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Purpose To compare multimodal imaging in detecting lacquer cracks in highly myopic eyes, and to correlate these findings with those of spectral-domain optical coherence tomography (SD-OCT). Methods An observational case series study. Patients with a refractive error worse than À 8 diopters and lacquer cracks were recruited. The rates of detection of the lacquer cracks using multimodal imaging including near-infrared reflectance (NIR) imaging, fundus autofluorescence (FAF) imaging, and fluorescence angiography (FA) were compared. The characteristic findings of multimodal imaging were correlated with those of SD-OCT. Results NIR imaging was more sensitive (92.9%) in detecting lacquer cracks than either FAF (12.5%) or FA (67.9%). Lacquer cracks showed hyperreflectance on NIR, and they were consistently associated with a continuous retinal pigment epitheliumBruch's membrane complex, thinner choroid, and acoustic shadows on SD-OCT. Conclusions NIR imaging is superior to blue laser light (FAF and FA) imaging in detecting lacquer cracks. SD-OCT in combination with NIR located primary pathological lacquer cracks in the intact retinal pigment epithelium-Bruch's membrane complex as well as thinner choroid. These findings indicate that multimodal cSLO and SD-OCT imaging allow for detecting of lacquer cracks in highly myopic eyes.

Cerebral cavernous malformations (CCMs) are common neurovascular lesions caused by loss-of-function mutations in one of three genes, including KRIT1 (CCM1), CCM2, and PDCD10 (CCM3), and generally regarded as an endothelial cell-autonomous disease. Here we report that proliferative astrocytes play a critical role in CCM pathogenesis by serving as a major source of VEGF during CCM lesion formation. An increase in astrocyte VEGF synthesis is driven by endothelial nitric oxide (NO) generated as a consequence of KLF2 and KLF4-dependent elevation of eNOS in CCM endothelium. The increased brain endothelial production of NO stabilizes HIF-1α in astrocytes, resulting in increased VEGF production and expression of a “hypoxic” program under normoxic conditions. We show that the upregulation of cyclooxygenase-2 (COX-2), a direct HIF-1α target gene and a known component of the hypoxic program, contributes to the development of CCM lesions because the administration of a COX-2 inhibitor significantly prevents progression of CCM lesions. Thus, non-cell-autonomous crosstalk between CCM endothelium and astrocytes propels vascular lesion development, and components of the hypoxic program represent potential therapeutic targets for CCMs.