scholarly journals P1001RENAL DAMAGE ASSOCIATED WITH INTRAVITREAL ADMINISTRATION OF ANTI-VEGF DRUGS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Maria Fernandez-Vidal ◽  
Candela Moliz ◽  
Beatriz Redondo ◽  
Teresa Bada Bosch ◽  
Lucia Aubert ◽  
...  
Keyword(s):  
Renal Function ◽  
Diabetic Patients ◽  
Vascular Endothelial ◽  
Median Dose ◽  
Anti Vegf ◽  
Group 2 ◽  
Endothelial Growth Factor ◽  
Group 1

Abstract Background and Aims Vascular endothelial growth factor inhibitors (anti-VEGF) have been shown to be effective in the treatment of macular degeneration and diabetic macular edema. It is known that systemic administration of these drugs can produce adverse renal effects, such as decreased glomerular filtration rate (eFGR), proteinuria, hypertension or thrombotic microangiopathy. However, there is little information about it when the administration is intravitreal. The aim of this study was analyzed the effect of anti-VEGF drugs on renal function and proteinuria. Method Observational and prospective study on diabetic patients, which were divided into two groups: non-cronic kidney disease (CKD) (group 1) and CKD (group 2). We analyzed clinical and analytical variables during follow-up. Results We included 45 diabetic patients (55.6% males) with a median age of 75 (50-91) years. Forty one patients (91.1%) were hypertensive and thirty three (73.3%) were CKD patients. Twenty six (57.8%) received bevazicumab, while the rest (42.2%) received ranibizumab, with a median dose of 6 (1-22). The median follow-up was 25 (9-94) months. The evolution of eFGR and albuminuria are described in Figure 1, where it stands out the increase in albuminuria in group 2. Regarding the drug type, there were no differences. Within the CKD group, one patient presented two episodes of decompensation of heart failure after the administration of an anti-VEGF drug, and two required the initiation of renal replacement therapy. Conclusion Based on the results of our cohort, we believe that it would be advisable to establish a closer monitoring in diabetic patients who are administered an intravitreal anti-VEGF drug, with determination of renal function as well as albuminuria to establish an early diagnosis of possible complications.

scholarly journals Association between Retinal Thickness Variability and Visual Acuity Outcome during Maintenance Therapy Using Intravitreal Anti-Vascular Endothelial Growth Factor Agents for Neovascular Age-Related Macular Degeneration

2021 ◽  
Vol 11 (10) ◽  
pp. 1024
Author(s):  
Timothy Y. Y. Lai ◽  
Ricky Y. K. Lai
Keyword(s):  
Visual Acuity ◽  
Retinal Thickness ◽  
Age Related Macular Degeneration ◽  
Vascular Endothelial ◽  
Anti Vegf ◽  
Age Related ◽  
Thickness Variability ◽  
The Mean ◽  
Endothelial Growth Factor

Previous studies based on clinical trial data have demonstrated that greater fluctuations in retinal thickness during the course of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD) is associated with poorer visual acuity outcomes. However, it was unclear whether similar findings would be observed in real-world clinical settings. This study aimed to evaluate the association between retinal thickness variability and visual outcomes in eyes receiving anti-VEGF therapy for nAMD using pro re nata treatment regimen. A total of 64 eyes which received intravitreal anti-VEGF therapy (bevacizumab, ranibizumab or aflibercept) for the treatment of nAMD were evaluated. Variability in spectral-domain optical coherence tomography (OCT) central subfield thickness (CST) was calculated from the standard deviation (SD) values of all follow-up visits after three loading doses from month 3 to month 24. Eyes were divided into quartiles based on the OCT CST variability values and the mean best-corrected visual acuity values at 2 years were compared. At baseline, the mean ± SD logMAR visual acuity and CST were 0.59 ± 0.39 and 364 ± 113 µm, respectively. A significant correlation was found between CST variability and visual acuity at 2 years (Spearman’s ρ = 0.54, p < 0.0001), indicating that eyes with lower CST variability had better visual acuity at 2 years. Eyes with the least CST variability were associated with the highest mean visual acuity improvement at 2 years (quartile 1: +9.7 letters, quartile 2: +1.1 letters, quartile 3: −2.5 letters, quartile 4: −9.5 letters; p = 0.018). No significant difference in the number of anti-VEGF injections was found between the four CST variability quartile groups (p = 0.21). These findings showed that eyes undergoing anti-VEGF therapy for nAMD with more stable OCT CST variability during the follow-up period were associated with better visual outcomes. Clinicians should consider adopting treatment strategies to reduce CST variability during the treatment course for nAMD.

Twenty-four-month outcomes of inflammatory choroidal neovascularisation treated with intravitreal anti-vascular endothelial growth factors: a comparison between two treatment regimens

2019 ◽  
Vol 104 (8) ◽  
pp. 1052-1056 ◽  
Author(s):  
Alessandro Invernizzi ◽  
Francesco Pichi ◽  
Richard Symes ◽  
Sophia Zagora ◽  
Aniruddha Kishandutt Agarwal ◽  
...  
Keyword(s):  
Choroidal Neovascularisation ◽  
Vascular Endothelial Growth Factors ◽  
Vascular Endothelial ◽  
Treatment Regimens ◽  
Anti Vegf ◽  
Endothelial Growth Factor ◽  
Endothelial Growth Factors ◽  
Established Treatment ◽  
Number Of Injections

Background and aimThere is still no established treatment regimen for eyes with inflammatory choroidal neovascularisation (iCNV) treated with intravitreal anti-vascular endothelial growth factor (VEGF) injections. This study compared the 24-month outcomes of two treatment regimens of anti-VEGF injections in eyes with iCNV.MethodsEyes with iCNV treated with anti-VEGF injections were divided into two groups: eyes treated with a loading phase of 3 monthly injections and then re-treated as needed (LOADING group) and eyes treated as needed from the beginning (PRN group). Visual acuity (VA), number of injections and iCNV recurrences at 24 months were compared between the groups.ResultsEighty-two eyes were included, 42 in the LOADING and 40 in the PRN group. Baseline VA (mean(SD)) was 57.3 (15.8) letters in the LOADING vs 60.7 (15.6) letters in the PRN group (p=0.32). The VA (mean (95% CI)) increased at 3 months (+14.8 (10.6 to 18.9) and +11.2 (6.4 to 16) letters in the LOADING and PRN group, respectively) and remained significantly higher than baseline over the entire follow-up in both groups (all p<0.001). At 24 months, there was no difference in VA between the LOADING and PRN group (72.3 (14.0) vs 74.7 (11.3) letters, p=0.36) but the LOADING group received significantly more injections (median (Q1–Q3)) than the PRN (4.5 (3–7) vs 2.5 (2–3.2), p<0.0001). The iCNV recurrences were similar in both groups.ConclusionsiCNV responded well to anti-VEGF with significant and sustained VA improvement. The loading phase did not confer any advantage in terms of outcomes. PRN regimen from the beginning was as effective as more intensive treatment.

scholarly journals EFFICACY OF CATHETER ABLATION FOR PERSISTENT ATRIAL FIBRILLATION IN PATIENTS WITH DIABETES MELLITUS PRESENT WITH TACHY-BRADY SYNDROME

2018 ◽  
Vol 7 (3) ◽  
pp. 24-32
Author(s):  
E. A. Archakov ◽  
R. E. Batalov ◽  
S. Yu. Usenkov ◽  
M. S. Khlynin ◽  
A. V. Smorgon ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Catheter Ablation ◽  
Antiarrhythmic Drug ◽  
Pacemaker Implantation ◽  
Diabetic Patients ◽  
Antiarrhythmic Drug Therapy ◽  
Ventricular Stimulation ◽  
Group 2 ◽  
Group 1

Aim. To estimate the efficacy of catheter ablation in patients with type 2 diabetes mellitus (T2D) present with atrial fibrillation and sick sinus syndrome (SSS) undergoing permanent pacemaker implantation.Methods. 56 patients (34 females) with persistent AF and SSS were enrolled in the study. The mean age of patients was 67.7±10.7 years. Dual chamber cardiac pacemaker with remote monitoring function were implanted in all patients. All the patients were assigned to two groups: Group 1 comprised 31 patients aged 67.3±9.6 years, and Group 2 comprised 25 patients aged 72.6±9.9 years, including 22 (39.2%) diabetic patients. 2-3 days after pacemaker implantation, group 1 patients underwent intracardiac electrophysiology study and RFA of the pulmonary vein ostia, mitral isthmus and the left atrial posterior wall. Group 2 patients received antiarrhythmic drug therapy. Results. 3 patients (9%) in Group 1 had recurrent AF within the 6-month follow-up. The efficacy of the RFA for AF was 55% (n = 17) 1 year after the indexed hospitalization. 8 patients had short paroxysmal attacks which gradually lessened and stopped after. 5 patients (21%) in Group 2 did not have any AF paroxysms within the 1-year follow-up (Х2 = 5.52, р = 0.02). All these patients received amiodarone as antiarrhythmic drug therapy, whereas the others had paroxysmal attacks. Frequent attacks in 10 patients (40%) led to a change in antiarrhythmic drug use. Hospital readmission rates for AF were 16% and 52%, respectively (Х2 = 4.15, р = 0.04). The impact of atrial and ventricular stimulation on the development of recurrent AF was statistically insignificant (atrial stimulation – X2 = 0.01, cc = 1, p = 0.90; ventricular stimulation – X2 = 0.15, cc = 1, p = 0.69). None paroxysmal attacks were recorded in 10 diabetic patients (45%) after the RFA within the 1-year follow-up.Conclusion. Catheter ablation for persistent AF and SSS treated with permanent pacemakers is highly effective and safe method. In addition, it is superior to pharmacological approach. The presence of T2D likely did not significantly affect the efficacy of RFA for persistent form of AF. 

scholarly journals Combination Treatment of Diabetic Macular Edema with Anti-Vascular Endothelial Growth Factor and Steroids: Analysis of DRCR.net Protocol U

2018 ◽  
Vol 1 ◽  
pp. 2
Author(s):  
Cindy Ung ◽  
Kareem Moussa ◽  
Yoshihiro Yonekawa
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Diabetic Patients ◽  
Vascular Endothelial ◽  
First Line ◽  
Second Line Therapy ◽  
Anti Vegf ◽  
Endothelial Growth Factor

Diabetic macular edema (DME) is the main cause of visual impairment in diabetic patients. Intravitreal anti-vascular endothelial growth factor (VEGF) therapy is considered the first-line treatment option in the management of DME with corticosteroids used as second-line therapy. The DRCR.net Protocol U study was a Phase II trial that sought to compare the combination of a steroid and anti-VEGF therapy to anti-VEGF monotherapy regarding visual acuity and anatomic outcomes. This review highlights the strengths, weaknesses, and clinical implications of this study.

Effect of Lisinopril and Verapamil on Angiopoietin 2 and Endostatin in Hypertensive Diabetic Patients with Nephropathy: A Randomized Trial

2021 ◽  
Vol 53 (07) ◽  
pp. 470-477
Author(s):  
Al-Aliaa M. Sallam ◽  
Mohamed Salem ◽  
Eman Abdel-Aleem ◽  
Hala O. El-Mesallamy
Keyword(s):  
Early Stage ◽  
Controlled Trial ◽  
Fasting Blood Glucose ◽  
Diabetic Patients ◽  
Converting Enzyme Inhibitors ◽  
Angiogenic Proteins ◽  
Group 2 ◽  
Angiopoietin 2 ◽  
Group 1

AbstractAngiogenesis is a multistep process implicated in the pathophysiology and progression of diabetic nephropathy (DN). Angiotensin-converting enzyme inhibitors (ACEI) and calcium channel blockers (CCB) have an important role in DN. We performed a randomized-controlled trial of lisinopril alone (an ACEI) or in combination with verapamil (a CCB) as a therapy for DN in type 2 diabetes mellitus (T2DM) patients with hypertension (HTN) and urinary albumin creatinine ratio (UACR) (30–300 mg/g) also to evaluate their effect on UACR, the angiogenic proteins: Angiopoietin 2 (Ang-2) and Endostatin (EST). Forty T2DM patients with microalbuminuria, aged 45–65 years were included. Patients were randomly assigned into group 1 receiving oral lisinopril and group 2 receiving oral lisinopril and verapamil once daily. After 3 months follow-up fasting blood glucose (FPG), HbA1c, lipid profile, UACR, serum urea and creatinine levels were assessed. EST and Ang-2 were measured using ELISA technique. Baseline Ang-2 and EST levels were elevated in both groups compared with controls (p<0.001). After follow-up, group 2 had significantly decreased FPG, HbA1c, UACR, EST and Ang-2 compared with their baseline levels (p<0.001 for all comparisons) and with group 1 (p<0.001). No adverse reactions were reported. Baseline EST and Ang-2 were positively correlated to UACR (r=0.753, p<0.001) (r=0.685, p<0.001). Lisinopril/verapamil combination enhanced glycemic control and kidney function via diminishing EST and Ang-2. This combination can be considered as a safe and effective approach for early stage nephropathy therapy in T2DM.

P1024INFLUENCE OF NON-ALCOHOLIC FATTY LIVER DISEASE IN THE EVOLUTION OF RENAL FUNCTION IN DIABETIC PATIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Lucia Aubert ◽  
Justo Sandino ◽  
Florencio Garcia ◽  
Elena Gutiérrez ◽  
Julian Segura ◽  
...  
Keyword(s):  
Renal Function ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Type 2 Dm ◽  
Significant Difference ◽  
Group 2 ◽  
Alcoholic Fatty Liver Disease ◽  
Group 1

Abstract Background and Aims Nowadays, there is growing evidence that non-alcoholic fatty liver disease (NAFLD) may be associated with renal impairment and have an impact on the evolution of renal function in patients with type 2 diabetes mellitus (DM). Our aim was to compare the effect on renal function and proteinuria in patients with type 2 DM according to the presence of NAFLD. Method Retrospective and observational study, including patients with type 2 DM, &lt; 70 years of age and with estimated glomerular filtration rate (eGFR) &gt; 30 ml/min/1,73 m2. NAFLD was defined with the presence of compatible ultrasonography and/or presence of fibrosis using NAFLD score. Metabolic syndrome (MSd) was defined as: obesity (body mass index (BMI) &gt; 30 kg/m2), hypertension and dyslipidaemia. Patients were classified according to the presence or absence of NAFLD. We analysed different clinical and analytical variables along the follow up. Results A total of 71 patients were included (66% males) with mean age of 57.4 ± 7.8 years. The median evolution of type 2 DM was 72.2 months (34.7 - 125.5 months) and 90.1% of the patients were treated with renin-angiotensin blockade. When comparing patients with (group 1, n=38) and without (group 2, n=33) NAFLD at the beginning of this study, we found no significant difference in eGFR (80.2 ± 40.4 ml/min vs 71.4 ± 31.8 ml/min), proteinuria (1.4 ± 2.7 g/24h vs 0.8 ± 1.0 g/24h) and glycated haemoglobin (6.8 ± 1.4% vs 7.2 ± 1.6%). On the other hand, we found significant difference in the presence of higher BMI (33.8 vs 29.3 kg/m2; .001) and presence of MSd (67.7 vs 32.3%; .03) in those patients with NAFLD. After a mean follow-up time of 74 months, we found significant differences in the loss of eFGR (-33.8 vs -13.9 ml/min; .003), but no difference in increase of proteinuria. We found an increase in incidence of chronic kidney disease in group 1 (50%) vs group 2 (10.5%). There were no differences in the need to initiate renal replacement therapy or all-cause mortality. Conclusion NAFLD in type 2 DM caused a mayor decline in renal function. We should, therefore, take into consideration the presence of NALFD and the presence of MSd to optimise treatment of associated risk factors.

scholarly journals Enlargement rate of geographic atrophy before and after secondary CNV conversion with associated anti-VEGF treatment

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jakob Siedlecki ◽  
Caroline Koch ◽  
Benedikt Schworm ◽  
Raffael Liegl ◽  
Thomas Kreutzer ◽  
...  
Keyword(s):  
Growth Rate ◽  
Geographic Atrophy ◽  
Vascular Endothelial ◽  
Anti Vegf ◽  
Significant Difference ◽  
Before And After ◽  
Endothelial Growth Factor ◽  
Mean Time ◽  
Larger Sample

Abstract Background To study the enlargement rate of primary geographic atrophy (GA) before and after diagnosis of a secondary choroidal neovascularization (CNV) treated with anti-vascular endothelial growth factor (VEGF) therapy. Methods Five hundred twenty-two consecutive eyes with primary GA were screened for the development of a complicating secondary CNV. Geographic atrophy was measured on blue autofluorescence (BAF) by two readers and calculated into mean growth rate before and after CNV diagnosis. Results Ten eyes of six patients were included in the study (six study eyes with GA complicated by CNV, four GA only partner eyes). Follow-up was 1.42 ± 0.48 years before and 3.64 ± 2.73 years after CNV. There was no significant difference between mean growth rate before and after CNV (1.58 ± 0.99 vs. 1.39 ± 0.65 mm2/year; p = 0.44) or between study and partner eyes (p = 0.86). Over a mean time of 3.64 ± 2.73 years, a mean of 8.3 ± 2.8 anti-VEGF injections were given. No correlation between the amount of anti-VEGF injections and change in growth rate could be observed (r = 0.58; p = 0.23). Conclusion In this pilot study, primary GA enlargement did not seem to be influenced by a secondary CNV. No association between the intensity of anti-VEGF treatment and changes in atrophy enlargement rates were found. Further studies with larger sample sizes are warranted.

scholarly journals Effect of Alternate Treatment with Intravitreal Corticosteroid and Anti-VEGF for Macular Edema Secondary to Retinal Vein Occlusion

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Young Hwan Bae ◽  
Seong Mi Kim ◽  
Jin Young Kim ◽  
So Hyun Bae ◽  
Hakyoung Kim ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Macular Edema ◽  
Retinal Vein Occlusion ◽  
Visual Outcome ◽  
Vascular Endothelial ◽  
Vein Occlusion ◽  
Anti Vegf ◽  
Treatment Naïve ◽  
Endothelial Growth Factor

Purpose. To evaluate whether treatment with intravitreal corticosteroid and anti-vascular endothelial growth factor (VEGF) injections alternately can improve treatment outcomes of macular edema (ME) caused by retinal vein occlusion (RVO). Methods. This dual-center retrospective study included 112 eyes with treatment-naïve ME secondary to RVO that were alternately treated with intravitreal corticosteroid and anti-VEGF injections (33 eyes, alternate group) or treated only with intravitreal anti-VEGF injections (79 eyes, anti-VEGF group) on a pro re nata basis. Results. During the 12-month follow-up period, the alternate group achieved a visual acuity gain of 0.39 logMAR, while the anti-VEGF group achieved a gain of 0.21 logMAR ( P = 0.042 ). The alternate group demonstrated a reduction in the central macular thickness of 229.9-μm, while the anti-VEGF group achieved a reduction of 220.1 μm ( P = 0.887 ). The alternate group required an average of 5.2 injections, while the anti-VEGF received 4.2 injections ( P < 0.001 ). In a propensity score-matched cohort to compensate for the differences in the injection numbers between the two groups, the alternate group achieved a better visual acuity gain than the anti-VEGF group at month 12 (0.39 logMAR vs. 0.17 logMAR, P = 0.048 ). Conclusions. In ME secondary to RVO, treatment with intravitreal corticosteroid and anti-VEGF injections alternately resulted in a more favorable visual outcome compared with intravitreal anti-VEGF monotherapy.

scholarly journals Inhibition of corneal neovascularization by topical application of nintedanib in rabbit models

2021 ◽  
Vol 14 (11) ◽  
pp. 1666-1673
Author(s):  
Juan Chen ◽  
◽  
Wei Du ◽  
Xin Tang ◽  
Wen-Zhen Yu ◽  
...  
Keyword(s):  
Western Blot ◽  
Corneal Neovascularization ◽  
Vascular Endothelial ◽  
Slit Lamp ◽  
Novel Therapy ◽  
Potential Efficacy ◽  
Group 3 ◽  
Group 2 ◽  
Endothelial Growth Factor ◽  
Group 1

AIM: To evaluate the potential efficacy and mechanisms of nintedanib in corneal neovascularization (NV) in rabbit models. METHODS: Corneal NV was induced using 1 mol/L NaOH. Rabbits (n=21) were randomized to 3 groups: Group 1 were treated with 0.9% NaCl, Group 2 with Avastin (5 mg/mL), and Group 3 with nintedanib (1 mg/mL). All treatments started 1d after alkaline burns and were topically performed 3 times a day for 2wk. Photographs were taken on a slit lamp microscope on day 7 and 14. The NV area, the length of the vascularization and angiogenesis index (AI) were used to evaluate the corneal NV. On day 14, the immunohistochemical (IHC) studies of the cornea were examined. Western blot was performed to test the expression levels of vascular endothelial growth factor (VEGF), Akt, p-Akt, P38, p-P38, MMP-2 and MMP-9. RESULTS: The corneal NV area, vessel length and AI in Group 3 were significantly lower than Group 2, with both being lower than Group 1. IHC staining showed that VEGF was significantly overexpressed in the epithelium and stroma of cornea following alkaline burns. In contrast, the level of VEGF was significantly suppressed in both Group 2 and Group 3. Western blot results further confirmed that, compared with Group 1, Group 3 had significantly reduced expressions of VEGF, Akt, p-Akt, p-P38, MMP-2, and MMP-9 in corneal tissues. Trends of lower levels of MMP-2, AKT, and p-AKT in Group 3 than Group 2 were identified. CONCLUSION: Nintedanib and Avastin can effectively inhibit corneal NV, with P38 MAPK and AKT signaling pathways being possibly involved. Nintedanib seems more effective than Avastin and has the potential to be a novel therapy for preventing corneal NV.

Synthesis, radiolabeling and quality control of 111In-DOTA-bevacizumab for radioimmunoscintigraphy of VEGF receptors

2013 ◽  
Vol 101 (9) ◽  
pp. 577-584
Author(s):  
A. Khorami-Moghadam ◽  
A. R. Jalilian ◽  
K. Yavari ◽  
B. Alirezapour ◽  
M. Mazidi ◽  
...  
Keyword(s):  
Radiochemical Purity ◽  
Human Colon ◽  
Vascular Endothelial ◽  
Tumor Uptake ◽  
Wild Type ◽  
Human Colon Cancer ◽  
Biodistribution Studies ◽  
Endothelial Growth Factor

Summary In this study, bevacizumab was successively labeled with 111In-InCl3 after conjugation with DOTA-NHS-ester followed by molecular filtration and determination of the average number ofDOTAconjugated per mAb (6 : 1) by spectrophotometric method. Radiochemical purity (> 97%, measured by ITLC and HPLC), integrity of protein after radiolabeling (gel electrophoresis) and stability of 111In-DOTA-Bevacizumab (in final formulation, human serum, liver/kidney homogenates) were determined in 24-72 h as well as biodistribution studies in wild-type rats and human colon cancer (SW-480) bearing mice. The accumulation of the radiolabeled antibody was consistent with the former reported Bevacizumab conjugates. Significant tumor uptake (8%) was observed at 72 h p.i. Tumor/muscle uptake ratios were 2.6 (24 h), 9.74 (48 h) and 25 (72 h). 111In- DOTA-Bevacizumab was prepared as a SPECT molecular imaging agent for diagnosis and follow-up of vascular endothelial growth factor A (VEGF-A) expression in oncology.

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