性，以及探討影響RNFL厚度測量的因素，這些因素包括（1）影像平均法的應用，（2）RNFL分層錯誤，和（3）視網膜血管的影響。此外，由於RNFL攝影是一個評估青光眼RNFL缺損的臨床參考標準，我們還將其對RNFL缺損的測量與頻域OCT的RNFL厚度偏差圖所作出的測量進行了比較。 / 首先，為了評估頻域OCT對RNFL厚度測量的重測再現性，15名正常人和15名青光眼患者連續四周每週均接受一次OCT掃描。正常組和青光眼組的RNFL厚度再現性係數分別為4.77-12.65微米和4.53-16.66微米，由於組內相關性係數均大於0.773，說明頻域OCT所作出的RNFL厚度測量是具備可重複性的。 / 其次，通過分析54隻眼（25名正常志願者和29名青光眼患者）的RNFL厚度測量值，本文對圖像平均法的應用是否會影響RNFL厚度的測量這一問題進行了探討。分析中，每一隻眼均接受了3次OCT掃描，3次掃描的圖像分別使用2、8、和16張連續的圖像進行影像平均。結果顯示，除了青光眼組的鼻下象限RNFL厚度測量值之外（P=0.036），不同的圖像幀數並不會對兩組的總體和其它各象限的RNFL厚度測量值產生顯著的影響（P≥0.055）。雖然圖像平均法的應用對RNFL厚度測量的影響並不顯著，但是視網膜血管和RNFL分層錯誤對青光眼,尤其是對RNFL非常薄的晚期青光眼患者的RNFL厚度測量有影響。結論來自對60個正常人，66個輕至中度青光眼（MD≥-6 dB）患者和54個嚴重青光眼（MD<-6 dB）患者的共180張OCT圖像的分析。視網膜血管相對於平均RNFL厚度的比例均值在正常組，輕至中度青光眼組，和嚴重青光眼組分別為11.2±2.3，12.6±2.5，和16.6±3.9。在人為調整了RNFL界限以糾正RNFL分層錯誤的前後，總體RNFL厚度的差異範圍在正常組為-3.0-2.5微米，輕至中度青光眼組為-2.5-5.0微米，嚴重青光眼組為-11.0-9.5微米組。 / 最後，通過對41名青光眼患者的51隻眼的RNFL缺損面積，位置，和覆蓋角度進行測量，本文將頻域OCT作出的測量結果和共焦鐳射掃描檢眼鏡（CSLO）RNFL反射影像圖的測量結果進行了比較，結果顯示：OCT不但可以檢測到所有出現在CSLO的RNFL反射影像圖上的RNFL缺損，更重要的是，OCT還可以檢測出額外的並未在RNFL反射影像圖上出現的RNFL缺損。 / 總之，頻域OCT是一種可提供高再現性RNFL厚度測量的影像方法。對青光眼,尤其是晚期青光眼的RNFL厚度測量值的詮釋，應當考慮到視網膜血管和RNFL分層錯誤的影響。OCT具備對RNFL缺損進行多維度量化（包括厚度，面積，位置，和覆蓋角度）的能力，在青光眼RNFL改變的檢測和監測方面，相對于傳統的RNFL攝影，OCT無疑是更有效的選擇。 / Glaucoma, a chronic progressive optic neuropathy, is the leading cause of irreversible blindness in the world. An early diagnosis and treatment of glaucoma is vital to reduce the risk of disease progression. Providing a cross-sectional view of the retina in vivo, optical coherence tomography (OCT) can objectively measure the changes of retinal nerve fiber layer (RNFL), which has been shown to be of relevance and importance in detecting glaucomatous damage of the optic nerve. / The latest generation of OCT, the spectral-domain OCT, has a faster scan speed and a higher image resolution compared to the time-domain OCT. It is expected that the spectral-domain OCT would allow a more reliable measurement of the RNFL thickness and assessment of RNFL defects. The objectives of this research project were to examine the test-retest reproducibility of spectral-domain OCT RNFL measurement and investigate factors including (1) image averaging, (2) segmentation failure, and (3) contribution of retinal blood vessels that might affect the measurement of RNFL thickness. As RNFL photography is a reference standard to evaluate RNFL defects in glaucoma, we also evaluated whether RNFL defects measured in the spectral-domain OCT RNFL thickness map would be comparable to those detected in RNFL photographs. / To evaluate the test-retest reproducibility of RNFL measurements obtained by the spectral-domain OCT, 15 normal individuals and 15 glaucoma patients were followed and imaged weekly for 4 consecutively weeks. The reproducibility coefficients of RNFL thicknesses ranged between 4.53 and 16.66 μm for the normal group, and 4.77 and 12.65 μm for the glaucoma group. The intraclass correlation coefficients were all above 0.773, indicating RNFL measurement with spectral-domain OCT was reproducible. / We then investigated if multiple-image averaging would influence the measurement of RNFL thickness. A total of 54 eyes from 25 normal volunteers and 29 glaucoma patients with RNFL images captured and averaged with 2, 8, and 16 consecutive image frames were analyzed. For both groups, there were no significant differences in global or sectoral RNFL thicknesses among the image series averaged with different number of image frames (all with P≥0.055) except for the inferonasal sector in the glaucoma group (P=0.036). Although the impact of image averaging on RNFL measurement was insignificant, the presence of retinal blood vessels and segmentation errors were influential on the measurement, particularly in advanced glaucoma patients when the RNFL was thin. Analyzing a total of 180 eyes from 60 normal individuals, 66 mild to moderate (MD≥-6 dB) and 54 advanced (MD<-6 dB) glaucoma patients, the mean proportion of retinal blood vessels relative to the average RNFL thickness was 11.2±2.3%, 12.6±2.5% and 16.6±3.9%, respectively. After correcting the segmentation errors by manually refining the RNFL boundaries, the differences in average RNFL thickness ranged from -3.0 to 2.5 m in the normal, -2.5 to 5.0 m in the mild to moderate glaucoma and -11.0 to 9.5 m in the advanced glaucoma groups. / Finally, we compared the area, the angular location, and the angular width of RNFL defects from 51 eyes of 41 glaucoma patients measured with the spectral-domain OCT and RNFL reflectance images obtained by a confocal scanning laser ophthalmoscope (CSLO). OCT was able to detect areas of RNFL abnormalities in all eyes with RNFL defects which were evident in the CSLO RNFL reflectance images. More important, OCT could identify additional RNFL thinning not apparent in RNFL reflectance images. / In summary, spectral-domain OCT could offer an effective approach in measuring RNFL with high reproducibility. Interpretation of RNFL measurement should take the contribution of the retinal blood vessels and segmentation errors into consideration, particularly in advanced glaucoma when the RNFL is thin. With the ability to quantify multiple dimensions of RNFL defects (thickness, area, angular location, and angular width), OCT could provide a useful alternative to detect and monitor RNFL changes in glaucoma. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Ye, Cong. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 117-130). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / ABSTRACT --- p.i / 摘要 (ABSTRACT IN CHINESE) --- p.v / DEDICATION --- p.viii / ACKNOWLEDGEMENT --- p.ix / TABLE OF CONTENTS --- p.x / PUBLICATIONS --- p.xiv / ABBREVIATIONS --- p.xvi / Chapter CHAPTER 1: --- INTRODUCTION --- p.1 / Chapter 1.1 --- Glaucoma --- p.2 / Definition of Glaucoma --- p.2 / Epidemiology of Glaucoma --- p.3 / Pathogenesis of Glaucoma --- p.4 / Diagnosis of Glaucoma --- p.7 / Chapter 1.2 --- Retinal Nerve Fiber Layer --- p.13 / Anatomy of Retinal Nerve Fiber Layer --- p.13 / Visualization of Retinal Nerve Fiber Layer --- p.14 / Retinal Nerve Fiber Layer Defect in Glaucoma --- p.16 / Significance of Detecting Retinal Nerve Fiber Layer Defect in Glaucoma --- p.18 / Chapter 1.3 --- Optical Coherence Tomography --- p.20 / Principle of Optical Coherence Tomography --- p.20 / Retinal Nerve Fiber Layer Imaging with OCT --- p.21 / Optic Nerve Head Imaging with OCT --- p.27 / Advantages and Disadvantages of Optical Coherence Tomography --- p.29 / Chapter 1.4 --- Research Objectives --- p.30 / Chapter CHAPTER 2: --- GENERAL MATERIALS AND METHODS --- p.32 / Chapter 2.1 --- Subject Enrollments --- p.33 / Chapter 2.2 --- Clinical Ophthalmic Examination --- p.34 / Chapter 2.3 --- Visual Field Examination --- p.35 / Definition of Normal and Glaucoma Groups --- p.35 / Chapter 2.4 --- Optical Coherence Tomography Imaging --- p.37 / Cirrus HD-OCT Imaging --- p.37 / Spectralis OCT Imaging --- p.37 / Chapter 2.5 --- Statistical Analysis --- p.39 / Chapter CHAPTER 3: --- RETINAL NERVE FIBER LAYER IMAGING WITH SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY --- p.40 / Chapter 3.1 --- Reproducibility and Agreement of Retinal Nerve Fiber Layer Measurement --- p.41 / Introduction and Study Objectives --- p.41 / Methods --- p.42 / Results --- p.45 / Discussion --- p.47 / Tables and Figures --- p.51 / Chapter 3.2 --- Effect of Multiple B-scans Averaging on Retinal Nerve Fiber Layer Measurement --- p.58 / Introduction and Study Objectives --- p.58 / Methods --- p.59 / Results --- p.61 / Discussion --- p.62 / Tables and Figures --- p.67 / Chapter 3.3 --- Impact of Blood Vessels and Segmentation Failure on Retinal Nerve Fiber Layer Measurement --- p.73 / Introduction and Study Objectives --- p.73 / Methods --- p.75 / Results --- p.78 / Discussion --- p.80 / Tables and Figures --- p.84 / Chapter 3.4 --- Agreement of Localized Retinal Nerve Fiber Layer Defect Assessment with Confocal Scanning Laser Ophthalmoscopy --- p.95 / Introduction and Study Objectives --- p.95 / Methods --- p.97 / Results --- p.101 / Discussion --- p.103 / Tables and Figures --- p.108 / Chapter CHAPTER 4: --- GENERAL CONCLUSIONS --- p.115 / REFERENCES --- p.117

Objetivo: A partir das medidas anatômicas isoladas (altura, diâmetro externo e interno) do BMI construir um novo índice prognóstico para a cirurgia de correção do Buraco Macular Idiopático (IPBM). Tipo de estudo: intervencional, série de casos. Pacientes e Métodos: Estudo realizado no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo e no Instituto Suel Abujamra, São Paulo-SP, entre outubro de 2005 e outubro de 2007. Foram incluídos 36 olhos de 36 pacientes com BMI, que foram avaliados segundo as medidas apresentadas ao exame de TCO (Stratus - Zeiss, versão 4.01) antes da cirurgia do BMI. Utilizando o compasso do TCO, obteve-se a medida dos maiores diâmetros externo e interno e da altura dos BMI. Por meio dessas medidas, foi criado o IPBM. Após vitrectomia posterior com retirada de Membrana Limitante Interna (MLI), sem utilização de corantes, os pacientes foram acompanhados por seis meses. Após a cirurgia, os pacientes foram avaliados no primeiro e sétimo dias, duas semanas, um, três e seis meses. Ao final do seguimento, o IBPM e outras variáveis (sexo, idade, raça, estádio do BMI pela classificação biomicroscópica de Gass, tempo decorrido desde a piora da acuidade visual informada pelo paciente e a acuidade visual pré-operatória), foram correlacionadas com o resultado anatômico e a acuidade visual pós-operatória. Resultados: Vinte e nove (80,6%) dos 36 olhos com BMI obtiveram fechamento anatômico ao final de seis meses de acompanhamento (8,86 ± 4,23 meses). Dezenove (52,7%) dos BMI eram do estádio IV de Gass, com tempo de duração maior que um ano em 21 pacientes (58,3%). A AV LogMAR corrigida pré-operatória média foi de 1,10 (0,60 a 1,62) e a pós-operatória média foi de 0,69 (0,0 a 1,60). A média de melhora da AV foi de 3,94 linhas. Em relação ao fechamento anatômico, não houve significância em relação ao tempo de história da doença entre os grupos aberto (grupo 1) e fechado (grupo 2) (Teste t-Student, p=0,072). O diâmetro da base interna foi maior no grupo 1 em relação ao grupo 2 (Teste t-Student, p=0,007). Na análise do índice IPBM, houve diferença significativa entre o grupo 1 (média 0,49) e o grupo 2 (média 0,91). (Teste t-Student, p< 0,001) A análise de regressão logística apontou que BMIs com IPBM maior que 0,53 apresentam chance de fechamento anatômico 9,6 vezes maior (Odds Ratio= 9,6, p = 0,018). Pacientes com IPBM > 0,53 apresentaram AV pós-operatória ao final do sexto mês significativamente melhor do que pacientes com IPBM < 0,53 (Mann-Whitney, p=0,005). O ganho percentual da AV foi de 41,93% nos pacientes com IBPM>0,53, quando comparado com os 7,14% do grupo com IPBM <0,53 (p=0,002). No que diz respeito à AV final LogMAR, todas as variáveis estudadas anteriormente foram submetidas ao teste de correlação de Pearson. Observou-se que o IPBM tem uma correlação negativa significante com a AV, e foi selecionado juntamente com a AV pré-operatória através de regressão linear como os melhores preditores de AV final (p<0,001 e p=0,005, respectivamente). O modelo aponta que 58,4% da AV pós-operatória está sendo explicada pelo IPBM e AV pré-operatória. Conclusões: Foi construído um novo índice Prognóstico do Buraco Macular Idiopático (IPBM) representado pela razão altura / diâmetro interno do BMI. Verificou-se que o IPBM pode ser utilizado como fator prognóstico de fechamento anatômico do BMI. O IPBM e a AV pré-operatória foram os fatores prognósticos com melhor relação para a AV no sexto mês após o tratamento cirúrgico do BMI. / Purpose: To create a new prognostic index for IMH surgery based on anatomical values of IMH height, external and internal diameters (MHPI). Type of Study: Prospective, interventional, case of series. Patients and Methods: 36 eyes with IMH of 36 patients followed at Hospital das Clinicas, University of São Paulo Medical School (HC-FMUSP) and Suel Abujamra Institute (ISA), São Paulo-SP, between October 2006 and October 2007, were included. IMH OCT measurements were obtained before surgery (Stratus - Zeiss version 4.01) Values of the larger external and internal diameters, and the IMH height were obtained using the OCT compass. The prognostic index of IMH (MHPI) was defined as the index height / internal base. MHPI was defined by using those OCT measurements. Patients underwent pars plana vitrectomy with ILM peeling without dye and were followed by 6 months. Patients were seen at days 1, 7, 14, and months 1, 2, 3, and 6 after surgery. At the end of the follow-up period, MHPI and, other variables (sex, age, ethnic group, stage of IMH following the biomicroscopic classification of Gass, the time of visual loss reported by the patient, and pre surgical visual acuity) were correlated with anatomical results and post-surgical visual acuity. Results: Twenty nine eyes (80.6%) of thirty six patients with IMH had anatomical closure at the end of the six-month follow-up (8.86 ± 4.23 months). Nineteen (52.7%) IMH were stage IV of Gass with more than one year duration in twenty one patients. Pre-surgical medium LogMAR VA was 1.10 (0.60 to 1.62) and post-surgical was 0.69 (0.0 to 1.60). Medium VA improvement was 3.94 lines. The internal base diameter (BINT) was larger in group 1 than in group 2 (t-Student Test, p=0.373). MHPI analisys showed significant difference between group 1 (average 0.49) and group 2 (average 0.91) (t-Student Test, p> 0.001). Logistical regression showed that IMH with MHPI higher than 0.53 present 9.6 times more risk of failure than those with MHPI lower than 0.53 (Mann-Whitney, p=0.005). The percentage gain of VA was 41.93% in patients with MHPI > 0.53, and 7.14% in patients with MHPI lower than 0.53 (p=0.002). In regards to the final LogMAR VA, all studied variables above submitted to Pearson correlation test. MHPI is inversely correlated with VA by linear regression with gradient procedure as best predictor of final VA (p< 0.001 and p= 0.005 respectively). The sample shows that 58.4% of post-surgery VA is being explained by the MHPI and pre-surgery VA. Conclusions: A new prognostic index for IMH surgery was defined as IMH height/internal diameter. We concluded that MHPI may be used as a prognostic factor for IMH anatomical closure after surgical treatment. MHPI and preoperatory VA were the best correlated prognostic factors for 6-month VA.

Orientador: Vital Paulino Costa / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-23T06:08:01Z (GMT). No. of bitstreams: 1 Cremasco_Fernanda_D.pdf: 5564009 bytes, checksum: bb04dfbdd0809568c204a7076f6df39f (MD5) Previous issue date: 2013 / Resumo: Esta pesquisa teve por finalidade avaliar a variabilidade intrasessão, intersessão e interexaminador das medidas de espessura da camada de fibras nervosas da retina peripapilar (CFNRP) com a Tomografia de Coerência Óptica de Domínio Espectral (TCO-DE). Foi incluído no estudo apenas um olho de 32 indivíduos saudáveis e de 34 pacientes com glaucoma. As medidas da CFNRP foram obtidas com o Cirrus HD-OCT 4000 (Carl Zeiss Meditec, Dublin, Califórnia, EUA) cinco vezes no mesmo dia, por um único examinador, para avaliação da variabilidade intrasessão. O mesmo examinador realizou medidas de espessura da CFNRP nos mesmos sujeitos em cinco dias diferentes, para avaliação da variabilidade intersessão. Um segundo examinador realizou medidas da espessura da CFNRP nos mesmos pacientes para avaliação da variabilidade interexaminador. O coeficiente de variação (CDV) e o coeficiente de correlação intraclasse (CCI) foram obtidos para os seguintes parâmetros: espessura média, espessura nos quadrantes e espessuras setoriais. Em relação à variabilidade intrasessão, em pacientes com glaucoma, os CDVs variaram de 4,51% a 11,84% e os CCIs variaram de 0,74 a 0,99; em indivíduos saudáveis, os CDVs variaram de 2,92% a 6,99% e os CCIs variaram de 0,89 a 0,98. Na análise da variabilidade intersessão observou-se que, em pacientes com glaucoma, os CDVs variaram de 3,68% a 10,50% e os CCIs variaram de 0,82 a 0,99; em indivíduos saudáveis, os CDVs variaram de 3,13% a 6,92% e os CCIs variaram de 0,87 a 0,99. Em relação à variabilidade interexaminador, em pacientes com glaucoma, os CDVs variaram de 2,62% a 14,94% e os CCIs variaram de 0,55 a 0,98; em indivíduos saudáveis, os CDVs variaram de 2,04% a 7,31% e os CCIs variaram de 0,86 a 0,98. Estes resultados indicam que as medidas de espessura da CFNRP com a TCO-DE apresentam reprodutibilidade excelente, com baixa variabilidade intrasessão, intersessão e interexaminador / Abstract: The purpose of this study was to evaluate the intrasession, intersession and interexaminer variabilities of peripapillary retinal nerve fiber layer (PRNFL) thickness measurements with Spectral Domain Optical Coherence Tomography. One eye of 32 healthy individuals and 34 patients with glaucoma were included in the study. The PRNFL measurements were obtained with the Cirrus HD-OCT Model 4000 (Carl Zeiss Meditec, Dublin, Califórnia, USA) five times during the same sitting by one examiner to assess intrasession variability. The same examiner performed PRNFL measurements in the same patients in five different days to assess intersession variability. A second examiner performed PRNFL measurements in the same patients to assess interexaminer variability. The coefficient of variation (COV) and the intraclass correlation coefficient (ICC) were obtained for the following parameters: average thickness, quadrant thickness and clock-hour thickness measurements. The analysis of the intrasession variability, in glaucoma patients, showed that COVs ranged from 4.51% to 11.84% and ICCs varied from 0.74 to 0.99, whereas in healthy individuals, COVs ranged from 2.92% to 6.99% and ICCs varied from 0.89 to 0.98. Regarding the intersession variability, in glaucoma patients COVs ranged from 3.68% to 10.50% and ICCs varied from 0.82 to 0.99; whereas in healthy individuals, COVs ranged from 3.13% to 6.92% and ICCs varied from 0.87 to 0.99. In interexaminer variability, between glaucoma patients, COVs ranged from 2.62% to 14.94% and ICCs varied from 0.55 to 0.98, whereas in healthy individuals, COVs ranged from 2.04% to 7.31% and ICCs varied from 0.86 to 0.98. These findings indicate that PRNFL measurements with Spectral Domain Optical Coherence Tomography display excellent reproducibility, with low intrasession, intersession and interexaminer variabilities / Doutorado / Oftalmologia / Doutor em Ciências Médicas

Objetivo: A partir das medidas anatômicas isoladas (altura, diâmetro externo e interno) do BMI construir um novo índice prognóstico para a cirurgia de correção do Buraco Macular Idiopático (IPBM). Tipo de estudo: intervencional, série de casos. Pacientes e Métodos: Estudo realizado no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo e no Instituto Suel Abujamra, São Paulo-SP, entre outubro de 2005 e outubro de 2007. Foram incluídos 36 olhos de 36 pacientes com BMI, que foram avaliados segundo as medidas apresentadas ao exame de TCO (Stratus - Zeiss, versão 4.01) antes da cirurgia do BMI. Utilizando o compasso do TCO, obteve-se a medida dos maiores diâmetros externo e interno e da altura dos BMI. Por meio dessas medidas, foi criado o IPBM. Após vitrectomia posterior com retirada de Membrana Limitante Interna (MLI), sem utilização de corantes, os pacientes foram acompanhados por seis meses. Após a cirurgia, os pacientes foram avaliados no primeiro e sétimo dias, duas semanas, um, três e seis meses. Ao final do seguimento, o IBPM e outras variáveis (sexo, idade, raça, estádio do BMI pela classificação biomicroscópica de Gass, tempo decorrido desde a piora da acuidade visual informada pelo paciente e a acuidade visual pré-operatória), foram correlacionadas com o resultado anatômico e a acuidade visual pós-operatória. Resultados: Vinte e nove (80,6%) dos 36 olhos com BMI obtiveram fechamento anatômico ao final de seis meses de acompanhamento (8,86 ± 4,23 meses). Dezenove (52,7%) dos BMI eram do estádio IV de Gass, com tempo de duração maior que um ano em 21 pacientes (58,3%). A AV LogMAR corrigida pré-operatória média foi de 1,10 (0,60 a 1,62) e a pós-operatória média foi de 0,69 (0,0 a 1,60). A média de melhora da AV foi de 3,94 linhas. Em relação ao fechamento anatômico, não houve significância em relação ao tempo de história da doença entre os grupos aberto (grupo 1) e fechado (grupo 2) (Teste t-Student, p=0,072). O diâmetro da base interna foi maior no grupo 1 em relação ao grupo 2 (Teste t-Student, p=0,007). Na análise do índice IPBM, houve diferença significativa entre o grupo 1 (média 0,49) e o grupo 2 (média 0,91). (Teste t-Student, p< 0,001) A análise de regressão logística apontou que BMIs com IPBM maior que 0,53 apresentam chance de fechamento anatômico 9,6 vezes maior (Odds Ratio= 9,6, p = 0,018). Pacientes com IPBM > 0,53 apresentaram AV pós-operatória ao final do sexto mês significativamente melhor do que pacientes com IPBM < 0,53 (Mann-Whitney, p=0,005). O ganho percentual da AV foi de 41,93% nos pacientes com IBPM>0,53, quando comparado com os 7,14% do grupo com IPBM <0,53 (p=0,002). No que diz respeito à AV final LogMAR, todas as variáveis estudadas anteriormente foram submetidas ao teste de correlação de Pearson. Observou-se que o IPBM tem uma correlação negativa significante com a AV, e foi selecionado juntamente com a AV pré-operatória através de regressão linear como os melhores preditores de AV final (p<0,001 e p=0,005, respectivamente). O modelo aponta que 58,4% da AV pós-operatória está sendo explicada pelo IPBM e AV pré-operatória. Conclusões: Foi construído um novo índice Prognóstico do Buraco Macular Idiopático (IPBM) representado pela razão altura / diâmetro interno do BMI. Verificou-se que o IPBM pode ser utilizado como fator prognóstico de fechamento anatômico do BMI. O IPBM e a AV pré-operatória foram os fatores prognósticos com melhor relação para a AV no sexto mês após o tratamento cirúrgico do BMI. / Purpose: To create a new prognostic index for IMH surgery based on anatomical values of IMH height, external and internal diameters (MHPI). Type of Study: Prospective, interventional, case of series. Patients and Methods: 36 eyes with IMH of 36 patients followed at Hospital das Clinicas, University of São Paulo Medical School (HC-FMUSP) and Suel Abujamra Institute (ISA), São Paulo-SP, between October 2006 and October 2007, were included. IMH OCT measurements were obtained before surgery (Stratus - Zeiss version 4.01) Values of the larger external and internal diameters, and the IMH height were obtained using the OCT compass. The prognostic index of IMH (MHPI) was defined as the index height / internal base. MHPI was defined by using those OCT measurements. Patients underwent pars plana vitrectomy with ILM peeling without dye and were followed by 6 months. Patients were seen at days 1, 7, 14, and months 1, 2, 3, and 6 after surgery. At the end of the follow-up period, MHPI and, other variables (sex, age, ethnic group, stage of IMH following the biomicroscopic classification of Gass, the time of visual loss reported by the patient, and pre surgical visual acuity) were correlated with anatomical results and post-surgical visual acuity. Results: Twenty nine eyes (80.6%) of thirty six patients with IMH had anatomical closure at the end of the six-month follow-up (8.86 ± 4.23 months). Nineteen (52.7%) IMH were stage IV of Gass with more than one year duration in twenty one patients. Pre-surgical medium LogMAR VA was 1.10 (0.60 to 1.62) and post-surgical was 0.69 (0.0 to 1.60). Medium VA improvement was 3.94 lines. The internal base diameter (BINT) was larger in group 1 than in group 2 (t-Student Test, p=0.373). MHPI analisys showed significant difference between group 1 (average 0.49) and group 2 (average 0.91) (t-Student Test, p> 0.001). Logistical regression showed that IMH with MHPI higher than 0.53 present 9.6 times more risk of failure than those with MHPI lower than 0.53 (Mann-Whitney, p=0.005). The percentage gain of VA was 41.93% in patients with MHPI > 0.53, and 7.14% in patients with MHPI lower than 0.53 (p=0.002). In regards to the final LogMAR VA, all studied variables above submitted to Pearson correlation test. MHPI is inversely correlated with VA by linear regression with gradient procedure as best predictor of final VA (p< 0.001 and p= 0.005 respectively). The sample shows that 58.4% of post-surgery VA is being explained by the MHPI and pre-surgery VA. Conclusions: A new prognostic index for IMH surgery was defined as IMH height/internal diameter. We concluded that MHPI may be used as a prognostic factor for IMH anatomical closure after surgical treatment. MHPI and preoperatory VA were the best correlated prognostic factors for 6-month VA.

Although the current OCT imaging system was designed to examine the retinal structures, a novel application in imaging the anterior chamber angle was studied in section 3.7. OCT was demonstrated to be clinically useful for visualization of the different patterns of angle configurations in different forms of angle closure glaucoma. / In section 3.5, RNFL measurement by OCT was cross-validated by another nerve fiber analyzer, scanning laser polarimetry (SLP). While both OCT and SLP demonstrated comparable diagnostic performance for glaucoma detection and high correlation in the respective RNFL measurements, OCT was found to provide a closer estimation of RNFL thickness with reference to the reported histological measurements. In section 3.6, the structural-functional relationship between RNFL thickness and visual sensitivity was evaluated and compared between OCT and SLP. The relationships were found to be dependent on the choice of the perimetry scale, the type of RNFL measuring devices and the characteristics of the studied subjects. It was concluded that regression analysis of the structural-functional profile could provide important information in the assessment of the trend and pattern of glaucoma progression. / In summary, optical coherence tomography was shown to be useful in the diagnosis of glaucoma and in the evaluation of the trend and pattern of disease progression. / Objectives. The research project was designed to investigate the applications of optical coherence tomography in the assessment of glaucoma. The goals are to identify sensitive and specific anatomic markers, and analytical method for detection of glaucomatous changes, to evaluate the intricate structural-functional relationships in glaucoma with regression analysis and to assess the potential application of optical coherence tomography imaging system in visualization of the anterior chamber angle with a view to obtain OCT data to help understanding the pathophysiology of different forms of angle-closure glaucoma. / Sections 3.1 to 3.3 were designed to identify the most sensitive and specific diagnostic marker(s) for glaucoma detection. Peripapillary retinal nerve fiber layer (RNFL), macular thickness, optic nerve head parameters measured with different reference planes, and a novel anatomic marker - macular nerve fiber layer were investigated. The averaged peripapillary RNFL thickness measured with a high resolution scan (512 scan point) was found to have the best discriminating power for detection of glaucoma. It also has the strongest correlation with visual function. To examine if utilization of the complete data profile of peripapillary RNFL could further improve diagnostic sensitivity, a novel approach with the use of neural network trained to recognize RNFL pattern was studied in section 3.4. It was concluded that neural network analysis could enhance the diagnostic performance for glaucoma detection. / Summary. Glaucoma is a progressive optic neuropathy characterized by the loss of retinal ganglion cells resulting in constriction of visual field and loss of vision as the disease progresses. Since structural damage in glaucoma occurs well before any detectable loss in visual function, clinical examination of the optic nerve head and its nerve fiber layer is crucial in establishing the diagnosis, monitoring the progression and initiating treatment before irreversible damage takes place. The present research project is composed of 7 coherent studies (sections 3.1 to 3.7), aiming to investigate the clinical applications of optical coherence tomography (OCT), an advanced imaging device for detailed examination of optic nerve head and nerve fiber layer, in the assessment of glaucoma. / Leung Kai-shun. / "June 2006." / Adviser: Chi Pui Pang. / Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6323. / Thesis (M.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 212-227). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / School code: 1307.

Glaucoma is characterized by progressive optic nerve head (ONH) deformation and retinal nerve fiber layer (RNFL) thinning but the relative sequence of ONH and RNFL changes in glaucoma remains largely uncertain. It has been proposed that structural damage of the optic nerve can often be detected before detectable functional loss. Therefore, investigating structural changes of the ONH and RNFL is of importance and relevance in the monitoring and management of glaucoma progression. Spectral domain optical coherence tomography (OCT), scanning laser polarimetry (SLP) and confocal scanning laser ophthalmoscopy (CSLO) are the three prevailing digital imaging technologies for measurement of RNFL thickness, RNFL retardance and ONH parameters, respectively. Although these instruments have been extensively investigated for detection of glaucomatous damage, less is known about their relative performance for detection of change in glaucoma progression. Although previous studies on non- human primates showed that disruption of the microtubule structure of the retinal ganglion cell axons detected by SLP as reduction of RNFL retardance, as well as ONH surface deformation detected by CSLO, could be detected prior to reduction of RNFL thickness measured with OCT, clinical data corroborating this observation are lacking. The sequence of change of RNFL thickness, RNFL retardance and ONH parameters has not been investigated in human glaucoma. / This research project aimed to investigate the performance of OCT, SLP and CLSO for change detection of RNFL and ONH damages, determine the relative sequence of change of RNFL retardance and RNFL thickness and ONH deformation, and evaluate if ocular biomechanical properties, measured as corneal hysteresis by the ocular response analyzer (ORA, Reichert Inc.), influence the detection of ONH and RNFL progression in glaucoma patients. We hypothesized that ONH deformation and loss of RNFL retardance could be detected before detectable RNFL thinning and that the baseline corneal hysteresis would be a risk factor for ONH and RNFL damage in glaucoma. / In the first study, we analyzed 184 eyes of 116 patients with glaucoma and 43 normal eyes of 23 healthy individuals followed for a mean of 4.6 years. All subjects had RNFL retardance and RNFL thickness measurements obtained with GDx ECC (Carl Zeiss Meditec) and Cirrus HD-OCT (Carl Zeiss Meditec), respectively, at 4-month intervals. Progressive reduction of RNFL retardance and RNFL thickness were evaluated with Guided Progression Analysis (GPA, Carl Zeiss Meditec) with reference to the RNFL retardance change map and RNFL thickness change map, respectively. Twenty seven eyes of 26 patients showed progressive RNFL thinning whereas 8 eyes of 8 patients had RNFL retardance reduction in the latest follow-up visit. Seven eyes of 7 patients had progressive RNFL thinning and reduction of RNFL retardance detected by both instruments; all had progressive RNFL thinning evident before reduction of RNFL retardance and the mean lag time was 13.4 months (range: 4.0-37.6 months). The survival time of eyes detected with RNFL thinning was significantly shorter than the survival time of eyes detected with reduction of RNFL retardance (P=0.001). No eyes in the normal group showed progressive RNFL changes during follow-up. Collectively, we showed that at a comparable specificity (100%, 95% confidence interval: 96.3%-100%), progressive RNFL thinning was detected more often than progressive reduction of RNFL retardance and the former preceded the latter in eyes with both progressive RNFL thinning and reduction of RNFL retardance. / In the second study using a similar study design, we investigated the sequence of change of ONH surface depression detected by CSLO (HRT 3, Heidelberg Engineering) and RNFL thinning detected by OCT (Cirrus HD-OCT, Carl Zeiss Meditec) in 146 eyes of 90 glaucoma patients followed at approximately 4-month intervals for an average of 5.4 years. Significant ONH surface depression and RNFL thinning were defined with reference to Topographic Change Analysis (TCA, Heidelberg Engineering) and Guided Progression Analysis (GPA, Carl Zeiss Meditec), respectively. At a specificity of 94.3% (95% confidence interval: 86.2%-97.8%) for both RNFL thinning and ONH surface depression (determined in a normal group comprising 70 eyes from 35 normal subjects), 57 eyes (39.0%) had ONH surface depression, 46 eyes (31.5%) had RNFL thinning, and 23 eyes (15.8%) had both in the glaucoma group. Among these 23 eyes, 19 (82.6%) had ONH surface depression detected prior to RNFL thinning and the median lag time was 15.8 months (range, 4.0-40.8 months). Although only 7.0% of eyes (4/57) had RNFL thinning at the onset of ONH surface depression, 45.7% (21/46) had ONH surface depression at the onset of RNFL thinning. The survival time of eyes with ONH surface depression was significantly shorter than the survival time of eyes detected with RNFL thinning (P=0.002). With reference to the HRT TCA and OCT GPA, ONH surface depression occurred before RNFL thinning in a significant proportion of patients with glaucoma at a comparable specificity. / Of note, a significant proportion of eyes had ONH surface depression without any detectable progressive RNFL thinning in the second study, and vice versa. Investigating whether the risk factors for ONH surface depression and RNFL progression are different is therefore important. In the final study, we investigated if baseline corneal hysteresis is a risk factor for progressive ONH surface depression and RNFL thinning. Following the same cohort of 146 eyes of 90 glaucoma patients for an average of 6.8 years, we detected that 65 eyes (44.5%) had progressive ONH surface depression, 55 eyes (37.7%) had progressive RNFL thinning and 20 eyes (13.7%) had visual field progression (based on the EMGT criteria). After adjusting for ages, CCT, baseline diastolic IOP, average IOP during follow-up, baseline disc area and baseline MD in the cox proportional hazards model, baseline corneal hysteresis was significantly associated with ONH surface depression (HR=0.70, P=0.008), visual field progression (HR=0.56, P=0.019), but not with progressive RNFL thinning (HR=0.96, P=0.751). For each 1-mmHg decrease of baseline CH, the hazards for ONH surface depression and visual field progression increased by 30% and 44%, respectively. / In summary, at a comparable level of specificity, progressive ONH surface depression detected by CSLO could be observed prior to progressive RNFL thinning detected by OCT, which preceded identified reduction of RNFL retardance detected by SLP. For eyes with concomitant ONH surface depression, RNFL thinning and visual field progression, ONH surface depression always preceded visual field progression. Our finding indicates that a time window for therapeutic intervention may exist upon detection of ONH surface depression before irreversible RNFL and visual field loss and that measurement of CH would be useful to predict ONH surface depression and visual field progression. / Further studies are required to investigate the sequence of optic nerve head change and RNFL progression with the same instrument. Whether IOP lowering treatment initiated at the time of ONH deformation would be effective to prevent or slow down RNFL and visual field loss needs to be further investigated. A more reliable and accurate measure of the ocular biomechanical properties is necessary for evaluation of their contribution to glaucoma progression. / 青光眼是一種進展性視神經病變，其特徵為﹕視神經乳頭變形，神經纖維層（RNFL）的變薄以及相應的視野缺損。然而，青光眼結構性改變和功能性變化發生的相對順序仍不清楚。視神經結構性改變被認為要早於功能性改變的發生。因此，研究視乳頭的結構性改變具有重要意義，有助於早期診斷青光眼的進展及隨訪青光眼患者。目前主要用於RNFL厚度，RNFL阻滯性以及視乳頭參數的影像學掃描儀器為頻域OCT，鐳射偏振光掃描器（SLP）和共聚焦鐳射掃描眼底鏡（CSLO）。儘管這三種儀器已經廣泛用於青光眼損傷的檢測，但在青光眼患者結構性變化的應用並不常見。既往在非人靈長類動物的實驗中，通過破壞神經節細胞軸突中的微小管結構，從而發現RNFL的阻滯性以及視乳頭的變化要先於RNFL厚度變化的發生。然而在臨床研究中並未得到證實。同時，在青光眼患者中，RNFL厚度變化，RNFL阻滯減少以及視神經頭參數改變之間的先後順序並未得到證實。 / 本次實驗研究的目的在於探討OCT，SLP及CSLO在診斷青光眼病人RNFL及視乳頭進展的能力，確定RNFL厚度變化，RNFL阻滯性減少以及視神經頭參數改變之間的相對順序，以及評估眼反應分析儀（ORA）測得的角膜粘滯性（CH）是否影響視乳頭及RNFL厚度的進展。我們假設：視神經乳頭的變形，RNFL阻滯性的減少要先於RNFL厚度的變化，基線角膜粘滯性的測量會影響視乳頭及RNFL進展的檢測。116個青光眼病人的184隻眼以及23個正常對照的43隻眼被納入第一個研究中。所有受試物件均接受每4個月一次的OCT以及SLP RNFL的掃描，平均隨訪時間為4.6年。通過OCT及SLP中Guided Progression Analysis（GPA, Carl Zeiss Meditec）程式，一系列RNFL厚度及粘滯性圖被自動分析從而獲得RNFL厚度及粘滯性的變化結果。26個青光眼患者的27隻眼表現為RNFL厚度的進行性變薄，8個患者的8隻眼表現為RNFL粘滯性的減少。其中7個患者的7隻眼同時表現為RNFL厚度變薄及粘滯性的減少，所有這7隻眼的RNFL變薄的發生要早於RNFL粘滯性的減少，兩者間隔時間平均為13.4月（4.0-37.6月）。RNFL厚度變薄者的生存概率明顯小於RNFL粘滯性減少的青光眼患者（P=0.001）。隨訪中，我們未發現正常對照組中RNFL厚度變薄或者粘滯性改變者。總體說來，在同一特異性水準（100%），RNFL厚度的變化頻率高於粘滯性的改變，RNFL厚度的變薄要早於粘滯性減少的發生。 / 採用相同於第一個研究的研究方法，我們研究CSLO測得的視乳頭表面凹陷以及測得OCT的RNFL厚度變化發生的相對順序。90個青光眼患者的146隻眼以及35個正常對照物件的70隻眼被納入第二個研究中。所有受試物件均接受4個月一次的CSLO及OCT掃描從而獲得一系列的視神經頭表面的拓撲圖像以及RNFL厚度圖。CSLO TCA及OCT GPA程式自動對比基線及隨訪中所獲得的視神經頭表面的拓撲圖像以及RNFL厚度圖，從而獲得視乳頭表面凹陷及RFNL進展報告。平均隨訪5.4年後，CSLO及OCT在診斷視神經頭及RNFL進展的特異性為94.3%，57只青光眼患眼（39.0%）表現為顯著性視乳頭表面凹陷，46隻眼（31.5%）表現為RFNL厚度的進行性變薄，而23隻眼（15.8%）同時表現為視乳頭面凹陷和RFNL的進行性變薄。在這23只眼中，19隻眼（82.6%）變現為視乳頭表面凹陷先於RFNL厚度變薄的發生，間隔時間的中值為15.8個月（4.0-40.8月）。儘管在顯著性視乳頭表面凹陷發生時，僅有7.0%的患眼表現為RNFL厚度的變薄；但是，在RNFL厚度發生顯著性變薄時已有45.7%的患眼表現為視乳頭表面凹陷。視乳頭表面凹陷患眼的生存概率差於RNFL厚度變薄患眼（P=0.002）。在青光眼患者的隨訪中，CLSO TCA測得的視乳頭表面凹陷要早於OCT GPA測得的RNFL厚度的變化。 / 最後的一個研究目在於評估眼反應分析儀（ORA）測得的基線角膜粘滯性（CH）是否為視乳頭表面凹陷及RNFL厚度變薄的危險因素。平均隨訪同一人群即第二個研究中的90個青光眼患者的146眼6.8年，65隻眼（44.5%）被檢測出具有進行性視乳頭表面凹陷，55隻眼（37.7%）表現為進行性RNFL厚度的變薄，20隻眼（13.7%）表現為進行性視野的缺損（基於EMGT標準）。基線CH與視乳頭表面凹陷，視野進展間具有顯著性相關關係（HR=0.70，P=0.008及HR=0.56，P=0.019），但CH與進行性RNFL厚度變薄間並無顯著性相關關係（HR=0.96，P=0.751）。每1毫米汞柱基線CH的降低，發生視乳頭表面凹陷及視野缺損的危險性將增加30%及44%。CH的測量值與青光眼進展的危險性具有顯著相關關係。 / 總之，在具有可比性特異性水準下，CSLO檢測的進展性視乳頭表面凹陷的發生要先於OCT檢測的進行性RNFL厚度的變薄，後者的發生早於SLP測得的RNFL粘滯性的改變。對於同時有視乳頭表面凹陷，RNFL厚度變薄及RNFL粘滯性改變的青光眼患眼，視乳頭表面凹陷的發生要早於視野的進展。我們的實驗研究表明了在青光眼患者發生視乳頭表面凹陷時，治療的時間窗的存在有助於避免不可逆的RNFL缺失及視野的缺損。角膜粘滯性的測量對於預測視乳頭表面凹陷及視野進展具有重要意義。 / 展望未來的研究中，用同一種儀器進行視乳頭及神經纖維層的隨訪，從而得出相對的變化次序很有必要。研究在視乳頭或者神經纖維層發生變化時進行眼壓的干預是否能避免視功能的進一步損傷顯得尤為重要。用於測量角膜生物學特性的更為準確，可信度更高的儀器真正研發中，以及進一步探討角膜生物學特性與青光眼進展之間的關係。 / Xu, Guihua. / Thesis Ph.D. Chinese University of Hong Kong 2015. / Includes bibliographical references (leaves 116-145). / Abstracts also in Chinese. / Title from PDF title page (viewed on 18, October, 2016). / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.

OBJETIVO: Descrever prospectivamente o curso da doença de Vogt-Koyanagi-Harada (DVKH) com integração de parâmetros de atividades clínicos, estruturais e funcionais. MÉTODOS: Foram incluídos pacientes com diagnóstico da DVKH na fase aguda (parte I) e não aguda (tempo de doença maior que 12 meses; parte II). Os pacientes na fase aguda receberam tratamento inicial padronizado com pulsoterapia de metilprednisolona seguido de corticoterapia oral em doses lentamente regressivas, pelo período de 15 meses. As avaliações consistiram em exame clínico, retinografia, angiografias com fluoresceína (AGF) e indocianina verde (AIV) e tomografia de coerência óptica (TCO). Foram realizadas nos seguintes momentos: parte I, no diagnóstico e meses 1, 2, 4, 6, 9 e 12; parte II, na inclusão e a cada três meses. Eletrorretinograma campo total (ERGct) e eletrorretinograma multifocal (ERGmf) foram realizados na parte I, no 1.o mês e a cada seis meses e, na parte II, na inclusão e com 12 meses. A leitura dos exames, na parte I, foi efetuada por duas leitoras, não mascaradas; na parte II, foi realizada por três leitores mascarados e treinados, sendo considerada a leitura concordante entre, pelo menos, dois examinadores. As angiografias e TCO foram realizadas no aparelho Spectralis® (HRA+OCT, Heidelberg Engineering). Tratamento adicional com corticoterapia em doses imunossupressoras ou intensificação da imunossupressão sistêmica foi indicado nos casos com recidivas clínicas, na presença de sinais de atividade à AGF ou duas pioras consecutivas >= 30% no ERGct. Os sinais de atividade detectados na AGF, AIV e TCO foram denominados sinais subclínicos. RESULTADOS: Na parte I, foram incluídos nove pacientes (7F/2M) com idade mediana de 33 anos e intervalo mediano entre início dos sintomas e tratamento de 13 dias. Na apresentação inicial, sinais clínicos característicos da doença (coroidite difusa com hiperemia do disco óptico, descolamento seroso de retina e uveíte anterior acompanhados de sinais extraoculares) melhoraram dentro dos primeiros 30 dias em todos os casos. Os principais sinais subclínicos variaram no tempo de melhora ou desaparecimento: espessura de coroide (EC) subfoveal diminuiu para o valor mediano de 347u m aos 30 dias; dark dots diminuíram ao longo do seguimento, porém ainda estavam presentes aos 12 meses. Piora da inflamação foi observada em 17 de 18 olhos no tempo mediano de sete meses quando a redução do corticoide oral atingiu a dose média de 0,3mg/kg/d. Os sinais subclínicos mais frequentemente observados foram dark dots, fuzzy vessels e aumento da EC. Em 10 destes 17 olhos a piora foi acompanhada de queda da função pelo ERG. Três padrões de evolução puderam ser caracterizados: sem recidivas clínicas ou subclínicas (padrão A, 1 olho), com recidivas subclínicas somente (padrão B, 11 olhos) e com recidivas clínicas (padrão C, 6 olhos). Identificou-se que a EC aos 30 dias após início do tratamento >= 506u m teve sensibilidade e especificidade > 80% na detecção dos casos com recidivas clínicas (padrão C). A função pelo ERGct e ERGmf permaneceu alterada em relação ao grupo controle com 24 meses, apesar da melhora progressiva observada desde o início do tratamento. Na análise longitudinal dos pacientes, a função entre 12 e 24 meses permaneceu estável no grupo de doentes que recebeu tratamento adicional (8 olhos), enquanto no grupo que não o recebeu (4 olhos) houve deterioração da função ( < 0,001). Na análise dos grupos segundo padrão de recidiva, observou-se que os olhos com padrão B sem tratamento adicional tinham piora funcional maior em relação àqueles com padrão C ou B tratados (p < 0,001). Na parte II, foram incluídos 20 pacientes (17F/3M), com idade mediana ao diagnóstico de 31 anos, intervalo mediano entre início de sintomas e tratamento de 19 dias e tempo mediano de doença à inclusão de 55 meses. Na avaliação da concordância interobservador na leitura dos sinais subclínicos, EC teve concordância substancial (kappa=0,8), enquanto sinais angiográficos tiveram concordância sutil (kappa < 0,2). O curso da doença em 85% dos pacientes foi com recidiva clínica (padrão C, 11 casos) ou recidiva subclínica (padrão B, 6 casos). Nas 11 avaliações com detecção de células na câmara anterior (CA), sinais subclínicos de inflamação de segmento posterior foram concomitantemente observados em 64% dos olhos. Esta mesma concomitância de sinais subclínicos de inflamação de segmento posterior na presença de células na CA foi observada na parte I do estudo. Nos pacientes com padrão B, a variação da EC foi o principal sinal subclínico observado. A função pelo ERG foi realizada sequencialmente em 13 casos. Olhos com padrão C (7 pacientes), com grande comprometimento funcional desde a inclusão, evoluíram com piora mais acentuada do que aqueles com padrão B (5 pacientes). Ao se individualizar os olhos com padrão B, observou-se que esse diferencial (padrão B melhor que C) devia-se ao grupo padrão B com tratamento (p < 0,001). CONCLUSÕES: Neste estudo prospectivo de pacientes com DVKH em seguimento mínimo de 12 meses, desde as fases aguda e não aguda, três padrões de evolução foram observados, sendo que 94% (parte I) e 85% (parte II) dos pacientes apresentaram recidiva/piora clínica (padrão C) e/ou subclínica (padrão B). Na parte I do estudo, a piora da inflamação foi detectada aos sete meses de evolução durante dose regressiva do corticoide equivalente a 0,3mg/kg/d, apesar do tratamento inicial com corticoides em altas doses lentamente regressivo. A EC aferida 30 dias após o início do tratamento acima de 506 ?m mostrou-se um fator com sensibilidade e especificidade acima de 80% na identificação dos casos que evoluíram com recidivas clínicas. Dentre os sinais para detecção de inflamação subclínica, as alterações na EC são confiáveis, enquanto que sinais angiográficos devem ser interpretados com cautela. Exames sequenciais tornam a leitura mais confiável. A presença de células na CA comportou-se como a \"ponta do iceberg\" de uma inflamação mais difusa. O estudo eletrorretinográfico demonstrou resultado subnormal mesmo após 24 meses de seguimento na parte I; tratamento adicional pode evitar piora funcional nos pacientes com sinais subclínicos de inflamação. A pior função da retina em pacientes com inflamação clínica (padrão C) da parte II e dos pacientes com inflamação subclínica (padrão B) de ambas as partes do estudo sugerem que o tratamento ideal das recidivas inflamatórias ainda deve ser alvo de futuros estudos / OBJECTIVES: To describe the course of Vogt-Koyanagi-Harada disease (VKHD) prospectively, integrating clinical, structural and functional parameters. METHODS: Patients with VKHD in the acute (part I) and non-acute (more than 12 months from diagnosis) phases (part II) were included. Patients in the acute phase received a standard treatment with methylprednisolone pulsetherapy followed by high-dose oral corticosteroids with slow tapering during 15 months. Evaluations included clinical exams, fluorescein (FA) and indocyanine green (ICGA) angiographies and optical coherence tomography (OCT). In part I, they were performed at inclusion, then after 1,2,4,6,9,and 12 months; in part II, they were performed at inclusion then every 3 months for up to 12 months. Functional evaluation using electroretinography (ERG) was performed at inclusion and every 6 months in part I and at inclusion and at 12 months in part II. Two non-blinded readers analyzed the imaging exams in part I. In part II, three trained and blinded-readers performed the imaging exams analysis. For study`s purpose, at least two concordant readings were considered. Imaging exams utilized the Spectralis® (HRA+OCT, Heidelberg engineering). Inflammatory signs detected on FA, ICGA and OCT were denominated as subclinical signs. Additional treatment with high doses of corticosteroids or more intensive systemic immunosuppression was indicated in cases with clinical signs of inflammation, with subclinical signs on FA or with two consecutive worsening > 30% on ERG. RESULTS: Nine patients (7F/2M) were included in part I; median age was 33 years old and median time elapsed from onset of symptoms to treatment was 13 days. At disease presentation, classic signs (choroiditis, anterior uveitis, serous retinal detachment, optic disc hyperemia and extraocular manifestations) were observed; they improved in 30 days after treatment. Subclinical signs improved in variable periods of time: subfoveal choroidal thickness (CT) decreased to a median value of 347 ?m, 30 days after the beginning of treatment, dark dots diminished during the follow-up but they were still observed at 12 months. Relapse (worsening of inflammation) was noticed in 17 of 18 eyes at a median follow up time of seven months, when tapering schedule corticosteroid dosage reached the mean dose of 0.3mg/kg/d of prednisone. Dark dots, fuzzy vessels and choroid thickening were the most frequent subclinical signs. Relapses in 10 of 17 eyes were concomitant with worsening on ERG. Three patterns of evolution could be delineated: no signs of inflammation (pattern A, 1 eye), only subclinical signs of inflammation (pattern B, 11 eyes) and clinical signs of inflammation (pattern C, 6 eyes). CT>=506 ?m 30 days after the beginning of treatment was more than 80% sensitive and specific to detect more severe cases (pattern C). ERG parameters at 24 months were subnormal as compared to the control group, despite improvement during follow-up. Further long-term results after 24 month demonstrated stabilization of ERG parameters in patients that had received additional treatment, whereas there was worsening in those patients who had not received additional treatment (p<0.001). Moreover, pattern B patients without additional treatment had a further decrease on ERG values compared to results observed in pattern C or B patients with additional treatment (p<0.001). In Part II, 20 patients (17F/3M) were included; median age at diagnosis was 31 years old, median lag time from onset of symptoms and treatment was 19 days and median time after diagnosis was 55 months. The interobserver agreement for CT reading was substantial (kappa 0.8), whereas for angiographic signs was slight (kappa < 0.2). Recurrences, clinically (pattern C, 11 cases) or subclinically (pattern B, 6 cases) detected, were observed in 85% of cases. Concomitant inflammation of posterior segment detected by subclinical signs was present in 64% of cases with cells in anterior chamber. Simultaneous signs of subclinical inflammation of posterior segment and anterior uveitis were also observed in part I. CT change was the main subclinical sign observed in pattern B patients. ERG evaluation was performed in 13 cases. Pattern C cases (7 patients) presented worse results than pattern B cases (5 patients). Further analysis depicted that pattern B patients who had an additional treatment had better results than pattern B non-treated and pattern C (p<0.001). CONCLUSION: Three patterns of evolution were observed in VKHD patients during this prospective study, 94% (part I) and 85% (part II) presented recurrence/worsening with clinical (pattern C) or subclinical (Pattern B) signs of inflammation. In part I, worsening was observed at seven months after treatment start when reaching mean dose of 0.3mg/Kg/d of prednisone even after initial high-dose of corticosteroids followed by slow tapering. At day 30 after treatment, CT >= 506 ?m had a greater than 80% sensitivity and specificity to detect cases with pattern C evolution. Considering subclinical signs, CT increase reliably detected recurrence, whereas angiographic signs required cautious interpretation. Sequential analysis was more conclusive than an isolated exam. Anterior chamber cells seemed to be the \"tip of the iceberg\" of a more diffuse inflammation. ERG analysis was subnormal even after 24 months of follow up since disease onset; additional treatment could prevent functional worsening in patients with subclinical signs of inflammation. Worse retinal function in patients with clinical recurrences (pattern C) in part II and subclinical recurrences (pattern B) in parts I and II suggest that ideal treatment of recurrences should be further pursued

OBJETIVO: Descrever prospectivamente o curso da doença de Vogt-Koyanagi-Harada (DVKH) com integração de parâmetros de atividades clínicos, estruturais e funcionais. MÉTODOS: Foram incluídos pacientes com diagnóstico da DVKH na fase aguda (parte I) e não aguda (tempo de doença maior que 12 meses; parte II). Os pacientes na fase aguda receberam tratamento inicial padronizado com pulsoterapia de metilprednisolona seguido de corticoterapia oral em doses lentamente regressivas, pelo período de 15 meses. As avaliações consistiram em exame clínico, retinografia, angiografias com fluoresceína (AGF) e indocianina verde (AIV) e tomografia de coerência óptica (TCO). Foram realizadas nos seguintes momentos: parte I, no diagnóstico e meses 1, 2, 4, 6, 9 e 12; parte II, na inclusão e a cada três meses. Eletrorretinograma campo total (ERGct) e eletrorretinograma multifocal (ERGmf) foram realizados na parte I, no 1.o mês e a cada seis meses e, na parte II, na inclusão e com 12 meses. A leitura dos exames, na parte I, foi efetuada por duas leitoras, não mascaradas; na parte II, foi realizada por três leitores mascarados e treinados, sendo considerada a leitura concordante entre, pelo menos, dois examinadores. As angiografias e TCO foram realizadas no aparelho Spectralis® (HRA+OCT, Heidelberg Engineering). Tratamento adicional com corticoterapia em doses imunossupressoras ou intensificação da imunossupressão sistêmica foi indicado nos casos com recidivas clínicas, na presença de sinais de atividade à AGF ou duas pioras consecutivas >= 30% no ERGct. Os sinais de atividade detectados na AGF, AIV e TCO foram denominados sinais subclínicos. RESULTADOS: Na parte I, foram incluídos nove pacientes (7F/2M) com idade mediana de 33 anos e intervalo mediano entre início dos sintomas e tratamento de 13 dias. Na apresentação inicial, sinais clínicos característicos da doença (coroidite difusa com hiperemia do disco óptico, descolamento seroso de retina e uveíte anterior acompanhados de sinais extraoculares) melhoraram dentro dos primeiros 30 dias em todos os casos. Os principais sinais subclínicos variaram no tempo de melhora ou desaparecimento: espessura de coroide (EC) subfoveal diminuiu para o valor mediano de 347u m aos 30 dias; dark dots diminuíram ao longo do seguimento, porém ainda estavam presentes aos 12 meses. Piora da inflamação foi observada em 17 de 18 olhos no tempo mediano de sete meses quando a redução do corticoide oral atingiu a dose média de 0,3mg/kg/d. Os sinais subclínicos mais frequentemente observados foram dark dots, fuzzy vessels e aumento da EC. Em 10 destes 17 olhos a piora foi acompanhada de queda da função pelo ERG. Três padrões de evolução puderam ser caracterizados: sem recidivas clínicas ou subclínicas (padrão A, 1 olho), com recidivas subclínicas somente (padrão B, 11 olhos) e com recidivas clínicas (padrão C, 6 olhos). Identificou-se que a EC aos 30 dias após início do tratamento >= 506u m teve sensibilidade e especificidade > 80% na detecção dos casos com recidivas clínicas (padrão C). A função pelo ERGct e ERGmf permaneceu alterada em relação ao grupo controle com 24 meses, apesar da melhora progressiva observada desde o início do tratamento. Na análise longitudinal dos pacientes, a função entre 12 e 24 meses permaneceu estável no grupo de doentes que recebeu tratamento adicional (8 olhos), enquanto no grupo que não o recebeu (4 olhos) houve deterioração da função ( < 0,001). Na análise dos grupos segundo padrão de recidiva, observou-se que os olhos com padrão B sem tratamento adicional tinham piora funcional maior em relação àqueles com padrão C ou B tratados (p < 0,001). Na parte II, foram incluídos 20 pacientes (17F/3M), com idade mediana ao diagnóstico de 31 anos, intervalo mediano entre início de sintomas e tratamento de 19 dias e tempo mediano de doença à inclusão de 55 meses. Na avaliação da concordância interobservador na leitura dos sinais subclínicos, EC teve concordância substancial (kappa=0,8), enquanto sinais angiográficos tiveram concordância sutil (kappa < 0,2). O curso da doença em 85% dos pacientes foi com recidiva clínica (padrão C, 11 casos) ou recidiva subclínica (padrão B, 6 casos). Nas 11 avaliações com detecção de células na câmara anterior (CA), sinais subclínicos de inflamação de segmento posterior foram concomitantemente observados em 64% dos olhos. Esta mesma concomitância de sinais subclínicos de inflamação de segmento posterior na presença de células na CA foi observada na parte I do estudo. Nos pacientes com padrão B, a variação da EC foi o principal sinal subclínico observado. A função pelo ERG foi realizada sequencialmente em 13 casos. Olhos com padrão C (7 pacientes), com grande comprometimento funcional desde a inclusão, evoluíram com piora mais acentuada do que aqueles com padrão B (5 pacientes). Ao se individualizar os olhos com padrão B, observou-se que esse diferencial (padrão B melhor que C) devia-se ao grupo padrão B com tratamento (p < 0,001). CONCLUSÕES: Neste estudo prospectivo de pacientes com DVKH em seguimento mínimo de 12 meses, desde as fases aguda e não aguda, três padrões de evolução foram observados, sendo que 94% (parte I) e 85% (parte II) dos pacientes apresentaram recidiva/piora clínica (padrão C) e/ou subclínica (padrão B). Na parte I do estudo, a piora da inflamação foi detectada aos sete meses de evolução durante dose regressiva do corticoide equivalente a 0,3mg/kg/d, apesar do tratamento inicial com corticoides em altas doses lentamente regressivo. A EC aferida 30 dias após o início do tratamento acima de 506 ?m mostrou-se um fator com sensibilidade e especificidade acima de 80% na identificação dos casos que evoluíram com recidivas clínicas. Dentre os sinais para detecção de inflamação subclínica, as alterações na EC são confiáveis, enquanto que sinais angiográficos devem ser interpretados com cautela. Exames sequenciais tornam a leitura mais confiável. A presença de células na CA comportou-se como a \"ponta do iceberg\" de uma inflamação mais difusa. O estudo eletrorretinográfico demonstrou resultado subnormal mesmo após 24 meses de seguimento na parte I; tratamento adicional pode evitar piora funcional nos pacientes com sinais subclínicos de inflamação. A pior função da retina em pacientes com inflamação clínica (padrão C) da parte II e dos pacientes com inflamação subclínica (padrão B) de ambas as partes do estudo sugerem que o tratamento ideal das recidivas inflamatórias ainda deve ser alvo de futuros estudos / OBJECTIVES: To describe the course of Vogt-Koyanagi-Harada disease (VKHD) prospectively, integrating clinical, structural and functional parameters. METHODS: Patients with VKHD in the acute (part I) and non-acute (more than 12 months from diagnosis) phases (part II) were included. Patients in the acute phase received a standard treatment with methylprednisolone pulsetherapy followed by high-dose oral corticosteroids with slow tapering during 15 months. Evaluations included clinical exams, fluorescein (FA) and indocyanine green (ICGA) angiographies and optical coherence tomography (OCT). In part I, they were performed at inclusion, then after 1,2,4,6,9,and 12 months; in part II, they were performed at inclusion then every 3 months for up to 12 months. Functional evaluation using electroretinography (ERG) was performed at inclusion and every 6 months in part I and at inclusion and at 12 months in part II. Two non-blinded readers analyzed the imaging exams in part I. In part II, three trained and blinded-readers performed the imaging exams analysis. For study`s purpose, at least two concordant readings were considered. Imaging exams utilized the Spectralis® (HRA+OCT, Heidelberg engineering). Inflammatory signs detected on FA, ICGA and OCT were denominated as subclinical signs. Additional treatment with high doses of corticosteroids or more intensive systemic immunosuppression was indicated in cases with clinical signs of inflammation, with subclinical signs on FA or with two consecutive worsening > 30% on ERG. RESULTS: Nine patients (7F/2M) were included in part I; median age was 33 years old and median time elapsed from onset of symptoms to treatment was 13 days. At disease presentation, classic signs (choroiditis, anterior uveitis, serous retinal detachment, optic disc hyperemia and extraocular manifestations) were observed; they improved in 30 days after treatment. Subclinical signs improved in variable periods of time: subfoveal choroidal thickness (CT) decreased to a median value of 347 ?m, 30 days after the beginning of treatment, dark dots diminished during the follow-up but they were still observed at 12 months. Relapse (worsening of inflammation) was noticed in 17 of 18 eyes at a median follow up time of seven months, when tapering schedule corticosteroid dosage reached the mean dose of 0.3mg/kg/d of prednisone. Dark dots, fuzzy vessels and choroid thickening were the most frequent subclinical signs. Relapses in 10 of 17 eyes were concomitant with worsening on ERG. Three patterns of evolution could be delineated: no signs of inflammation (pattern A, 1 eye), only subclinical signs of inflammation (pattern B, 11 eyes) and clinical signs of inflammation (pattern C, 6 eyes). CT>=506 ?m 30 days after the beginning of treatment was more than 80% sensitive and specific to detect more severe cases (pattern C). ERG parameters at 24 months were subnormal as compared to the control group, despite improvement during follow-up. Further long-term results after 24 month demonstrated stabilization of ERG parameters in patients that had received additional treatment, whereas there was worsening in those patients who had not received additional treatment (p<0.001). Moreover, pattern B patients without additional treatment had a further decrease on ERG values compared to results observed in pattern C or B patients with additional treatment (p<0.001). In Part II, 20 patients (17F/3M) were included; median age at diagnosis was 31 years old, median lag time from onset of symptoms and treatment was 19 days and median time after diagnosis was 55 months. The interobserver agreement for CT reading was substantial (kappa 0.8), whereas for angiographic signs was slight (kappa < 0.2). Recurrences, clinically (pattern C, 11 cases) or subclinically (pattern B, 6 cases) detected, were observed in 85% of cases. Concomitant inflammation of posterior segment detected by subclinical signs was present in 64% of cases with cells in anterior chamber. Simultaneous signs of subclinical inflammation of posterior segment and anterior uveitis were also observed in part I. CT change was the main subclinical sign observed in pattern B patients. ERG evaluation was performed in 13 cases. Pattern C cases (7 patients) presented worse results than pattern B cases (5 patients). Further analysis depicted that pattern B patients who had an additional treatment had better results than pattern B non-treated and pattern C (p<0.001). CONCLUSION: Three patterns of evolution were observed in VKHD patients during this prospective study, 94% (part I) and 85% (part II) presented recurrence/worsening with clinical (pattern C) or subclinical (Pattern B) signs of inflammation. In part I, worsening was observed at seven months after treatment start when reaching mean dose of 0.3mg/Kg/d of prednisone even after initial high-dose of corticosteroids followed by slow tapering. At day 30 after treatment, CT >= 506 ?m had a greater than 80% sensitivity and specificity to detect cases with pattern C evolution. Considering subclinical signs, CT increase reliably detected recurrence, whereas angiographic signs required cautious interpretation. Sequential analysis was more conclusive than an isolated exam. Anterior chamber cells seemed to be the \"tip of the iceberg\" of a more diffuse inflammation. ERG analysis was subnormal even after 24 months of follow up since disease onset; additional treatment could prevent functional worsening in patients with subclinical signs of inflammation. Worse retinal function in patients with clinical recurrences (pattern C) in part II and subclinical recurrences (pattern B) in parts I and II suggest that ideal treatment of recurrences should be further pursued

PURPOSE: To examine foveal structure in amblyopia using spectral-domain optical coherence tomography (SD-OCT). DESIGN: Prospective, cross-sectional study. PARTICIPANTS AND CONTROLS: Two subject groups were recruited to the study: 85 amblyopes (34 adults, 51 children) and 110 visually normal controls (44 adults, 66 children). METHODS: A detailed eye examination, including an SD-OCT scan, was performed in all participants. A total of 390 eyes of 195 subjects were imaged using a 3-dimensional (3D) macula scan covering a nominal 6 x 6-mm area with a resolution of 256 x 256 (65,536 axial scans). Data from the B-scans bisecting the fovea both horizontally and vertically were fitted with a mathematical model of the fovea to determine a range of foveal parameters. MAIN OUTCOME MEASURES: Foveal thickness, foveal pit depth, and foveal pit slope. RESULTS: Bilateral differences between the eyes of amblyopes compared with visually normal controls were found. The difference between foveal structure in amblyopic participants relative to structure in subjects with normal vision persisted even when variables such as age, ethnicity, axial length, and sex were taken into account. Amblyopes showed increased foveal thickness (+8.31 mum; P = 0.006) and a reduction in pit depth in the horizontal meridian (-10.06 mum; P = 0.005) but not in the vertical meridian (P = 0.082) when compared with subjects with normal vision. Foveal pit slopes were found to be approximately 1 degree flatter in the nasal (P = 0.033) and temporal (P = 0.014) meridians in amblyopes, but differences between amblyopes and controls in the superior (P = 0.061) and inferior (P = 0.087) meridians did not reach statistical significance. No statistically significant interocular differences were found in the foveal structure between amblyopic and fellow eyes. CONCLUSIONS: Differences were found in the foveal structure in both eyes of amblyopes compared with subjects with normal vision. These differences consisted of increased foveal thickness, reduced pit depth when measured along the horizontal meridian, and flattening of the nasal and temporal sides of the foveal pit.