Vitreous has been reported to prevent tumor angiogenesis, but our previous findings indicate that vitreous activate the signaling pathway of phosphoinositide 3-kinase (PI3K)/Akt, which plays a critical role in angiogenesis. The goal of this research is to determine which role of vitreous plays in angiogenesis-related cellular responses in vitro. We found that in human retinal microvascular endothelial cells (HRECs) vitreous activates a number of receptor tyrosine kinases including Anexelekto (Axl), which plays an important role in angiogenesis. Subsequently, we discovered that depletion of Axl using CRISPR/Cas9 and an Axl-specific inhibitor R428 suppress vitreous-induced Akt activation and cell proliferation, migration, and tuber formation of HRECs. Therefore, this line of research not only demonstrate that vitreous promotes angiogenesis in vitro, but also reveal that Axl is one of receptor tyrosine kinases to mediate vitreous-induced angiogenesis in vitro, thereby providing a molecular basis for removal of vitreous as cleanly as possible when vitrectomy is performed in treating patients with proliferative diabetic retinopathy.
PURPOSE: Identify key en face multimodal imaging features of optic disc drusen (ODD). DESIGN: Retrospective cross-sectional study. METHODS: . SETTING: Single academic center. PATIENT OR STUDY POPULATION: 786 patients (age 10-82 years) with diagnostic codes for ODD or the term "optic disc drusen" in clinical notes extracted using natural language processing. INTERVENTION OR OBSERVATION PROCEDURES: Color fundus image, green-light and blue-light fundus autofluorescence (FAF), near-infrared reflectance (NIR), and enhanced-depth imaging optical coherence tomography (EDI-OCT). MAIN OUTCOME MEASURES: Ophthalmic imaging characteristics and sensitivity of en face imaging compared with EDI-OCT. RESULTS: 38 (61 eyes) of 786 patients had high-quality EDI-OCT and en face multimodal imaging. Green-light FAF had the highest sensitivity (96.8%) and showed homogeneously hyperautofluorescence while blue-light FAF differentiated superficial and deep ODD by the heterogeneous brightness of FAF. Blue-light FAF (93.5%) and NIR (91.8%) were also sensitive and provided important features including the location, size, and depth of ODD and morphology of the optic disc and ODD-associated features such as horizontal hyperreflective lines and peripapillary hyperreflective ovoid mass-like structures (PHOMS), respectively. Color fundus imaging had the lowest sensitivity (82%). There was good inter-rater reliability for all en face imaging modalities (P < .0001 for all). CONCLUSIONS: Green-light FAF had the highest sensitivity in diagnosis of ODD, while blue-light FAF and NIR provided more information regarding the severity, location, depth, and size of ODD. In eyes that are negative on green-light FAF, EDI-OCT can be performed and provides the highest-resolution characterization of the entire optic disc to rule out ODD.