scholarly journals Vascular Complications and Diabetes: Current Therapies and Future Challenges

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Abbott L. Willard ◽  
Ira M. Herman
Keyword(s):  
Clinical Trials ◽  
Diabetic Retinopathy ◽  
Vascular Complications ◽  
Mural Cell ◽  
Chronic Hyperglycemia ◽  
Anti Vegf ◽  
Future Challenges ◽  
Current Therapies ◽  
Endothelial Growth Factor ◽  
Retinal Complications

Diabetic retinal complications, including macular edema (DME) and proliferative diabetic retinopathy (PDR), are the leading cause of new cases of blindness among adults aged 20–74. Chronic hyperglycemia, considered the underlying cause of diabetic retinopathy, is thought to act first through violation of the pericyte-endothelial coupling. Disruption of microvascular integrity leads to pathologic consequences including hypoxia-induced imbalance in vascular endothelial growth factor (VEGF) signaling. Several anti-VEGF medications are in clinical trials for use in arresting retinal angiogenesis arising from DME and PDR. Although a review of current clinical trials shows promising results, the lack of large prospective studies, head-to-head therapeutic comparisons, and potential long-term and systemic adverse events give cause for optimistic caution. Alternative therapies including targeting pathogenic specific angiogenesis and mural-cell-based therapeutics may offer innovative solutions for currently intractable clinical problems. This paper describes the mechanisms behind diabetic retinal complications, current research supporting anti-VEGF medications, and future therapeutic directions.

scholarly journals Neuroprotection as a Therapeutic Target for Diabetic Retinopathy

2016 ◽  
Vol 2016 ◽  
pp. 1-18 ◽  
Author(s):  
Cristina Hernández ◽  
Massimo Dal Monte ◽  
Rafael Simó ◽  
Giovanni Casini
Keyword(s):  
Clinical Trials ◽  
Diabetic Retinopathy ◽  
Animal Studies ◽  
Vision Loss ◽  
Vascular Lesions ◽  
Vascular Endothelial ◽  
Neuroprotective Strategies ◽  
Current Therapies ◽  
Retinal Neurodegeneration ◽  
Endothelial Growth Factor

Diabetic retinopathy (DR) is a multifactorial progressive disease of the retina and a leading cause of vision loss. DR has long been regarded as a vascular disorder, although neuronal death and visual impairment appear before vascular lesions, suggesting an important role played by neurodegeneration in DR and the appropriateness of neuroprotective strategies. Upregulation of vascular endothelial growth factor (VEGF), the main target of current therapies, is likely to be one of the first responses to retinal hyperglycemic stress and VEGF may represent an important survival factor in early phases of DR. Of central importance for clinical trials is the detection of retinal neurodegeneration in the clinical setting, and spectral domain optical coherence tomography seems the most indicated technique. Many substances have been tested in animal studies for their neuroprotective properties and for possible use in humans. Perhaps, the most intriguing perspective is the use of endogenous neuroprotective substances or nutraceuticals. Together, the data point to the central role of neurodegeneration in the pathogenesis of DR and indicate neuroprotection as an effective strategy for treating this disease. However, clinical trials to determine not only the effectiveness and safety but also the compliance of a noninvasive route of drug administration are needed.

scholarly journals Incidence and Risk Factors for Tractional Macular Detachment after Anti-Vascular Endothelial Growth Factor Agent Pretreatment before Vitrectomy for Complicated Proliferative Diabetic Retinopathy

2019 ◽  
Vol 8 (11) ◽  
pp. 1960
Author(s):  
Andrea Russo ◽  
Antonio Longo ◽  
Teresio Avitabile ◽  
Vincenza Bonfiglio ◽  
Matteo Fallico ◽  
...  
Keyword(s):  
Risk Factors ◽  
Vascular Endothelial Growth Factor ◽  
Diabetic Retinopathy ◽  
Growth Factor ◽  
Proliferative Diabetic Retinopathy ◽  
Vitreous Hemorrhage ◽  
Vascular Endothelial ◽  
Macular Detachment ◽  
Anti Vegf ◽  
Endothelial Growth Factor

The study’s purpose was to determine the incidence, risk factors, and outcomes of tractional macular detachment after anti-vascular endothelial growth factor (VEGF) pretreatment before vitrectomy for complicated proliferative diabetic retinopathy. Patients who underwent primary vitrectomy for complicated proliferative diabetic retinopathy, from January 2012 to 31 December 2018, were enrolled. Ophthalmic and pre-operative data were extracted from electronic record systems. All eyes with a valuable Optical Coherence Tomography (OCT)performed within 5 days before injection of anti-VEGF and on the day of vitrectomy were included. Multivariable logistic regression showed that significant risk factors for developing tractional macular detachment included days between anti-VEGF and vitrectomy (OR, 0.71 [95% CI 0.65–0.76]; p < 0.001), vitreous hemorrhage (OR, 0.23 [95% CI 0.11–0.49]; p < 0.001), and age (OR, 1.05 [95% CI 1.02–1.08]; p < 0.001). Decision-tree analysis showed that the stronger predictors of tractional macular detachment were the time between anti-VEGF injection and vitrectomy (p < 0.001). Secondary predictors were the presence of vitreous hemorrhage (p = 0.012) in eyes that underwent vitrectomy between 6 and 10 days after anti-VEGF injection and younger age (p = 0.031) in eyes that underwent vitrectomy 10 days after anti-VEGF injection. Tractional macular detachment occurs in 10% of eyes after anti-VEGF injection, the main risk factors being days between anti-VEGF injection and vitrectomy, vitreous hemorrhage, and age.

scholarly journals Update on the Effects of Antioxidants on Diabetic Retinopathy: In Vitro Experiments, Animal Studies and Clinical Trials

Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 561 ◽  
Author(s):  
Jose Javier Garcia-Medina ◽  
Elena Rubio-Velazquez ◽  
Elisa Foulquie-Moreno ◽  
Ricardo P Casaroli-Marano ◽  
Maria Dolores Pinazo-Duran ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Diabetic Retinopathy ◽  
Animal Studies ◽  
Pressure Control ◽  
Vascular Endothelial Growth Factors ◽  
Vascular Endothelial ◽  
In Vitro Experiments ◽  
Current Therapies ◽  
Endothelial Growth Factors

Current therapies for diabetic retinopathy (DR) incorporate blood glucose and blood pressure control, vitrectomy, photocoagulation, and intravitreal injections of anti-vascular endothelial growth factors or corticosteroids. Nonetheless, these techniques have not been demonstrated to completely stop the evolution of this disorder. The pathophysiology of DR is not fully known, but there is more and more evidence indicating that oxidative stress is an important mechanism in the progression of DR. In this sense, antioxidants have been suggested as a possible therapy to reduce the complications of DR. In this review we aim to assemble updated information in relation to in vitro experiments, animal studies and clinical trials dealing with the effect of the antioxidants on DR.

scholarly journals Short term visual and structural outcomes of anti-vascular endothelial growth factor (anti-VEGF) treatment delay during the first COVID-19 wave: A pilot study

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247161
Author(s):  
Ameay V. Naravane ◽  
Rusdeep Mundae ◽  
Yujia Zhou ◽  
Christopher Santilli ◽  
Frederik J. G. M. van Kuijk ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Diabetic Retinopathy ◽  
Pilot Study ◽  
Growth Factor ◽  
Macular Edema ◽  
Age Related Macular Degeneration ◽  
Vascular Endothelial ◽  
Anti Vegf ◽  
Delayed Group ◽  
Endothelial Growth Factor

Regularly scheduled intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are essential to maintaining and/or improving many ocular conditions including: neovascular age-related macular degeneration (nAMD), diabetic retinopathy, and retinal vein occlusions with macular edema (RVO). This study aims to assess the effect of unintended delays in anti-VEGF treatment during the first wave of the COVID-19 pandemic. This retrospective case series identified patients receiving regularly scheduled anti-VEGF intravitreal injections based on current procedural terminology (CPT) code at two practices in Minnesota. Diagnoses were limited to nAMD, diabetic macular edema (DME), proliferative diabetic retinopathy, and RVO. Patients were divided into two groups based on whether they maintained or delayed their follow-up visit by more than two weeks beyond the recommended treatment interval during the COVID-19 lockdown. The ‘COVID-19 lockdown’ was defined as the period after March, 28th, 2020, when a lockdown was declared in Minnesota. We then compared the visual acuity and structural changes to the retina using ocular coherence tomography (OCT) to assess whether delayed treatment resulted in worse visual outcomes. A total of 167 eyes from 117 patients met criteria for inclusion in this study. In the delayed group, the average BCVA at the pre- and post-lockdown visits were 0.614 and 0.715 (logMAR) respectively (p = 0.007). Central subfield thickness (CST) increased from 341 to 447 in the DME delayed group (p = 0.03) while the CST increased from 301 to 314 (p = 0.4) in the nAMD delayed group. The results of this pilot study suggests that treatment delays may have a negative impact on the visual and anatomic outcomes of patients with nAMD and DME. Future studies with larger sample sizes are required for further investigation.

Combination Antivascular Endothelial Growth Factor and Modified Panretinal Photocoagulation in Management of Proliferative Diabetic Retinopathy

2020 ◽  
Vol 4 (5) ◽  
pp. 401-410
Author(s):  
Amy Q. Lu ◽  
Bozho Todorich
Keyword(s):  
Diabetic Retinopathy ◽  
Growth Factor ◽  
Proliferative Diabetic Retinopathy ◽  
Case Series ◽  
Disease Suppression ◽  
Final Visit ◽  
Panretinal Photocoagulation ◽  
Anti Vegf ◽  
Antivascular Endothelial Growth Factor ◽  
Endothelial Growth Factor

Purpose: This work evaluates the effects of combined intravitreal antivascular endothelial growth factor (anti-VEGF) and modified panretinal photocoagulation (PRP) for management of proliferative diabetic retinopathy (PDR). Methods: This retrospective case series included 37 eyes of 33 patients with high-risk PDR. Anti-VEGF injections (≥ 2) were followed by modified, midperipheral PRP performed in 2 or more sessions. Visual and anatomic outcomes were tracked for 1 year after treatment. Regression analysis was performed for factors predictive of final outcomes. Results: Mean visual acuity (VA) at initial and final visit were 20/50 and 20/40 ( P = .22), respectively, over a mean follow-up duration of 341.4 days. Central foveal thickness decreased from 321.8 µm to 258.6 µm ( P = .01). Resolution of PDR was achieved in 94.6% of eyes, with 5.4% of eyes requiring additional anti-VEGF for persistent neovascularization. Final VA was significantly associated with baseline VA, VA at 1 month, and any adverse anatomical events. Treatment noncompliance was present in 24.3%; compliance decreased with increasing medical comorbidities, but was not significantly associated with final VA. Conclusions: Combination of anti-VEGF and modified PRP preserved VA and yielded PDR regression in the majority of eyes. This combination provides rapid PDR regression with anti-VEGF while achieving durable disease suppression in this real-world cohort without traditional PRP.

scholarly journals Changes in retinal and choriocapillaris density in diabetic patients receiving anti-vascular endothelial growth factor treatment using optical coherence tomography angiography

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Felipe F. Conti ◽  
Weilin Song ◽  
Eduardo B. Rodrigues ◽  
Rishi P. Singh
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Optical Coherence Tomography ◽  
Diabetic Retinopathy ◽  
Growth Factor ◽  
Optical Coherence Tomography Angiography ◽  
Vascular Endothelial ◽  
Optical Coherence ◽  
Anti Vegf ◽  
Retinal Capillary ◽  
Endothelial Growth Factor

Abstract Background Optical coherence tomography angiography (OCTA) enables detailed, non-invasive assessment of ocular vasculature. This study uses OCTA imaging to evaluate choriocapillaris and retinal capillary perfusion density (CPD) changes in diabetic retinopathy following anti-vascular endothelial growth factor (VEGF) treatment. Methods Records of 38 eyes at a single institution were reviewed, grouped as non-diabetic controls (19 eyes), diabetes mellitus patients with diabetic retinopathy (DR, 19 eyes) and macular edema (DME). DR eyes were imaged at baseline, 6-months and 12-months after anti-VEGF treatment. Quantitative analyses assessed CPD of the choriocapillaris and retinal plexus. Results DR eyes showed decreased choriocapillaris whole-image CPD (62.6 ± 6.1 vs. 68.4 ± 5.1, p < 0.003), foveal CPD (61.2 ± 7.4 vs. 66.3 ± 9.8, p < 0.014), and parafoveal CPD (61.9 ± 6.6 vs. 68.2 ± 4.8, p < 0.002) at baseline. DR eyes also showed decreased retinal density, including whole-image CPD (46.9 ± 5.1 vs. 50.7 ± 5.6, p < 0.04), foveal CPD (27.6 ± 5.9 vs. 34.1 ± 6.1, p < 0.002), and parafoveal CPD (49.0 ± 5.6 vs. 53.1 ± 6.0, p < 0.011). Following 12 months of anti-VEGF treatment, no changes to retinal or choriocapillaris or CPD were observed. Retinal central subfield thickness decreased (397.1 ± 93.2 µm vs. 294.2 ± 71.5 µm, p < 0.005). Lastly, FAZ area (0.307 ± 0.133 mm2 vs. 0.184 ± 0.058 mm2, p = 0.008) and perimeter (2.415 ± 0.692 mm2 vs. 1.753 ± 0.408 mm2, p = 0.002) were increased in DR eyes at baseline. No changes to FAZ area or perimeter were seen with anti-VEGF treatment in DR eyes. Conclusions Compared to control, choriocapillaris and retinal CPD are reduced in DR, while FAZ area and perimeter are increased. No retinal capillary or choriocapillaris CPD changes were observed in DR eyes following anti-VEGF treatment.

scholarly journals Cytokine Levels in Human Vitreous in Proliferative Diabetic Retinopathy

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1069
Author(s):  
Dean F. Loporchio ◽  
Emily K. Tam ◽  
Jane Cho ◽  
Jaeyoon Chung ◽  
Gyungah R. Jun ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Proliferative Diabetic Retinopathy ◽  
Vitreous Humor ◽  
Reactive Protein ◽  
Amyloid A ◽  
Intracellular Adhesion Molecule ◽  
Cytokine Levels ◽  
Quantitative Immunoassay ◽  
Current Therapies ◽  
Endothelial Growth Factor

In this study, we compare the vitreous cytokine profile in patients with proliferative diabetic retinopathy (PDR) to that of patients without PDR. The identification of novel cytokines involved in the pathogenesis of PDR provides candidate therapeutic targets that may stand alone or work synergistically with current therapies in the management of diabetic retinopathy. Undiluted vitreous humor specimens were collected from 74 patients undergoing vitrectomy for various vitreoretinal disorders. Quantitative immunoassay was performed for a panel of 36 neuroinflammatory cytokines in each specimen and assessed to identify differences between PDR (n = 35) and non-PDR (n = 39) patients. Levels of interleukin-8 (IL-8), IL-15, IL-16, vascular endothelial growth factor (VEGF), VEGF-D, c-reactive protein (CRP), serum amyloid-A (SAA), and intracellular adhesion molecule-1 (ICAM1) were significantly increased in the vitreous of PDR patients compared to non-PDR patients (p < 0.05). We report novel increases in IL-15 and IL-16, in addition to the expected VEGF, in the human vitreous humor of patients with PDR. Additionally, we confirm the elevation of ICAM-1, VCAM-1, SAA, IL-8 and CRP in the vitreous of patients with PDR, which has previously been described.

scholarly journals Nanomedicine for Treating Diabetic Retinopathy Vascular Degeneration

2021 ◽  
Vol 1 (3) ◽  
pp. 306-322
Author(s):  
Tatiana Borodina ◽  
Dmitry Kostyushev ◽  
Andrey A. Zamyatnin ◽  
Alessandro Parodi
Keyword(s):  
Diabetic Retinopathy ◽  
Vision Loss ◽  
Surface Modifications ◽  
Posterior Segment ◽  
Chronic Hyperglycemia ◽  
Pathological Conditions ◽  
Current Therapies ◽  
Inflammatory Drugs ◽  
Topical Treatments ◽  
Number Of Injections

The incidence of diabetes and the pathological conditions associated with chronic hyperglycemia is increasing worldwide. Among them, diabetic retinopathy represents a leading cause of vision loss, causing a significant structural and functional impairment of the retinal and choroidal capillary network. Current therapies include anti-angiogenic and anti-inflammatory drugs administered through repetitive and invasive intraocular injections, and associated with significant adverse effects. The presence of ocular barriers affects the efficiency of topically administered therapeutics for treating the posterior segment of the eye. In this scenario, nanomedicine could improve current therapies for diabetic retinopathy by providing tools that can decrease the number of injections thanks to their controlled release properties, while some materials showed a natural ability to mitigate pathological neo-angiogenesis. Moreover, specific surface modifications could open new scenarios for the development of topical treatments. This review describes current advances in generating nanomedicine for diabetic retinopathy, focusing on the properties of the different materials tested explicitly for this purpose.

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