Abstract 3764: Increased shedding of Endothelial Microparticles following Anti-VEGF therapy of Human Proliferative Diabetic Retinopathy

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Mounir Benzerroug ◽  
Aurélie Leroyer ◽  
Serge Picaud ◽  
Alain Gaudric ◽  
Gérard Brasseur ◽  
...  

Background: Development of retinal neovascularization in proliferative diabetic retinopathy (PDR) is correlated to vitreous VEGF levels. Intravitreal administration of Bevacizumab, a humanized recombinant antibody that binds all isoforms of VEGF, causes at least short-term involution of retinal neovascularization. We hypothesized that endothelial microparticles (MP), which are submicron membrane vesicles released following endothelial cell activation or apoptosis, accumulate in vitreous fluid from patients with PDR following anti-VEGF therapy. Methods and results: Undiluted vitreous fluid samples were collected at the start of standard surgery for the treatment of retinal disease in diabetic (D, n=14, 61±3yrs, 7.5±0.2% HbA1c) and non-diabetic (ND, with macular hole, epiretinal membrane or retinal detachment; n=15, 65±4yrs) patients. Four patients with PDR received intravitreal injection of Bevacizumab (50 μL; 25 μg/ μL) one week before surgery. Levels and cellular origins of MP in vitreous fluid were analysed by flow cytometry, using markers for platelet (CD41), endothelial (CD144), microglial (Bandeiraea Simplicifolia Lectin; ILB4) and photoreceptor (Arachis hypogaea Lectin; PNA) cells. Vitreous levels of endothelial and platelet MPs were markedly increased in PDR when compared to ND patients (139±53 vs 21±5 CD41+MP/μl (p=0.02); 238±61 vs. 62±12 CD144+MP/μl (p=0.004); respectively). Levels of MPs of microglial or photoreceptor origin did not differ significantly in D and ND vitreous samples (89±51 vs. 17±6 PNA+MP/μl (p=0.234); 47±25 vs. 20±13 ILB4+MP/μl (p=0.32); respectively). Intravitreal injection of anti-VEGF antibody led to a tenfold increase in endothelial MPs shedding (2418±673 CD144+MP/μl) and a complete disappearance of platelet-derived CD41+MPs in PDR vitreous samples. Anti-VEGF treatment also reduced microglial ILB4+MPs levels (3±3 MP/μl; p<0.16). Conclusion: Microparticle identification in vitreous samples indicates that local anti-VEGF therapy induces massive vascular endothelial cell apoptosis. In addition, augmented platelet MPs levels in diabetic vitreous samples suggests that PDR is associated with an increased endothelial permeability, which is restored to basal level by anti-VEGF therapy

2020 ◽  
Vol 3 (2) ◽  
pp. 51-57
Author(s):  
Defayudina Dafilianty Rosataria ◽  
Ramzi Amin

ABSTRACT Introduction : In general, diabetic retinopathy is classified into early stage, namely non proliferative diabetic retinopathy (NPDR), and advanced stage, proliferative diabetic retinopathy (PDR). Diabetic macular edema is the most common cause of visual impairment in cases of early stage or NPDR. Purpose : To describe Diabetic Macular Edema (DME) with intravitreal injection of anti-VEGF as a treatment. Case report : 43 old female, came with chief complaint of blurred vision on her right eye since six months ago. Blurring is felt slowly. Patient has a history of uncontrolled diabetes since 10 years and a history of hypercholesterolemia since 1 year ago. visual acuity of the right eye is 4/60. On posterior segment examination, neovascularization of the papilla was found. Decreased foveal reflex (+), hard exudates (+) within 500 µm from the central macula. Microaneurism (+), dot hemorrhage (+), blot (+) in 4 quadrants, hard exudates (+) in 2 quadrants in her right eye. The patient was planned for intravitreal injection of anti-VEGF on her right eye. Conclusion : Intravitreal injection of anti-VEGF can improve visual acuity and reduce exudate and hemorrhage in retina from ophthalmoscope and fundus photography examination. In addition, the investigation with OCT was found to improve with reduced macular thickness.  


Author(s):  
A.S. Golovin ◽  
◽  
O.A. Sinyavskiy ◽  
R.L. Troyanovsky ◽  
◽  
...  

Purpose. Optimization and identification of key conditions for successful surgical treatment of PDR in patients with permanent hemodialysis. Material and methods. The results of surgical treatment of 8 patients (10 eyes) with PDR who received permanent hemodialysis were analyzed. All patients underwent surgery 18-20 hours after the hemodialysis session. 25G vitrectomy with phacoemulsification 1-5 days after intravitreal injection inhibitor of anti-VEGF. Results. In 9 cases, an improvement in visual functions was achieved. Visual acuity of 0.08-0.1 in 5 cases, 0.1-0.2 in 3 cases and 0.3 in one case on a single eye. Conclusions. The described stereotype is the optimal approach for the surgical treatment of PDR in patients with permanent hemodialysis. Key words: proliferative diabetic retinopathy, hemodialysis, vitrectomy.


2021 ◽  
Vol 4 (2) ◽  
pp. 150
Author(s):  
Syntia Nusanti ◽  
Kirana Sampurna ◽  
Ari Djatikusumo ◽  
Anggun Rama Yudantha ◽  
Joedo Prihartono

Introduction :  Diabetic Retinopathy (DR) is one of the major cause of visual acuity deterioration in diabetic patients. The loss of central visual acuity in diabetic patients are mainly due to macula edema, which is found in 29% diabetic patients with the over 20 years duration of disease. The aim of this study is to evaluate and investigate the possible correlation among changes of visual acuity (VA), central macular thickness (CMT) using Spectral Domain Optical Coherence Tomography (SD-OCT). Electrophysiological responses using multifocal electroretinography (MfERG) in diabetic macular edema (DME) following intravitreal injection of bevacizumab. Methods: Single arm clinical trial. Thirty-three eyes of 33 DME patients (16 non-proliferative diabetic retinopathy and 17 non-high-risk proliferative diabetic retinopathy), receives intravitreal bevacizumab 1,25mg. All patients underwent complete ophthalmic examination including ETDRS VA testing, Sixty-one scaled hexagon MfERG and SD-OCT scan at baseline, 1-week and 1-month post-injection. Components of the first order kernel (N1, N2 and P1) in central 2o were measured. Result : MfERG showed reduced P1 amplitude (P<0.05) at 1-week after injection followed by increased P1 amplitude (P>0.05) at 1-month after treatment as compared to the baseline in all subjects. There was 19% improvement CMT and 0.2Logmar VA improvement in 1-month post-injection compared to the baseline (P<005). This study showed no serious ocular adverse effects. There was no significant correlation between changes in visual acuity with changes in CMT or other MfERG parameters. Conclusion: Intravitreal injection bevacizumab resulting in improved VA, reduction in CMT and mild improvement in the MfERG responses. Although VA changes did not correlate with reduced CMT nor with improved responses of MfERG, the combined use of SD-OCT and MfERG may be used to evaluate macular function in DME patient with worsened visual acuity post anti-VEGF injection.


2021 ◽  
Vol 10 (11) ◽  
pp. 2309
Author(s):  
Sarah R. Weber ◽  
Yuanjun Zhao ◽  
Christopher Gates ◽  
Jingqun Ma ◽  
Felipe da Veiga Leprevost ◽  
...  

Vitreous fluid is becoming an increasingly popular medium for the study of retinal disease. Numerous studies have demonstrated that proteomic analysis of the vitreous from patients with proliferative diabetic retinopathy yields valuable molecular information regarding known and novel proteins and pathways involved in this disease. However, there is no standardized methodology for vitreous proteomic studies. Here, we share a suggested protocol for such studies and outline the various experimental and analytic methods that are currently available. We also review prior mass spectrometry-based proteomic studies of the vitreous from patients with proliferative diabetic retinopathy, discuss common pitfalls of these studies, and propose next steps for moving the field forward.


2021 ◽  
Vol 49 (1) ◽  
pp. 030006052098536
Author(s):  
Yuan Tao ◽  
Pengfei Jiang ◽  
Min Liu ◽  
Ying Liu ◽  
Lihua Song ◽  
...  

Objective To evaluate whether diabetic retinopathy can be reversed after aflibercept, based on improvements in diabetic macular edema, hard exudates (HEs) of the posterior pole, and retinal microaneurysms (MAs). Methods This was a single-center retrospective study of 30 patients (34 eyes) with severe non-proliferative diabetic retinopathy (NPDR) who were treated between August and October 2018. Best-corrected visual acuity (BCVA), central foveal thickness (CFT), area of HEs, and number of MAs were compared before and after treatment. Results The mean patient age was 61.4 ± 7.1 years; 14 patients (46.7%) were men. The mean number of injections per patient was 3.5 ± 0.5. The time between the last injection and the last follow-up was 82 days (range, 78–110 days). Six months after the first intravitreal injection, significant improvement was observed in BCVA (from 0.70 ± 0.18 to 0.42 ± 0.19 logMAR), CFT (from 377.17 ± 60.41 to 261.21 ± 31.50 µm), and number of MAs (from 182.2 ± 77.4 to 101.5 ± 59.6). Observations over 6 months after the first intravitreal injection showed a statistically significant reduction in the area of HEs (P = 0.007). No adverse events occurred during the treatment period. Conclusion Diabetic retinopathy might be partially reversed by aflibercept treatment, as indicated by BCVA, CFT, number of MAs, and area of HEs.


2021 ◽  
Vol 8 ◽  
Author(s):  
Guanrong Wu ◽  
Baoyi Liu ◽  
Qiaowei Wu ◽  
Changting Tang ◽  
Zijing Du ◽  
...  

Purpose: To investigate the expression of various angiogenesis and inflammation mediators in the vitreous fluid of eyes with proliferative diabetic retinopathy (PDR).Methods: A total of 38 eyes with PDR and 37 control eyes were included. Vitreous fluid was collected during vitrectomy. Vitreous levels of colony stimulating factor-1 receptor (CSF-1R), syndecan-1, placental growth factor (PIGF), and angiopoietin-like protein 4 (ANGPTL-4) were measured by multiplex immunoassay. Vitreous levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) were measured by cytometric beads array. Levels of these mediators were compared between the PDR and control eyes. Correlations between levels of different mediators and between these mediators and kidney function metrics in the PDR group were also analyzed.Results: Vitreous levels of syndecan-1, PIGF, ANGPTL-4, VEGF, and IL-8 were significantly higher in the PDR group compared to the control group (all p &lt; 0.05). Levels of VEGF were significantly correlated with levels of syndecan-1, PIGF, and ANGPTL-4 (r = 0.370 to 0.497, all p &lt; 0.05). Significant positive correlations were detected between levels of any two of the following mediators including syndecan-1, PIGF, ANGPTL-4, and IL-8 (r = 0.370 to 0.906, all p &lt; 0.05). Apart from VEGF, levels of these mediators were positively correlated with serum creatinine and blood urea nitrogen (r = 0.328 to 0.638, all p &lt; 0.05), and negatively correlated with fasting blood glucose and estimated glomerular filtration rate (r = −0.325 to −0.603, all p &lt; 0.05).Conclusions: Correlations between different angiogenesis and inflammation mediators were observed in eyes with PDR, suggesting cross-talks of different angiogenesis and inflammation pathways in the pathogenesis of PDR. The levels of angiogenesis and inflammation in PDR are correlated with kidney damage, indicating possible common pathways in diabetic retinopathy and nephropathy.


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