Changes in Diabetic Retinopathy Severity When Treating Diabetic Macular Edema With Ranibizumab

Bressler, Susan B.; Odia, Isoken; Glassman, Adam R.; Danis, Ronald P.; Grover, Sandeep; Hampton, G. Robert; Jampol, Lee M.; Maguire, Maureen G.; Melia, Michele

doi:10.1097/iae.0000000000002302

Cited by 51 publications

(42 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Current therapeutic options for DR, a blinding disease that seriously affects quality of life in type-1/2 diabetic patients, have significant limitations. Rates of improvement in visual function following 5-year ranibizumab treatment were 33% and 23%, respectively, for nonproliferative and proliferative DR 19. Likewise, other anti-VEGF agents like VEGF-Trap Eye achieved similar gains in only approximately 34% of DR patients 20.…”

Section: Discussionmentioning

confidence: 93%

COMP-Ang1 Stabilizes Hyperglycemic Disruption of Blood-Retinal Barrier Phenotype in Human Retinal Microvascular Endothelial Cells

Rochfort

Carroll

Barabás

et al. 2019

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Purpose Current treatments for diabetic retinopathy (DR) have considerable limitations, underpinning the need for new therapeutic options. In this article, the ability of an engineered angiopoietin-1 variant (COMP-Ang1) to ameliorate the injurious effects of hyperglycemia on barrier integrity in a human retinal microvascular endothelial cell (HRMvEC) model is comprehensively investigated. Methods Confluent HRMvECs were treated (0–72 hours) with d -glucose (5 or 30 mM) in the absence and presence of COMP-Ang1 (10–200 ng/mL). l -glucose (30 mM) was used as osmotic control. Posttreatment, intact cell monolayers were monitored for permeability to FITC-dextran 40 kDa. Cells were also harvested for analysis of interendothelial junction targets by RT-qPCR and Western blotting. The impact of receptor tyrosine kinase Tie2 gene silencing on COMP-Ang1 efficacy was also evaluated. Results Treatment with 30 mM d -glucose (but not l -glucose) demonstrated a time-dependent elevation in the mean rate of FITC-dextran diffusion across intact HRMvEC monolayers, in parallel with significant reductions in mRNA/protein levels of occludin, claudin-5, ZO-1, and VE-Cadherin. These effects were all attenuated by COMP-Ang1 in a concentration-dependent fashion, with 200 ng/mL recovering barrier function by ∼88%, and recovering reduced interendothelial junction protein levels by more than 50%. Finally, Tie2 knockdown by small interfering RNA silencing blocked the ability of COMP-Ang1 to mitigate against hyperglycemia-induced permeabilization of HRMvECs and depletion of junctional expression levels. Conclusions In summary, this article presents a reproducible in vitro cell study that quantifies the concentration-dependent efficacy of COMP-Ang1 to mitigate the injurious effects of hyperglycemic challenge on HRMvEC barrier properties via Tie2-mediated signaling.

show abstract

Section: Discussionmentioning

confidence: 93%

COMP-Ang1 Stabilizes Hyperglycemic Disruption of Blood-Retinal Barrier Phenotype in Human Retinal Microvascular Endothelial Cells

Rochfort

Carroll

Barabás

et al. 2019

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

show abstract

“…The lower amount of injections administered during the second year of treatment might be related to the disease-modifying character of anti-VEGF in DME. 25 VA increased by 4.8 and 9.2 letters in years one and two when compared to baseline (60.1 ± 14.5 letters; p≤ 0.01). This functional improvement went along with a decrease in CRT from 419 µm to 298 µm after one year and to 319 µm after two years.…”

Section: Main Findingsmentioning

confidence: 87%

<p>Two Year Visual Acuity and Structural Outcomes in Patients with Diabetic Macular Oedema Treated with Intravitreal Aflibercept – A Retrospective Cohort Study</p>

Kern¹,

Schiefelbein²,

Fu³

et al. 2020

OPTH

View full text Add to dashboard Cite

Purpose: To assess visual and anatomical outcomes of intravitreal aflibercept for clinically significant diabetic macular oedema (DME). Methods: For this retrospective single-center cohort study at a tertiary referral center, we performed a data warehouse query to identify 117 treatment-naive patients (139 eyes) undergoing intravitreal treatment with aflibercept for DME between January 2014 and May 2018. Changes in best-corrected visual acuity (BCVA) values (as measured with ETDRS letters), central retinal thickness (CRT) and total macular volume (TVOL) are reported over a two-year period at various time-points. Results: The total number of injections per study eye was 5.5 ± 1.4 after one and 8.7 ± 2.2 injections after two years. Baseline visual acuity (VA) was 60.1 ± 14.5 letters. A gain of 4.8 and 9.2 letters from baseline was observed after one and two years, respectively (both p ≤ 0.01). In comparison to the mean CRT at baseline (419 ± 174 µm), a CRT decrease was observed after one and two years of treatment (298 ± 115 µm and 319 ± 119 µm, respectively; both p ≤ 0.01). Similarly, TVOL decreased from 10.12 ± 2.05 mm 3 to 8.96 ± 0.96 mm 3 and 9.01 ± 1.29 mm 3 (both p ≤ 0.01). Conclusion: This study demonstrates that treating DME with intravitreal aflibercept yields positive functional and structural outcomes over a two-year period. However, we observed fewer injection numbers, along with inferior VA and structural outcomes than has been reported in randomized clinical trials. Our results show similar results as in patients treated with ranibizumab due to DME in real-life settings.

show abstract

“…In Protocol I, Protocol S, and the RIDE/RISE open-label extension, DR severity improvements with ranibizumab were maintained with a marked reduction in treatment frequency for long periods of time (up to 5 years in Protocol I) after the end of monthly treatment, suggesting that the risk of progression may remain low for up to 18 months after treatment discontinuation. 8,35,36 This may not be true for all patients, or among different anti-VEGF agents, however, and should be considered a limitation of the study. Sixthly, the model did not include the potential effect of adverse effects from the injections.…”

Section: Discussionmentioning

confidence: 98%

<p>Diabetic Population-Based Model to Estimate Impact of Ranibizumab on Diabetic Retinopathy Severity in Patients with Diabetic Macular Edema</p>

Varma

Bressler

Doan³

et al. 2020

OPTH

View full text Add to dashboard Cite

Purpose: Estimate effects of ranibizumab on diabetic retinopathy (DR) severity in US Hispanic and non-Hispanic white persons with center-involved diabetic macular edema (DME) causing vision impairment for whom ranibizumab treatment would be considered. Patients and Methods: This model simulated DR severity outcomes over 2 years in the better-seeing eye using US census, National Health and Nutrition Examination Survey, Wisconsin Epidemiologic Study of Diabetic Retinopathy, and Los Angeles Latino Eye Study data. Baseline DR severity estimated from Diabetic Retinopathy Clinical Research Network trial data. Changes in DR severity after 2 years, with/without monthly ranibizumab (0.3 or 0.5 mg), were estimated from Phase III clinical trial data (RIDE/RISE) using a 2-dimensional Monte Carlo simulation model. Number of patients over a 2-year period for whom 1) DR severity worsening was avoided, 2) DR severity improved, and 3) selected clinical events related to proliferative DR (PDR) occurred, was estimated. Results: An estimated 37,274 US Hispanic and non-Hispanic white persons were projected to have DR with center-involved DME and be eligible for ranibizumab treatment. The number of persons with moderately severe non-proliferative DR (NPDR) or less severe DR at baseline who would worsen to PDR and experience a PDR complication over 2 years would be reduced from 437 with no ranibizumab to 19 with ranibizumab (95% reduction; 95% simulation interval [SI], 79-100%). The number of persons with severe NPDR or less severe DR at baseline who would be expected to improve by ≥2 DR severity levels over 2 years would increase from 1706 with no ranibizumab to 13,042 with ranibizumab (682% increase; 95% SI, 478-967%). Conclusion: This model estimates that ranibizumab treatment in US Hispanic and non-Hispanic white patients with center-involved DME causing vision impairment would potentially reduce the number of patients with worsening DR and potentially increase the number with DR improvements.

show abstract

Changes in Diabetic Retinopathy Severity When Treating Diabetic Macular Edema With Ranibizumab

Cited by 51 publications

References 26 publications

COMP-Ang1 Stabilizes Hyperglycemic Disruption of Blood-Retinal Barrier Phenotype in Human Retinal Microvascular Endothelial Cells

COMP-Ang1 Stabilizes Hyperglycemic Disruption of Blood-Retinal Barrier Phenotype in Human Retinal Microvascular Endothelial Cells

<p>Two Year Visual Acuity and Structural Outcomes in Patients with Diabetic Macular Oedema Treated with Intravitreal Aflibercept – A Retrospective Cohort Study</p>

<p>Diabetic Population-Based Model to Estimate Impact of Ranibizumab on Diabetic Retinopathy Severity in Patients with Diabetic Macular Edema</p>

Contact Info

Product

Resources

About