Dataset Information

SAVE-AMD: Safety of VEGF Inhibitors in Age-Related Macular Degeneration.

ABSTRACT: To determine whether intraocular treatment with vascular endothelial growth factor (VEGF) inhibitors change systemic endothelial function (EF) in patients with neovascular age-related macular degeneration (AMD).In this prospective, randomized, 2-center, double-masked controlled interventional trial, patients with neovascular and dry AMD were enrolled. Eligible neovascular AMD patients received 2 intravitreal loading doses of either ranibizumab 0.5 mg or bevacizumab 1.25 mg at 4-week intervals and were subsequently followed every 4 weeks and treated according to a pro re nata regime for up to 1 year. Patients with dry AMD served as controls. The primary endpoint was the change in EF assessed by flow-mediated dilatation (FMD) after 2 months of treatment with VEGF inhibitors in patients with AMD compared to patients with dry AMD. FMD was assessed with B-mode high-resolution ultrasonography of the left brachial artery.24 patients with neovascular AMD and 26 patients with dry ADM were included in the trial. Treatment with VEGF inhibitors did not significantly change FMD (from 4.7 ± 2.4 to 3.9 ± 1.9% after 8 weeks, p = 0.07, and to 5.1 ± 2.0% after 1 year; p = 0.93 vs. baseline, respectively).EF did not significantly differ between patients with neovascular AMD treated with intravitreal VEGF inhibition and patients with dry AMD.

SUBMITTER: Enseleit F

PROVIDER: S-EPMC5804860 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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SAVE-AMD: Safety of VEGF Inhibitors in Age-Related Macular Degeneration.

Enseleit Frank F Michels Stephan S Sudano Isabella I Stahel Marc M Zweifel Sandrine S Schlager Oliver O Becker Matthias M Winnik Stephan S Nägele Matthias M Flammer Andreas J AJ Neidhart Michel M Graf Nicole N Matter Christian M CM Seifert Burkhardt B Lüscher Thomas F TF Ruschitzka Frank F

Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde 20170902 4

<h4>Objective</h4>To determine whether intraocular treatment with vascular endothelial growth factor (VEGF) inhibitors change systemic endothelial function (EF) in patients with neovascular age-related macular degeneration (AMD).<h4>Methods</h4>In this prospective, randomized, 2-center, double-masked controlled interventional trial, patients with neovascular and dry AMD were enrolled. Eligible neovascular AMD patients received 2 intravitreal loading doses of either ranibizumab 0.5 mg or bevacizu ...[more]

PMID: 28866675

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Project description:Age-related macular degeneration (AMD) is the most prevalent form of irreversible blindness worldwide in the elderly population. The pathology of dry AMD consists of macular degeneration of photoreceptors and the RPE, lipofuscin (A2E) accumulation, and drusen formation. Mice have been widely used for generating models that simulate human AMD features for investigating the pathogenesis, treatment and prevention of the disease. Although the mouse has no macula, focal atrophy of photoreceptors and RPE, lipofuscin accumulation, and increased A2E can develop in aged mouse eyes. However, drusen are rarely seen in mice because of their simpler Bruch's membrane and different process of lipofuscin extrusion compared with humans. Thus, analyzing basal deposits at the ultrastructural level and understanding the ultrastructural pathologic differences between various mouse AMD models are critical to comprehending the significance of research findings and response to possible therapeutic options for dry AMD. Based on the multifactorial pathogenesis of AMD, murine dry AMD models can be classified into three groups. First, genetically engineered mice that target genes related to juvenile macular dystrophies are the most common models, and they include abcr(-/-) (Stargardt disease), transgenic ELOVL4 (Stargardt-3 dominant inheritary disease), Efemp1(R345W/R345W) (Doyne honeycomb retinal dystrophy), and Timp3(S156C/S156C) (Sorsby fundus dystrophy) mice. Other murine models target genes relevant to AMD, including inflammatory genes such as Cfh(-/-), Ccl2(-/-), Ccr2(-/-), Cx3cr1(-/-), and Ccl2(-/-)/cx3cr1(-/-), oxidative stress associated genes such as Sod1(-/-) and Sod2 knockdown, metabolic pathway genes such as neprilysin(-/-) (amyloid beta), transgenic mcd/mcd (cathepsin D), Cp(-/-)/Heph(-/Y) (ferroxidase ceruloplasmin/hepaestin, iron metabolism), and transgenic ApoE4 on high fat and high cholesterol diet (lipid metabolism). Second, mice have also been immunologically manipulated by immunization with carboxyethylpyrrole (CEP), an oxidative fragment of DHA found in drusen, and found to present with dry AMD features. Third, natural mouse strains such as arrd2/arrd2 (Mdm gene mutation) and the senescence accelerated mice (SAM) spontaneously develop features of dry AMD like photoreceptor atrophy and thickening of Bruch's membrane. All the aforementioned models develop retinal lesions with various features that simulate dry AMD lesions: focal photoreceptor degeneration, abnormal RPE with increased lipofuscin, basal infolding, decreased melanosomes and degeneration. However, Bruch's membrane changes are less common. Most mice develop retinal lesions at an older age (6-24 months, depending on the models), while the Ccl2(-/-)/cx3cr1(-/-) mice develop lesions by 4-6 weeks. Although murine models present various degrees of retinal and/or RPE degeneration, classical drusen is extremely rare. Using electron microscopy, small drusenoid deposits are found between RPE and Bruch's membrane in a few models including Efemp1(R345W/R345W), Ccl2(-/-)/cx3cr1(-/-), neprilysin(-/-), transgenic mcd/mcd, and ApoE4 transgenic mice on a high fat diet. High A2E levels are measured in the retinas of abcr(-/-), transgenic ELOVL4, and Ccl2(-/-)/cx3cr1(-/-) mice. In summary, murine models provide useful tools for studying AMD pathogenesis and evaluating novel therapies for this disease. This review compares the major dry AMD murine models and discusses retinal pathology at the ultrastructural level.

Dataset Information

SAVE-AMD: Safety of VEGF Inhibitors in Age-Related Macular Degeneration.

Publications

SAVE-AMD: Safety of VEGF Inhibitors in Age-Related Macular Degeneration.

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