本文選題：角膜上皮 + 角膜緣　； 參考：《復(fù)旦大學(xué)》2014年博士論文

【摘要】：作為角膜的最外層組織,角膜上皮不僅是眼表重要的生物學(xué)屏障,它在維持淚膜穩(wěn)定性、角膜透明性、正常視功能等方面都發(fā)揮著重要的作用。角膜上皮的更新和修復(fù)有賴于角膜緣上皮基底部干細(xì)胞的不斷增殖、分化和遷移。隨著人們對(duì)角膜和眼表疾病認(rèn)識(shí)的加深,角膜和角膜緣上皮厚度的應(yīng)臨床用價(jià)值得到了越來(lái)越多的關(guān)注。精確測(cè)量角膜和角膜緣上皮厚度不僅可以為早期診斷圓錐角膜、指導(dǎo)屈光手術(shù)的開(kāi)展、評(píng)估手術(shù)療效等提供重要的參考依據(jù),也對(duì)干眼癥、角膜緣干細(xì)胞缺乏、角膜手術(shù)后上皮愈合不良等有一定的提示作用。近年來(lái),應(yīng)用眼前節(jié)光學(xué)相干斷層成像系統(tǒng)(optical coherence tomography, OCT)定量分析角膜和角膜緣上皮成為眼科研究中的熱點(diǎn)。既往對(duì)正常人角膜上皮厚度的研究多局限于某個(gè)年齡段或角膜的某個(gè)區(qū)域,對(duì)于其在整個(gè)角膜的分布特點(diǎn)及其年齡變化規(guī)律等特征描繪甚少。本研究應(yīng)用傅里葉域OCT (Fourier-domain OCT, FD-OCT)觀察不同年齡段正常人群的角膜和角膜緣的形態(tài)結(jié)構(gòu),在不同方位對(duì)其上皮厚度進(jìn)行測(cè)量,分析角膜和角膜緣上皮厚度在不同方位、不同各年齡組之間的差異及其與年齡的相關(guān)性,總結(jié)其空間分布特點(diǎn)和隨年齡變化的規(guī)律。一方面為正常人角膜及角膜緣上皮厚度數(shù)據(jù)庫(kù)補(bǔ)充中國(guó)人群的資料,另一方面有助于臨床醫(yī)生在充分了解角膜和角膜緣上皮特征的基礎(chǔ)上開(kāi)展診療工作。第一部分FD-OCT對(duì)不同年齡正常人群角膜上皮厚度的測(cè)量研究目的：應(yīng)用FD-OCT觀察不同年齡正常人群角膜并測(cè)量其上皮厚度值,分析角膜上皮厚度的空間分布特點(diǎn)及其隨年齡變化的規(guī)律。方法：橫斷面研究。招募健康受試者180例(80男100女),根據(jù)年齡分為4組：A組(≤20歲)45例,B組(21-40歲)45例,C組(41-60歲)54例,D組(60歲)36例。隨機(jī)選取受試者單眼(正常眼)進(jìn)行FD-OCT檢查。利用RTVue-100OCT儀Pachymetry模式掃描受試者中央6mm角膜,系統(tǒng)內(nèi)置軟件可自動(dòng)探測(cè)角膜上皮的前后邊界并計(jì)算出前后界之間的上皮厚度,然后繪制出掃描區(qū)域內(nèi)的角膜上皮厚度圖。在每張圖上,中央6mm角膜被劃分為17個(gè)區(qū)域：中央2mm區(qū),內(nèi)環(huán)(2-5mm)8個(gè)區(qū),外環(huán)(5-6mm)8個(gè)區(qū)；各區(qū)域均有其角膜上皮厚度平均值的直觀呈現(xiàn)。對(duì)各年齡組各區(qū)域的角膜上皮厚度進(jìn)行統(tǒng)計(jì)分析。結(jié)果：(1)總體人群中央6mm角膜上皮厚度平均值為(52.4±2.7)μm,各區(qū)域角膜上皮厚度不同：中央2mm區(qū)為(53.2±2.9)μm,上半?yún)^(qū)為(51.9±2.9)μn,下半?yún)^(qū)為(53.1±3.0)μm,下半?yún)^(qū)角膜上皮比上半?yún)^(qū)厚(P0.05)；外環(huán)上1/8區(qū)(50.2±3.3)μm為最薄,內(nèi)環(huán)下1/8區(qū)(53.4±3.1)μm為最厚,最薄點(diǎn)與最厚點(diǎn)的厚度差值為(-7.2±3.6)μm。(2)中央6mm角膜上皮平均厚度,男性為(53.2±2.9)μm,女性為(51.7±2.4)μm；在各區(qū)域,男性角膜上皮均比女性厚。(3) A, B, C, D各組中央6mm角膜上皮厚度平均值分別為(53.21±2.39) μm、 (52.91±2.72) μm、(51.88±2.42) μm、(51.33±3.15) μm,差異有統(tǒng)計(jì)學(xué)意義(P=0.004)。各區(qū)域角膜上皮厚度的統(tǒng)計(jì)學(xué)分析顯示：在中央2mm區(qū)域,A、B、C、D組角膜上皮厚度分別為(53.4±2.8)μm、(53.4±2.7) μm、(53.2±3.0) μm、(52.9±3.3)μm,各年齡組間無(wú)顯著性差異(P=0.848)；在旁中央2-6mmm區(qū)域,除內(nèi)環(huán)顳下方1/8區(qū)外,其余區(qū)域角膜上皮厚度與年齡均呈負(fù)相關(guān)(P0.05)。隨年齡增大,中央6mm角膜上皮厚度以0.34μm/10y的平均速率遞減；外環(huán)區(qū)的遞減速率較內(nèi)環(huán)區(qū)大,分別為0.51μm/10y和0.30μm/10y。此外,上皮厚度最小最大值之差(Min-Max)和上皮厚度變異度(Std-Dev)均與年齡呈負(fù)相關(guān)(ρ=-0.326, P0.001; ρ=+0.348, P0.001)。結(jié)論：中央6mm角膜上皮并非均一厚度層,其厚度的空間分布差異表現(xiàn)為：下厚上薄,中央略高于鼻顳側(cè)。年齡越大,角膜上皮厚度在各區(qū)域的分布越不均勻。年齡對(duì)中央2mm角膜上皮厚度無(wú)明顯影響。旁中央角膜上皮隨年齡增長(zhǎng)而變��；越靠近中央,變薄速率越小。第二部分FD-OCT對(duì)不同年齡正常人群角膜緣上皮厚度的測(cè)量研究目的：應(yīng)用FD-OCT觀察不同年齡正常人群角膜緣并測(cè)量其上皮厚度值,分析角膜緣上皮厚度的空間分布特點(diǎn)及其隨年齡變化的規(guī)律。方法：橫斷面研究。招募健康受試者180例(80男100女),根據(jù)年齡分為4組：A組(≤20歲)45例,B組(21-40歲)45例,C組(41-60歲)54例,D組(60歲)36例。隨機(jī)選取受試者單眼(正常眼)進(jìn)行FD-OCT檢查。利用RTVue-100OCT儀Cross-Line模式掃描受試者鼻側(cè)、顳側(cè)、上方、下方的角膜緣,并記錄各方位角膜緣的橫截面圖。在OCT圖上,采用手動(dòng)法對(duì)角膜緣各層結(jié)構(gòu)進(jìn)行劃分并測(cè)量角膜緣上皮厚度。然后對(duì)各方位、各年齡組的角膜緣上皮厚度進(jìn)行統(tǒng)計(jì)分析。結(jié)果：(1) FD-OCT測(cè)量正常人鼻側(cè)、顳側(cè)、上方、下方的角膜緣上皮厚度值分別為(53.4±6.8) μm、(54.2±7.4) μm、(67.4±10.6)μm、(67.7±10.7)μm。統(tǒng)計(jì)學(xué)分析表明,四個(gè)方位角膜緣上皮厚度存在顯著性差異(P=0.000)。Tamhane法進(jìn)行各方位的兩兩比較分析表明,鼻、顳側(cè)角膜緣上皮明顯薄于上、下方(P=0.000),鼻側(cè)和顳側(cè)相近(P=0.947),下方略比上方厚、但二者無(wú)統(tǒng)計(jì)學(xué)差異(P=1.000)。各年齡組角膜緣上皮厚度的空間分布特點(diǎn)與總體人群相同。(2)對(duì)各年齡組同一方位的角膜緣上皮厚度進(jìn)行比較：在鼻、顳側(cè),A組的測(cè)量值比其余三組大(P0.05)；在上、下方,B組的測(cè)量值最大,但各組間無(wú)顯著性差異。各方位角膜緣上皮厚度與年齡的相關(guān)性分析結(jié)果為：鼻側(cè)(p=-0.332,P=0.000)、顳側(cè)(p=-0.372,P=0.000)、上方(p=-0.048,P=0.594)、下方(p=-0.032,P=0.725)。隨著年齡增大,鼻側(cè)、顳側(cè)、上方、下方角膜緣上皮厚度的遞減速率分別為1.12pm/10y、1.31μm/10y、0.37μm/10y、0.21μm/10y。結(jié)論：正常人角膜緣上皮厚度存在空間分布差異,鼻、顳側(cè)角膜緣上皮較薄,上、下方較厚。出生后隨著年齡的增長(zhǎng),鼻、顳側(cè)角膜緣上皮逐漸變��；而上、下方角膜緣上皮呈現(xiàn)先厚再薄的變化規(guī)律,其厚度值在成年后達(dá)到最大。瞼裂處水平方位的角膜緣上皮厚度更易受年齡影響,其變化速率大于垂直方位的角膜緣上皮。
[Abstract]:The corneal epithelium is not only an important biological barrier in the ocular surface, but also plays an important role in maintaining tear film stability, corneal transparency and normal visual function. Corneal epithelium regeneration and repair depend on the proliferation, differentiation and migration of the stem cells in the basal limbal epithelium. More and more attention has been paid to the clinical value of corneal and ocular surface diseases. The accurate measurement of corneal and limbal epithelium thickness can not only provide important reference for early diagnosis of keratoconus, guide the development of refractive surgery, and evaluate the effect of the operation, but also for dry eye and angle. In recent years, the quantitative analysis of corneal and limbal epithelium with optical coherence tomography (OCT) has become a hot spot in the study of Ophthalmology. A certain area of the cornea or a certain area of the cornea is rarely described in the characteristics of the distribution of the whole cornea and the law of age change. This study used Fourier domain OCT (Fourier-domain OCT, FD-OCT) to observe the morphological structure of the cornea and limbus of normal people of different ages, and measure the thickness of the epithelium at different directions. To analyze the difference of corneal and limbal epithelium thickness between different azimuth, different age groups and their correlation with age, sum up their spatial distribution characteristics and the regularity with age. On the one hand, the data of the normal people's cornea and limbal epithelial thickness database are supplemented by the Chinese population, on the other hand it is helpful to the clinicians. On the basis of understanding the characteristics of corneal and limbal epithelium, diagnosis and treatment work. Part 1 FD-OCT measurement of corneal epithelium thickness in normal people of different ages: the use of FD-OCT to observe the corneal thickness in normal people of different ages and to measure the thickness of the epithelial thickness of the cornea, and to analyze the spatial distribution of the corneal thickness and its age. Method: cross sectional study. 180 healthy subjects (80 men and 100 women) were recruited and divided into 4 groups according to age: group A (< 20 years old) 45 cases, group B (21-40 years) 45, group C (41-60 year old) 54, and group D (60 years old) 36. Random selected subjects (normal eyes) performed FD-OCT examination. RTVue-100OCT instrument Pachymetry mode was used to scan the central 6mm cornea of subjects. In each picture, the central 6mm cornea is divided into 17 regions: the central 2mm region, the inner ring (2-5mm) 8 regions, the outer ring (5-6mm) 8 regions, and the cornea in each region. Visual presentation of the average thickness of epithelial thickness. Results: (1) the average thickness of the central 6mm corneal epithelium was (52.4 + 2.7) mu m in the population of the population, and the thickness of corneal epithelium in each region was different: the central 2mm area was (53.2 + 2.9) mu m, the upper half was (51.9 + 2.9) n, and the lower half was (53.1 + 3) m, The lower half area of the corneal epithelium was thicker than the upper half area (P0.05); the 1/8 region on the outer ring (50.2 + 3.3) mu m was the thinnest, the 1/8 region under the inner ring (53.4 + 3.1) mu m was the thickest, the thickness difference between the thinnest point and the thickest point was (-7.2 + 3.6) mu m. (2) Central 6mm corneal epithelium average thickness, male was (53.2 + 2.9) u m, and the female was (51.7 + 2.4) mu m; in all regions, the male corneal epithelium was all (3) A, B, C, the mean values of corneal epithelial thickness in the central 6mm were (53.21 + 2.39) mu m, (52.91 + 2.72) mu m, (51.88 + 2.42) micron m and (51.33 + 3.15) m (P=0.004). Statistical analysis of corneal epithelium thickness in all regions showed that the thickness of corneal epithelium in central 2mm region was 53. 4 + 2.8) mu m, (53.4 + 2.7) mu m, (53.2 + 3) mu m and (52.9 + 3.3) mu m, there was no significant difference between all age groups (P=0.848). In the adjacent central 2-6mmm region, the corneal epithelium thickness was negatively correlated with age except the 1/8 region below the inner ring temporal region (P0.05), and the central 6mm corneal epithelial thickness decreased with the average rate of 0.34 u m/10y with age. The rate of deceleration in the outer ring area was larger than that of the inner ring area, 0.51 m/10y and 0.30 m/10y. respectively. The difference of the minimum thickness of the epithelial thickness (Min-Max) and the epithelial thickness variation (Std-Dev) were all negatively correlated with age (P =-0.326, P0.001; P =+0.348, P0.001). Conclusion: the central 6mm corneal epithelium is not a homogeneous thickness, and the spatial distribution of its thickness is poor. The difference in the thickness of the lower thickness was slightly higher than the nasal temporal side. The older the age was, the more uneven the thickness of the corneal epithelium was in each region. Age had no obvious influence on the thickness of the central 2mm corneal epithelium. The adjacent central corneal epithelium thinned with age; the closer to the central area, the thinner the thinner the rate was. The second part of the FD-OCT was to the normal population of different ages. Objective: To observe the thickness of corneal limbal epithelium. FD-OCT was used to observe the corneal edge of normal people of different ages and to measure the thickness of the epithelial thickness. The spatial distribution of the thickness of the limbal epithelium and its regularity with age. Methods: a cross-sectional study. 180 healthy subjects (80 men and 100 women) were recruited and divided into 4 groups according to age: group A ( 20 years old) 45 cases, B group (21-40 year old) 45 cases, C group (41-60 year old) 54 cases, D group (60 year old) 36 cases. Randomly selected the subjects' single eye (normal eye) for FD-OCT examination. Use RTVue-100OCT Cross-Line mode to scan the nasal side, temporal, upper and lower cornea margin of the subjects, and record the cross section of the corneal limbus in each direction. On the OCT map, the manual diagonal diagonal method is used. The thickness of corneal limbus epithelium in all directions and age groups was statistically analyzed. Results: (1) FD-OCT measured the thickness of normal human nasal, temporal, upper, and lower limbal epithelial thickness (53.4 + 6.8) mu m, (54.2 + 7.4) mu m, (67.4 + 10.6) mu m, (67.7 + 10.7) mu m. The analysis showed that there was a significant difference between the four azimuth corneal limbal epithelium (P=0.000).Tamhane method. The 22 comparison of the azimuth showed that the nasal epithelium and the temporal limbal epithelium were obviously thinner than the upper, lower (P=0.000), the nasal side and the temporal side (P=0.947), and the lower part of the cornea was slightly thicker than the upper part, but there was no statistical difference between the two groups (P=1.000). The spatial distribution of the thickness of the epithelia of the membrane was the same as that in the general population. (2) the thickness of the limbal epithelium in the same azimuth of all age groups was compared: in the nasal and temporal side, the measured values of the A group were larger than the other three groups (P0.05); in the upper, lower, group B, the measured values were the largest, but there was no significant difference between the groups. The thickness of the corneal limbal epithelium and the age in each azimuth. The results of correlation analysis were: p=-0.332 (P=0.000), temporal (p=-0.372, P=0.000), above (p=-0.048, P=0.594), lower (p=-0.032, P=0.725). With age, the decreasing rate of the thickness of the limbal epithelium at the lateral, temporal, upper and lower limbal epithelium was respectively 1.12pm/10y, 1.31 mu m/10y, 0.37 mu m/10y, 0.21 micron m/10y. conclusion: normal corneal limbal epithelium. The thickness of the nasal and temporal limbal epithelium was thinner and thicker. As the age increased, the nasal epithelium and the temporal limbal epithelium gradually thinned, and the upper limbal epithelium showed a thicker and thinner change in the lower limbal epithelium. The thickness of the cornea was the largest in the adult. The thickness of the corneal limbal epithelium at the level of the eyelid fissure was more thick. It is susceptible to age and the rate of change is greater than that of the limbal epithelium.

【學(xué)位授予單位】：復(fù)旦大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R770.4

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