目的：探讨光学相干断层扫描血管成像(optical coherence tomography angiography，OCTA)在糖尿病性视网膜病变中的应用。方法：选取2021年中山大学附属第七医院眼科63例糖尿病患者为研究对象，分为无糖尿病性视网膜病变(T0，21眼)、轻度非增殖期(T1，21眼)、中重度非增殖期(T2，14眼)及增殖期(T3，7眼)。收集各组生化指标，包括空腹血糖、糖化血红蛋白、谷丙转氨酶、谷草转氨酶、碱性磷酸酶、血清尿素氮、肌酐、尿素氮肌酐比值，及OCTA数据，即中心视网膜厚度、Angiography3×3及Angiography6×6血管线性密度及血管灌注密度等。采用单因素方差分析比较各组间差异。结果：T2组、T3组与T0组相比，T3组与T1组相比，糖尿病病程延长；T3组与其他各组相比，尿素氮升高；T1组、T2组、T3组与T0组相比，T3组与T1组相比，6 mm ×6 mm外层血流线性密度减少；与T0组相比，T1组、T2组及T3组6 mm ×6 mm完整血流线性密度减少；与T0相比，T2组、T3组6 mm ×6 mm外层血流灌注密度减少；与T0组相比，T3组6 mm ×6 mm完整血流灌注密度减少；T2组、T3组与T0组相比，T3与T1相比，3 mm ×3 mm内层血流线性密度明显减少；T3组与T0组及T1组相比，3 mm ×3 mm完整血流线性密度减少。结论：随着糖尿病性视网膜病变的进展，患者的尿素氮及肌酐逐渐升高，OCTA的血流线性密度及血流灌注密度逐渐减少。与血流灌注密度相比，血流线性密度对于早期糖尿病性视网膜病变筛查可能更为敏感。而利用Angiography6×6模式可能可以更早地发现糖尿病性视网膜病变的视网膜血流变化。
Objective: To explore the applications of optical coherence tomography angiography (OCTA) in diabetic retinopathy. Methods: A total of 63 diabetic patients in the Department of Ophthalmology, Seventh Affiliated Hospital of Sun Yat-sen University in 2021 were divided into 4 groups: the patients without diabetic retinopathy (T0, n=21), mild non-proliferative diabetic retinopathy (T1, n=21), moderate-to-severe non-proliferative diabetic retinopathy (T2, n=14) and proliferative diabetic retinopathy (T3, n=7). Biochemical Indicators were collected in all patients, such as fasting plasma glucose (FPG), glycated hemoglobin A1c (HbA1c), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), the blood urea nitrogen (BUN), creatinine (CRE) and the ratio of blood urea nitrogen and creatinine (BUN/CRE). The Macular Cube 521×128, Angiography3×3, and Angiography6×6 models of OCTA were used to obtain central retinal thickness (CRT), vascular density (VD) and perfusion density (PD) of each group. The data of all subjects was applied to do one-way ANOVA. Results: Prolonged duration of diabetes in T2 and T3 compared to T0 and in T3 compared to T1. Elevated BUN in T3 compared to all other groups. When T1, T2 and T3 were compared to T0, and T3 was compared to T1, the VD of the 6 mm ×6 mm outer layer decreased. Reduced VD of intact 6 mm ×6 mm region in T1, T2 and T3 compared to T0. Declining PD of the 6 mm ×6 mm outer layer in T2 and T3 compared to T0. Diminished PD of whole 6 mm ×6 mm area at T3 compared to T0. The VD of 3 mm ×3 mm inner layer was significantly reduced in T3 compared to T0 and T1. The VD of 3 mm ×3 mm intact area gradually dwindled in T3 compared with T0 and T1 (P<0.05). Conclusion: With the progression of diabetic retinopathy, the levels of BUN and CRE gradually increased, and the OCTA-derived vascular density and perfusion density gradually decrease. Vascular density may be more sensitive for early diabetic retinopathy screening than perfusion density.The use of the Angiography6×6 model may result in an earlier detection of changes in retinal blood flow in diabetic retinopathy.
目的：探讨无糖尿病性视网膜病变(diabetic retinopathy，DR)的糖尿病人群中，糖尿病与近视对黄斑区节细胞-内丛状层(ganglion cell layer and inner plexiform layer，GCIPL)厚度纵向变化的影响。方法：纳入广州糖尿病眼病研究中1165名基线无视网膜病变的糖尿病和正常对照者，纵向随访2年。根据是否存在近视[等效球镜(spherical equivalent，SE)≤-3屈光度(diopter，D)]和糖尿病分为健康组(n=508)、糖尿病组(n=525)及糖尿病合并近视组(n=132)。扫频光学相干断层成像(swept source-optical coherence tomography，SS-OCT)技术测量并比较三组间GCIPL厚度的变化，以确定糖尿病和近视的影响，三组间差异使用协方差分析，采用线性混合模型分析评估GCIPL厚度与相关因素的关系。结果：对照组的SE为(1.07±1.06) D，糖尿病组为(1.02±1.00) D，糖尿病合并近视组为(-5.36±2.30) D，组间差异有统计学意义(P<0.001)。对照组基线GCIPL厚度为(71.1±0.3) μm，糖尿病组为(74.4±0.2)μm，糖尿病合并近视组为(71.7±0.5) μm。在2年随访过程中，对照组GCIPL厚度下降-0.10(95%CI：-2.03~0.05) μm/年，糖尿病组GCIPL厚度下降的速度为对照组的12倍[-1.21(95%CI：-24.04~0.05) μm/年，P<0.001]，糖尿病合并近视组GCIPL厚度下降的速度为对照组的22倍[-2.17(95%CI：-21.63~0.10)μm/年，P<0.001]。结论：近视是无DR的糖尿病患者中GCIPL加速变薄的危险因素，糖尿病和近视在GCIPL损伤中可能存在协同作用。
Objective: To investigate the association between myopia and ganglion cell layer and inner plexiform layer (GCIPL) in diabetic population without diabetic retinopathy (DR). Methods: In this Guangzhou Diabetic Eye study, a total of 1 165 patients aged 30–80 years were recruited followed up longitudinally for 2 years. According to the presence or absence of myopia [spherical equivalence (SE)≤-3 diopter (D)] and diabetics, the patients were divided into a healthy group (n=508), a diabetes mellitus group (n=525), and a diabetes mellitus + myopia group (n=132). GCIPL was measured via swept-source optical coherence tomography. Univariable and multivariable mixed models were used to show the association of GCIPL change and baseline parameters. Results: SE was (1.07±1.06) D in the healthy group, (1.02±1.00) D in the diabetes mellitus group and (-5.36±2.30) D in the diabetes mellitus + myopia group (P<0.001). The baseline GCIPL thickness were (71.1±0.3), (74.4±0.2), and (71.7±0.5) μm, respectively. The slope of GCIPL thickness was -0.10 (95% CI: -2.03 to 0.05) μm/year in the healthy group, which was 12 folds faster than those in the diabetes mellitus group [-1.21(95% CI: -24.04 to 0.05 μm/year, P<0.001] and 22 folds higher among those in diabetes mellitus + myopia group [-2.17 (95% CI: -21.63 to 0.10) μm/year, P=0.009]. Conclusion: Both myopia and diabetes status accelerate macular ganglion cell layer and inner plexiform layer thinning in diabetic patients without diabetic retinopathy.
本文根据上海鹰瞳医疗科技有限公司的创新产品《糖尿病视网膜病变眼底图像辅助诊断软件》在国家药品监督管理局(NMPA，原CFDA)历时两年半的上市前创新申报与注册申报经历，介绍了人工智能类医疗器械产品的产品研发、注册申报流程及相关重点难点，并且列明了在整个过程中需要遵循和参考的法律法规，为此类产品的上市前注册工作提供参考。
Based on the NMPA premarket application through two and a half years for the computer aided diagnosis software using fundus images of diabetic retinopathy, which is an innovative medical device of Shanghai EagleVision Medical Technology Co., Ltd. (Airdoc), this article introduced the development process, the premarket application, and the key points in the application of this artificial intelligence device, also lists the related regulations and guidelines as references to provide some ideas for the follow-up premarketing application of such kind of products.
脂质代谢异常是糖尿病性视网膜病变可能的危险因素。糖尿病性视网膜病变被认为是致盲的主要原因。近年来研究认为总胆固醇、三酰甘油等血脂与糖尿病性视网膜病变及糖尿病黄斑水肿的进展有关，降脂药物的应用能够延缓糖尿病性视网膜病变进展。随着色谱分离和质谱分析等脂质组学分析方法的发展，除了常规的血清脂质标志物以外的各种脂质成分也被发现可能与糖尿病性视网膜病变进展有关。现总结脂质及其衍生物在糖尿病性视网膜病变发病机制中的作用，阐述糖尿病性视网膜病变脂质代谢治疗的潜在靶点和前景。
Abstract Abnormal lipid metabolism is a possible risk factor for diabetic retinopathy. Diabetic retinopathy is considered to be the main cause of blindness. In recent years, studies have shown that serum lipids, such as total cholesterol, triglycerides, are related to the progress of diabetic retinopathy and diabetic macular edema, and lipid-lowering drugs can delay the progress of diabetic retinopathy. With the development of lipidomics analysis methods such as chromatographic separation and mass spectrometry, lipid components other than conventional serum lipid markers have also been found to be related to the progression of diabetic retinopathy. The review summarizes the role of lipids and their derivatives in the pathogenesis of diabetic retinopathy, and highlights the potential targets and prospects of lipid metabolism treatment for diabetic retinopathy.
晚期糖尿病(diabetes mellitus，DM)患者常出现的糖尿病性视网膜病变能够被发现，而糖尿病性角膜病变(diabetic keratopathy，DK)却时常被人们忽略。近年来的许多研究表明，DK对角膜的结构、代谢、生理功能等多个方面均有重要影响。目前临床上尚无根治DK的有效疗法，现主流疗法多集中于对症治疗以维持光滑湿润的眼表，最大限度地减少视觉损失以及提高舒适度，如局部滴用人工泪液、使用角膜绷带镜及局部使用抗炎药物等，但这些现有的治疗方法对于角膜组织损伤的修复能力有限。近年来出现神经生长因子、胰岛素疗法等新兴的治疗方法，有望未来应用于临床。
The diabetic retinopathy which often occurs in patients with advanced diabetes mellitus (DM) can usually be realized, but diabetic keratopathy (DK) could sometimes be ignored. In recent years, many studies have found out that DK can cause significant abnormal changes in many ways, including structure, metabolism and physiological functions of the cornea. At present, there is no effective therapy to cure DK. The current mainstream therapy mostly focuses on symptomatic treatment to maintain a smooth and moist ocular surface, minimize visual loss and improve comfort, such as local drip of artificial tears, use of corneal bandage lens and local use of anti-inflammatory drugs. However, these existing treatment methods have limited repair ability for corneal tissue damage. In recent years, a number of new treatment methods have emerged, which are expected to be clinically used in the future, such as nerve growth factors and insulin therapy.
糖尿病视网膜病变(diabetic retinopathy，DR)在糖尿病肾病(diabetic nephropathy，DN)人群，特别是终末期糖尿病肾病(end stage diabetic nephropathy，ESRD)患者中的发病率和严重程度明显高于糖尿病人群。其中ESRD的一项重要治疗手段——血液透析(Hemodialysis，HD)可能会增加机体氧化应激反应、出血风险以及视神经的缺血缺氧，加重DR的发生发展；但另一方面也可通过清除尿毒症毒素、控制血压以及清除多余体液等途径改善糖尿病和DN对眼部的损伤。
The incidence and severity of diabetic retinopathy (DR) in patients with diabetic nephropathy (DN), especially those with end-stage renal disease (ESRD), were higher than those with diabetes. Hemodialysis (HD), an important treatment of ESRD, may aggravate DR by increasing the oxidative stress, fundus hemorrhage and hypoxia of the optic nerve. On the other hand, HD can improve the ocular damage caused by diabetes mellitus and DN by removing uremia toxin, controlling blood pressure and removing excess body fluid.
