Correlation between improvement in visual acuity and QOL after Ranibizumab treatment for age-related macular degeneration patients: QUATRO study.

Background: To evaluate the correlation between visual acuity improvement and vision-related QOL after ranibizumab treatment in Japanese patients with AMD.

Methods: In this one-year prospective, interventional, open-label, multicenter study involving four sites, patients with neovascular AMD were enrolled and observed for 12 months. Treatment-naïve patients received 0.

[Comparison of 12 Months Outcome of As-needed Intravitreal Aflibercept or Ranibizumab for the Treatment of Naïve Patients with Age-related Macular Degeneration].

Purpose: To compare pro re nata (PRN) intravitreal injections of aflibercept (IVA) and ranibizumab (IVR) in patients with treatment naïve age-related macular degeneration (AMD).

Material And Methods: We analyzed 42 eyes that receive 3 times monthly IVA as introduction phase and subsequently received PRN retreatment at the recurrence. As the control, 56 eyes received the same IVR treatments as the IVA criteria.

[Background factors of recurrence after remission maintenance with photodynamic therapy for age-related macular degeneration].

Purpose: To investigate the factors associated with recurrence following remission of at least 12 months after photodynamic therapy in patients with age-related macular degeneration (AMD).

Subjects And Methods: We analyzed 42 eyes with AMD in 41 patients who did not require additional treatment within 12 months of their photodynamic therapy (PDT). Additional treatment for recurrence beyond 12 months after the last PDT was required in 20 eyes in the recurrent group (n = 20).

Equine infectious anemia viral vector-mediated codelivery of endostatin and angiostatin driven by retinal pigmented epithelium-specific VMD2 promoter inhibits choroidal neovascularization.

Equine infectious anemia virus (EIAV) is a nonprimate lentivirus that does not cause human disease. Subretinal injection into mice of a recombinant EIAV lentiviral vector in which lacZ is driven by a CMV promoter (EIAV CMV LacZ) resulted in rapid and strong expression of LacZ in retinal pigmented epithelial (RPE) cells and some other cells including ganglion cells, resulting in the presence of 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside within the optic nerve. Substitution of the RPE-specific promoter from the vitelliform macular dystrophy (VMD2) gene for the CMV promoter resulted in prolonged (at least 1 year) expression of LacZ that was restricted to RPE cells, albeit reduced 6- to 10-fold compared with the CMV promoter.

Topical administration of a multi-targeted kinase inhibitor suppresses choroidal neovascularization and retinal edema.

Age-related macular degeneration, diabetic retinopathy, and retinal vein occlusions are complicated by neovascularization and macular edema. Multi-targeted kinase inhibitors that inhibit select growth factor receptor tyrosine kinases and/or components of their down-stream signaling cascades (such as Src kinases) are rationale treatment strategies for these disease processes. We describe the discovery and characterization of two such agents.

Development of prodrug 4-chloro-3-(5-methyl-3-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}-1,2,4-benzotriazin-7-yl)phenyl benzoate (TG100801): a topically administered therapeutic candidate in clinical trials for the treatment of age-related macular degeneration.

Age-related macular degeneration (AMD) is one of the leading causes of loss of vision in the industrialized world. Attenuating the VEGF signal in the eye to treat AMD has been validated clinically. A large body of evidence suggests that inhibitors targeting the VEGFr pathway may be effective for the treatment of AMD.

Suppression and regression of choroidal neovascularization by systemic administration of an alpha5beta1 integrin antagonist.

Integrin alpha(5)beta(1) plays an important role in developmental angiogenesis, but its role in various types of pathologic neovascularization has not been completely defined. In this study, we found strong up-regulation of alpha(5)beta(1) in choroidal neovascularization. Implantation of an osmotic pump delivering 1.

Intraocular injection of an aptamer that binds PDGF-B: a potential treatment for proliferative retinopathies.

Platelet-derived growth factor-B (PDGF-B) has been implicated in the pathogenesis of proliferative retinopathies and other scarring disorders in the eye. In this study, we sought to test the therapeutic potential of an aptamer that selectively binds PDGF-B, ARC126, and its PEGylated derivative, ARC127. Both ARC126 and ARC127 blocked PDGF-B-induced proliferation of cultured fibroblasts with an IC50 of 4 nM.

Vascular targeting of ocular neovascularization with a vascular endothelial growth factor121/gelonin chimeric protein.

Tumors provide an extremely abnormal microenvironment that stimulates neovascularization from surrounding vessels and causes altered gene expression within vascular cells. Up-regulation of vascular endothelial growth factor (VEGF) receptors has allowed selective destruction of tumor vessels by administration of a chimeric protein consisting of VEGF121 coupled to the toxin gelonin (VEGF/rGel). We sought to determine whether there is sufficient up-regulation of VEGF receptors in endothelial cells participating in ocular neovascularization to permit a similar strategy.

Different effects of angiopoietin-2 in different vascular beds: new vessels are most sensitive.

In this study, we used double transgenic mice with inducible expression of angiopoietin-2 (Ang2) to investigate the role of Ang2 in the retinal and choroidal circulations and in three models of ocular neovascularization (NV). Mice with induced expression of Ang2 ubiquitously, or specifically in the retina, survived and appeared grossly normal. They also had normal-appearing retinal and choroidal circulations, demonstrating that high levels of Ang2 did not induce regression of mature retinal or choroidal vessels.

Angiopoietin 1 prevents retinal detachment in an aggressive model of proliferative retinopathy, but has no effect on established neovascularization.

Vascular endothelial growth factor (VEGF) plays a central role in vasoproliferative diseases in the retina, however, other gene products modulate its effects. The angiopoietins are particularly important in this regard. Angiopoietin 2 (Ang2) collaborates with VEGF to stimulate neovascularization (NV) in some situations, but in other situations causes regression of NV.

Expression of ephrinB2 and its receptors on fibroproliferative membranes in ocular angiogenic diseases.

Purpose: To determine whether ephrinB2 plays a role in ocular angiogenesis, we investigated the expression of ephrinB2 and EphB receptors on retinal fibroproliferative membranes.

Design: Experimental study of the expression of ephrinB2 and EphB receptors within fibroproliferative membranes in patients with ocular angiogenic diseases collected during vitrectomy.

Methods: Fibroproliferative membranes were obtained at the time of vitrectomy from 20 patients with proliferative diabetic retinopathy (PDR) and from 40 patients who had stage 5 retinopathy of prematurity.

Colocalization of Tie2, angiopoietin 2 and vascular endothelial growth factor in fibrovascular membrane from patients with retinopathy of prematurity.

Purpose: The tyrosine kinase receptor Tie2 and its ligands, the angiopoietins (Angs), play important roles in vascular integrity and neovascularization, modulating vascular endothelial growth factor (VEGF) activity. To elucidate the potential role of Angs and the Tie2 system in retinopathy of prematurity (ROP), we have investigated the expression of Angs, Tie2 and VEGF within fibroproliferative membranes in ROP.

Methods: Fibroproliferative membranes were obtained from 38 cases with stage 5 ROP at the time of vitrectomy.

Non-paralleled increase of hepatocyte growth factor and vascular endothelial growth factor in the eyes with angiogenic and nonangiogenic fibroproliferation.

Vascular endothelial growth factor (VEGF) has been known as principal angiogenic factor in vasculogenesis, tumor angiogenesis and ocular angiogenesis. Currently, hepatocyte growth factor (HGF) has been reported to play a major role in ocular angiogenesis. We studied distribution of both growth factors in angiogenic and non-angiogenic fibroproliferation to determine the correlation of VEGF and HGF in retinal angiogenesis.