【作者】 朱颖；

【导师】 徐格致；

【作者基本信息】 复旦大学 ， 临床医学， 2014， 博士

【摘要】 糖尿病视网膜病变(diabetic retinopathy, DR)是糖尿病最常见的微血管并发症之一,常见于糖尿病病程10年以上的患者,给患者的视力造成极大的威胁。作为目前的主要治疗方法,激光治疗广泛应用于临床并获得了肯定的疗效。全视网膜光凝术(panretinal photocoagulation, PRP)通过破坏周边部的视网膜而降低视网膜的氧耗,以保证后极部能得到充分的氧供。传统的ETDRS (Early Treatment Diabetic Retinopathy Study)激光因激光能量较高、作用时间长而对视网膜及脉络膜造成一定损伤,术后患者发生黄斑水肿的概率增加。先进的Pascal激光系统采用创新性的点阵式激光模式,且激光作用时间缩短为20毫秒,大大提高了治疗效率,减轻了激光损伤。随着光学相干断层扫描(Optical Coherence Tomography, OCT)技术的飞速发展,其对于视网膜10层结构的分辨已相当清楚。近两年出现的EDI (enhanced-depth imaging)技术使脉络膜在OCT上清晰地显示成为了可能。脉络膜作为外层视网膜的主要血供来源,在DR这一类视网膜血管性疾病中扮演了怎样的角色呢?已有研究发现DR患者的脉络膜较正常对照组变薄,那么激光治疗前后脉络膜的厚度是否会发生变化呢?这一变化是否与视力预后相关呢?这是本课题的核心研究所在。作为视网膜功能学和形态学的客观评价工具,多焦视网膜电图(multifocal electroretinography, mfERG)和OCT已被用于多种疾病的视力预后研究,包括糖尿病视网膜病变、糖尿病黄斑水肿等。但尚未见到关于PRP的相关报道,那么mfERG与OCT是否与DR行全视网膜光凝术的预后密切相关呢?这是本课题关注的另一重点。第一部分糖尿病视网膜病变全视网膜光凝术前后脉络膜厚度变化目的研究糖尿病视网膜病变全视网膜光凝后黄斑区和光斑区脉络膜厚度变化。方法本部分研究纳入了34例需行全视网膜光凝的糖尿病视网膜病变患者(包括严重非增殖期糖尿病视网膜病变和早期增殖期糖尿病视网膜病变患者)。分别在基线、激光后1个月和激光后3个月,利用光学相干断层扫描仪的EDI模式扫描了黄斑区和光斑区的脉络膜厚度,并测量了患者的最佳矫正视力(best corrected visual acuity, BCVA)。结果黄斑区脉络膜厚度基线为307.2±70.7μm,激光后1个月为318.0±76.4μm(P<0.001),3个月为317.4±75.3μm(P<0.001),脉络膜厚度的增加具有统计学差异。而光斑区的脉络膜厚度则从基线的227.5±45.0μm降至术后一个月的206.9±41.1μm(P<0.001)和术后三个月的206.0±41.4μm(P<0.001)。无论是在PRP术后一个月还是三个月,脉络膜厚度的变化均与视力变化无关。在多元线性回归分析中,仅PRP术前的视力和中心凹视网膜厚度与视力变化具有统计学意义的相关性。结论在严重NPDR和早期PDR患者中,黄斑区平均脉络膜在PRP术后增加,而光斑区平均脉络膜厚度则减少。这一结果可能提示了PRP术后脉络膜血流的重新分布,对于保证视网膜的代谢至关重要。第二部分糖尿病视网膜病变全视网膜光凝术预后相关因素分析目的研究mfERG和OCT在判断糖尿病视网膜病变行全视网膜光凝术的预后中的价值。方法本部分研究纳入了42例需行全视网膜光凝的糖尿病视网膜病变患者(包括严重非增殖期糖尿病视网膜病变和早期增殖期糖尿病视网膜病变患者)。在基线时进行mfERG、OCT和BCVA的测量,并在PRP术后6个月再次测量BCVA。PRP术前的数据与术后6个月视力的关系采用了Pearson相关分析和多元线性回归进行分析。结果入选的42例患眼中,31例(73.8%)视力较术前提高或维持原状,11例(26.2%)激光术后视力下降。在全部9个区域中,最终BCVA与mfERG振幅和潜伏期均密切相关,且振幅与视力的相关性更显著。中心凹层面光感受器细胞内外节连接(photoreceptor inner and outer segment junction, IS/OS)和外界膜(external limiting membrane, ELM)连续性,以及大部分区域的视网膜厚度也与最终视力密切相关。在综合以上多种因素的多元线性回归模型中,中心区域的mfERG振幅、中心凹IS/OS连续性、患者PRP术前视力及患者年龄与最终BCVA的相关性具有统计学差异。在大部分区域,视网膜厚度也与mfERG振幅和潜伏期相关,颞侧和下方区域更明显,特别是外环。结论mfERG的振幅偏低或中心凹IS/OS紊乱与PRP术后视力预后不良关系密切。综上所述,本研究发现PRP术后黄斑区脉络膜厚度增加而光斑区脉络膜厚度减少,可能提示PRP引起了脉络膜血流的重分布,尽管与视力变化无直接关系,但是视网膜代谢的保障。mfERG和OCT检查所提供的视网膜结构和功能两方面信息均对PRP术后糖尿病视网膜病变患眼的视力预后有一定影响。其中,多焦视网膜电图的振幅和中心凹IS/OS连续性是最有价值的预测指标。更多还原

【Abstract】 As one of the most common micro-vascular complications, diabetic retinopathy usually affects people who have diabetes mellitus for over ten years and threatens patients’visual acuity tremendously. As the main stream therapy for DR, panretinal photocoagulation (PRP) is widely practiced by ophthalmologists and gains world-wide recognition for its effect. PRP guarantees enough oxygen supply for macular area by destroying peripheral retina. Traditional ETDRS photocoagulation could cause damage to retina and choroid due to its high energy and long action time, so patients may have a higher incidence of diabetic macular edema after PRP. The advanced Pascal laser system adopts an array spots model and diminishes the action time to 20ms. It not only improve the efficiency of photocoagulation, but also reduced the damage caused by laser.With the rapid development of optical coherence tomography (OCT), the delicate multiple layers of retina are clearly visible. The recently invented enhaced-depth imaging(EDI) mode made the in vivo observation of choroid possible. As the main blood supply for the outer part of retina, will it play a role in retinal vascular disease (e.g. DR)? It has been reported that patients with DR had a thinner choroid than the controls. Will there be a change in choroidal thickness before and after PRP? If so, will the change be related to visual acuity prognosis? This is the core of the present study.As objective tools to evaluate the structure and function of retina, multifocal electroretinography (mfERG) and OCT are widely used in prognosis analysis for a variety of diseases (including DR and diabetic macular edema). But no reports about PRP was found. Will mfERG and OCT be useful in predicting visual prognosis of patients receiving PRP? This is another focus of the present study.Part Ⅰ Choroidal thickness change after panretinal photocoagulation in diabetic patients Purpose:To investigate the changes in choroidal thickness in the macular and photocoagulated areas of patients with diabetic retinopathy after panretinal photocoagulation (PRP) using enhanced-depth imaging optical coherence tomography (EDI-OCT).Methods:Patients with severe non-proliferative diabetic retinopathy (NPDR) or early proliferative diabetic retinopathy (PDR) who needed PRP were included in this study. Choroidal thickness (CT) in the macula and the photocoagulated area was measured with EDI-OCT at baseline, one month, and three months after PRP.Results:The mean subfoveal CT increased significantly at one (318.0±76.4μm, P<0.001) and three months (317.4±75.3μm, P<0.001) post-PRP when compared to baseline (307.2±70.7μm). The mean CT in the photocoagulated area decreased significantly from 227.5±45.0μm to 206.9±41.1μm (P<0.001) at one and 206.0±41.4μm (P<0.001) at three months post-PRP. Unlike the mean change in CT or patients’ systemic conditions, only BCVA and foveal thickness before PRP were statistically significantly correlated with the mean change in BCVA after PRP.Conclusions:In patients with severe NPDR or early PDR, the mean choroidal thickness increased significantly in the macular area and decreased significantly in the photocoagulated area after PRP. The results might reflect a redistribution of choroidal blood flow following PRP, which may be critical for retinal metabolism.Part Ⅱ Prognisis of visual acuity after panretinal photocoagulation in diabetic patientsPurpose:To investigate the prognostic value of multi-focal electroretinography (mfERG) and optical coherence tomography (OCT) in diabetic eyes receiving pan-retinal photocoagulation (PRP).Methods:Patients with severe non-proliferative diabetic retinopathy (NPDR) or early proliferative diabetic retinopathy (PDR) who needed PRP were included in this study. MfERG and OCT data were recorded before PRP, while the final best corrected visual acuity (BCVA) was recorded at 6 months following PRP. The 1-3-6 mm ETDRS macular grid was superimposed over the mfERG hexagonal pattern. For each area of the 9 sectors, the responses from the corresponding hexagons were summed for analysis. The correlation between pre-PRP data and post-PRP BCVA was analyzed using Pearson’s correlation analysis and multivariate linear regression analysis.Results:Among the 42 eyes included,31 eyes (73.8%) had improvement or remained stable in visual acuity while 11 eyes (26.2%) had deterioration in BCVA. The final BCVA was significantly correlated with the amplitude and latency of mfERG in all nine sectors, and the amplitude had a stronger correlation than latency. The foveal photoreceptor inner and outer segment junction (IS/OS) and the external limiting membrane (ELM) status, as well as the retinal thickness in most sectors, were also correlated with the final BCVA. In a multivariate linear regression model, age, pre-PRP BCVA, amplitude of mfERG in the central sector and foveal IS/OS status were significantly correlated with the final BCVA. The retinal thickness was found to be correlated with the amplitude or latency of mfERG in some sectors, and the correlation was tighter in temporal and inferior sectors, especially in the outer ring.Conclusions:A lower amplitude of mfERG and disrupted foveal IS/OS status were significantly correlated with a worse visual prognosis in diabetic eyes after PRP.In summary, the present study found that choroidal thickness in the macular area increased after PRP while choroidal thickness in the photocoagulated area decreased. Though not directed related to change in visual acuity, the shift of blood distribution induced by PRP might be a perquisite for healthy retinal metabolism. The information about retinal structure and function provided by mfERG and OCT played a role in visual prognosis after PRP. Among those various indicators, the amplitude of mfERG and foveal IS/OS status were the most valuable.更多还原