scholarly journals Human Platelets Take up Anti-VEGF Agents

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
B. Sobolewska ◽  
B. Fehrenbacher ◽  
P. Münzer ◽  
H. Kalbacher ◽  
S. Geue ◽  
...  
Keyword(s):  
Systemic Exposure ◽  
Human Platelets ◽  
Cytochalasin D ◽  
Coated Vesicles ◽  
Immunogold Staining ◽  
Anti Vegf ◽  
Protein Kinase C Inhibitor ◽  
Arterial Thromboembolic Events ◽  
Visualization Techniques ◽  
Endothelial Growth Factor

Purpose. Growing evidence suggests different systemic exposure of anti-vascular endothelial growth factor (anti-VEGF) agents with repeated intravitreal application. Since the penetration of anti-VEGF agents through vascular barrier was reported, the interaction of anti-VEGF with nonresident platelets has become a topic of interest. The purpose of this study was to evaluate, with the help of visualization techniques, whether platelets take up the anti-VEGF agents ranibizumab, aflibercept, and bevacizumab. Methods. The uptake of anti-VEGF agents with or without VEGF treatment was investigated using immunofluorescence and immunogold staining in human platelets. The role of actin filaments and clathrin-coated vesicles in the transport of ranibizumab, aflibercept, and bevacizumab was evaluated by two pharmacologic inhibitors: staurosporine (protein kinase C inhibitor) and cytochalasin D. Results. All three anti-VEGF agents were taken up by platelets and colocalized with VEGF. Ranibizumab and aflibercept were mainly detected in alpha-granules; however, bevacizumab was equally localized in alpha-granules and in platelet vesicles. Both staurosporine and cytochalasin D completely inhibited the uptake of aflibercept into platelets. Both pharmacological inhibitors also decreased the transport of ranibizumab and bevacizumab into platelets. Bevacizumab was significantly more frequently colocalized within clathrin-coated vesicles than ranibizumab and aflibercept. Conclusion. All three anti-VEGF agents are taken up by platelets and internalized in alpha-granules, which may result in a higher local exposure of anti-VEGF after the activation of platelets, potentially contributing to arterial thromboembolic events. Clathrin-coated vesicles seem to be more prominent in the transport of bevacizumab than ranibizumab and aflibercept. Nevertheless, whether the different localization and transport of bevacizumab are truly related to specific differences of receptor-mediated endocytosis has to be revealed by further research.

scholarly journals Screening auf Frühgeborenenretinopathie – die wichtigsten Änderungen in der neuen deutschen Leitlinie 2020

2021 ◽  
Author(s):  
Jeany Q. Li ◽  
Ulrich Kellner ◽  
Birgit Lorenz ◽  
Andreas Stahl ◽  
Tim U. Krohne
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Retinopathy Of Prematurity ◽  
Vascular Endothelial ◽  
Anti Vegf ◽  
Zone Ii ◽  
Endothelial Growth Factor ◽  
Rop Screening

Zusammenfassung Hintergrund Durch Verbesserungen in der neonatologischen Versorgung von Frühgeborenen und die Entwicklung neuer Behandlungsmöglichkeiten der Frühgeborenenretinopathie („retinopathy of prematurity“ [ROP]) haben sich die Anforderungen an das ROP-Screening seit der Veröffentlichung der letzten Fassung der deutschen Leitlinie zum ROP-Screening im Jahr 2008 verändert. Auf Grundlage aktueller Studiendaten wurde die Leitlinie in 2020 grundlegend überarbeitet und in einer aktualisierten Fassung veröffentlicht. Ziel Dieser Artikel fasst die wichtigsten Änderungen in der neuen Leitlinie zusammen. Ergebnisse Die Altersgrenze für einen Screeningeinschluss wurde für Kinder ohne zusätzliche Risikofaktoren auf ein Gestationsalter von unter 31 Wochen gesenkt. Die Mindestdauer für eine Sauerstoffsupplementation, die einen Einschluss in das Screening bei Frühgeborenen erforderlich macht, wurde auf über 5 Tage angehoben. Eine Behandlung bei ROP in Zone II kann nun schon bei jedem Stadium 3 mit Plus-Symptomatik unabhängig von der Anzahl der betroffenen Uhrzeiten erfolgen. Für die Nachkontrollen nach Anti-VEGF („vascular endothelial growth factor“)-Therapie wurden Kriterien zur Frequenz und Dauer definiert. Das verbindliche Dokument für diese und weitere neue Empfehlungen ist die Leitlinie selber. Schlussfolgerungen Die Empfehlungen der Leitlinie ermöglichen eine zuverlässige Identifikation von Kindern mit ROP-Risiko für den Einschluss in das Screening und eine rechtzeitige Erkennung fortgeschrittener Krankheitsstadien für die Therapieeinleitung, um so Erblindung durch ROP zu verhindern.

scholarly journals Increased expression of adenosine 2A receptors in metastatic renal cell carcinoma is associated with poorer response to anti-vascular endothelial growth factor agents and anti-PD-1/Anti-CTLA4 antibodies and shorter survival

2021 ◽  
Author(s):  
Takao Kamai ◽  
Toshiki Kijima ◽  
Toyonori Tsuzuki ◽  
Akinori Nukui ◽  
Hideyuki Abe ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Vascular Endothelial Growth Factor ◽  
Overall Survival ◽  
Cell Death ◽  
Growth Factor ◽  
Vascular Endothelial ◽  
Primary Tumors ◽  
Anti Vegf ◽  
Programmed Cell Death 1 ◽  
Endothelial Growth Factor

Abstract Background Adenosine and its adenosine 2A receptors (A2AR) mediate the immunosuppressive mechanism by which tumors escape immunosurveillance and impede anti-tumor immunity within the tumor microenvironment. However, we do not know whether the adenosine pathway (CD39/CD73/A2AR) plays a role in renal cell carcinoma (RCC). Therefore, we studied the role of immunosuppression in RCC by assessing the adenosine pathway in patients with RCC treated with anti-vascular endothelial growth factor (anti-VEGF) agents or immune checkpoints inhibitors (ICIs) or both. Methods In 60 patients with metastatic RCC, we examined the expression of CD39, CD73, A2AR, and programmed cell death 1 ligand 1 (PD-L1) immunohistochemically in surgically resected tumor tissues and studied the clinicopathological characteristics of these patients. Patients were treated by cytoreductive nephrectomy with systemic therapy with anti-VEGF agent or a combination of the ICIs anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibody and programmed cell death 1 (PD-1) antibody. Results Increased expression of A2AR in the primary tumors was associated with metastatic profiles. Patients treated with anti–PD-1 antibody in monotherapy, a combination of anti-PD-1 and anti-CTLA4 antibodies, or anti-VEGF agents showed better response and longer overall survival if the primary tumor had higher PD-L1 expression and lower A2AR expression. In Cox multivariate regression analysis, higher expression of A2AR was associated with shorter overall survival. Conclusions Our findings suggest that the expression of A2AR and PD-L1 in the primary tumors in RCC might predict the outcomes of treatment with anti-VEGF agents and ICIs and that the A2AR pathway might be a molecular target for immunotherapy.

P0590ADVERSE RENAL OUTCOME FOLLOWING ADMINISTRATION OF INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITORS IN A SINGLE TERTIARY CENTRE IN MALAYSIA

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Maisarah Jalalonmuhali ◽  
Tengku Ain Fathlun Tengku Kamalden ◽  
Nurul 'Ain Sham Ismail ◽  
See Yen Yong ◽  
Wei Ting Teo ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Serum Creatinine ◽  
Post Treatment ◽  
Angiogenic Factor ◽  
Renal Outcome ◽  
Vascular Endothelial ◽  
Anti Vegf ◽  
Endothelial Growth Factor

Abstract Background and Aims Intravenous (IV) anti-vascular endothelial growth factor(VEGF) is a potent anti-angiogenic factor for the treatment of solid tumours. While, intravitreal anti-VEGF injection is used in the treatment for macular and retinal diseases. The effects of IV anti-VEGF agents are well documented to cause hypertension, renal impairment and proteinuria. However only few reports showed the significance of intravitreal anti-VEGF injection causing minimal change disease (MCD) and acute kidney injury (AKI). Hence, this study is to determine the outcome of renal function following intravitreal anti-VEGF injection. Method This is a prospective, cross sectional study recruiting patients from ophthalmology day-care operation theatre that were scheduled for intravitreal anti-VEGF injection in University Malaya Medical Centre (UMMC). On the day of the injection of anti-VEGF, patients’ demographic data (age, gender, medical background, medications), blood pressure, height, weight and investigations for serum creatinine and urine protein creatinine ratio (PCR) were collected. Following these, they will receive the intravitreal anti-VEGF as per schedule. All these patients were given a follow-up within 72hours to reassess blood pressure, serum creatinine and urine PCR. Results A total of 90 patients were recruited. However, 15 patients were subsequently excluded as there was no repeated serum creatinine at 72-hours post treatment. Their mean age was 67.25 ± 10.41. Among all, 3 patients had significance increased in serum creatinine (4%) with significance changed of urine PCR post treatment. Table 1 showed baseline parameters prior to treatment and table 2 was post treatment parameters. Higher serum creatinine and proteinuria pre intravitreal anti-VEGF were identified to have higher OR of 1.018 (95% CI 1.001-1.035) (p=0.043) and OR 1.004 (1.000-1.007) (p=0.025) respectively among those who developed AKI. In assessing the association between higher pre-treatment creatinine and proteinuria (independent variable) and development of AKI (dependent variable) estimated by logistic regression with no AKI as a reference group we found that there were no significance. Conclusion Following intravitreal anti-VEGF administration, there were no significant changes in blood pressure. However, 4% from our cohort had AKI and worsening proteinuria at 72 hours post treatment. These patients had higher serum creatinine and proteinuria prior to treatment. However, our study is underpowered to establish the relationship between intravitreal anti-VEGF and development of AKI. Further study with larger sample size and longer-term outcome is needed.

scholarly journals Retinal venous pressure is decreased after anti-VEGF therapy in patients with retinal vein occlusion–related macular edema

2021 ◽  
Author(s):  
Teruyo Kida ◽  
Josef Flammer ◽  
Katarzyna Konieczka ◽  
Tsunehiko Ikeda
Keyword(s):  
Macular Edema ◽  
Intravitreal Injection ◽  
Retinal Vein Occlusion ◽  
Venous Pressure ◽  
Decisive Role ◽  
Retinal Venous Pressure ◽  
Vein Occlusion ◽  
Anti Vegf ◽  
Significant Difference ◽  
Endothelial Growth Factor

Abstract Purpose The pathomechanism leading to retinal vein occlusion (RVO) is unclear. Mechanical compression, thrombosis, and functional contractions of veins are discussed as the reasons for the increased resistance of venous outflow. We evaluated changes in the retinal venous pressure (RVP) following intravitreal injection of anti-vascular endothelial growth factor (VEGF) agent to determine the effect on RVO-related macular edema. Methods Twenty-six patients with RVO-related macular edema (16 branch RVOs [BRVOs] and 10 central RVOs [CRVOs], age 72.5 ± 8.8 years) who visited our hospital were included in this prospective study. Visual acuity (VA), intraocular pressure (IOP), central retinal thickness (CRT) determined by macular optical coherence tomography, and RVP measured using an ophthalmodynamometer were obtained before intravitreal injection of ranibizumab (IVR) and 1 month later. Results Comparison of the BRVOs and CRVOs showed that VA was significantly improved by a single injection in BRVOs (P < 0.0001; P = 0.1087 for CRVOs), but CRT and RVP were significantly decreased without significant difference in IOP after the treatment in both groups (P < 0.0001). Conclusion The anti-VEGF treatment resulted in a significant decrease in the RVP, but the RVP remained significantly higher than the IOP. An increased RVP plays a decisive role in the formation of macula edema, and reducing it is desirable.

Choroidal neovascular membrane in paediatric patients: clinical characteristics and outcomes

2017 ◽  
Vol 102 (9) ◽  
pp. 1232-1237 ◽  
Author(s):  
Tapas Ranjan Padhi ◽  
Bradley J Anderson ◽  
Ashkan M Abbey ◽  
Yoshihiro Yonekawa ◽  
Maxwell Stem ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Adult Population ◽  
Initial Therapy ◽  
Macular Dystrophy ◽  
Vascular Endothelial ◽  
Fluorescein Angiogram ◽  
Anti Vegf ◽  
Treatment Indications ◽  
Endothelial Growth Factor

PurposeTo analyse the clinical characteristics and treatment outcomes of choroidal neovascular membranes (CNVM) in paediatric subjects at three paediatric retina referral centres.MethodsMedical charts of patients aged 18 years or less with a diagnosis of CNVM were retrospectively reviewed. The demographic profile, laterality, presenting complaint, corrected vision, underlying pathology, fundus, fundus fluorescein angiogram and optical coherence tomogram (OCT) were analysed. CNVM type, frequency, treatment indications, recurrences and final visual acuity were noted.ResultsThere were a total of 35 subjects (43 eyes) with a mean age of 11.2 years. The CNVMs were mostly type 2 (90.0%), classic (90.9%), subfoveal (59.09%) and active (84.1%). Best vitelliform macular dystrophy was found to be the most common association (32.5%). Intravitreal injection of an anti-vascular endothelial growth factor (VEGF) agent was the initial therapy of choice in all. Eyes with CNVMs responsive to anti-VEGF alone required a mean of 2.11 injections. Patients with recurrent disease (21.21%) had an average of 1.14 episodes per eye. While 50% of recurrent CNVMs stabilised with repeat anti-VEGF treatment, the remaining patients required photodynamic therapy, laser or surgery.ConclusionPaediatric CNVMs in this series differed from those in the adult population with regard to aetiology, OCT and angiographic characteristics, treatment response and rate of recurrence.

Isolated juxtapapillary retinal capillary haemangioblastoma and exudative maculopathy in an elderly patient without von Hippel-Lindau syndrome: combined proton beam radiotherapy and intravitreal anti-VEGF

2021 ◽  
Vol 14 (8) ◽  
pp. e244077
Author(s):  
Ahmed Adan ◽  
Luke Carine ◽  
Heinrich Heimann ◽  
Marta Ugarte
Keyword(s):  
Proton Beam ◽  
Combined Therapy ◽  
Tumour Size ◽  
Subretinal Fluid ◽  
Proton Beam Radiotherapy ◽  
Von Hippel Lindau ◽  
Anti Vegf ◽  
Retinal Capillary ◽  
Endothelial Growth Factor ◽  
Von Hippel Lindau Syndrome

A 71-year-old Caucasian man presented with an isolated juxtapapillary retinal capillary haemangioblastoma on the superior and temporal left optic disc with active exudation resulting in macular intraretinal and subretinal fluid, reduced vision, scotoma and distortion with progression over 6 weeks. He did not have von Hippel-Lindau syndrome. After proton beam radiotherapy (PBR), the tumour size remained unchanged, but did not stop the exudation. Three anti-vascular endothelial growth factor (VEGF) (ie, bevacizumab) injections at monthly intervals resulted in reduced macular oedema. Combined therapy with PBR and anti-VEGF injections sustained our patient’s vision at 12 months follow-up.

scholarly journals De-novo multilayering in fibrovascular pigment epithelial detachment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Manoj Soman ◽  
Jay U. Sheth ◽  
Asmita Indurkar ◽  
Padmanabhan Meleth ◽  
Unnikrishnan Nair
Keyword(s):  
De Novo ◽  
Median Number ◽  
Final Visit ◽  
Low Grade ◽  
Vascular Endothelial ◽  
Pigment Epithelial Detachment ◽  
Pigment Epithelial ◽  
Anti Vegf ◽  
Significant Difference ◽  
Endothelial Growth Factor

AbstractThis study describes the occurrence of multilayered pigment-epithelial detachment (MLPED) as a De-novo phenomenon (DN-MLPED) and compare the features with multi-layering secondary to chronic anti-vascular endothelial growth factor (anti-VEGF) therapy (s-MLPED). We did a retrospective evaluation of spectral-domain optical coherence tomography (SD-OCT) features, treatment-profile, and visual-acuity (VA) outcomes in eyes with MLPED. Out of 17 eyes with MLPED, 7 eyes had DN-MLPED and 10 eyes had s-MLPED. There was no significant difference in baseline and final VA between the groups. At the final visit, no significant visual improvement was noted in both the groups, although a possible trend towards an improvement was seen in DN-MLPED eyes while the s-MLPED demonstrated a declining trend (DN-MLPED—LogMAR-BCVA: Baseline = 0.79 [∼ 20/123] ± 0.91; Final = 0.76 [∼ 20/115] ± 0.73; p = 0.87; s-MLPED—LogMAR BCVA: Baseline = 0.43 [∼ 20/54] ± 0.68; Final = 0.94 [∼ 20/174] ± 0.71; p = 0.06). Moreover, after presentation, the median number of injections in DN-MLPED eyes were significantly lower compared to s-MLPED eyes (DN-MLPED:4; s-MLPED:12; p = 0.03) (Median follow-up: DN-MLPED = 26 months; s-MLPED = 54 months; p = 0.15). Subretinal hyperreflective-material (SHRM) deposition heralded the onset of multilayering and was seen to progress in all DN-PED eyes and 1/4 eyes of s-MLPED. To conclude, MLPED is a unique form of cicatrizing fibrovascular-PED which can evolve denovo too. Long-standing disease with intermittent or low-grade activity can potentially explain this unique phenomenon. With fewer anti-VEGF therapy, the de-novo MLPED eyes show more visual stability as compared to s-MLPED eyes.

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.

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