病理性近视脉络膜新生血管的诊断与治疗

病理性近视是全世界范围内引起患者视力下降的主要原因之一,在亚洲国家尤为多见。而脉络膜新生血管是病理性近视的最严重并发症之一,它可以引起眼底黄斑区病变,导致视力下降,出现中心暗点,视物变形,视野缺损等,如长期不治疗可能导致失明。光学相干断层扫描、光学相干断层扫描血管成像、荧光素眼底血管造影等检查方法在诊断病理性近视继发的脉络膜新生血管中起到很大帮助,可以较为明确的显示新生血管的位置,大小等,不论其是否处于活动期。目前对于病理性近视引起的脉络膜新生血管主要治疗方法有光动力治疗及抗血管内皮生长因子(VEGF)治疗,近年来,玻璃体腔内注射抗VEGF药物成为病理性近视与脉络膜新生血管的首选治疗方法,通过减少新生血管的形成,减轻黄斑区水肿,从而达到改善视力及更好的预后效果。论文主要综合整理近期关于病理性近视脉络膜新生血管的诊断及治疗的研究,为临床工作提供帮助。     

Ultra-Widefield Indocyanine Green Angiography Reveals Patterns of Choroidal Venous Insufficiency Influencing Pachychoroid Disease

PurposeTo compare patterns of choroidal venous drainage in eyes with pachychoroid disease to those of healthy subjects using ultra-widefield indocyanine green angiography (UWF ICGA).MethodsPatients with pachychoroid disease and healthy controls were recruited at two referral centers. UWF ICGA images were used to evaluate the proportion of the postequatorial fundus drained by major vortex vein systems in each quadrant and to study the incidence and topography of choroidal vascular hyperpermeability (CVH) and intervortex venous anastomoses. Widefield swept-source optical coherence tomography (SS-OCT) was used to evaluate choroidal thickness at the posterior pole in eyes with pachychoroid disease.ResultsFifty-two pachychoroid eyes and 26 healthy eyes were evaluated. Eyes with pachychoroid disease showed a significant within-subject variance in the proportion of the postequatorial fundus drained by each vortex vein system (range, 4.1%–48.1%; P < 0.0001) that was not seen in controls (range, 17.3%–31.7%; P = 0.11). CVH was present in all pachychoroid disease eyes and three of 26 controls. Intervortex venous anastomoses were present in 46 of 52 pachychoroid disease eyes and nine of 26 control eyes. Vortex vein systems with large drainage areas showed greater density of CVH spots. SS-OCT demonstrated asymmetric choroidal drainage in the macula of 59% of pachychoroid eyes. CVH and intervortex venous anastomoses were more prominent in areas showing maximal choroidal thickness.ConclusionsIn eyes with pachychoroid disease, imbalanced choroidal venous drainage with congestion of specific vortex vein systems may contribute to a state of choroidal venous insufficiency characterized by regional choroidal thickening, CVH and remodeling of venous drainage routes.     

Forkhead Domain Inhibitor-6 Suppresses Corneal Neovascularization and Subsequent Fibrosis After Alkali Burn in Rats

PurposeThe purpose of this study was to investigate the effects of Forkhead Domain Inhibitor-6 (FDI-6) on regulating inflammatory corneal angiogenesis and subsequent fibrosis induced by alkali burn.MethodsA corneal alkali burn model was established in Sprague Dawley rats using NaOH and the rat eyes were topically treated with FDI-6 (40 µM) or a control vehicle four times daily for 7 days. Corneal neovascularization, inflammation and epithelial defects were observed on days 1, 4, and 7 under a slit lamp microscope after corneal alkali burn. Analysis of angiogenesis-, inflammation-, and fibrosis-related indicators was conducted on day 7. Murine macrophages (RAW264.7 cells) and mouse retinal microvascular endothelial cells (MRMECs) were used to examine the effects of FDI-6 on inflammatory angiogenesis in vitro.ResultsTopical delivery of FDI-6 significantly attenuated alkali burn-induced corneal inflammation, neovascularization, and fibrosis. FDI-6 suppressed the expression of angiogenic factors (vascular epidermal growth factor, CD31, matrix metalloproteinase-9, and endothelial NO synthase), fibrotic factors (α-smooth muscle actin and fibronectin), and pro-inflammatory factor interleukin-6 in alkali-injured corneas. FDI-6 downregulated the expression of monocyte chemotactic protein-1, pro-inflammatory cytokines (interleukin-1β and tumor necrosis factor-alpha), nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3, and vascular endothelial growth factor in RAW264.7 cells and inhibited the proliferation, migration, and tube formation of MRMECs in vitro.ConclusionsFDI-6 can attenuate corneal neovascularization, inflammation, and fibrosis in alkali-injured corneas.     

CXCR7在碱烧伤小鼠角膜组织中的表达

目的:研究基质细胞衍生因子-1(stromal cell-derived factor-1,SDF-1)的受体即人CXC趋化因子受体7(C-X-C chemokine receptor type 7,CXCR7)在碱烧伤小鼠角膜组织的表达,探讨CXCR7是否参与小鼠碱烧伤后角膜新生血管(corneal neovascularization,CNV)的形成。方法:采用在角膜鼻侧放置NaOH滤纸片40 s的方法构建BALB/c小鼠碱烧伤诱导CNV动物模型,通过real-time PCR、Western blotting法分别检测碱烧伤后3 d、7 d、14 d角膜组织中SDF-1、CXCR4、CXCR7和血管内皮生长因子(vascular endothelial growth factor,VEGF)的mRNA及蛋白的表达情况,免疫荧光法检测碱烧伤后14 d CXCR7蛋白的表达。结果:小鼠角膜新生血管在碱烧后14 d内持续生长。Real-time PCR结果显示,与正常对照组相比,碱烧伤后3d、7 d、14 d小鼠角膜组织中SDF-1、CXCR4、CXCR7及VEGF的mRNA表达均明显升高(P<0.05)。Western blotting结果显示,与正常组相比,碱烧伤后7 d组与14 d组中SDF-1、CXCR4、CXCR7及VEGF蛋白的相对表达量均升高(P<0.05),但7d组与14 d组差异无统计学意义。免疫荧光检测显示,正常小鼠角膜上皮层有CXCR7蛋白弱阳性蛋白表达;碱烧伤后14 d,角膜上皮层、基质层及新生血管CXCR7蛋白的表达升高。结论:CXCR7在碱烧伤后小鼠角膜组织中表达增加,提示其可能在碱烧伤后的CNV形成中发挥重要作用。     

动态增强MRI评价脊柱肿瘤血供与DSA的相关性

目的 确定动态增强磁共振成像(DCE-MRI)在评价脊柱肿瘤血供与DSA染色的相关性.方法 40例诊断为脊柱肿瘤的患者在行栓塞术前作MR检查.根据血管造影表现,肿瘤分为富血供组、中等血供组和乏血供组.通过对肿瘤强化区域的感兴趣区(ROI)分析,应用常规MR的强化程度和DCE-MRI参数评价肿瘤血供.结果 40例肿瘤分为乏血供组(16例)、中等血供组(12例)和富血供组(12例).MRI强化程度在乏血供组和富血供组间没有统计学差异(P>0.05).而DCE-MRI在两组间显示差异有统计学意义(P＜0.01).而且相对于MRI强化程度,DCE-MRI参数与DSA的关系更加密切.RSlopemax临界值为1.325时预测乏血供肿瘤的特异度和灵敏度最高,分别为100％和87.5％,而临界值为1.85时用于预测富血供肿瘤的特异度和灵敏度最高,分别为100％和96.4％.结论 与常规MRI相比,DCE-MRI可以更准确地评价脊柱肿瘤血供,而且显示与DSA更好的相关性.     

Moderately Acidic pH Promotes Angiogenesis: An In Vitro and In Vivo Study

IntroductionThis study evaluated the effect of different pH values of 4.4, 5.4, 6.4, 7.4, 8.4, and 9.4 on angiogenesis.MethodsEndothelial cells were isolated from the mice molar teeth and placed in 42 Matrigel (Corning, NY)-coated wells, which were prepared and divided into 6 groups (n = 7). Synthetic tissue fluid was prepared and divided into 6 parts, and their pH values were adjusted to 4.4, 5.4, 6.4, 7.4, 8.4, and 9.4. A 2-mL volume from each group was diluted in the growth medium at a ratio of 1:3 and used for tubulogenesis assay. Forty-two 6-week-old mice in 6 groups (n = 7) were used for choroidal neovascularization (CNV). A 2-μL volume from each group or saline (control) was delivered by intravitreal injection on the day of laser application and 1 week later. Data on the number of nodes, the total length of the branches, and CNV areas (μm²) were determined using ImageJ software (National Institutes of Health, Bethesda, MD) and analyzed with 1-way analysis of variance and post hoc Tukey tests. The correlation was assessed between the tested variables.ResultsThe number of nodes decreased with changes in pH values as follows: 6.4 > 5.4 > 7.4 > 8.4 > 9.4 > 4.4. The total branch length decreased with pH value changes as follows: 6.4 > 4.4 > 6.4 > 7.4 > 8.4 > 9.4, and the CNV areas decreased with pH value changes as follows: 6.4 > 5.4 > 4.4 > 7.4 > 8.4 > 9.4.ConclusionsModerately acidic pH values (5.4 and 6.4) enhanced angiogenesis, whereas moderately alkaline pH values (8.4 and 9.4) suppressed angiogenesis.     

Temporal progression of angiogenesis and basal lamina deposition after contusive spinal cord injury in the adult rat

After spinal cord injury (SCI), the absence of an adequate blood supply to injured tissues has been hypothesized to contribute to the lack of regeneration. In this study, blood vessel changes were examined in 28 adult female Fischer 344 rats at 1, 3, 7, 14, 28, and 60 days after a 12.5 g x cm NYU impactor injury at the T9 vertebral level. Laminin, collagen IV, endothelial barrier antigen (SMI71), and rat endothelial cell antigen (RECA-1) immunoreactivities were used to quantify blood vessel per area densities and diameters in ventral gray matter (VGM), ventral white matter (VWM), and dorsal columns (DC) at levels ranging 15 mm rostral and caudal to the epicenter. This study demonstrates an angiogenic response, defined as SMI71/RECA-1-immunopositive endothelial cells that colocalize with a robust deposition of basal lamina and basal lamina streamers, 7 days after injury within epicenter VGM. This angiogenesis diminishes concurrent with cystic cavity formation. GAP43- and neurofilament- (68 kDa and 210 kDa) immunopositive fiber outgrowth was associated with these new blood vessels by day 14. Between 28 and 60 days after injury, increases in SMI71-immunopositive blood vessel densities were observed in the remaining VWM and DC with a corresponding increase in vessel diameters up to 15 mm rostral and caudal to the epicenter. This second angiogenesis within VWM and DC, unlike the acute response observed in VGM, did not correspond to any previously described changes in locomotor behaviors in this model. We propose that therapies targeting angiogenic processes be directed at the interval between 3 and 7 days after SCI.