En-face optical coherence tomography in the diagnosis and management of age-related macular degeneration and polypoidal choroidal vasculopathy

Optical coherence tomography (OCT) is a noninvasive imaging modality providing high-resolution images of the central retina that has completely transformed the field of ophthalmology. While traditional OCT has produced longitudinal cross-sectional images, advancements in data processing have led to the development of en-face OCT, which produces transverse images of retinal and choroidal layers at any specified depth. This offers additional benefit on top of longitudinal cross-sections because it provides an extensive overview of pathological structures in a single image. The aim of this review was to discuss the utility of en-face OCT in the diagnosis and management of age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). En-face imaging of the inner segment/outer segment junction of retinal photoreceptors has been shown to be a useful indicator of visual acuity and a predictor of the extent of progression of geographic atrophy. En-face OCT has also enabled high-resolution analysis and quantification of pathological structures such as reticular pseudodrusen (RPD) and choroidal neovascularization, which have the potential to become useful markers for disease monitoring. En-face Doppler OCT enables subtle changes in the choroidal vasculature to be detected in eyes with RPD and AMD, which has significantly advanced our understanding of their pathogenesis. En-face Doppler OCT has also been shown to be useful for detecting the polypoid lesions and branching vascular networks diagnostic of PCV. It may therefore serve as a noninvasive alternative to fluorescein and indocyanine green angiography for the diagnosis of PCV and other forms of the exudative macular disease.     

Choroidal thickness profile in healthy Indian children

Purpose:

The purpose was to study choroidal thickness and its profile based on location in healthy Indian children using enhanced depth spectral-domain-optical coherence tomography (SD-OCT).

Methods:

In this cross-sectional observational study 255 eyes of 136 children with no retinal or choroidal disease were consecutively scanned using enhanced depth SD-OCT. Eyes with any ocular disease or axial length (AXL) >25 mm or < 20 mm were excluded. A single observer measured choroidal thickness from the posterior edge of the retinal pigment epithelium to the choroid/sclera junction at 500-microns intervals up to 2500 microns temporal and nasal to the fovea. Generalized estimating equations were used to evaluate the correlation between choroidal thickness at various locations and age, AXL, gender and spherical equivalent (SEq).

Results:

Mean age of the subjects was 11.9 ± 3.4 years (range: 5–18 years). There were 62 Females and 74 males. The mean AXL was 23.55 ± 0.74 mm. Mean subfoveal choroidal thickness was 312.1 ± 45.40 μm. Choroid was found to be thickest subfoveally, then temporally. Age, AXL and SEq showed a significant correlation with choroidal thickness, whereas gender did not affect choroidal thickness.

Conclusion:

Our study provides a valid normative database of choroidal thickness in healthy Indian children. This database could be useful for further studies evaluating choroidal changes in various chorioretinal disorders. Age and AXL are critical factors, which negatively correlated with choroidal thickness.     

MEK/ERK参与大鼠脉络膜新生血管基质金属蛋白酶-2和基质金属蛋白酶-9的表达调控

目的 探讨基质金属蛋白酶2(matrix metalloproteinase-2,MMP-2)和MMP-9在大鼠脉络膜新生血管(choroidal neovascularization,CNV)内的表达及其可能的调控机制.方法 将23只成年雄性棕色挪威大鼠随机分为2组,一组为玻璃体内注药组,视网膜光凝后即刻玻璃体内注射3μL PD98059;另一组为单纯光凝组,单纯行视网膜光凝.观察时间为光凝后3d、7d和14 d.各时间点处死大鼠后摘除眼球,免疫组织化学法和免疫荧光法观察MMP-2和MMP-9在大鼠CNV内不同时间点的表达特点.眼底荧光血管造影(fundusfluorescence angiography,FFA)和HE法观察玻璃体内注射PD98059对CNV生成的作用,Western blotting检测观察注药对CNV内MMP-2和MMP-9表达的影响.结果 光凝后3d,单纯光凝组光凝区即有MMP-2和MMP-9的阳性表达;光凝后7d和14 d二者表达均逐渐增强.光凝后7d,玻璃体内注药组MMP-2和MMP-9均显著被抑制,分别被抑制约69％和80％.Western blotting检测结果示玻璃体内注射组可显著抑制ERK的磷酸化,光凝后3d及7d的抑制率分别为54％和60％,而对ERK总量的表达无明显作用.FFA和HE显示,玻璃体内注药组光凝后14 d减少光凝局部CNV的荧光素渗漏约51％,抑制CNV厚度达57％.免疫荧光法检测结果示光凝后7d,玻璃体内注药组抑制MMP-2和MMP-9的表达分别为73％和64％.结论 MMP-2和MMP-9参与了大鼠CNV的生成,光凝后3d即有阳性表达,至光凝后14 d表达进一步增强,MEK/ERK通路至少部分参与了MMP-2和MMP-9在CNV内的生成调控.     

The Association between Choroidal Thickness Variations and Response to Intravitreal Bevacizumab in Central Serous Chorioretinopathy

PurposeTo analyze differences in the subfoveal choroidal thickness (SFChT) between bevacizumab responders (BevRs) and nonresponders (BevNRs) in patients with idiopathic central serous chorioretinopathy (CSC).MethodsThe medical records of 30 unilateral chronic CSC patients who were treated with intravitreal bevacizumab (IVB) as a first line treatment were reviewed. Patients were categorized as BevNRs when CSC did not completely resolve after a minimum of 3 IVB treatments. Enhanced depth imaging-optical coherence tomography was used and SFChT was measured before and after treatment. Choroidal hyperpermeability was also evaluated using indocyanine angiography.ResultsTwenty and 10 eyes were classified as BevRs or BevNRs, respectively. The mean number of IVB treatments was 2.22 ± 0.89 in BevRs, and 4.80 ± 1.03 in BevNRs. Compared with BevNRs, BevRs demonstrated significantly greater pretreatment SFChT (441.25 ± 88.09 vs. 364.10 ± 61.97 µm); SFChT reduction following IVB was significantly greater in BevRs than BevNRs. SFChT in the unaffected eyes was also greater in BevRs than BevNRs. Choroidal hyperpermeability was detected less frequently in BevNRs (hypofluorescence on late-phase, 0.0% and 33.3% in BevNRs and BevRs, respectively; p= 0.049).ConclusionsCompared with CSC eyes that did not respond well to IVB, BevRs demonstrated significantly thicker SFChT at baseline, greater reduction in SFChT after IVB treatment, and hyperfluorescence on late-phase indocyanine green angiography. We recommend IVB injection as the first-line therapy for CSC eyes with relatively high SFChT and hyperfluorescence on late-phase indocyanine green angiography.     

PDT联合ranibizumab玻璃体腔注射治疗年龄相关性黄斑变性合并CNV

目的：观察 PDT 联合玻璃体腔注射 ranibizumab (雷珠单抗)治疗老年性黄斑变性脉络膜新生血管( choroidal neovascularization,CNV)的疗效。
　　方法：将符合纳入标准,经吲哚青绿脉络膜血管造影(indocyanine green angiography, ICGA)、光学相干断层扫描( optical coherence tomography, OCT)检查确诊为黄斑区脉络膜新生血管( CNV)患者27例27眼,经PDT治疗后3~7 d内行 ranibizumab 玻璃体腔注射。观察治疗后1,3,6 mo、末次随访时行最佳矫正视力、FFA、ICGA、OCT 检查及有无并发症发生情况。
　　结果：最佳矫正视力提高17眼(63%),最佳矫正视力稳定6眼(22%),最佳矫正视力下降4眼(15%)。27例27眼治疗前平均渗漏面积为1005.69±105.47μm,治疗后1,3mo后平均875.54±103.27,423.37±79.68μm,与治疗前比较差异有统计学意义(P<0.01),视网膜黄斑中央厚度27例27眼治疗前平均厚度为485.58±122.59μm,治疗后1,3mo后平均398.84±105.32,297.74±89.18μm,与治疗前比较差异有统计学意义(P<0.01)。
　　结论：PDT 封闭 CNV 后,联合玻璃体内腔内注射ranibizumab,有效阻断新生血管复发,减少PDT再次治疗次数和并发症,可提高治疗效果。     

脉络膜厚度与CSCR的病例对照研究与Meta分析

目的：定量分析中心性浆液性脉络膜视网膜病变( central serous chorioretinopathy,CSCR)患者黄斑中心凹下脉络膜厚度( subfoveal choroidal thickness,SFCT)改变。
　　方法：采用病例对照研究及Meta分析。连续的CSCR患者46例纳入研究,CSCR患者散瞳后前置镜眼底检查,荧光素眼底血管造影和吲哚菁绿血管造影检查确诊。选择同期年龄、性别、屈光度及眼轴匹配的正常人62例62眼作为正常对照组。用加强成像深度扫描OCT检测并比较CSCR组及对照组SFCT。单因素和多因素分析 SFCT 与各临床资料之间的关系。 Meta分析用Stata软件计算两组之间的加权均数差。
　　结果：CSCR患者的平均SFCT为397.34±83.91μm,正常对照组为274.48±62.57μm。 CSCR组SFCT较对照组明显增厚,差异有统计学意义(P<0.01)。单因素与多因素线性回归分析, SFCT与CSCR诊断显著相关。 Meta分析结果：CSCR组的黄斑中央凹下脉络膜较正常组厚,加权平均差异为156.13μm(95% CI：137.43,174.83)。
　　结论：CSCR患者黄斑中央凹下脉络膜较正常眼厚,增厚的SFCT与CSCR诊断存在相关性。     

On the atrial response to focal discharges in man

INTRODUCTION: Triggers and vulnerability are key factors for the occurrence of atrial fibrillation (AF). The aim of this study was to assess spatial dispersion of atrial refractoriness and vulnerability in response to both focal discharges as well as programmed electrical stimulation in patients undergoing ablation of atrial arrhythmogenic foci. METHODS AND RESULTS: Twenty-nine patients were studied, and 12 right atrial unipolar electrograms were recorded. Inducibility of AF was assessed by a pacing protocol that started with one extrastimulus, followed by more aggressive pacing until AF was obtained. Mean fibrillatory intervals were used to assess the local refractoriness of each recording site. Spatial dispersion of refractoriness was calculated as the coefficient of dispersion (CD value: standard deviation of the mean of all local mean fibrillatory intervals as a percentage of the overall mean fibrillatory interval). Based on our previous study, a CD value 3.0 was considered enhanced spatial dispersion of refractoriness. Fifteen of 29 patients had normal dispersion of refractoriness (mean CD value 1.65 +/- 0.43), and AF was inducible with burst pacing only. These patients had focal discharges causing rapid atrial tachycardia with a focal activation pattern. Activation mapping of focal activity was possible in 14 of 15 patients. Focal triggering of AF occurred in only 1 of 15 patients. Fourteen of 29 patients had enhanced dispersion (mean CD value 4.2 +/- 0.72). AF was inducible with a single extrastimulus in 11 of 14 patients (P < 0.001). Focal triggering of AF occurred in all 14 patients. CONCLUSION: Spatial dispersion of atrial refractoriness determines whether focal atrial discharges trigger AF with disorganized activity or, alternatively, only rapid atrial tachycardia.     

媒介与媒介生物性疾病

该文在收集分析文献材料的基础上，探讨了媒介与媒介生物性疾病等概念及其相互关系。（1）狭义的媒介生物即传染病流行三环节中的生物性传播因素，即有关的节肢动物；广义的媒介生物即世界卫生组织所定义的、包括人畜共患病的脊椎和非脊椎动物的终宿主和中间宿主以及动物贮存宿主。（2）当前世界范围内广泛接受的媒介生物性疾病概念为由节肢动物、鼠类和软体动物起主要传播作用的传染病。（3）自然疫源性疾病的概念当前仪见使用于中俄两国，分原始的和后来扩展的两种，且后者定义不甚严格，但当前我国对该概念的使用已远远超出其原始定义的范围，按照原始定义，自然疫源性疾病必然同时既是人畜共患病，又是一种狭义的媒介生物性疾病。（4）媒介生物性疾病与人畜共患病及按原始定义的自然疫源性疾病三者的关系可以概括为：媒介生物性疾病与自然疫源性疾病是整体与部分的关系，后者是前者的一部分；媒介生物性疾病与人畜共患病的关系是绝大部分重叠的关系。三个概念中目前在世界范围内应用最多的足人畜共患病，其次是媒介生物性疾病，应用最少的为自然疫源性疾病。     

Integrin and extracellular matrix interactions regulate engraftment of transplanted hepatocytes in the rat liver

BACKGROUND & AIMS: Recognition and circumvention of the hepatic endothelial barrier is critical in the engraftment of transplanted cells. We examined whether interactions between integrin and extracellular matrix component receptors could be manipulated for improving transplanted cell engraftment and liver repopulation. METHODS: Fischer 344 rat hepatocytes were transplanted into syngeneic dipeptidyl peptidase IV-deficient rats. Coating of cells or of liver sinusoids with natural collagen, natural laminin, or an engineered fibronectin-like polymer was studied with analysis of cell engraftment and liver repopulation using histologic and molecular assays. Focal adhesion complexes were identified by vinculin immunostaining. The role of integrin receptors in cell engraftment was analyzed with RGD peptide inhibition assays. RESULTS: Coating of cells with extracellular matrix components before transplantation did not enhance cell engraftment. In contrast, intraportal infusion of collagen or fibronectin-like polymer in recipients prior to cell transplantation increased cell engraftment. Adherence of transplanted cells to the hepatic endothelium resulted in rapid activation of vinculin-containing focal adhesion complexes. Superior cell engraftment in animals treated with fibronectin-like polymer was RGD sensitive, verifying the integrin-dependent nature of this process. Moreover, studies in the retrorsine-partial hepatectomy rat model showed that intraportal infusion of the fibronectin-like polymer before cell transplantation significantly accelerated liver repopulation. CONCLUSIONS: Integrin-extracellular matrix component interactions can be manipulated for enhancing cell engraftment in the liver. Such mechanisms will be relevant for engraftment of other cell types and for strategies concerning liver-directed cell therapy.