Molecular Biomarkers of Neovascular Age-Related Macular Degeneration With Incomplete Response to Anti-Vascular Endothelial Growth Factor Treatment

The standard treatment for neovascular age-related macular degeneration (nAMD) consists of intravitreal anti-vascular endothelial growth factors (VEGF). However, for some patients, even maximal anti-VEGF treatment does not entirely suppress exudative activity. The goal of this study was to identify molecular biomarkers in nAMD with incomplete response to anti-VEGF treatment. Aqueous humor (AH) samples were collected from three groups of patients: 17 patients with nAMD responding incompletely to anti-VEGF (18 eyes), 17 patients affected by nAMD with normal treatment response (21 eyes), and 16 control patients without any retinopathy (16 eyes). Proteomic and multiplex analyses were performed on these samples. Proteomic analyses showed that nAMD patients with incomplete anti-VEGF response displayed an increased inflammatory response, complement activation, cytolysis, protein-lipid complex, and vasculature development pathways. Multiplex analyses revealed a significant increase of soluble vascular cell adhesion molecule-1 (sVCAM-1) [ p = 0.001], interleukin-6 (IL-6) [ p = 0.009], bioactive interleukin-12 (IL-12p40) [ p = 0.03], plasminogen activator inhibitor type 1 (PAI-1) [ p = 0.004], and hepatocyte growth factor (HGF) [ p = 0.004] levels in incomplete responders in comparison to normal responders. Interestingly, the same biomarkers showed a high intercorrelation with r2 values between 0.58 and 0.94. In addition, we confirmed by AlphaLISA the increase of sVCAM-1 [ p < 0.0001] and IL-6 [ p = 0.043] in the incomplete responder group. Incomplete responders in nAMD are associated with activated angiogenic and inflammatory pathways. The residual exudative activity of nAMD despite maximal anti-VEGF treatment may be related to both angiogenic and inflammatory responses requiring specific adjuvant therapy. Data are available via ProteomeXchange with identifier PXD02247

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Changes оf vascular endothelial growth factor concentration in patients with exudative age related macular degeneration and primary open-angled glaucoma on the anti-VEGF therapy

POINT OF VIEW EAST – WEST ◽

10.25276/2410-1257-2018-2-59-62 ◽

2018 ◽

pp. 59-62

Author(s):

O.А. Zhabina ◽

◽

I.V. Andreeva ◽

A.S. Rudko ◽

A.A. Plyukhova ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Macular Degeneration ◽

Age Related Macular Degeneration ◽

Vascular Endothelial ◽

Anti Vegf ◽

Age Related ◽

Endothelial Growth Factor ◽

Factor Concentration

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Relationship Between Claims Data and the Preferences and Trends Survey: An Analysis of Anti-Vascular Endothelial Growth Factor Medication Choice for Age-Related Macular Degeneration

Journal of VitreoRetinal Diseases ◽

10.1177/2474126417753433 ◽

2018 ◽

Vol 2 (2) ◽

pp. 96-99 ◽

Cited By ~ 2

Author(s):

Ravi Parikh ◽

Paula W. Feng ◽

Lucian V. Del Priore ◽

Ron A. Adelman ◽

Nauman A. Chaudhry

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Macular Degeneration ◽

Claims Data ◽

Practice Patterns ◽

Age Related Macular Degeneration ◽

Vascular Endothelial ◽

Anti Vegf ◽

Age Related ◽

Endothelial Growth Factor

Purpose: To compare published self-reported practice patterns among retina specialists with published claims data representing actual practice patterns for the use of anti-vascular endothelial growth factor (anti-VEGF) medications in the treatment of age-related macular degeneration (AMD) in the United States. Methods: We compared physician self-reported preference for anti-VEGF medications to treat AMD in the American Society of Retina Specialists’ Preferences and Trends (PAT) survey with a previously published study using claims data from 2006 to 2015 from OptumLabs Data Warehouse as a data source. A Pearson χ2 test compared the relative proportions of drug use between the 2 groups, with <.05 indicating statistical significance. Results: From 2006 to 2015, the PAT surveys had approximately 3548 respondents to questions on which anti-VEGF medication was used for the treatment of AMD. Over the study period, 62.3% (2211/3548) of respondents preferred bevacizumab, 30.4% (1078/3548) ranibizumab, and 7.3% (259/3548) aflibercept in the treatment of AMD. Claims data on anti-VEGF use for AMD noted 59.7% (359 267/601 917) of injections were for bevacizumab, 23.8% (143 200/601 917) were for ranibizumab, and 16.5% (99 450/601 917) were for aflibercept. The difference in the relative use of bevacizumab, ranibizumab, and aflibercept use was not significant between the data sets ( P = .1991). Conclusions: The PAT survey responses appear to reflect actual physician practices based upon claims data and demonstrate the prevalence of bevacizumab as the prevailing treatment for AMD.

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Treat and Extend Dosing Regimen with Anti-vascular Endothelial Growth Factor Agents for Neovascular Age-related Macular Degeneration

American Journal of Ophthalmic Clinical Trials ◽

10.25259/ajoct-2-2018 ◽

2018 ◽

Vol 1 ◽

pp. 1 ◽

Cited By ~ 5

Author(s):

Karen M. Wai ◽

Rishi P. Singh

Keyword(s):

Vascular Endothelial Growth Factor ◽

Clinical Trials ◽

Growth Factor ◽

Macular Degeneration ◽

Age Related Macular Degeneration ◽

Vascular Endothelial ◽

Dosing Regimen ◽

Anti Vegf ◽

Age Related ◽

Endothelial Growth Factor

Anti-vascular endothelial growth factor (anti-VEGF) agents are the mainstay of therapy for treatment of neovascular age-related macular degeneration (nvAMD), one of the leading causes of blindness in the developed world. There have been a variety of different treatment regimens that have been examined for the administration of anti-VEGF therapies, including continuous fixed dosing, pro re nata administration, and treat and extend (TAE) protocols. There is no clear consensus on which dosing regimen optimizes visual and anatomical outcomes while accounting for factors such as cost and patient burden. Based on recent surveys in 2014 and 2017 by the American Society of Retina Specialists (ASRS), the majority of ophthalmology providers are utilizing TAE protocol for anti-VEGF dosing for the management of nvAMD. Although there are a number of clinical trials that have examined TAE dosing, the ALTAIR study is the first, large, prospective randomized controlled trial to compare two different TAE protocols utilizing the anti-VEGF agent aflibercept for nvAMD. The ALTAIR study, in conjunction with other previous clinical trials, suggests that TAE protocol with aflibercept is an effective anti-VEGF dosing regimen for patients with nvAMD as it produces good visual gains and minimizes cost and burden for the patient.

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