The Angiopoietin/Tie Pathway in Retinal Vascular Diseases

Heier, Jeffrey S.; Singh, Rishi P.; Wykoff, Charles C.; Csaky, Karl G.; Lai, Timothy Y. Y.; Loewenstein, Anat; Schlottmann, Patricio G.; Paris, Liliana P; Westenskow, Peter D.; Ruiz, Carlos Quezada

doi:10.1097/iae.0000000000003003

Cited by 57 publications

(38 citation statements)

References 79 publications

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“…Another upcoming antibody for nAMD treatment, faricimab, is a bi-specific monoclonal antibody that binds VEGF-A and angiopoietin-2 (Ang-2), the latter being up-regulated in neovascular membranes and promoting vascular leakage in combination with VEGF-A [ 64 , 65 ]. Recently released data from the phase 3 TENAYA and LUCERNE studies [ 66 ] have demonstrated that faricimab is non-inferior to aflibercept in terms of functional and structural outcomes in nAMD patients, but can be used with longer treatment intervals of up to 16 weeks, compared to every 8 weeks for patients treated with aflibercept.…”

Section: Novel Therapies On the Horizon For Pcvmentioning

confidence: 99%

Evolving treatment paradigms for PCV

Fenner

Cheung

Sim

et al. 2021

Eye

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Polypoidal choroidal vasculopathy (PCV) is a subtype of neovascular AMD (nAMD) that accounts for a significant proportion of nAMD cases worldwide, and particularly in Asia. Contemporary PCV treatment strategies have closely followed those used in typical nAMD, though there are significant gaps in knowledge on PCV management and it remains unclear if these strategies are appropriate. Current clinical trial data suggest intravitreal anti-vascular endothelial growth factor (VEGF) therapy alone or in combination with photodynamic therapy is effective in managing haemorrhage and exudation in PCV, although the optimal treatment interval, including as-needed and treat-and-extend approaches, is unclear. Newer imaging modalities, including OCT angiography and high-resolution spectral domain OCT have enabled characterisation of unique PCV biomarkers that may provide guidance on how and when treatment and re-treatment should be initiated. Treatment burden for PCV is a major focus of future therapeutic research and several newly developed anti-VEGF agents, including brolucizumab, faricimab, and new modes of drug delivery like the port delivery system, offer hope for dramatically reduced treatment burden for PCV patients. Beyond anti-VEGF therapy, recent developments in our understanding of PCV pathophysiology, in particular the role of choroidal anatomy and lipid mediators in PCV pathogenesis, offer new treatment avenues that may become clinically relevant in the future. This article explores the current management of PCV and more recent approaches to PCV treatment based on an improved understanding of this unique disease process.

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Section: Novel Therapies On the Horizon For Pcvmentioning

confidence: 99%

Evolving treatment paradigms for PCV

Fenner

Cheung

Sim

et al. 2021

Eye

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“…Furthermore, treatments targeting additional mechanisms of action may also bring value to this space in the near future. For example, investigations into manipulating the Tie-2 and kallikrein systems for additive benefit among patients with DR and DME are ongoing [ 27 , 28 ].…”

Section: Discussionmentioning

confidence: 99%

Real-Time Diabetic Retinopathy Severity Score Level versus Ultra-Widefield Leakage Index-Guided Management of Diabetic Retinopathy: Two-Year Outcomes from the Randomized PRIME Trial

Ehlers

Sevgi

et al. 2021

JPM

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The prospective PRIME trial applied real-time, objective imaging biomarkers to determine individualized retreatment needs with intravitreal aflibercept injections (IAI) among eyes with diabetic retinopathy (DR). 40 eyes with nonproliferative or proliferative DR without diabetic macular edema received monthly IAI until a DR severity scale (DRSS) level improvement of ≥2 steps was achieved. Eyes were randomized 1:1 to DRSS- or PLI- guided management. At the final 2-year visit, DRSS level was stable or improved compared to baseline in all eyes, and mean PLI decreased by 11% (p = 0.73) and 23.6% (p = 0.25) in the DRSS- and PLI-guided arms. In both arms, the percent of pro re nata (PRN) visits requiring IAI was significantly higher in year 2 versus 1 (p < 0.0001). The percent of PRN visits receiving IAI during year 1 was significantly correlated with the percent of PRN visits with IAI during year 2 (p < 0.0001). Through week 104, 77.4% of instances of DRSS level worsening in the DRSS-guided arm were preceded by or occurred alongside an increase of PLI. Overall, consistent IAI re-treatment interval requirements were observed longitudinally among individual patients. Additionally, PLI increases appeared to precede DRSS level worsening, highlighting PLI as a valuable biomarker in the management of DR.

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“…Faricimab showed positive results across four phase III studies in AMD and DME. Faricimab clinical trials proved a non-inferiority efficacy evidence, compared to aflibercept (115,116).…”

Section: F O R P U B L I C a T I O Nmentioning

confidence: 96%

Pricing for Multi Indication Medicines: A Discussion With Italian Experts

Pani¹,

Cicchetti²,

A³

et al. 2022

Pharm Adv

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Diabetic retinopathy (DR) is a secondary complication of diabetes mellitus and represents the most common cause of irreversible vision loss in working people of industrialized countries. DR is generally considered a microvascular complication of diabetes, although the inflammatory component plays a key role. The main cause of vision loss in diabetic patients with proliferative diabetic retinopathy (PDR) is the diabetic macular edema (DME), that is responsible to the retinal detachment. DME is mainly caused by new angiogenesis, which is a hallmark of the advanced stage of DR (proliferative diabetic retinopathy, PDR). Retinal neovascularization is principally driven by pro-angiogenic factors (e.g., VEGF-A, PlGF), inflammatory mediators (TNF-α, interleukins, chemokines) and oxidative stress-related elements. Chronic hyperglycemia is the primary causative factor of DR, however, several points of DR etiopathogenesis are still unclear. Many other factors are involved during the early stages of DR such as the retinal hypoxia, that is a trigger of VEGF release in the back of the eye. Up to now, the pharmacological approaches for DR are intravitreal anti-VEGF agents and corticosteroids. However, some patients can be refractory to anti-VEGF therapy, therefore, efforts must be carried out to discover novel pharmacological targets to handle DR. Hereby, the current literature will be revised about novel potential pharmacological targets, with a focus on PlGF, miRNAs and purinergic P2X7 receptor. Future drug development campaigns on these targets might lead to better clinical outcomes, possibly in the early phase of the disease.

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The Angiopoietin/Tie Pathway in Retinal Vascular Diseases

Cited by 57 publications

References 79 publications

Evolving treatment paradigms for PCV

Evolving treatment paradigms for PCV

Real-Time Diabetic Retinopathy Severity Score Level versus Ultra-Widefield Leakage Index-Guided Management of Diabetic Retinopathy: Two-Year Outcomes from the Randomized PRIME Trial

Pricing for Multi Indication Medicines: A Discussion With Italian Experts

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