结节性硬化症(tuberous sclerosis complex，TSC)是一种累及多系统的常染色体显性遗传病，早期呈单一表现，容易漏诊、误诊，以眼部症状为首发特征的新生儿期病例少有报道。本文报告1例早产男婴，出生后1 d眼底筛查发现右眼视网膜散在多个灰白色半透明隆起灶及脱色素斑，回溯胎儿期超声心动图异常高度怀疑TSC，进一步行头颅MRI检查及家族基因检测，在新生儿期明确了这一诊断。
Tuberous sclerosis complex is a multisystemic disease with an autosomal dominant inheritance pattern. Missed diagnosis and misdiagnosis are common for patients with single manifestation in the early stage. There are few documented neonatal cases with ocular symptoms as primary presentation. Here we report a newborn boy presented with retinal hamartoma, retinal achromic patch, fetal cardiac rhabdomyoma and subependymal nodules.Subsequent genetic tests confirm a diagnosis of TSC.
目的：玻璃膜疣主要成分胆固醇对人视网膜色素上皮细胞ARPE-19中细胞膜钙ATP酶1(plasma membrane Ca2+ ATPase 1，PMCA1)、L型电压依赖性钙离子通道(L-type voltage-dependent calcium channel，LVDCC)和细胞膜钠钙交换蛋白1(sodium calcium exchange protein 1，NCX1)表达的影响。方法：体外培养ARPE-19细胞，将细胞分为对照组和胆固醇处理组(2.5 mg/mL)，取样时间为0、6、12、24、48、72 h。通过实时定量PCR检测PMCA1、LVDCC和NCX1 mRNA的表达水平，用蛋白质印迹法检测蛋白质的表达水平。结果：主要负责细胞内钙离子外排的PMCA1的mRNA和蛋白表达水平在胆固醇处理下出现下调。在胆固醇处理下，钙流入通道LVDCC和钙稳态调控蛋白NCX1的mRNA和蛋白表达明显增多，并且呈现时间依赖性，都是在24 h或48 h表达最多后出现回落。其中LVDCC表达上调倍数较大。结论：玻璃膜疣主要成分胆固醇可以影响人视网膜色素上皮细胞中钙转运通道蛋白的表达，PMCA1的表达受到胆固醇抑制， LVDCC和NCX1的表达受到胆固醇处理上调。这可能会影响细胞内钙离子外排，引起钙离子内流，是否能进一步导致细胞内钙超载而引起细胞凋亡，值得探讨。
Objective: To study the effects of cholesterol, the main component of drusen, on the expression plasma membrane Ca2+ ATPase 1 (PMCA1), L-type voltage-dependent calcium channel (LVDCC) and cell membrane sodium calcium exchange protein 1 (NCX1) of ARPE-19 cells. Methods: The ARPE-19 cell line was cultured in vitro, and the cells were divided into a control group and a cholesterol treatment group (2.5 mg/mL). The treatment time was 0, 6, 12, 24, 48, 72 hours. Real-time quantitative PCR was used to detect the expression of PMCA1, LVDCC and NCX1 at the mRNA level, and western blot was used to detect the expression at the protein level. Results: The mRNA and protein expression levels of PMCA1 which mainly responsible for the efflux of intracellular calcium ions, was down regulated under cholesterol treatment. Meanwhile, the expression of the mRNA and protein of the calcium inflow channel LVDCC and calcium stability regulatory protein NCX1 were significantly increased, and the time-dependency was present, which was up expressed to 24 or 48 h and then fell back. Among them, the LVDCC expression had a large number of times. Conclusion: Cholesterol, the main component of drusen, can affect the expression of calcium channels in human retinal pigment epithelial cells. The expression of PMCA1 was suppressed by cholesterol, and expression of LVDCC and NCX1 were up-regulated with cholesterol treatment, which may affect intracellular calcium efflux then cause calcium influx. Whether it can further cause intracellular calcium overload and cell death is worth exploring.
目的：测量黄斑区视网膜神经节细胞层和内界膜-视网膜色素上皮层厚度，分析其与新发缺血性脑卒中的相关性。方法：采用前瞻性研究，选择2021年12月至2022年3月在潍坊医学院附属医院体检的健康者30例(60眼)为对照组(A组)；选择同期收治且年龄匹配的新发缺血性脑卒中患者30例(60眼)为卒中组(B组)。比较两组黄斑区神经节细胞层(ganglion cell layer,GCL)和内界膜-视网膜色素上皮层(inner limiting membrane-Retinal pigment epithelium,ILM-RPE)厚度及平均GCL厚度/ILM-RPE平均容积厚度(GCL/ILM-RPE厚度比)。结果：共纳入120只眼，A、B组分别60只眼。A组的平均GCL为(83.5±4.7)μm，B组的平均GCL厚度为(78.7±10.5)μm，组间比较差异有统计学意义(P<0.001)。A组的GCL最小厚度为(80.4±4.4)μm，B组的GCL最小厚度为(70.7±16.3)μm，组间比较差异有统计学意义(P<0.001)。A组的ILM-RPE中心子区厚度为(247.5±19.8)μm，B组的ILM-RPE中心子区厚度为(241.6±36.3)μm，组间比较差异无统计学意义(P=0.393)。A组的ILM-RPE平均容积厚度为278.4±9.8μm，B组的ILM-RPE平均容积厚度为(278.5±15.3)μm，组间比较差异无统计学意义(P=0.448)。A组的GCL/ILM-RPE厚度比为0.300 3±0.012 2，B组的GCL/ILM-RPE厚度比为0.286 2±0.028 6，组间比较差异有统计学意义(P<0.001)。结论：缺血性脑卒中影响GCL厚度和GCL/ILM-RPE厚度比， GCL厚度和GCL/ILM-RPE厚度比与新发缺血性脑卒中可能有关。
Objective: To measure the thickness of retinal ganglion cell layer and inner limiting membrane-retinal pigment epithelium layer in the macular region, and analyze its correlation with new-onset ischemic stroke. Methods: By using a prospective study, 30 healthy subjects (60 eyes) who underwent physical examination in Affiliated Hospital of Weifang Medical University from December 2021 to March 2022 were selected as the control group (Group A). Thirty age-matched patients with new-onset ischemic stroke admitted at the same time (60 eyes) were selected as the stroke group (Group B). The ganglioncelllayer (GCL) and innerlimitingmembrane-Retinalpigmentepithelium (ILM-RPE) were compared between the two groups. It included the thickness and mean GCL thickness/Mean Volume thickness of ILM-RPE (GCL/ILM-RPE thickness ratio). Results: A total of 120 eyes were included, with 60 eyes in group A and B. The average GCL thickness in group A was (83.5±4.7) μm, and the average GCL thickness in group B was (78.7±10.5) μm,and the difference between groups was statistically significant (P<0.001). The minimum thickness of GCL in group A was (80.4±4.4) μm, and the minimum thickness of GCL in group B was (70.7±16.3) μm, showing statistical significance(P<0.001). The thickness of the central subregion of ILM-RPE in group A was (247.5±19.8) μm, and the thickness of the central subregion of ILM-RPE in group B was (241.6±36.3) μm, and the difference was not statistically significant between two groups (P=0.393). The mean volumetric thickness of ILM-RPE in group A was (278.4±9.8) μm, and the mean volumetric thickness of ILM-RPE in group B was (278.5±15.3) μm, and the difference was not statistically significant (P=0.448). The GCL/ILM-RPE thickness ratio of group A was (0.300 3±0.012 2), and that of group B was (0.286 2±0.028 6), showing a statistical difference between groups (P<0.001). Conclusion: Ischemic stroke affects the GCL thickness and the thickness ratio of GCL/ILM-RPE, which may be related to new-onset ischemic stroke.
目的：借助于人工智能(artificial intelligence,AI)眼底筛查远程接转诊系统，探索“患者-社区-医院”远程筛查模式，推进眼科分级诊疗和双向转诊实施，为地市级医疗机构开展眼底疾病人工智能筛查工作提供一定的经验借鉴。方法：通过AI辅助远程筛查基层医疗机构的4886例患者，完成眼科检查并经AI初判、人工复核形成眼底诊断结论。通过医联体和专科联盟模式，对基层医疗机构的4886例患者的AI诊断系统结果和上级医师审核结果进行对照分析，分析AI诊断系统在眼科常见病种筛查中的推广应用的可信度和可行性。结果：AI检出DR的灵敏度为94.70%，特异度96.06%；DME的灵敏度96.43%，特异度96.55%；AMD的灵敏度77.55%，特异度95.74%；同时，其在病理性近视、白内障、青光眼等常见病种眼底筛查中也有一定作用。结论：AI辅助远程筛查系统对于绝大多数眼底疾病有较高的敏感性和特异性，适用于眼底疾病的筛查工作，利于基层医院或社区医院对于眼底疾病的初步诊断，落实眼科分级诊疗，有借鉴推广意义。
Objective: With the help of artificial intelligence (AI) based fundus screening remote referral telemedicine system,it enables us to explore the remote screening mode of patient-community-hospital, and promote the two-way referral and ophthalmic graded diagnosis. This investigation provides certain practice experiences for prefecture-level medical institutions to carry out AI screening for fundus diseases. Methods: Ophthalmologic examination was performed on 4,886 patients in primary medical institutions through AI-aided remote screening, and the final fundus diagnosis conclusion was formed after AI preliminary judgment and manual review. Through the Medical Consortium and specialty alliance model, the results of the AI diagnosis system and the audit results of superior physicians for 4 886 patients in primary care institutions were compared and analyzed, and the credibility and feasibility of the AI diagnosis system application in the screening of common ophthalmic diseases were discussed. Results: The sensitivity and specificity of AI detection of diabetic retinopathy were 94.70% and 96.06%, respectively. In the diabetic macular edema classification, the sensitivity and specificity were 96.43% and 96.55%, respectively. In the age-related macular degeneration classification, the sensitivity and specificity were 77.55% and 95.74%, respectively. Meanwhile, it also plays a role in screening common fundus diseases such as pathological myopia, cataract and glaucoma. Conclusion: The AI-aided remote screening system has high sensitivity and specificity for most of fundus diseases, indicating it is promising for fundus diseases screening in primary medical institutions. It is conducive for primary hospitals or community hospitals to carry out the initial diagnosis of fundus diseases, as well as the implementation of graded diagnosis and treatment of ophthalmology, which has reference and promotion significance.
目的：应用Cirrus HD-OCT 5000对正常眼黄斑及视盘血流参数进行血管成像测量，评估其可重复性及再现性。方法：纳入40只正常眼进行前瞻性研究。操作者A于一周内3天的同一时段(T1，T2，T3)对正常受试者的同一眼黄斑及视盘进行3次血管成像扫描，扫描过程中均开启FastTracTM图像跟踪功能，操作者B在T 2时间点再次对受试者同一眼进行相同程序扫描，使用Angio PlexMetrixTM量化软件(版本10.0)自动测量黄斑和视盘的血管长度密度(vessel length density，VD)和血管灌注密度(vascular perfusion density，PD)。应用单因素方差分析或非参数检验比较3次扫描的VD、PD是否有差异。采用组内相关系数(intraclass correlation coefficient，ICC)、变异系数(coefficient of variation，CV)评价操作者A的可重复性，采用一致性相关系数(consistent correlation coefficient，CCC)、重复性系数(repeatability coefficient，CR)、C V评价操作者间的再现性。结果：操作者A对黄斑及视盘各区域3次扫描的V D、P D之间差异无统计学意义(P >0.05)。操作者A对黄斑和视盘V D、PD 3次扫描的ICC值分别为0.260~0.517、0.362~0.898，黄斑及视盘各区域V D、P D的C V值均<8.1%。黄斑和视盘V D、P D的操作者间CCC值分别为0.3130~0.5665、0.5149~0.7801；黄斑VD和PD的CR值分别为3.2212~4.6399、0.0574~0.0832；视盘VD和PD的CR值分别为2.0675~4.0630、0.0447~0.0730。黄斑CV值均<9.0%，视盘CV值均<6.9%。结论：非同日的同一时段视盘浅层血流参数具有较好的重复性及再现性，黄斑浅层血流参数的重复性及再现性相对较差。
Objective: To evaluate the repeatability and reproducibility of quantification of macular and peri-papillary superficial capillaries in normal eyes using Cirrus HD-OCT 5000 angiography. Methods: Forty normal eyes were included in this prospective study. Angiography 3 mm × 3 mm scan protocol centered on the disc or macula of the same eye was repeated 3 times by operator A in the same period on 3 days (T1, T2, T3) within 1 week,and the FastTracTM image tracking function was turned on during the scan. Operator B repeated the same scan independently at T2 after operator A. Angio Plex MetrixTM quantification software (version 10.0) was used to automatically measure the vessel length density (VD) and vascular perfusion density (PD) of macular and peri-papillary superficial capillaries. One-way analysis of variance or nonparametric test was used to compare the VD and PD measurements of the 3 scans. The intraclass correlation coefficient (ICC) and coefficient of variation (CV)were calculated to evaluate the intra-operator repeatability. Consistent correlation coefficient (CCC), repeatability coefficient (CR), and CV were calculated to evaluate the inter-operator reproducibility. Results: There was no statistically significant difference in the measurements of VD and PD between the 3 scans of the macular and peri-papillary superficial capillaries by operator A (P>0.05). The ICC values for the 3 scans of VD and PD of the macular and peri-papillary superficial capillaries by operator A were 0.260–0.517 and 0.362~0.898, respectively.The CV values of the VD and PD of the macular and peri-papillary superficial capillaries were all <8.1%. The inter-operator CCC values of the macular and peri-papillary superficial capillaries were 0.3130–0.5665 and 0.5149~0.7801,respectively; the CR values of the VD and PD of macula were 3.2212–4.6399 and 0.0574–0.0832, respectively; the CR values of the VD and PD of optic disc were 2.0675–4.0630 and 0.0447–0.0730, respectively. The CV values of macular were all <9.0%, and the CV values of optic disc were all <6.9%. Conclusion:The macular and peri-papillary superficial capillaries parameters in the same period on different days have a good repeatability and reproducibility,while the superficial macular blood flow parameters have relatively poor repeatability and reproducibility.
目的：探讨原发性慢性闭角型青光眼(chronic primary angle-closure glaucoma，CPACG)患者的视网膜血流密度(vessel density，VD)与视野缺损程度的相关性。方法：光学相干断层血管成像技术(optical coherence tomography angiography，OCTA)测量89例(112眼)视野缺损的CPACG患者的黄斑区VD、视盘旁VD，分析VD与视野缺损程度的相关性。结果：视盘旁VD与视野缺损程度成负相关(r>–0.728，P<0.05)。黄斑浅层总VD的受试者工作曲线(receiver operating characteristic，ROC)及曲线下面积(area under the curve，AUC)为0.874。在控制年龄、眼压及视力的情况下，黄斑总浅层VD每降低1%，视野平均缺损(mean deviation，MD)值增加–0.639 dB。结论：CPACG患者VD与视野缺损呈线性负相关，OCTA可以方便无创地观察青光眼患者眼底血流情况，在视野缺损前发现视网膜VD降低，从而可以作为CPACG早期诊断的参考指标。
Objective: To investigate the correlation between the retinal vessel density (VD) and the degree of visual field loss in chronic primary angle-closure glaucoma (CPACG). Methods: Eighty-nine CPACG patients (112 eyes)with different degrees of visual field loss were measured with optical coherence tomography angiography (OCTA) for macular VD and para-optic microcirculation VD, and the correlation between them and the degree of visual field defect were analyzed. Results: There was a negative correlation between the VD of the microcirculation in each zone next to the optic disc and the degree of visual field loss (r>–0.728, P<0.05). The receiver operating characteristic (ROC) and area under the curve (AUC) of the total VD of the superficial macula is 0.874. Under the condition of controlling age, intraocular pressure and vision, for every 1% decrease in the total superficial macular VD, the average visual field defect mean deviation (MD) value increases –0.639 dB. Conclusion: The VD of CPACG patients is linearly negatively correlated with visual field defects. OCTA can conveniently and non-invasively observe the blood flow of the fundus in patients with glaucoma. It is found that the retinal VD is reduced before visual field defects, which can be used as a reference index for early diagnosis of CPACG.
抗血管内皮生长因子(vascular endothelial growth factor，VEGF)治疗视网膜静脉阻塞(retinal vein occlusion，RVO)继发黄斑水肿(macular edema，ME)的有效性及安全性已得到广泛证实。但抗VEGF治疗方案尚无统一标准。现行的治疗方案主要包括固定治疗方案、按需(pro re nata，PRN)治疗方案、稳定性标准驱使的按需(stabilization criteria-driven PRN)治疗方案、治疗与延长(treat and extend，T&E)方案。近年来不少研究综合比较了各个治疗方案在改善视功能、量化评估疾病活动性、调整随访频率等多个维度的表现，为临床医生提供选择抗VEGF治疗方案的参考依据。本文旨在回顾并总结近年来对抗VEGF药物治疗RVO继发ME的研究，阐述抗VEGF治疗方案的研究进展。
The efficacy and safety of anti-vascular endothelial growth factor (VEGF) in the treatment of macular edema (ME) secondary to retinal vein occlusion (RVO) have been widely confirmed. However, there is no unified standard for anti-VEGF treatment regimens. Current treatment regimens mainly include fixed treatment regimen, pro re nata (PRN) treatment regimen, stabilization criteria-driven PRN treatment regimen, and treat and extend (T&E) regimen. In recent years, many studies have compared different treatment regimens in composite dimensions,including improving visual function, assessing disease activity quantitatively and adjusting the follow-up frequency,to provide clinicians with a reference of choosing anti-VEGF treatment regimens. The purpose of this article is to review and summarize recent researches on anti-VEGF drugs in the treatment of ME secondary to RVO, and to clarify the research progress in the anti-VEGF treatment regimens.
目的：探究特发性黄斑前膜(idiopathic macular epiretinal membrane，IMEM)患者在光学相干断层扫描(optical coherence tomography，OCT)的形态学改变与视力的相关性。方法：回顾性研究。基于OCT图像4级分级方案，纳入3级及以下的特发性黄斑前膜患者35例共37只眼进行OCT扫描，并借助第三方软件分析并获取每只眼在黄斑中心凹直径分别为1、3、6 mm共3个同心圆区域内视网膜各层的平均厚度值，并按照是否存在内核层(inner nuclear layer，INL)囊样改变分为两组。通过建立最小分辨角对数(minimum resolution angle in logarithmic，logMAR)最佳矫正视力(best corrected vision acuity，BCVA)与视网膜各层厚度值的多元线性回归方程，以及比较有INL囊样改变及无INL囊样改变两组的视力，分析视力与视网膜各层厚度值及INL囊样改变的关系。结果：多元线性回归分析显示，在直径1 mm的区域内，logMAR BCVA与神经纤维层(retina nerve fiber layer，RNFL)、INL的厚度值均呈正相关(均P<0.05)，而在直径3 mm和6 mm的区域内，logMAR BCVA仅与INL的厚度值呈正相关(均P<0.05)。与无INL囊样改变组相比，有INL囊样改变组视力及INL厚度差异均有统计学意义(均P<0.05)。结论：特发性黄斑前膜患者当前的视力主要与RNFL和INL厚度值相关。发生在INL层的囊样改变可能很好的提示INL增厚，其与视力具有相关性，具有这种囊样改变的患者往往视力也较差。
Objective: To investigate the morphological changes detected by spectral domain optical coherence tomography (OCT) and their relevance to vision in patients with idiopathic macular epiretinal membranes (IMEM). Methods: This is a retrospective study. OCT recorded 37 eyes with stage 3 and below IMEM according to the 4-level grading system based on OCT images among 35 patients. We managed to obtain thickness of all retina layers in three concentric circular regions with a diameter of 1 mm, 3 mm and 6 mm across macular fovea with the help of a third-party software. Plus we divided all 37 eyes into two groups according to whether there were cystic changes in the inner nuclear layer (INL). Multiple linear regression analyses were performed between thickness of all retina layers and current minimum resolution angle in logarithmic (logMAR) best corrected visual acuity (BCVA). The difference of BCVA between groups with cystic changes and without was also compared. Thus, the relationships between visual acuity and thickness of retina layers, cystic changes in INL were analyzed. Results: Multiple linear regression analyses revealed that thickness of both retina nerve fiber layer (RNFL) and inner nuclear layer have positive correlation with logMAR BCVA in the region with a diameter of 1 mm (P<0.05), while in regions of a diameter of 3 mm and 6 mm, only INL thickness remained positively relevant (all P<0.05). There were significant differences in BCVA and thickness of INL between groups with INL cystic changes and without (all P<0.05). Conclusion: Current visual acuity among preoperative IMEM patients was mostly associated with thickness of RNFL and INL. Cystic change in INL layer may be a good indicator of INL thickening and was visually correlated. Those with this change tend to have worse vision.
目的：研究玻璃膜疣主要成分胆固醇对人视网膜色素上皮细胞ARPE-19中金属硫蛋白表达的影响。方法：体外培养ARPE-19细胞，将细胞分为对照组和胆固醇处理组(2.5 mg/mL)，取样时间为0，6，12，24，48，72h。通过实时定量PCR检测hMT1a，hMT2a和hMT3在转录水平的表达，用蛋白质印迹法检测总金属硫蛋白的表达。结果：在转录水平上hMT1a，hMT2a和hMT3受到胆固醇影响mRNA表达上调，且hMT3上调倍数最大；总金属硫蛋白的蛋白表达随着胆固醇处理时间延长明显增多。结论：玻璃膜疣主要成分胆固醇可以上调人视网膜色素上皮细胞中金属硫蛋白的表达，提示金属硫蛋白表达可受到玻璃膜疣形成起始阶段的刺激，其检测是否能用于年龄相关性黄斑变性的早期发现及早期诊断还需深入探讨。
Objective: To study the effects of cholesterol, the main component of drusen, on the expression of metallothionein of ARPE-19 cells. Methods: The ARPE-19 cell line was cultured in vitro, and the cells were divided into a control group and a cholesterol treatment group (2.5 mg/mL). The treatment time was 0, 6, 12, 24, 48, 72 hours. Real- time quantitative PCR was used to detect the expression of hMT1a, hMT2a and hMT3 at the mRNA level, and Western blot was used to detect the expression at the protein level. Results: The mRNA expression of hMT1a, hMT2a and hMT3 were up-regulated by cholesterol and the protein expression of total MTs was increased with cholesterol treatment. Conclusion: Cholesterol, the main component of drusen, can up-regulate the expression of metallothionein in human retinal pigment epithelial cells, suggesting that the expression of metallothionine can be stimulated by the initial stage of drusen formation. However, whether its detection can be used for the early detection and early diagnosis of age-related macular degeneration or not still needs to be further explored.
眼结核的表现形式多样，有时会被误诊漏诊。本病例为一年轻男性，以右眼视力突发下降为主诉就诊，眼部表现可见黄斑区脉络膜占位病灶及视网膜内小病灶，经γ-干扰素释放试验、胸部CT等检查，确诊为血型播散性肺结核，眼部诊断为结核性脉络膜结节联合视网膜结节，全身接受抗结核治疗后，眼部病灶消退。
Ocular tuberculosis encompasses a variety of clinical manifestations, which is easily misdiagnosed sometimes. In this article, a young male was admitted to our hospital with a chief complaint of sudden blurred vision in his right eye. His ocular examination detected a tiny mass in the choroid and a small lesion in the retina. After interferon-gamma release assay (IGRA) and chest CT scan, the patient was diagnosed with military tuberculosis. The ocular examination confirmed the diagnosis of choroidal tubercle complicated with intrarentinal tubercle, which were healed after systemic anti-tuberculosis therapy.
