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 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 Endothelial Cells Derived From Patients With Diabetic Macular Edema Recapitulate Clinical Evaluations of Anti-VEGF Responsiveness Through the Neuronal Pentraxin 2 Pathway

Diabetes ◽  
2020 ◽  
Vol 69 (10) ◽  
pp. 2170-2185 ◽  
Author(s):  
Marta Vilà González ◽  
Magdalini Eleftheriadou ◽  
Sophia Kelaini ◽  
Hojjat Naderi-Meshkin ◽  
Shonagh Flanagan ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Clinical Evaluations ◽  
Anti Vegf ◽  
Neuronal Pentraxin

scholarly journals Clinical efficacy of antiangiogenic therapy for diabetic macular edema in real clinical practice (2-year results)

2021 ◽  
Vol 14 (2) ◽  
pp. 42-49
Author(s):  
A. Zh. Fursova ◽  
A. S. Derbeneva ◽  
M. S. Tarasov ◽  
M. V. Vasil’eva ◽  
J. A. Gamza ◽  
...  
Keyword(s):  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Clinical Efficacy ◽  
Initial Level ◽  
Antiangiogenic Therapy ◽  
Visual Outcome ◽  
First Year ◽  
Anti Vegf ◽  
Flexible Planning ◽  
Second Year

Purpose:to evaluate the clinical efficacy of anti-VEGF therapy of patients with diabetic macular edema (DMO) in T & E regimen for 96 weeks. Materials and methods. The study included 59 patients (101 eyes) with DMO. The average number of intravitreal injections of anti-VEGF agent (IIAVA) — aflibercept given during the whole period was 12.87 ± 3.56, including 7.78 ± 1.20 in the first year, and 4.82 ± 2.66 in the second year. Results.All patients showed an increase in visual functions (+0.33, p < 0.001) with a maximum achieved after 5 injections (+0.24; p = 0.001). Central macular thickness decreased from 397.36 ± 100,00 μm at the initial level to 276.59 ± 52.90 after 5 loading injections (-120.8 μm), to 263.85 ± 45.20 (-133, 91 μm) after 1 year and to 248.6 ± 46.9 (-148.76 μm) after 2 years. A resorption of retinal neuroepithelial detachment was observed in 84.16 % of cases as soon as loading injections were given, and reached 100 % of cases by the 48th week of observation. Strong inverse correlations were revealed between the initial presence of medium and large intraretinal cysts and visual acuity, both initial and final (-0.35 and -0.42, p < 0.01). The disorganization of retina inner layers at the initial level was a predictor of a worse visual outcome at the end of the observation period. By the end of this period, 44 patients (43.5 %) received IIAVA with an interval of 12 weeks, the maximum interval between injections was 16 weeks and was achieved in 19 (28.01 %) eyes. Conclusion.The results of a 2-year retrospective study of the efficacy of aflibercept in DME showed that T&E regimen can be used with highfunctional results. Due to flexible planning of the number of IIAVA in the second year, over-treatment could be avoided without reducing the expected efficacy.

scholarly journals Review on Recent Trials Evaluating the Effect of Intravitreal Injections of Anti-VEGF Agents on the Macular Perfusion of Diabetic Patients with Diabetic Macular Edema

2020 ◽  
Vol 15 (3) ◽  
pp. 188-198
Author(s):  
Ayman G. Elnahry ◽  
Ahmed A. Abdel-Kader ◽  
Ahmed E. Habib ◽  
Gehad A. Elnahry ◽  
Karim A. Raafat ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Vision Loss ◽  
Case Series ◽  
Diabetic Patients ◽  
Long Term Effects ◽  
Randomized Controlled Clinical Trials ◽  
Randomized Controlled ◽  
Anti Vegf

Background: Diabetic macular edema (DME) is a major cause of vision loss in diabetics worldwide. Anti-vascular endothelial growth factor (anti-VEGF) agents have become the mainstay of treatment of vision loss due to DME. Long-term effects of these agents on the macular perfusion (MP) are a current concern. Objective: To review recently published studies that evaluated the effect of intravitreal injection of anti-VEGF agents on the MP of diabetics with DME. Methods: Different databases were searched including PubMed, Medline, Ovid, Science Direct, and Google Scholar for relevant studies published between 2010 and 2019. All studies found were compared regarding methodology and results and included in this review. Some studies relating to retinal perfusion in general and not strictly MP were also included for comprehensiveness. Results: Several studies utilizing different anti-VEGF agents were identified. All the large randomized controlled clinical trials identified utilized primarily fluorescein angiography (FA) and human graders and found generally no worsening of MP associated with anti-VEGF agents use in diabetic patients with DME. Some of these studies, however, depended on post-hoc analysis. Several more recent, but smaller case series, have utilized the relatively new and non-invasive optical coherence tomography angiography (OCTA) in this evaluation and found more conflicting results. Conclusion: The large clinical trials recently performed depended mainly on FA in the analysis of MP changes following injections and generally found no worsening of MP. More recently, smaller case series have utilized OCTA in this analysis, yielding more conflicting results. Large randomized controlled trials using OCTA are thus needed.

scholarly journals Ellipsoid Zone Integrity and Visual Acuity Changes during Diabetic Macular Edema Therapy: A Longitudinal Study

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Lucy J. Kessler ◽  
Gerd U. Auffarth ◽  
Dmitrii Bagautdinov ◽  
Ramin Khoramnia
Keyword(s):  
Visual Acuity ◽  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Visual Outcome ◽  
Long Term Results ◽  
First Year ◽  
Ellipsoid Zone ◽  
Anti Vegf ◽  
Potential Biomarker

Purpose. Ellipsoid zone (EZ) integrity is identified as a potential biomarker for therapy surveillance and outcome prediction of visual acuity (VA). However, only a few studies report long-term results of over 1 year of clinical and anatomical changes in patients with diabetic macular edema (DME). This study is aimed at describing the long-term VA and anatomical outcomes in spectral domain optical coherence tomography (OCT) (relative ellipsoid zone reflectivity ratio, central macular thickness, and volume) in patients with DME treated with antivascular endothelial growth factor (anti-VEGF) therapy. Furthermore, we studied the correlation between EZ integrity and changes in visual acuity. Methods. 71 eyes of 71 patients were included in this retrospective study. Clinical characteristics were reviewed yearly. OCT data were assessed at baseline and after 1, 3, and 5 years. EZ parameters were quantified automatically. OCT parameters and visual outcome were correlated and analyzed in multivariable regression models. Results. EZ reflectivity ratio correlated with functional outcome in DME patients from baseline to fifth year at all time points (for all p < 0.05 ). EZ reflectivity improved the most in the first year of treatment (0.68 to 0.75; p < 0.05 ) and declined gradually until year 5 of therapy (0.71; compared to baseline p > 0.05 ). Similarly, best VA was achieved after 1 year (0.40 logarithm of the minimum angle of resolution (logMAR) to 0.28 logMAR; p < 0.001 ) and declined gradually until year 5. Final VA in year 5 was comparable to baseline (0.45 logMAR, compared to baseline p > 0.05 ). Together with baseline VA, baseline EZ parameters did predict VA outcome after 1 year ( p < 0.05 ). Concordantly, VA and EZ parameters from year 1 were associated with VA outcome in year 2. Conclusion. This study described the long-term course of EZ changes during anti-VEGF treatment in DME patients. In addition, our results underlined the potential of EZ parameters as novel OCT biomarkers for prediction of VA outcomes during therapy.

scholarly journals Prediction of Anti-VEGF Response in Diabetic Macular Edema After 1 Injection

2017 ◽  
Vol 1 (3) ◽  
pp. 169-174 ◽  
Author(s):  
Ankoor R. Shah ◽  
Yoshihiro Yonekawa ◽  
Bozho Todorich ◽  
Lily Van Laere ◽  
Rehan Hussain ◽  
...  
Keyword(s):  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Roc Curve ◽  
Vision Loss ◽  
Case Series ◽  
Early Response ◽  
Curve Analysis ◽  
Response To Treatment ◽  
Roc Curve Analysis ◽  
Anti Vegf

Purpose: With multiple anti–vascular endothelial growth factor (VEGF) and steroid therapies available for diabetic macular edema (DME), there is a need for early determination of the best treatment for a particular patient to prevent irreversible vision loss from chronic DME. In this study, we classify patients as responders or nonresponders to anti-VEGF monotherapy in the treatment of DME after a single anti-VEGF injection. Methods: The study was designed as a single-center, retrospective, interventional case series. We included patients who received 3 consecutive monthly injections with the same anti-VEGF agent. We excluded patients who were treated for DME in the preceding 3 months with any form of anti-VEGF therapy. Visual acuity and central retinal thickness (CRT) data were followed for 1 year. Receiver operating characteristic (ROC) curve analysis was performed in order to identify the cutoff values for identifying responders. Results: One hundred seven eyes were reviewed, with 40 eyes of 34 patients meeting all inclusion criteria. Based on ROC curve analysis, a reduction in CRT by >15% at 1 month identified eyes that responded to treatment and had a >25% reduction in CRT at 3 months (sensitivity, 0.75; specificity, 0.92). Conclusion: Diabetic macular edema eyes that have early response to anti-VEGF treatment by reduction in CRT will have significant response to treatment by 3 months.

scholarly journals Aflibercept for diabetic macular edema: a concise review

2017 ◽  
Vol 6 (5) ◽  
pp. 1031
Author(s):  
Sujithera Haridoss ◽  
Soundaram Meenakshi Sundaram ◽  
Melvin George ◽  
Damal Kandadai Sriram
Keyword(s):  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Laser Photocoagulation ◽  
Vision Loss ◽  
Standard Of Care ◽  
Management Options ◽  
Treatment Regimens ◽  
Anti Vegf ◽  
Patients With Diabetes ◽  
Vasculogenesis And Angiogenesis

Diabetic retinopathy and diabetic macular edema are associated with loss of vision in patients with diabetes worldwide. The treatment requires a multidisciplinary interventional approach. Among the available management options for DME, laser photocoagulation has been the standard of care. Due to its slow progression and inability to reverse the vision loss, an alternative treatment is needed. The role of vascular endothelial growth factors (VEGF) and inflammatory mediators led to the development of anti-VEGF agents, that stimulates retinal vasculogenesis and angiogenesis. Intravitreal aflibercept is an anti-angiogenic soluble decoy receptor with trap technology employed by fusion of multiple endogeneous receptor component, approved for the treatment of DME. Clinical trials of aflibercept comparing it with laser photocoagulation and other anti-VEGF have shown reliable efficacy, providing significantly positive visual and anatomical results. However, treatment regimens with monthly clinical visits and injections, challenge the patients comfort, thereby requiring the need to identify better strategies to lower injection frequencies.

Long-term Visual Outcomes and Morphologic Biomarkers of Vision Loss in Eyes with Diabetic Macular Edema treated with Anti-VEGF Therapy

2021 ◽  
Author(s):  
Enrico Borrelli ◽  
Domenico Grosso ◽  
Costanza Barresi ◽  
Giorgio Lari ◽  
Riccardo Sacconi ◽  
...  
Keyword(s):  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Vision Loss ◽  
Visual Outcomes ◽  
Anti Vegf

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 Anti-VEGF for the Management of Diabetic Macular Edema

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Francisco Rosa Stefanini ◽  
Emmerson Badaró ◽  
Paulo Falabella ◽  
Michael Koss ◽  
Michel Eid Farah ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Vision Loss ◽  
Cochrane Library ◽  
Public Health Issue ◽  
Anti Vegf ◽  
Significant Public Health ◽  
Endothelial Growth Factor

Diabetic retinopathy (DR) is an important cause of vision loss around the world, being the leading cause in the population between 20 and 60 years old. Among patients with DR, diabetic macular edema (DME) is the most frequent cause of vision impairment and represents a significant public health issue. Macular photocoagulation has been the standard treatment for this condition reducing the risk of moderate visual loss by approximately 50%. The role of vascular endothelial growth factor (VEGF) in DR and DME pathogenesis has been demonstrated in recent studies. This review addresses and summarizes data from the clinical trials that investigated anti-VEGF for the management of DME and evaluates their impact on clinical practice. The literature searches were conducted between August and October 2013 in PubMed and Cochrane Library with no date restrictions and went through the most relevant studies onpegaptanib,ranibizumab,bevacizumab, andafliberceptfor the management of DME. The efficacy and safety of intravitreal anti-VEGF as therapy for DME have recently been proved by various clinical trials providing significantly positive visual and anatomical results. Regarding clinical practice, those outcomes have placed intravitreal injection of anti-VEGF as an option that must be considered for the treatment of DME.

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