Aims: To evaluate abnormalities in the choroidal circulation in cases of central serous chorioretinopathy (CSC). Methods: A complete clinical ophthalmological examination was performed using simultaneous fluorescein and indocyanine green (ICG) angiography with a confocal scanning laser ophthalmoscopy and the digital images analysed in 36 consecutive patients with acute CSC. To quantify the choroidal circulation, the foveal choroidal blood flow was measured in 11 patients using laser Doppler flowmetry. Results: Fluorescein angiography showed focal leakage from the retinal pigment epithelium in all patients. ICG angiography revealed delays in arterial filling in 27 eyes (75%), and fluorescein angiography showed small hypofluorescent points around the leakage in 27 eyes (75%). Abnormal choroidal hyperfluorescence was observed in 30 eyes (83%). The choroidal blood flow in eyes with CSC was 45% lower than in fellow eyes (p<0.01). Conclusion: Decreased choroidal blood flow in CSC was demonstrated for the first time. The decreased choroidal blood flow might be correlated with the small, localised hypofluorescent areas, which may indicate non-perfused areas of the choriocapillaris that are frequently seen during ICG angiography. C entral serous chorioretinopathy (CSC) is characterised by a focal serous detachment of the neurosensory retina. Fluorescein angiography shows dye leakage from the retinal pigment epithelium (RPE) and subretinal dye pooling. However, fluorescein angiography has not been useful in determining the pathogenesis of CSC because of limitations in imaging the choroidal vessels. Thus, while the clinical features of CSC have been described, its pathogenesis is controversial. 1-5Numerous recent reports have described abnormalities of the choroidal circulation using indocyanine green (ICG) angiography.6-13 ICG is a dye that has several advantages over sodium fluorescein for choroidal angiography, in that it binds tightly to plasma proteins and thus prevents marked leakage from fenestrated vessels such as the choriocapillaris. The dye also absorbs and fluoresces in the near infrared range, which enhances visualisation of the fluorescence through haemoglobin, RPE, or xantophyll. Using ICG angiography, choroidal vascular abnormalities, such as filling delays of the choroidal arteries and choriocapillaris, 6 10 12 venous dilatation, 10 12 and focal hyperfluorescence of the choroid, 6-12 which indicate hyperpermeability of choroidal vessels, have been reported.In the present study, we performed simultaneous ICG and fluorescein angiography using scanning laser ophthalmoscopy 14 in patients with CSC. We observed delayed arterial filling and hyperfluorescence of the choroid, which had been reported previously. In addition, small, localised hypofluorescent areas around the leaking point found in fluorescein angiography were frequently observed by ICG angiography. To assess the quantitatively analysis of the choroidal circulation, measurements of the choroidal blood flow in the centre of the fovea were performed in...

Retinal neovascularization is a leading cause of human blindness. However, little is known concerning the molecular mechanisms controlling retinal neovascularization in vivo. Here we provide evidence that exposure of a collagen type IV cryptic epitope detected by monoclonal antibody (mAb) HUIV26, delineates sites of vascular bud formation and represents one of the earliest structural remodeling events required before vessel out-growth. Exposure of these cryptic sites was inhibited in matrix metalloproteinase (MMP)-9-deficient but not MMP-2-deficient mice implicating MMP-9 in their exposure. Retinal endothelial cell interactions with the HUIV26 epitopes induced endothelial cell migration, which was blocked by mAb HUIV26. Importantly, subcutaneous administration of mAb HUIV26 potently inhibited retinal angiogenesis in vivo. Taken together, these findings suggest a novel mechanism in which MMP-9 facilitates exposure of HUIV26 cryptic sites, thereby promoting retinal endothelial cell migration and neovascularization in vivo.

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Retinal and choroidal neovascularization are the most frequent causes of severe and progressive vision loss. Studies have demonstrated that Tie2, an endothelial-specific receptor tyrosine kinase, plays a key role in angiogenesis. In this study, we determined whether adenovirus-mediated gene delivery of extracellular domain of the Tie2 receptor (ExTek) could inhibit experimental retinal and choroidal neovascularization. Immunofluorescence histochemistry with a monoclonal antibody to human Tie2 showed that Tie2 expression is prominent around and within the base of newly formed blood vessels of retinal and choroidal neovascular lesions. A single intramuscular injection of adenovirus expressing ExTek genes achieved plasma levels of ExTek exceeding 500 microg/ml in mice for 10 days (in neonates) and 7 days (in adults). This treatment inhibited retinal neovascularization by 47% (p < 0.05) in a murine model of ischemia-induced retinopathy. The same treatment reduced the incidence and extent of sodium fluorescein leakage from choroidal neovascular lesions by 52% (p < 0.05) and 36% (p < 0.01), respectively, in a laser-induced murine choroidal neovascularization model. The same mice showed a 45% (p < 0.001) reduction of integrated area of the choroidal neovascularization. These findings indicate that Tie2 signaling is a common component of the angiogenic pathway in both retinal and choroidal neovascularization, providing a potentially useful target in the treatment of intraocular neovascular diseases.