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 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>

Change in Visual Acuity in Relation to Central Macular Thickness after Intravitreal Bevacizumab in Diabetic Macular Edema

2020 ◽  
Vol 36 (3) ◽  
Author(s):  
Muhammad Ali Haider ◽  
Uzma Sattar ◽  
Syeda Rushda Zaidi
Keyword(s):  
Visual Acuity ◽  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Intravitreal Bevacizumab ◽  
Macular Thickness ◽  
Rank Test ◽  
P Value ◽  
Central Macular Thickness ◽  
Anti Vegf ◽  
Quasi Experimental

Purpose: To evaluate the change in visual acuity in relation to decrease in central macular thickness,after a single dose of intravitreal Bevacizumab injection.Study Design: Quasi experimental study.Place and Duration of Study: Punjab Rangers Teaching Hospital, Lahore, from January 2019 to June 2019.Material and Methods: 70 eyes with diabetic macular edema were included in the study. Patients having high refractive errors (spherical equivalent of > ± 7.5D) and visual acuity worse than +1.2 or better than +0.2 on log MAR were excluded. Central macular edema was measured in μm on OCT and visual acuity was documentedusing Log MAR chart. These values were documented before and at 01 month after injection with intravitrealBevacizumab. Wilcoxon Signed rank test was used to evaluate the difference in VA beforeand after the anti-VEGF injection. Difference in visual acuity and macular edema (central) was observed,analyzed and represented in p value. P value was considered statistically significant if it was less than 0.01%.Results: Mean age of patients was 52.61 ± 1.3. Vision improved from 0.90 ± 0.02 to 0.84 ± 0.02 on log MARchart. The change was statistically significant with p value < 0.001. Central macular thickness reduced from 328 ±14 to 283 ± 10.6 μm on OCT after intravitreal anti-VEGF, with significant p value < 0.001.Conclusion: A 45 μm reduction in central macular thickness was associated with 0.1 Log MAR unit improvementin visual acuity after intravitreal Bevacizumab in diabetic macular edema.

Outcomes of patients with active diabetic macular edema at the time of cataract surgery managed with intravitreal anti-VEGF injections

2021 ◽  
Author(s):  
Matthew R. Starr ◽  
Michael A. Mahr ◽  
Wendy M. Smith ◽  
Raymond Iezzi ◽  
Andrew J. Barkmeier ◽  
...  
Keyword(s):  
Cataract Surgery ◽  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Anti Vegf
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