Association between outer retinal alterations and microvascular changes in intermediate stage age-related macular degeneration: an optical coherence tomography angiography study

AIMS: To investigate associations between changes in retinal vessels and alterations detected by spectral domain optical coherence tomography (SD-OCT) scans in intermediate stage age-related macular degeneration (AMD). METHODS: Thirty eyes of 30 patients with intermediate dry AMD were enrolled in the study. Of the cohort study, 15 eyes (changes-AMD group) showed OCT changes preceding the development of drusen-associated atrophy. A control group of healthy subjects was selected for statistical comparisons. All patients underwent an ophthalmologic evaluation, including OCT angiography (OCTA) and SD-OCT scans. Main outcome measures were superficial vessel density, deep vessel density, macular thickness. RESULTS: Foveal macular thickness was 215.2\ub132.9\u2005\u3bcm in changes-AMD patients and was significantly thinner than no changes-AMD patients (248.3\ub123.3\u2005\u3bcm, p=0.002) and healthy subjects (268.1\ub119.2\u2005\u3bcm, p<0.0001). Furthermore, in the parafoveal area, the thicknesses of both the inner retina and the outer retina were reduced in the changes-AMD group, after comparison with the two other groups. Parafoveal superficial vascular plexus flow density was 43.3\ub12.7% in changes-AMD patients and was decreased compared with the no changes-AMD group (48.7\ub13.3%, p=0.003) and healthy controls (50.4\ub16.1%, p=0.001). A direct correlation of the superficial plexus flow density with the inner retina parafoveal macular thickness (R2=0.761, p=0.028) was found. CONCLUSIONS: We demonstrated an association between SD-OCT signs and retinal blood supply in patients with intermediate AMD and we showed that patients with signs predicting development of geographic atrophy have a reduced flow in superficial vascular plexus and damage of the inner and the outer retina

Anatomical and Functional Changes of the Retina and the Choroid after Resolved Chronic CSCR

BACKGROUND: To investigate anatomical/functional changes after oral eplerenone therapy for chronic central serous chorioretinopathy (CCSC) in successfully treated eyes and fellow eyes and assess timing of foveal subretinal fluid (SRF) resolution. METHODS: Twenty-one eyes of 21 patients suffering from CCSC with monolateral foveal SRF successfully treated with oral eplerenone were enrolled in this retrospective study (group 1). The fellow eyes (21 eyes; group 2), healthy or affected by CCSC, without foveal SRF were considered in the analysis. A control healthy group was enrolled as well (healthy controls; n = 21). Main outcome measures during follow-up included changes of best corrected visual acuity (BCVA, logMAR), central macular thickness (CMT; \ub5m), SRF (\ub5m), subfoveal choroidal thickness (SFCT; \ub5m), superficial capillary plexus density (SCPD, %), deep capillary plexus density (DCPD, %), and choriocapillaris density (CCD, %) and percentage of eyes showing foveal SRF resolution at different time points. RESULTS: Functional and anatomical parameters significantly improved during the study in group 1. BCVA increased significantly (p < 0.001), while CMT, SFCT, and SRF decreased significantly (p < 0.001; p < 0.001, and p = 0.037, respectively). SCPD, DCPD, and CCD did not show any statistically significant difference during follow-up. In 71.4% of eyes, resolution of SRF was observed within 60 days and in the remaining 28.6%, at 120 days. In fellow eyes, SFCT decreased significantly (p < 0.001), whilst all other parameters did not modify. CONCLUSIONS: Eplerenone treatment in chronic CSCR potentially improves recovery of retinal and choroidal morphology as well as visual acuity gain. A complete resolution of foveal SRF was observed in all eyes during a 4-month follow-up, with most eyes healing at 2 months. KEYWORDS: choriocapillaris density; chronic central serous chorioretinopathy; eplerenone therapy; optical coherence tomography angiography; subfoveal choroidal thickness; superficial capillary plexus densit

Choroidal and Retinal Imaging Biomarkers in Different Types of Macular Neovascularization

Background: The aim of this study was to investigate optical coherence tomography (OCT) and OCT angiography (OCTA) parameters in patients with neovascular age-related macular degeneration (nAMD) and macular neovascularization (MNV) type 1, type 2, and type 3. Methods: In this retrospective study, 105 treatment-naïve eyes of 105 patients (60 men and 45 women) with a definite diagnosis of active nAMD and MNV of different types and 105 frequency-matched age and gender healthy subjects were evaluated (61 men and 44 women). All subjects underwent a full ophthalmic examination and multimodal imaging assessment, including spectral domain (SD) OCT and OCTA. The main outcome measures were choroidal vascularity index (CVI), subfoveal choroidal thickness (SFCT), central macular thickness (CMT), and outer retina to choriocapillaris (ORCC) MNV flow area (ORCCFA). Results: Significant differences were found in terms of CVI, CMT, and ORCCFA between MNV 1 and the two other groups. CVI was significantly different between MNV 1 and healthy control patients (p < 0.001) and between MNV 1 and MNV 2 (p < 0.001). ORCCFA and CMT were significantly different between MNV1 and MNV2 (p < 0.005). The difference in subfoveal CT between the three groups was not statistically significant (p = 0.458). A significant negative correlation was found between CVI and ORCCFA. Furthermore, CVI showed a positive correlation with subfoveal CT

TFEB controls vascular development by regulating the proliferation of endothelial cells

Transcription factor TFEB is thought to control cellular functions-including in the vascular bed-primarily via regulation of lysosomal biogenesis and autophagic flux. Here, we report that TFEB also orchestrates a non-canonical program that controls the cell cycle/VEGFR2 pathway in the developing vasculature. In endothelial cells, TFEB depletion halts proliferation at the G1-S transition by inhibiting the CDK4/Rb pathway. TFEB-deficient cells attempt to compensate for this limitation by increasing VEGFR2 levels at the plasma membrane via microRNA-mediated mechanisms and controlled membrane trafficking. TFEB stimulates expression of the miR-15a/16-1 cluster, which limits VEGFR2 transcript stability and negatively modulates expression of MYO1C, a regulator of VEGFR2 trafficking to the cell surface. Altered levels of miR-15a/16-1 and MYO1C in TFEB-depleted cells cause increased expression of plasma membrane VEGFR2, but in a manner associated with low signaling strength. An endothelium-specific Tfeb-knockout mouse model displays defects in fetal and newborn mouse vasculature caused by reduced endothelial proliferation and by anomalous function of the VEGFR2 pathway. These previously unrecognized functions of TFEB expand its role beyond regulation of the autophagic pathway in the vascular system

The TFEB-TGIF1 axis regulates EMT in mouse epicardial cells

Epithelial-mesenchymal transition (EMT) is a complex and pivotal process involved in organogenesis and is related to several pathological processes, including cancer and fibrosis. During heart development, EMT mediates the conversion of epicardial cells into vascular smooth muscle cells and cardiac interstitial fibroblasts. Here, we show that the oncogenic transcription factor EB (TFEB) is a key regulator of EMT in epicardial cells and that its genetic overexpression in mouse epicardium is lethal due to heart defects linked to impaired EMT. TFEB specifically orchestrates the EMT-promoting function of transforming growth factor (TGF) beta, and this effect results from activated transcription of thymine-guanine-interacting factor (TGIF)1, a TGF beta/Smad pathway repressor. The Tgif1 promoter is activated by TFEB, and in vitro and in vivo findings demonstrate its increased expression when Tfeb is overexpressed. Furthermore, Tfeb overexpression in vitro prevents TGF beta-induced EMT, and this effect is abolished by Tgif1 silencing. Tfeb loss of function, similar to that of Tgif1, sensitizes cells to TGF beta, inducing an EMT response to low doses of TGF beta. Together, our findings reveal an unexpected function of TFEB in regulating EMT, which might provide insights into injured heart repair and control of cancer progression.Epithelial-mesenchymal transition (EMT) is a complex process involved in organogenesis. Here, the authors show that the transcription factor EB (TFEB) regulates EMT in epicardium during heart development by tuning sensitivity to TGF beta signaling