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研究生:陳幸宜
研究生(外文):Hsin-Yi Chen
論文名稱:青光眼視神經病變影像診斷與致病機轉之探討
論文名稱(外文):Imaging diagnosis and pathogenesis study on glaucoma optic neuropathy
指導教授:陳汶吉
學位類別:博士
校院名稱:中國醫藥大學
系所名稱:臨床醫學研究所博士班
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2015
畢業學年度:103
語文別:英文
論文頁數:49
中文關鍵詞:青光眼視神經病變影像診斷致病機轉
外文關鍵詞:glaucoma optic neuropathyImaging diagnosispathogenesis
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研究背景 青光眼視神經病變影像診斷與致病機轉探討是兩個重要研究議題.研究發現Stratus 與Cirrus 光電同調斷層掃描儀對視神經纖維層厚度的測量有好的一致性.然而,非常少研究探討比較這兩種光電同調斷層掃描儀對不同青光眼類型有不同表現.在第一個研究, 比較這兩種光電同調斷層掃描儀在台灣地區中國人不同青光眼型態的診斷率. 內皮細胞素-1 已被發現在青光眼致病機轉有重要角色, 在第二個研究, 探討不同青光眼型態病患血漿中內皮細胞素-1濃度是否跟視野與視神經纖維層厚度變化有關. 睡眠呼吸中止症候群特色是上呼吸道局部或全部阻塞, 產生睡眠障礙, 自律神經失調, 夜間睡眠時缺氧.青光眼被發現跟睡眠呼吸中止症候群有強烈相關. 在第三個研究,探討不同治療方式是否有不同青光眼風險.
研究方法 第一個研究中,我們由21位高眼壓症病患,27位疑似青光眼病患,35位原發性隅角開放型病患,26位原發性隅角閉鎖型病患,及52位正常人中其中一隻眼睛選出來分析.我們定義初期青光眼為所有青光病眼中視野缺損在-9 dB以上.所有個案都在同一天接受兩台光電同調斷層掃描儀檢查.我們用最佳接收者操作特徵曲線下面積(AROC)概念去鑑別正常眼與高眼壓眼, 疑似青光眼眼,原發性隅角開放型眼,原發性隅角閉鎖型眼;及分析每一個參數在內建正常人資料庫的敏感性跟特異性.第二個研究,由31位原發性隅角開放型病患,18 位正常眼壓性青光眼,16位原發性隅角閉鎖型病患,及37位正常人血漿中測得內皮細胞素-1. 所有個案都做視野及光電同調斷層掃描儀量測視神經纖維層厚度.我們分析每一組的每一個案隨機的一隻眼睛的視野的平均缺損值與視神經纖維層厚度的改變與內皮細胞素-1的相關性.第三個研究,我們應用健保資料庫2000年版做回朔性群體研究.2528睡眠呼吸中止症候群病患及隨機選樣10112沒有睡眠呼吸中止症候群個案作對照組.探討睡眠呼吸中止症候群病患是否因不同處理方式有不同青光眼風險(沒有治療,有手術,用連續正壓口罩治療,及多種方式治療).多變項回歸法用來估算校正性別,年紀,高血壓??糖尿病,高血脂及冠狀動脈疾病的危險值.
研究結果 第一個研究,正常眼比高眼壓眼,最佳接收者操作特徵曲線下面積(AROC)是平均厚度(Stratus,0.693; Cirrus,0.697).正常眼比疑似青光眼,最佳ARO值是平均厚度(Stratus,0.807;Cirrus,0.776).正常眼比原發性隅角開放型青光眼,最佳AROC值是平均厚度(Stratus, 0.943; Cirrus,0.930).正常眼比原發性隅角閉鎖型青光眼是在五點鐘厚度(Stratus,0.830; Cirrus,0.817).正常眼比初期青光眼,最佳AROC 值在Stratus (0.868)是平均厚度, Cirrus (0.876)是五點鐘厚度.以內建資料庫來看,五組在這兩台光電同調斷層掃描儀的敏感度差不多.第二個研究,內皮細胞素-1 數值在原發性隅角開放型青光眼這組(平均視野缺損為 -14.09±8.76 dB)是3.27±1.25 pg/mL,在正常眼壓性青光眼這組(平均視野缺損為-8.87±6.15 dB)為 3.12±1.46 pg/mL ,在原發性隅角閉鎖型眼這組(平均視野缺損,-14.55± 10.2 dB)為 2.58±.22 pg/mL,在正常人組為1.53±1.49 pg/mL .雖然平均內皮細胞素-1 數值在這三組青光眼統計上高出正常人組,然在這三組青光眼當中沒有顯著差異.此外,內皮細胞素-1 與眼睛結構或功能在不同青光眼類型也沒明顯相關.第三個研究,我們發現睡眠呼吸中止症候群跟正常人比較,罹患青光眼的風險高出1.88倍(95% CI: 1.46–2.42).沒有治療的病人,其青光眼風險高出2.15 倍(95% CI: 1.60–2.88).有治療睡眠呼吸中止症候群病患跟正常人比,除了選擇用連續正壓口罩治療那組(adjusted HR = 1.65, 95% CI = 1.09–2.49),青光眼的風險跟正常人比沒有顯著差別.
研究結論Cirrus and Stratus 這兩台光電同調斷層掃描儀在台灣地區中國人初期青光眼, 高眼壓眼,疑似青光眼,原發性隅角開放型,原發性隅角閉鎖型青光眼診斷率是一致的.然,這兩台機器的內建正常人資料庫在我們人種的應用性卻是一個值得再研究的議題.血漿內皮細胞素-1數值與青光眼嚴重度沒有相關. 內皮細胞素-1 在青光眼致病角色仍待進一步探討.睡眠呼吸中止症候群病患得青光眼風險比較高.接受手術可以減低睡眠呼吸中止症候群病患得青光眼的風險.



Background: Imaging diagnostic and pathogenetic mechanism study on glaucoma optic neuropathy are both important study issues. Previous studies have reported good agreement between the Stratus and Cirrus optical coherence tomography (OCT) in retinal nerve fiber layer (RNFL) measurements; however, there are still few studies addressing the comparison of the 2 OCT units for different glaucoma types. In first study, we aim to compare the glaucoma diagnostic power of Stratus and Cirrus OCTs in our Taiwan Chinese population with different glaucoma types. Endothelin-1 (ET-1) has been suggested to play an important role in the pathogenesis of glaucoma. In secondary study, we studied whether increased levels of plasma ET-1 are associated with changes in the visual field and changes in OCT measured RNFL thickness in patients with different types of glaucoma. Obstructive sleep apnea (OSA) is characterized by total or partial obstruction of the upper airway, which leads to impaired sleep, autonomic dysfunction, and transient nighttime hypoxemia. Glaucoma has been shown to have strong relationship with OSA. In third study, we investigate if different treatment strategy of OSA was associated different glaucoma risk.
Methods: In study 1, one eye each was chosen from 21 ocular hypertension (OH) patients, 27 glaucoma-suspect (GS) patients, 35 primary open-angle glaucoma (POAG) patients, 26 primary angle closure glaucoma (PACG) patients, and 52 normal subjects. Early glaucoma (EG) was identified among glaucomatous eyes on the basis of the visual field severity (better than -9 dB). All participants were imaged using 2 OCT units at the same visit. The area under the receiver operator characteristic (AROC) curve was used to differentiate normal eyes from OH, GS, POAG, PACG, and EG eyes, and the sensitivity and specificity of each parameter from internal normative classifications were analyzed. In study 2, plasma concentration of ET-1 was determined in 31 patients with POAG, 18 patients with normal tension glaucoma, 16 patients with PACG and in 37 normal controls. In all participants, visual field testing was performed and OCT was used to measure RNFL thickness. The correlation between mean ET-1 level and changes in the visual field (mean deviation, dB) and changes in OCT-measured RNFL thickness in 1 randomly selected eye from each patient in each group was then evaluated. In study 3, population-based retrospective cohort study was conducted using data sourced from the Longitudinal Health Insurance Database 2000.We included 2528 OSA patients and randomly selected and matched 10112 subjects without OSA as the control cohort. The risk of glaucoma in OSA patients was investigated based on the managements of OSA (without treatment, with surgery, with continuous positive airway pressure (CPAP) treatment, and with multiple modalities). The multivariable Cox regression was used to estimate hazard ratio (HR) after adjusting for sex, age, hypertension, diabetes, hyperlipidemia, and coronary artery disease.
Results: In study one, for normal versus OH eyes, the best AROC value was the average thickness (Stratus, 0.693; Cirrus, 0.697). For normal versus GS eyes, the best AROC value was the average thickness (Stratus, 0.807; Cirrus, 0.776). For normal versus POAG eyes, the best AROC value was the average thickness (Stratus, 0.943; Cirrus, 0.930). For normal versus PACG eyes, the best AROC value was the 5-o’clock hour (Stratus, 0.830; Cirrus, 0.817). For normal versus EG eyes, the best AROC value was the average thickness with Stratus (0.868) and the 5-o’clock hour with Cirrus (0.876). All sensitivities in the 5 groups were fair on the basis of the internal normal classification database of both OCTs. In study 2, the ET-1 level was 3.27±1.25 pg/mL in the POAG group (-14.09±8.76 dB), 3.12±1.46 pg/mL in the normal tension glaucoma group (-8.87±6.15 dB), 2.58±.22 pg/mL in the PACG group (-14.55± 10.2 dB), and 1.53±1.49 pg/mL in the control group. Although mean ET-1 levels were significantly higher in all 3 of the glaucoma groups than in the control group, there was no significant difference in ET-1 level among the 3 glaucoma groups. In addition, no significant correlation was found between levels of plasma ET-1 and structural or functional changes in patients with different types of glaucoma. In study 3, the adjusted HR of glaucoma for OSA patients was 1.88 (95% CI: 1.46–2.42), compared with controls. For patients without treatment, the adjusted HR was 2.15 (95% CI: 1.60–2.88). For patients with treatments, the adjusted HRs of glaucoma were not significantly different from controls, except for those with CPAP (adjusted HR = 1.65, 95% CI = 1.09–2.49).
Conclusions: Cirrus and Stratus OCTs showed equal diagnostic power in EG, OH, GS, POAG, and PACG eyes in our Taiwan Chinese population. However, the utility of the current internal databases of both OCT units for the Chinese population is an interesting issue that needs to be addressed in the future. There was no correlation between plasma levels of ET- 1 and severity of glaucoma. The role ET-1 plays in the pathogenesis of glaucoma remains to be determined. OSA is associated with an increased risk of glaucoma. However, surgery reduces slightly the glaucoma hazard for OSA patients.



目錄
中文摘要………………………………………………………………………II, III
英文摘要……………………………………………………………………IV,V
誌謝辭………………………………………………………………………………VI
論文正文:
1. Comparison of glaucoma diagnosis using Stratus OCT and Cirrus Optical Coherence Tomography in different glaucoma types in a Chinese Population
1.1 前言
1.1.1研究背景…………………………………………………………………1.
1.1.2 研究目的…………………………………………………………… …1
1.2 研究方法
1.2.1研究材料& 方法…………………………………………………………1-3
1.2.2 統計方法……………………………………………………………… 4
1.3 研究結果……………………………………………………………………4-14
1.4討論 …………………………………………………………………………15-17
1.5結論………………………………………………………………………………18
2. Association between plasma endothelin-1 and severity of different types of glaucoma
2.1 前言
2.1.1研究背景……………………………………………………………………19
2.1.2 研究目的…………………………………………………………………19
2.2 研究方法
2.2.1研究材料& 方法…………………………………………………………20,21
2.2.2 統計方法…………………………………………………………………22
2.3 研究結果……………………………………………………………………22-28
2.4討論………………………………………………………………………… 29-31
2.5結論…………………………………………………………………………31
3. Obstructive sleep apnea patients having surgery are less associated with glaucoma
3.1前言
3.1.1研究背景………………………………………………………………32
3.1.2 研究目的………………………………………………………………32
3.2 研究方法
3.2.1研究材料& 方法………………………………………………………32,33
3.2.2統計方法………………………………………………………………33,34
3.3 研究結果……………………………………………………………………34-40
3.4 討論………………………………………………………………………41-43
3.5 結論…………………………………………………………………………43
4. 參考文獻…………………………………………………………………44-49


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