Abstract: Purpose: Ciliary neurotrophic factor (CNTF) is a well-characterized neurotrophic factor currently in clinical trials for the treatment of macular telangiectasia type II. Our previous work showed that CNTF-induced STAT3 signaling is a potent inhibitor of pathologic preretinal neovascular tuft formation in the mouse model of oxygen-induced retinopathy. In this study, we investigated the effect of CNTF on outer retinal and choroidal angiogenesis and the mechanisms that underpin the observed decrease in outer retinal neovascularization following CNTF treatment. Methods: In the Vldlr-/- and laser-CNV mouse models, mice received a one-time injection (on postnatal day [P] 12 in the Vldlr-/- model and 1 day after laser in the Choroidal Neovascularization (CNV) model) of recombinant CNTF or CxCl10, and the extent of neovascular lesions was assessed 6 days posttreatment. STAT3 downstream targets affected by CNTF treatment were identified using quantitative PCR analysis. A proteome array was used to compare media conditioned by CNTF-treated and control-treated primary Müller cells to screen for CNTF-induced changes in secreted angiogenic factors. Results: Intravitreal treatment with recombinant CNTF led to significant reduction in neovascularization in the Vldlr-/- and laser-CNV mouse models. Treatment effect in the Vldlr-/- was long-lasting but time sensitive, requiring intravitreal treatment before P19. Mechanistic workup in vitro as well as in vivo confirmed significant activation of the STAT3-signaling pathway in Müller cells in response to CNTF treatment and upregulation of CxCl10. Intravitreal injections of recombinant CxCl10 significantly reduced outer retinal neovascularization in vivo in both the Vldlr-/- and laser-CNV mouse models. Conclusions: CNTF treatment indirectly affects outer retinal and choroidal neovascularization by inducing CxCl10 secretion from retinal Müller cells

Abstract: Pathological neovascularization of the outer retina is the hallmark of neovascular age-related macular degeneration (nAMD). Building on our previous observations that semaphorin 3F (Sema3f) is expressed in the outer retina and demonstrates anti-angiogenic potential, we have investigated whether Sema3f can be used to protect against subretinal neovascularization in two mouse models. Both in the very low-density lipid-receptor knockout (Vldlr−/−) model of spontaneous subretinal neovascularization as well as in the mouse model of laser-induced choroidal neovascularization (CNV), we found protective effects of Sema3f against the formation of pathologic neovascularization. In the Vldlr−/− model, AAV-induced overexpression of Sema3f reduced the size of pathologic neovascularization by 56%. In the laser-induced CNV model, intravitreally injected Sema3f reduced pathologic neovascularization by 30%. Combined, these results provide the first evidence from two distinct in vivo models for a use of Sema3f in protecting the outer retina against subretinal neovascularization

Abstract: Objective: To describe vascular changes in different stages of Stargardt disease (STGD) via double swept-source optical coherence tomography angiography. Methods and analysis: Prospective, cross-sectional case-control study. Twenty-three patients (45 eyes) with ABCA4 mutations graded according to the Fishman STGD classification and 23 controls (23 eyes) were included. Two independent investigators quantified the foveal avascular zone (FAZ) in the superficial and deep capillary plexus (SCP/DCP) and the areas presenting rarefied flow and complete vascular atrophy in the outer retina to choriocapillaris (ORCC) and choriocapillaris (CC) slab. Results: The mean age at first diagnosis of STGD was 24.0 years (range 9-50) and 37.9 years (range 18-74) at the time of examination. Eleven patients were assigned to the Fishman STGD classification stage (S) 1, three to S2, eight to S3 and one to S4. The FAZ in SCP and DCP was increased in all stages compared with controls (p0.01). Areas with rarefied flow signal and vascular atrophy were detected in the ORCC and the CC layer and grew with increasing stage of disease (p0.01). The duration of disease correlated with the extent of the enlarged FAZ in the SCP/DCP and with the area of reduced flow in the ORCC and CC layer (p

Abstract: Purpose: To compare spectral-domain (SD) and swept-source (SS) optical coherence tomography angiography (OCTA) for imaging retinal capillary hemangioblastomas (RCHs) in von Hippel-Lindau disease (VHLD). Methods: Prospective single-center cross-sectional study. Tumor size (TS) of perfused RCHs was assessed clinically in relation to the optic disc size. For both technologies, SD-OCTA and SS-OCTA, corresponding images with a scan size of 3 × 3 mm2 and 6 × 6 mm2, respectively, were overlaid according to the set of marker positions to determine the TS. Results: From 200 patients with VHLD, 48 patients showed 84 RCHs. SD-OCTA images of 39 RCHs (46.4%) and SS-OCTA images of 48 RCHs (57.2%) were suitable for analysis. The average in OCTA-measured TS of 1.60 ± 2.58 mm2 (range, 0.01-10.43) was congruent to the clinically assessed TS in 81.3% of cases (r = 0.86, P 0.0001). TS measured in SD-OCTA compared to SS-OCTA showed similar values and a high correlation (all P 0.0001). Nevertheless, despite the similarities, a slight trend in SS-OCTA was observed whereby with increasing TS, an elevated TS was detected compared to SD-OCTA (3 × 3-mm2 scans: mean difference of 0.03 ± 0.04 mm2, 6 × 6-mm2 scans: 0.08 ± 0.19 mm2). However, within the same imaging technology method, TS values almost did not differ (SD-OCTA: mean difference of 0.01 ± 0.02 mm2, SS-OCTA: 0.001 ± 0.01 mm2).brbrConclusions: OCTA may serve as an additional tool for diagnosis and monitoring of RCHs. Nevertheless, due to the differences between the technologies, the values cannot be used interchangeably.