Switch of Intravitreal Therapy for Macular Edema Secondary to Retinal Vein Occlusion from Anti-VEGF to Dexamethasone Implant and Vice Versa

Purpose. To evaluate the anatomical and functional outcome of intravitreal dexamethasone implant for macular edema secondary to central (C) or branch (B) retinal vein occlusion (RVO) in patients with persistent macular edema (ME) refractory to intravitreal antivascular endothelial growth factor (VEGF) treatment compared to treatment naïve patients and to dexamethasone-refractory eyes switched to anti-VEGF. Methods. Retrospective, observational study including 30 eyes previously treated with anti-VEGF (8 CRVO, 22 BRVO, mean age 69 ± 10 yrs), compared to 11 treatment naïve eyes (6 CRVO, 5 BRVO, 73 ± 11 yrs) and compared to dexamethasone nonresponders (2 CRVO, 4 BRVO, 69 ± 12). Outcome parameters were change in best-corrected visual acuity (BCVA) and central foveal thickness (CFT) measured by spectral-domain optical coherence tomography. Results. Mean BCVA improvement after switch to dexamethasone implant was 4 letters (p=0.08), and treatment naïve eyes gained 10 letters (p=0.66), while we noted no change in eyes after switch to anti-VEGF (p=0.74). Median CFT decrease was most pronounced in treatment naïve patients (−437 μm, p=0.002) compared to anti-VEGF refractory eyes (−170 μm, p=0.003) and dexamethasone-refractory eyes (−157, p=0.31). Conclusions. Dexamethasone significantly reduced ME secondary to RVO refractory to anti-VEGF. Functional gain was limited compared to treatment naïve eyes, probably due to worse BCVA and CFT at baseline in treatment naïve eyes

CNTF Attenuates Vasoproliferative Changes Through Upregulation of SOCS3 in a Mouse-Model of Oxygen-Induced Retinopathy

PURPOSE. Retinal vascular disease represents a major cause for vision loss in the Western world. Recent research has shown that neuronal and vascular damage are closely related in retinal disease. Ciliary neurotrophic factor (CNTF) is a well-studied neurotrophic factor that is currently being tested in clinical trials for the treatment of retinal degenerative diseases and macular telangiectasia. However, little is known about its effect on retinal vasculature. In this study, we investigate the effects of CNTF in retinal neovascular disease using the mouse model of oxygen-induced retinopathy (OIR). METHODS. Newborn pups were exposed to 75% oxygen from postnatal day (P) 7 to P12 and subsequently returned to room air. Ciliary neurotrophic factor was injected intravitreally at OIR P12 and the vaso-obliterated and neovascular areas were quantified at OIR P17. Immunohistochemistry, RNA, and protein analysis were used to identify CNTF-responsive cells. In vitro experiments were performed to analyze the effect of CNTF on endothelial and astroglial cells. RESULTS. In the OIR model, CNTF facilitated capillary regrowth and attenuated preretinal neovascularization in a dose-dependent manner. The protective effect of CNTF was mediated via activation of the JAK/STAT3/SOCS3 signaling pathway. Immunohistochemical studies identified endothelial cells among others as CNTF-responsive cells in the retina. In vitro studies confirmed the anti-angiogenic effect of CNTF on endothelial cell sprouting. CONCLUSIONS. This study provides evidence for a therapeutic potential of CNTF beyond degenerative retinal disease. Vasoproliferative retinopathies may benefit from a CNTF-dependent and SOCS3-mediated angiomodulatory effect

Additional file 1: of Systemic confounders affecting serum measurements of omega-3 and -6 polyunsaturated fatty acids in patients with retinal disease

This file contains a list of all fatty acids analyzed for this study. (DOC 41 kb

Sema3f Protects Against Subretinal Neovascularization In Vivo

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