Emerging Pharmacologic Therapies for Wet Age-Related Macular Degeneration

Ni, Zhaohui; Hui, Peng

doi:10.1159/000228926

Cited by 62 publications

(49 citation statements)

References 83 publications

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“…It is intended for intravitreal application in age-dependent macular dystrophia and is currently undergoing phase I clinical trials (174). With JPE-1375 and JSM-7717, there now exists even more C5aR antagonists that are in preclinical evaluation for the treatment of inflammatory, renal and ocular diseases.…”

Section: Immunomodulation Of Complementmentioning

confidence: 99%

New Insights of an Old Defense System: Structure, Function, and Clinical Relevance of the Complement System

Ehrnthaller

Ignatius

Gebhard

et al. 2010

Mol Med

188

154

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The complement system was discovered a century ago as a potent defense cascade of innate immunity. After its first description, continuous experimental and clinical research was performed, and three canonical pathways of activation were established. Upon activation by traumatic or surgical tissue damage, complement reveals beneficial functions of pathogen and danger defense by sensing and clearing injured cells. However, the latest research efforts have provided a more distinct insight into the complement system and its clinical subsequences. Complement has been shown to play a significant role in the pathogenesis of various inflammatory processes such as sepsis, multiorgan dysfunction, ischemia/reperfusion, cardiovascular diseases and many others. The three well-known activation pathways of the complement system have been challenged by newer findings that demonstrate direct production of central complement effectors (for example, C5a) by serine proteases of the coagulation cascade. In particular, thrombin is capable of producing C5a, which not only plays a decisive role on pathogens and infected/damaged tissues, but also acts systemically. In the case of uncontrolled complement activation, "friendly fire" is generated, resulting in the destruction of healthy host tissue. Therefore, the traditional research that focuses on a mainly positive-acting cascade has now shifted to the negative effects and how tissue damage originated by the activation of the complement can be contained. In a translational approach including structure-function relations of this ancient defense system, this review provides new insights of complement-mediated clinical relevant diseases and the development of complement modulation strategies and current research aspects.

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Section: Immunomodulation Of Complementmentioning

confidence: 99%

New Insights of an Old Defense System: Structure, Function, and Clinical Relevance of the Complement System

Ehrnthaller

Ignatius

Gebhard

et al. 2010

Mol Med

188

154

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“…Three months after the single injection, 24 patients showed stable VA, with four patients experiencing a clinically significant improvement in vision. Other approaches currently under investigation for exudative ARMD involve nicotinic receptor antagonists, vaccination, immunomodulators and immunosuppressants [65, 66]. However, as yet none of these have been demonstrated to be safe and effective in phase III multi-centre clinical trials.…”

Section: Recent Developmentsmentioning

confidence: 99%

Recent trends in the management of maculopathy secondary to pathological myopia

Mitry

Zambarakji

2011

Graefes Arch Clin Exp Ophthalmol

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This updated clinical perspective demonstrates that CNV and vitreomacular disorders in pathological myopia are treatable conditions. There are numerous medical and surgical interventions that have significantly improved the outcome of myopic maculopathy and several others currently under investigation. Nonetheless, as technology advances, further well-designed studies are necessary to establish a uniform evidence-based approach for classification and treatment.

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“…The occurrence of AMD increases with age, so it is expected to become more prevalent in developed countries as life expectancy continues to increase (1)(2)(3)(4)(5) . Although exudative (or neovascular) AMD is less common than dry AMD, occurring in approximately 10 to 20% of the patients, it is usually responsible for most severe cases of vision loss (1,(6)(7) .…”

Section: Introductionmentioning

confidence: 99%

“…With greater understanding of the role of VEGF in the pathogenesis of neovascular AMD, drugs inhibiting the bioactivity of VEGF have been developed and introduced in the clinical setting. Nowadays, intravitreal anti-VEGF represents a new paradigm in exudative AMD therapy due to its better outcomes (1)(2)(3)(4)7,(9)(10) . Bevacizumab (Avastin ® ) is a recombinant humanized fulllength anti-VEGF derived from a murine antibody with a molecular weight of 148 kD.…”

Section: Introductionmentioning

confidence: 99%

“…It has also been frequently and successfully used as an off-label intravitreal treatment of neovascular AMD since 2006. Bevacizumab has a longer halflife than ranibizumab, the actual most efficient anti-VEGF approved by ANVISA for AMD treatment, and is supposed to require less frequent dosing (1)(2)(3)(4)(5)(6)(7)(10)(11)(12) . Despite the better visual results achieved with bevacizumab therapy for choroidal neovascularization, its benefits seem to be temporary.…”

Section: Introductionmentioning

confidence: 99%

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