Aflibercept for the Treatment of Diabetic Retinopathy and Diabetic Macular Edema

2018 ◽  
pp. 147-154
Keyword(s):  
Diabetic Retinopathy ◽  
Growth Factor ◽  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Vision Loss ◽  
Developed Countries ◽  
Inhibitory Effect ◽  
Duration Of Action ◽  
Anti Vegf ◽  
Working Age

Diabetic macular edema (DME) is a common complication of diabetic retinopathy (DR) and is a leading cause of vision loss in developed countries during the working age. Understanding the role of vascular endothelial growth factor (VEGF) in the pathogenesis of DME has emphasized the importance of using anti-VEGF agents in treatment. Anti-VEGF drugs such as pegaptanib, ranibizumab, bevacizumab, and aflibercept have been studied in the treatment of DME. Aflibercept is a recombinant fusion protein with an inhibitory effect on VEGF-A, VEGF-B, placental growth factor (PIGF) 1 and 2. It is believed that this agent has a longer duration of action than other anti-VEGF molecules due to its high-affinity binding to the VEGF molecule. This review summarizes the pharmacological properties of aflibercept in terms of clinical efficacy, use, and tolerability in the treatment of DME.

scholarly journals The Evolving Treatment Options for Diabetic Macular Edema

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Atul Jain ◽  
Neeta Varshney ◽  
Colin Smith
Keyword(s):  
Diabetic Retinopathy ◽  
Visual Impairment ◽  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Vision Loss ◽  
Treatment Options ◽  
Previous Treatment ◽  
Common Cause ◽  
Working Age

Diabetic retinopathy (DR) is the leading cause of vision loss in working-age adults, and diabetic macular edema (DME) is the most common cause of visual impairment in individuals with DR. This review focuses on the pathophysiology, previous treatment paradigms, and emerging treatment options in the management of DME.

Anti-VEGF Deficiency, Treatment Resistance, Pharmaceutical Changes and Combined Treatments in Diabetic Macular Edema

2018 ◽  
pp. 165-169
Keyword(s):  
Diabetic Retinopathy ◽  
Combination Therapy ◽  
Visual Impairment ◽  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Treatment Resistance ◽  
Developed Countries ◽  
Combined Treatments ◽  
Anti Vegf ◽  
Treatment Switch

Diabetic retinopathy is the most important cause of blindness in developed countries today. The most important cause of visual impairment is complications related to diabetic macular edema (DME) and proliferative retinopathy. Intravitreal anti-VEGF agents are the first treatment option for central involvement in diabetic macular edema (DME). Despite anti-VEGF agents, some cases are refractory (persistent) to multiple anti-VEGF treatments. In this review, unresponsiveness to anti-VEGF treatment, switch, and combination therapy in DME is mentioned.

scholarly journals Endothelial cells derived from patients with diabetic macular edema recapitulate clinical evaluations of anti-VEGF responsiveness through the Neuronal Pentraxin 2 pathway

2020 ◽  
Author(s):  
Ada Admin ◽  
Marta Vila Gonzalez ◽  
Magdalini Eleftheriadou ◽  
Sophia Kelaini ◽  
Hojjat Naderi-Meshkin ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Vision Loss ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
First Year ◽  
Differential Outcomes ◽  
Anti Vegf ◽  
Neuronal Pentraxin

Diabetic macular edema (DME) remains a leading cause of vision loss worldwide. DME is commonly treated with intravitreal injections of vascular endothelial growth factor (VEGF) neutralising antibodies. Anti-VEGFs are effective but not all patients fully respond to them. Given their potential side effects, inconvenience and high cost, identifying who may not respond appropriately to anti-VEGFs and why is essential. <p>Herein, we determine first the response to anti-VEGFs in a cohort of DME patients using spectral-domain optical coherence tomography scans obtained throughout the first year of treatment. We found that in 28% of eyes full clearance of fluid occurred at any time during the first year (“full responders”); in 66% fluid cleared only partly (“partial responders”); in 6% fluid remained unchanged (“non-responders”). To understand this differential response, we generated induced pluripotent stem cells (iPS) from “full responders” and “non-responders” and from diabetic subjects with no DME and age-matched non-diabetic volunteers and differentiated them into endothelial cells (iPS-ECs). Monolayers of iPS-ECs derived from diabetics showed marked and prolonged increased permeability upon exposure to VEGF when compared with non-diabetic controls; the response was significantly exaggerated in iPS-ECs from “non-responders” when compared with “full responders”. Moreover, phosphorylation of key cellular proteins in response to VEGF, including VEGFR2, and gene expression profiles, such as Neuronal Pentraxin 2 (NPTX2) expression, differed between “full responders” and “non-responders”. </p> <p>In the current study, iPS were used to predict patient response to anti-VEGF and identify key mechanisms underpinning the differential outcomes observed in the clinic. This approach has identified NPTX2 as playing a significant role in patient-linked responses and has potential as a new therapeutic target for DME. </p>

scholarly journals Current multimodal diagnostic tools for diabetic macular edema to select a management strategy

2021 ◽  
Vol 21 (4) ◽  
pp. 210-214
Author(s):  
M.V. Pshenichnov ◽  
Keyword(s):  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Management Strategy ◽  
Low Vision ◽  
Management Strategies ◽  
Developed Countries ◽  
Diagnostic Tools ◽  
Published Data ◽  
Working Age ◽  
Diagnostic Approaches

Diabetes is a severe chronic disease that significantly affects the quality of life of individuals, their families, and society worldwide. Diabetic retinopathy, particularly diabetic macular edema (DME), is the leading cause of blindness and low vision among adults of working age in developed countries and Russia. A recent multimodal approach to diagnose DME resulted in new classifications of this disorder and slightly modified earlier views. The analysis of DME biomarkers allows for selecting management strategies for each patient, prescribing adequate medical treatment, and predicting potential treatment response. This paper aimed to analyze published data and up-to-date diagnostic approaches to DME. These tools provide a correct therapeutic strategy based on the DME pattern. Keywords: diabetic macular edema, optical coherence tomography, anti-VEGF treatment. For citation: Pshenichnov M.V. Current multimodal diagnostic tools for diabetic macular edema to select a management strategy. Russian Journal of Clinical Ophthalmology. 2021;21(4):210–214 (in Russ.). DOI: 10.32364/2311-7729-2021-21-4-210-214.

Evaluation of Patients Receiving Intravitreal Antivascular Endothelial Growth Factor for Diabetic Macular Edema in Clinical Practice in the United States

2020 ◽  
pp. 247412642095306
Author(s):  
John D. Pitcher ◽  
Andrew A. Moshfeghi ◽  
Genevieve Lucas ◽  
Nick Boucher ◽  
Hadi Moini ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Growth Factor ◽  
Macular Edema ◽  
Diabetic Macular Edema ◽  
The United States ◽  
Treatment Frequency ◽  
Anti Vegf ◽  
Injection Frequency ◽  
Antivascular Endothelial Growth Factor ◽  
Endothelial Growth Factor

Purpose: We assessed the effect of treatment frequency with intravitreal antivascular endothelial growth factor (anti-VEGF) agents on visual acuity (VA) in diabetic macular edema (DME). Methods: This retrospective analysis assessed electronic medical records of eyes newly diagnosed with DME and treated with an anti-VEGF agent at US clinics using the Vestrum Health (Naperville, Illinois) treatment and outcomes database. Eyes were divided into 2 injection frequency subcohorts (≤ 6 vs > 6 injections/y); treatment frequency and change in mean VA (Early Treatment Diabetic Retinopathy Study letters) were evaluated. Results: Among 155 240 eyes assessed, 3028 met inclusion criteria for analysis in year 1 and 1292 in year 2. During year 1 of treatment, 57% (n = 1725) received > 6 injections; most continued to receive the same injection frequency during year 2. Mean VA gain from baseline at year 1 was lower in the ≤ 6 than in the > 6 injections/year subcohort (3.7 vs 8.0 letters, respectively; P < .001). Mean VA change from the end of year 1 to year 2 for eyes receiving ≤ 6 injections in year 1 generally remained unchanged, irrespective of year 2 dosing frequency. In eyes that received > 6 injections in year 1, mean VA loss was significantly greater for eyes receiving less-frequent dosing in year 2 than in those maintained on > 6 injections. Conclusions: More than 50% of eyes with DME in routine clinical practice that completed at least 1 year of follow-up received > 6 injections of an anti-VEGF agent during the first year, resulting in better VA gains than eyes treated less frequently.

Diabetic Retinopathy—Update on Prevention Techniques, Present Therapies, and New Leads

2014 ◽  
Vol 10 (01) ◽  
pp. 25
Author(s):  
Lauren M Marozas ◽  
Patrice E Fort ◽  
◽  
Keyword(s):  
Diabetic Retinopathy ◽  
Vision Loss ◽  
Developed Countries ◽  
Detection Methods ◽  
Retinal Microvasculature ◽  
Increased Risk ◽  
Patients With Diabetes ◽  
Combined Control ◽  
Working Age ◽  
Proactive Measures

Diabetic retinopathy is the major ocular complication associated with diabetes, and represents the leading cause of legal blindness in the working-age population of developed countries. Although classically diagnosed based on abnormalities of the retinal microvasculature, diabetic retinopathy is now widely recognized as a neurovascular disease. While all patients with diabetes are at increased risk for eye disease including diabetic retinopathy, proactive measures, and timely intervention can prevent or delay subsequent vision loss. Systemic management of diabetes by combined control of glycemia, blood pressure, and serum lipid levels remains the most important method of preventing diabetic retinopathy onset and progression. Once detected, surgical and medical interventions including photocoagulation, vitrectomy, and intravitral drug injection can help preserve vision. However, the need for improved detection methods and therapies that will allow earlier diagnosis and treatment remains apparent. This review summarizes current techniques for the prevention and intervention for diabetic retinopathy, and examines ongoing developments in the search for new endpoints and therapies as they apply to preventing vision loss associated with diabetes.

scholarly journals Flavoprotein Fluorescence Correlation with Visual Acuity Response in Patients Receiving Anti-VEGF Injection for Diabetic Macular Edema

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Jorge S. Andrade Romo ◽  
Giselle Lynch ◽  
Kevin Liu ◽  
Daniel Kim ◽  
Michael Jansen ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Therapeutic Response ◽  
Diagnostic Methods ◽  
Fundus Photography ◽  
Additional Information ◽  
Structural Improvement ◽  
Anti Vegf ◽  
Patients With Diabetes

Anti-VEGF treatment of diabetic macular edema (DME) complicating diabetic retinopathy (DR) has greatly improved structural and visual outcomes for patients with diabetes mellitus. However, up to 50% of patients are either nonresponsive or refractory to anti-VEGF treatment (no improvement in BCVA or central macular thickness (CMT)). It is believed that factors such as mitochondrial structural and functional damage, due to oxidative stress, are partially responsible for this lack of improvement. Flavoprotein fluorescence (FPF) has been shown to be a sensitive marker of mitochondrial function and has been found to correlate with the degree of diabetic retinopathy. FPF may also provide additional information regarding therapeutic response of patients receiving anti-VEGF treatment for DME. Eight patients with DR and DME with clinically significant DME (CSDME) who underwent anti-VEGF (bevacizumab) treatment were imaged before injection and at follow-up visit using FPF in addition to standard color fundus photography and OCT CMT. A strong correlation r=0.98 (p=0.000015) between the FPF decrease and the BCVA improvement was observed; BCVA improved as FPF values decreased. Notably, in the same patients, the correlation between OCT CMT decrease and BCVA improvement (r=0.688) was not found to be significant (p=0.13). These findings suggest that FPF can detect improvement in metabolic function preceding structural improvement and even with small changes in edema. Additionally, FPF may be supplementary to current diagnostic methods for earlier detection of therapeutic response to anti-VEGF treatment in patients with DME.

scholarly journals Diabetic retinopathy: treatment and prevention

2007 ◽  
Vol 4 (3_suppl) ◽  
pp. S9-S11 ◽  
Author(s):  
Paul M Dodson
Keyword(s):  
Diabetic Retinopathy ◽  
Standard Therapy ◽  
Vision Loss ◽  
Early Stage ◽  
Developed Countries ◽  
Relative Reduction ◽  
Treatment And Prevention ◽  
Working Age ◽  
Capillary Occlusion

Diabetic eye disease is the major cause of blindness and vision loss among working-age people in developed countries. Microangiopathy and capillary occlusion underlie the pathogenesis of disease. While laser treatment is regarded as the standard therapy, intensive medical management of glycaemia and hypertension is also a priority in order to reduce the risk of diabetic retinopathy. Recent data have prompted a re-evaluation of the role of lipid-modifying therapy in reducing diabetic retinopathy. The Fenofibrate Intervention for Event Lowering in Diabetes (FIELD) study demonstrated a significant 30% relative reduction in the need for first retinal laser therapy in patients with (predominantly early-stage) type 2 diabetes treated with fenofibrate 200 mg daily, from 5.2% with placebo to 3.6% with fenofibrate, p=0.0003. The benefit of fenofibrate was evident within the first year of treatment. These promising data justify further evaluation of the mechanism and role of fenofibrate, in addition to standard therapy, in the management of diabetic retinopathy.

scholarly journals Combination Treatment of Diabetic Macular Edema with Anti-Vascular Endothelial Growth Factor and Steroids: Analysis of DRCR.net Protocol U

2018 ◽  
Vol 1 ◽  
pp. 2
Author(s):  
Cindy Ung ◽  
Kareem Moussa ◽  
Yoshihiro Yonekawa
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Diabetic Patients ◽  
Vascular Endothelial ◽  
First Line ◽  
Second Line Therapy ◽  
Anti Vegf ◽  
Endothelial Growth Factor

Diabetic macular edema (DME) is the main cause of visual impairment in diabetic patients. Intravitreal anti-vascular endothelial growth factor (VEGF) therapy is considered the first-line treatment option in the management of DME with corticosteroids used as second-line therapy. The DRCR.net Protocol U study was a Phase II trial that sought to compare the combination of a steroid and anti-VEGF therapy to anti-VEGF monotherapy regarding visual acuity and anatomic outcomes. This review highlights the strengths, weaknesses, and clinical implications of this study.

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