Akihiro Ishibazawa

BACKGROUND AND PURPOSE: Cerebral aneurysm is a frequent cerebrovascular event and a major cause of fatal subarachnoid haemorrhage, but there is no medical treatment for this condition. Haemodynamic stress and, recently, chronic inflammation have been proposed as major causes of cerebral aneurysm. Nevertheless, links between haemodynamic stress and chronic inflammation remain ill-defined, and to clarify such links, we evaluated the effects of prostaglandin E(2) (PGE(2) ), a mediator of inflammation, on the formation of cerebral aneurysms. EXPERIMENTAL APPROACH: Expression of COX and prostaglandin E synthase (PGES) and PGE receptors were examined in human and rodent cerebral aneurysm. The incidence, size and inflammation of cerebral aneurysms were evaluated in rats treated with COX-2 inhibitors and mice lacking each prostaglandin receptor. Effects of shear stress and PGE receptor signalling on expression of pro-inflammatory molecules were studied in primary cultures of human endothelial cells (ECs). KEY RESULTS: COX-2, microsomal PGES-1 and prostaglandin E receptor 2 (EP(2) ) were induced in ECs in the walls of cerebral aneurysms. Shear stress applied to primary ECs induced COX-2 and EP(2) . Inhibition or loss of COX-2 or EP(2) in vivo attenuated each other's expression, suppressed nuclear factor κB (NF-κB)-mediated chronic inflammation and reduced incidence of cerebral aneurysm. EP(2) stimulation in primary ECs induced NF-κB activation and expression of the chemokine (C-C motif) ligand 2, essential for cerebral aneurysm. CONCLUSIONS AND IMPLICATIONS: These results suggest that shear stress activated PGE(2) -EP(2) pathway in ECs and amplified chronic inflammation via NF-κB. We propose EP(2) as a therapeutic target in cerebral aneurysm.

Purpose: To characterize the morphology of neovascularization at the disc (NVD) and neovascularization elsewhere (NVE) in treatment-naïve or previously treated proliferative diabetic retinopathy (PDR) patients using optical coherence tomography (OCT) angiography. Methods: En face OCT angiograms of NVD/NVE in 40 eyes of 33 patients with PDR were acquired using RTVue XR Avanti OCT. The morphology of NVD/NVE on OCT angiograms was evaluated, and the activity was determined by biomicroscopy and fluorescein angiography (FA). In 12 eyes that were treated or treatment-naïve, changes in the morphology and vessel area of NVD/NVE before and after panretinal photocoagulation (PRP) were investigated. Results: Twenty eyes had treatment-naïve PDR, whereas 20 eyes were previously treated with PRP. All treatment-naïve NVD/NVE had remarkable (i.e., active) leakage in early-phase FA. Ninety-five percent of treatment-naïve NVD/NVE observed by OCT angiography had exuberant vascular proliferation (EVP), identified as irregular proliferation of fine (smaller-caliber) new vessels; whereas, the presence of EVP in previously treated eyes (13/20) was significantly less than in treatment-naïve eyes (65% vs. 95%, P = 0.043). The remaining seven treated eyes had pruned NVD/NVE without EVP, observed as fibrotic changes or faint (inactive) leakage in FA. The vessel areas of NVD/NVE significantly decreased following PRP (n = 12, P = 0.019), and NVD/NVE morphology showed pruning and decreased EVP. Conclusions: Exuberant vascular proliferation on OCT angiograms should be considered as an active sign of neovascularization; therefore, morphologic evaluation of neovascularization using OCT angiography may be useful to estimate the activity of each neovascularization in eyes with PDR.

PURPOSE: We quantitatively analyzed the features of a radial peripapillary capillary (RPC) network visualized using wide-field montage optical coherence tomography (OCT) angiography in healthy human eyes. METHODS: Twenty eyes of 20 healthy subjects were recruited. En face 3 × 3-mm OCT angiograms of multiple locations in the posterior pole were acquired using the RTVue XR Avanti, and wide-field montage images of the RPC were created. To evaluate the RPC density, the montage images were binarized and skeletonized. The correlation between the RPC density and the retinal nerve fiber layer (RNFL) thickness measured by an OCT circle scan was investigated. RESULTS: The RPC at the temporal retina was detected as far as 7.6 ± 0.7 mm from the edge of the optic disc but not around the perifoveal area within 0.9 ± 0.1 mm of the fovea. Capillary-free zones beside the first branches of the arterioles were significantly (P < 0.0001) narrower than those beside the second ones. The RPC densities at 0.5, 2.5, and 5 mm from the optic disc edge were 13.6 ± 0.8, 11.9 ± 0.9, and 10.4 ± 0.9 mm-1. The RPC density also was correlated significantly (r = 0.64, P < 0.0001) with the RNFL thickness, with the greatest density in the inferotemporal region. CONCLUSIONS: Montage OCT angiograms can visualize expansion of the RPC network. The RPC is present in the superficial peripapillary retina in proportion to the RNFL thickness, supporting the idea that the RPC may be the vascular network primarily responsible for RNFL nourishment.