Pharmacologic management of neovascular age-related macular degeneration: systematic review of economic evidence and primary economic evaluation

Hodge, William; Brown, Allan; Kymes, Steve; Cruess, Alan F.; Blackhouse, Gord; Hopkins, Robert; McGahan, Lynda; Sharma, Sanjay; Pan, Irene; Blair, Jason; Vollman, David; Morrison, Andra

doi:10.3129/i10-047

Cited by 19 publications

(7 citation statements)

References 23 publications

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“…Intravitreal injection may have injection-related side effects, and avoiding this risk would be a great benefit for the patient. In addition, intravitreal injections have to be performed by health-care professionals and the associated costs with repetitive injections are substantial [13, 14]. Topical treatment of posterior segment disease with eye drops has the potential to both cut these costs and improve the safety of the procedure.…”

Section: Resultsmentioning

confidence: 99%

“…The requirement for monthly or bimonthly injection regimens with the currently available substances [11, 12] are due to a relatively low efficacy and fast ocular clearance of these drugs. As a consequence, an individual patient’s risk for injection-associated complications like endophthalmitis or retinal tears increases cumulatively over a prolonged treatment period and not only represents a burden for the affected patient but also leads to substantial healthcare costs associated with the repeated injections [13, 14]. …”

Section: Introductionmentioning

confidence: 99%

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Highly potent VEGF-A-antagonistic DARPins as anti-angiogenic agents for topical and intravitreal applications

Stahl¹,

Stumpp

Schlegel

et al. 2012

Angiogenesis

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The next-generation ophthalmic anti-VEGF therapeutics must aim at being superior to the currently available agents with regard to potency and improved drug delivery, while still being stable and safe to use at elevated concentrations. We show here the generation of a set of highly potent VEGF-A antagonistic DARPins (designed ankyrin repeat proteins) delivering these properties. DARPins with single-digit picomolar affinity to human VEGF-A were generated using ribosome display selections. Specific and potent human VEGF-A binding was confirmed by ELISA and endothelial cell sprouting assays. Cross-reactivity with VEGF-A of several species was confirmed by ELISA. Intravitreally injected DARPin penetrated into the retina and reduced fluorescein extravasation in a rabbit model of vascular leakage. In addition, topical DARPin application was found to diminish corneal neovascularization in a rabbit suture model, and to suppress laser-induced neovascularization in a rat model. Even at elevated doses, DARPins were safe to use. The fact that several DARPins are highly active in various assays illustrates the favorable class behavior of the selected binders. Anti-VEGF-A DARPins thus represent a novel class of highly potent and specific drug candidates for the treatment of neovascular eye diseases in both the posterior and the anterior eye chamber.Electronic supplementary materialThe online version of this article (doi:10.1007/s10456-012-9302-0) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Highly potent VEGF-A-antagonistic DARPins as anti-angiogenic agents for topical and intravitreal applications

Stahl¹,

Stumpp

Schlegel

et al. 2012

Angiogenesis

View full text Add to dashboard Cite

show abstract

“…For best therapeutic outcome, injections need to be repeated on a monthly base [8]. Monthly intravitreal injections are a considerable burden for the patient and the executive clinics [9].…”

Section: Introductionmentioning

confidence: 99%

Fucoidan Reduces Secretion and Expression of Vascular Endothelial Growth Factor in the Retinal Pigment Epithelium and Reduces Angiogenesis In Vitro

et al. 2014

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Fucoidan is a polysaccharide isolated from brown algae which is of current interest for anti-tumor therapy. In this study, we investigated the effect of fucoidan on the retinal pigment epithelium (RPE), looking at physiology, vascular endothelial growth factor (VEGF) secretion, and angiogenesis, thus investigating a potential use of fucoidan for the treatment of exudative age-related macular degeneration. For this study, human RPE cell line ARPE-19 and primary porcine RPE cells were used, as well as RPE/choroid perfusion organ cultures. The effect of fucoidan on RPE cells was investigated with methyl thiazolyl tetrazolium – assay, trypan blue exclusion assay, phagocytosis assay and a wound healing assay. VEGF expression was evaluated in immunocytochemistry and Western blot, VEGF secretion was evaluated in ELISA. The effect of fucoidan on angiogenesis was tested in a Matrigel assay using calcein-AM vital staining, evaluated by confocal laser scanning microcopy and quantitative image analysis. Fucoidan displays no toxicity and does not diminish proliferation or phagocytosis, but reduces wound healing in RPE cells. Fucoidan decreases VEGF secretion in RPE/choroid explants and RPE cells. Furthermore, it diminishes VEGF expression in RPE cells even when co-applied with bevacizumab. Furthermore, fucoidan reduces RPE-supernatant- and VEGF-induced angiogenesis of peripheral endothelial cells. In conclusion, fucoidan is a non-toxic agent that reduces VEGF expression and angiogenesis in vitro and may be of interest for further studies as a potential therapy against exudative age-related macular degeneration.

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“…2004) suggesting an important role for gene and environment interactions. Both DR and AMD generate a considerable burden to the health service (Javitt & Aiello 1996; Hodge et al. 2010) and are expected to increase owing to the predicted rise in the prevalence of diabetes and the predicted demographic transition with a substantial increase in the number and proportion of elderly people (Khaw 1999; Wild et al.…”

Section: Introductionmentioning

confidence: 99%

The Tromsø Eye Study: study design, methodology and results on visual acuity and refractive errors

et al. 2012

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ABSTRACT.Purpose: To describe the study design and methodology of the Tromsø Eye Study (TES), and to describe visual acuity and refractive error in the study population. Methods:The Tromsø Eye Study is a sub-study of the Tromsø Study, a population-based multipurpose longitudinal study in the municipality of Tromsø, Norway. The Tromsø Eye Study was a part of the sixth survey of the Tromsø Study, conducted from October 2007 through December 2008. The eye examination included information on self-reported eye diseases, assessment of visual acuity and refractive errors, retinal photography and optical coherence tomography. Retinal images were graded for diabetic retinopathy and age-related macular degeneration, and with computer-assisted measurements of arteriolar and venular diameters. In addition, TES researchers have access to the large comprehensive Tromsø Study database including physical examination results, carotid artery ultrasound, electrocardiogram, bone densitometry, cognitive tests, questionnaires, DNA, blood and urine samples and more from the present and the five previous surveys.Results: Visual acuity was assessed in 6459 subjects and refraction in 6566 subjects aged 38-87 years.Snellen visual acuity <20 ⁄ 60 was found in 1.2% (95% CI 0.95-1.5) of the participants and there was no gender difference. Visual impairment increased with age, and in the age group 80-87 years, the overall visual acuity <20 ⁄ 60 was 7.3% (95% CI 3.3-11.2). Spherical equivalent showed an increasing trend with age and there was no clinically relevant difference between men and women. Retinal photography was performed in 6540 subjects.Conclusion: Prevalence of visual impairment was low but increased with age. There was a trend towards hyperopia with age and no clinically relevant difference in refraction between the sexes. TES aims to provide epidemiological research on several eye and eye-related diseases. Owing to a comprehensive data collection, it has the opportunity to explore issues related to environmental factors, cognition and their interaction with diseases in this community.

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Pharmacologic management of neovascular age-related macular degeneration: systematic review of economic evidence and primary economic evaluation

Cited by 19 publications

References 23 publications

Highly potent VEGF-A-antagonistic DARPins as anti-angiogenic agents for topical and intravitreal applications

Highly potent VEGF-A-antagonistic DARPins as anti-angiogenic agents for topical and intravitreal applications

Fucoidan Reduces Secretion and Expression of Vascular Endothelial Growth Factor in the Retinal Pigment Epithelium and Reduces Angiogenesis In Vitro

The Tromsø Eye Study: study design, methodology and results on visual acuity and refractive errors

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