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Despite extensive use of intravitreal anti-vascular endothelial growth factor (anti-VEGF) biologics for over a decade, neovascular age-related macular degeneration (nAMD) or choroidal neovascularization (CNV) continues to be a major cause of irreversible vision loss in developed countries. Many nAMD patients demonstrate persistent disease activity or experience declining responses over time despite anti-VEGF treatment. The underlying mechanisms of anti-VEGF resistance are poorly understood, and no effective treatment strategies are available to date. Here we review evidence from animal models and clinical studies that supports the roles of neovascular remodeling and arteriolar CNV formation in anti-VEGF resistance. Cholesterol dysregulation, inflammation, and ensuing macrophage activation are critically involved in arteriolar CNV formation and anti-VEGF resistance. Combination therapy by neutralizing VEGF and enhancing cholesterol removal from macrophages is a promising strategy to combat anti-VEGF resistance in CNV. [ABSTRACT FROM AUTHOR]

Regorafenib is the first multikinase inhibitor for treating metastatic colorectal cancer (mCRC). Proteinuria is a frequently encountered adverse effect, regardless of prior administration of vascular endothelial growth factor inhibitors. Herein, we aimed to assess the impact of baseline preexisting proteinuria on regorafenib-induced problematic proteinuria during real-world mCRC therapy. Patients with mCRC receiving regorafenib (n = 100) were retrospectively assessed and divided into control and preexisting proteinuria (baseline grade of 1–2) groups. The primary endpoint was the development of grade ≥ 2 (grade ≥ 3 in case of baseline grade 2 patients) proteinuria. Propensity score-matching was performed to confirm the robustness of primary analyses. Defined proteinuria occurred in 30.7 and 57.9% of patients in the control and preexisting proteinuria groups, respectively, with significant differences in the all-patient population (P = 0.01). The preexisting proteinuria group exhibited significant defined proteinuria development within 7 days of regorafenib initiation, grade ≥ 3 symptoms, and treatment suspension owing to proteinuria. Similar results were obtained in the propensity score-matched population. According to multivariate logistic regression analysis, baseline proteinuria was a singular risk factor for defined proteinuria development (adjusted odds ratio; 3.76, 95% confidence interval; 1.45–9.75, P = 0.007). Collectively, our study revealed that patients with preexisting proteinuria develop regorafenib-induced proteinuria degradation. [ABSTRACT FROM AUTHOR]

Background: Rivoceranib is an oral, selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2. ANGEL (NCT03042611) was a global, randomized, double-blinded, placebo-controlled, phase 3 study evaluating rivoceranib as 3rd-line or ≥4th-line therapy in patients with advanced/metastatic gastric or gastroesophageal junction (GEJ) cancer. Methods: Patients had failed ≥2 lines of chemotherapy and were randomized 2:1 to rivoceranib 700 mg once daily or placebo with best supportive care. Primary endpoint: overall survival (OS) in the intention-to-treat population. Secondary endpoints: progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) by blinded independent central review (BICR). Results: In total, 460 patients (rivoceranib n = 308, placebo n = 152) were enrolled. OS was not statistically different for rivoceranib versus placebo (median 5.78 vs. 5.13 months; hazard ratio [HR] 0.93, 95% CI 0.74–1.15; p = 0.4724). PFS by BICR (median 2.83 vs. 1.77 months; HR 0.58, 95% CI 0.47–0.71; p < 0.0001), ORR (6.5% vs. 1.3%; p = 0.0119), and DCR (40.3 vs. 13.2%; p < 0.0001) were improved with rivoceranib versus placebo. In patients receiving ≥4th-line therapy, OS (median 6.34 vs. 4.73 months; p = 0.0192) and PFS by BICR (median 3.52 vs. 1.71 months; p < 0.0001) were improved with rivoceranib versus placebo. The most common grade ≥ 3 treatment-emergent adverse events with rivoceranib were hypertension (17.9%), anemia (10.4%), aspartate aminotransferase increased (9.4%), asthenia (8.5%), and proteinuria (7.5%). Conclusions: This study did not meet its primary OS endpoint. Compared to placebo, rivoceranib improved PFS, ORR, and DCR. Rivoceranib also improved OS in a prespecified patient subgroup receiving ≥4th-line therapy. [ABSTRACT FROM AUTHOR]

Background: Vascular endothelial growth factor inhibitors, including tyrosine kinase inhibitors (TKIs) and anti‐angiogenics, are first‐line therapies for advanced and metastatic hepatocellular carcinoma. Although TKIs have a greater potential for off‐target adverse effects compared with bevacizumab (anti‐angiogenics), a direct comparison of the risk of cardiovascular adverse events between these two types of therapies has not been performed. Objective: To compare the incidence of and characterize cardiovascular adverse events in patients with hepatocellular carcinoma receiving TKIs versus bevacizumab. Methods: This cohort study included adult patients with hepatocellular carcinoma who received first‐line TKIs (sorafenib or lenvatinib) or bevacizumab at two academic medical centers and one community cancer center from September 2018 to August 2021. The primary outcome was risk of cardiovascular adverse events. Major secondary outcomes included the incidence of individual types of cardiovascular adverse events and risk factors associated with major adverse cardiovascular events (MACE). Results: The study included 221 patients (159 TKI patients; 62 bevacizumab patients). At a median follow‐up of 5 months, the probability of cardiovascular adverse events was not significantly different between the two groups (hazard ratio [HR]: 0.85; 95% confidence interval [95% CI]: 0.58–1.24; p = 0.390). The cumulative incidence of cardiovascular events was highest in patients receiving lenvatinib (sub‐distribution hazard ratio [SHR]: 1.53; 95% CI: 1.02–2.30) compared with those receiving sorafenib (reference) or bevacizumab (SHR: 1.05; 95% CI: 0.68–1.64) after adjustment for comorbidities, liver transplant status, and presence of portal vein thrombosis at baseline. Cardiovascular adverse events were observed in 151 (68%) patients, and MACE were observed in 27 (12%) patients. Risk factors associated with MACE were hypertension (SHR: 3.5; 95% CI: 0.9087–15.83; p = 0.086), prior history of MACE (SHR: 2.01; 95% CI: 0.83–4.87; p = 0.124), and tobacco use (SHR: 2.85; 95% CI: 0.90–8.97; p = 0.074). Conclusions: Cardiovascular risk was not significantly different between TKIs and bevacizumab. Lenvatinib appears to have the highest risk of cardiovascular adverse events among these first‐line VEGF inhibitors. [ABSTRACT FROM AUTHOR]

Intravitreal (IVT) injection of anti-vascular endothelial growth factor (anti-VEGF) has greatly improved the treatment of many retinal disorders, including wet age-related macular degeneration (wAMD), which is the third leading cause of blindness. However, frequent injections can be difficult for patients and may lead to various risks such as elevated intraocular pressure, infection, and retinal detachment. To address this issue, researchers have found that IVT injection of anti-VEGF proteins at their maximally viable concentration and dose can be an effective strategy. However, the intrinsic protein structure can limit the maximum concentration due to stability and solution viscosity. To overcome this challenge, we developed a novel anti-VEGF protein called nanoFc by fusing anti-VEGF nanobodies with a crystallizable fragment (Fc). NanoFc has demonstrated high binding affinity to VEGF165 through multivalency and potent bioactivity in various bioassays. Furthermore, nanoFc maintains satisfactory chemical and physical stability at 4°C over 1 month and is easily injectable at concentrations up to 200 mg/mL due to its unique architecture that yields a smaller shape factor. The design of nanoFc offers a bioengineering strategy to ensure both strong anti-VEGF binding affinity and high protein concentration, with the goal of reducing the frequency of IV injections. [ABSTRACT FROM AUTHOR]

Objective: This longitudinal research aimed to assess visual outcomes in those with "Age- Related Macular Degeneration (AMD)" undergoing "Anti-Vascular Endothelial Growth Factor (anti-VEGF)" treatment. Methods: A cohort of 100 AMD subjects receiving anti-VEGF treatment was ensued a year. "Best-corrected visual acuity (BCVA)" and "Central Retinal Thickness (CRT)" were measured at regular intervals. Statistical analyses were performed to evaluate changes over time. Results: Significant enhancements in BCVA (p < 0.001) and decreases in CRT (p < 0.001) were witnessed. At month 12, BCVA increased by +10 ETDRS letters, and CRT decreased from 350 µm to 260 µm. No significant adverse events were reported. Conclusion: Anti-VEGF treatment demonstrated effectiveness in advancing visual acuity and reducing retinal edema in AMD subjects. Regular monitoring and personalized treatment approaches are crucial for optimizing outcomes. [ABSTRACT FROM AUTHOR]

Background: In patients with wet age-related macular degeneration (AMD), loss to follow-up (LTFU) leads to unplanned interruptions in therapy and the risk of visual loss. Methods: This retrospective and prospective case–control cohort study compared AMD patients with (LTFU YES) and without (LTFU NO) LTFU during anti-VEGF treatment over 12 years. LTFU was defined as missing any treatment or monitoring visits, or not scheduling follow-ups for six months. Results: Significant differences between LTFU NO (n = 298) and LTFU YES (n = 174) groups were age, treatment phase, baseline and final best-corrected visual acuity (BCVA), type of anti-VEGF drug, treatment switch, commuting distance, and escort during commuting. A multivariate logistic regression analysis identified the need for an escort during the commuting and treatment phase as the only significant difference. The four most common reasons for LTFU were general health worsening (21.8%), patient-missed appointments (16.7%), COVID-19-related issues (14.9%), and treatment dissatisfaction (8.6%). Conclusions: The factors associated with increased LTFU rates were older age, inactive treatment phase, lower baseline and final BCVA, bevacizumab treatment, monotherapy, longer travelling distance, and commuting with an escort. According to the multivariate logistic regression analysis, only the escort during the commuting and treatment phases was significant. These findings could direct research to explore social support in treatment adherence and highlight the importance of treatment phases in practice. [ABSTRACT FROM AUTHOR]

Background: We aim to evaluate the value of an integrated multimodal radiomics with machine learning model to predict the pathological complete response (pCR) of primary tumor in a prospective cohort of esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (nCRT) and anti-PD-1 inhibitors. Materials and Methods: Clinical information of 126 ESCC patients were included for analysis. Radiomics features were extracted from 18F-FDG PET and enhanced plan CT images. Four machine learning algorithms, including SVM (Support Vector Machine), Random Forest (RF), and eXtreme Gradient Boosting (XGB) and logistic regression (LR), were applied using k-fold cross-validation to predict pCR after nCRT. The predictive ability of the models was assessed using receiver operating characteristics (ROC) curve analysis. Results: A total of 842 features were extracted. Among the four machine learning algorithms, SVM achieved the most promising performance on the test set for PET(AUC:0.775), CT (AUC:0.710) and clinical model (AUC:0.722). For all combinations of various modalities-based models, the combination model of 18F-FDG PET, CT and clinical features with SVM machine learning had the highest AUC of 0.852 in the test set when compared to single-modality models in various algorithms. The other combined models had AUC ranged 0.716 to 0.775. Conclusion: Machine learning models utilizing radiomics features from 18FFDG PET and enhanced plan CT exhibit promising performance in predicting pCR in ESCC after nCRT and anti-PD-1 inhibitors. The fusion of features from multiple modalities radiomics and clinical features enhances the better predictive performance compared to using a single modality alone. [ABSTRACT FROM AUTHOR]

Purpose: Prediction of the early treatment response is important in neovascular age‐related macular degeneration (nAMD). Hence, we aimed to test if non‐invasive measurements of the retinal vascular structure were able to predict a successful outcome of initial intravitreal treatment. Methods: In 58 eyes of 58 patients with treatment‐naïve nAMD, advanced markers of retinal vascular structure were measured by Singapore I Vessel Assessment prior to initial intravitreal treatment with three monthly injections of aflibercept with subsequently categorization of patients as full treatment responders (FTR) or non/partial treatment responders (N/PR), with the former defined as loosing fewer than five Early Treatment Diabetic Retinopathy Study letters and having no residual intra‐ or subretinal fluid or macular haemorrhage. Results: Of 54 eyes attending follow‐up, 44.4% were categorized as FTR. Patients with FTR were older (81.5 vs. 77 years, p = 0.04), and prior to treatment those eyes had a lower retinal arteriolar fractal dimension (Fd) (1.21 vs. 1.24 units, p = 0.02) and venular length‐diameter ratio (LDR) (7.3 vs. 15.9 units, p = 0.006), but did not differ with respect to other retinal vascular parameters. In multiple logistic regression models, a lower chance of FTR was independently predicted by a higher retinal venular LDR (odds ratio [OR] 0.91, 95% CI 0.82–0.99, p = 0.03, for each 1 unit increment) and marginally by a higher retinal arteriolar Fd (OR 0.83, 95% CI 0.68–1.00, p = 0.05, for each 0.01 unit increment). Conclusion: Retinal venular LDR independently predicted the initial treatment response in nAMD. If confirmed by long‐term, prospective studies, this might help to guide treatment. [ABSTRACT FROM AUTHOR]

In this meta‐analysis, we aim to compare the efficacy and safety of pars plana vitrectomy (PPV) versus tap‐and‐inject (TAI) of intravitreal antibiotics for the management of endophthalmitis secondary to intravitreal injections of anti‐vascular endothelial growth factor (VEGF) agents. A systematic literature search was conducted on Ovid MEDLINE, EMBASE, and Cochrane Central (January 2005–October 2022). The primary analysis compared initial PPV versus TAI and the secondary analysis examined the efficacy and safety of TAI alone compared to TAI followed by PPV. The quality of non‐randomized observational studies was assessed using the Newcastle‐Ottawa Scale. The quality of the evidence was assessed for each outcome. A random effects meta‐analysis was performed. Weighted mean differences (WMDs) with 95% confidence intervals were reported. Of the 7474 screened studies, nine studies reporting on 153 eyes were included. The change in mean best corrected visual acuity (BCVA) between endophthalmitis presentation and last follow‐up did not significantly differ between the initial TAI versus PPV groups (WMD = 0.05 units; 95% CI −0.12 to 0.22; p = 0.59; heterogeneity p = 0.41). The difference in pre‐ to post‐treatment mean BCVA did not significantly differ between eyes that received TAI alone or TAI followed by PPV (WMD = 0.04 units; 95% CI −0.42 to 0.51; p = 0.85; heterogeneity p = 0.74). While the meta‐analysis revealed no significant difference in the change in BCVA between PPV and TAI to treat endophthalmitis secondary to anti‐VEGF agents, the quality of evidence was low with potential for confounding and selection bias. Further well‐designed studies in this setting are needed. [ABSTRACT FROM AUTHOR]

Retinal vein occlusions are the second most common retinal vascular conditions, with central retinal vein occlusions (CRVOs) generally responsible for the most significant vision loss. A PubMed search for 'central retinal vein occlusions' was performed from 2013 to 2023. Online searches were performed for biosimilars and recently approved drugs. Relevant studies were reviewed and referred to in the manuscript. Drugs that inhibit the actions of vascular endothelial growth factor have become standard-of-care for CRVO-associated macular edema. Bevacizumab, ranibizumab, and aflibercept each decreases central subfield thickness and improves visual acuity (VA) by an average of + 15 to + 17 letters, but retrospective and database studies show that patients outside of registration trials generally receive fewer injections and achieve poorer improvements in VA. Some comparison studies show no differences in peak efficacies whereas others suggest that aflibercept produces the best gains in BCVA. Similarly, studies that report switching of drugs due to poor initial responses, report mixed data or show aflibercept superiority. During the past 10 years, only two ranibizumab biosimilars have been approved for CRVO, but over the next five years, approvals of faricimab, aflibercept 8 mg, and additional ranibizumab and aflibercept biosimilars are likely. [ABSTRACT FROM AUTHOR]

Extracranial arteriovenous malformations (AVMs) are regarded as rare diseases and are prone to complications such as pain, bleeding, relentless growth, and high volume of shunted blood. Due to the high vascular pressure endothelial cells of AVMs are exposed to mechanical stress. To control symptoms and lesion growth pharmacological treatment strategies are urgently needed in addition to surgery and interventional radiology. AVM cells were isolated from three patients and exposed to cyclic mechanical stretching for 24 h. Thalidomide and bevacizumab, both VEGF inhibitors, were tested for their ability to prevent the formation of circular networks and proliferation of CD31+ endothelial AVM cells. Furthermore, the effect of thalidomide and bevacizumab on stretched endothelial AVM cells was evaluated. In response to mechanical stress, VEGF gene and protein expression increased in patient AVM endothelial cells. Thalidomide and bevacizumab reduced endothelial AVM cell proliferation. Bevacizumab inhibited circular network formation of endothelial AVM cells and lowered VEGF gene and protein expression, even though the cells were exposed to mechanical stress. With promising in vitro results, bevacizumab was used to treat three patients with unresectable AVMs or to prevent regrowth after incomplete resection. Bevacizumab controlled bleeding, pulsation, and pain over the follow up of eight months with no patient-reported side effects. Overall, mechanical stress increases VEGF expression in the microenvironment of AVM cells. The monoclonal VEGF antibody bevacizumab alleviates this effect, prevents circular network formation and proliferation of AVM endothelial cells in vitro. The clinical application of bevacizumab in AVM treatment demonstrates effective symptom control with no side effects. Mechanical stress increases VEGF expression in endothelial AVM cells, possibly causing the VEGF upregulation in the microenvironment of AVM cells. The resulting RAS/RAF/MEK/ERK signaling in leads to progression of fast-flow malformations. The monoclonal VEGF-A antibody bevacizumab alleviates this effect, prevents circular network formation and proliferation of AVM endothelial cells in vitro. Sporadically occurring slow-flow malformations (LMs, VMs) have mutations in TEK or PIK3CA. TEK encodes the endothelial receptor tyrosine kinase TIE2. Sporadic extracranial fast-flow malformations (AVMs) show mutations in KRAS, BRAF and MAP2K1, which encodes the dual specificity mitogen-activated protein kinase MEK1. Combined targeting of the molecular causes of the disease could be key to achieve symptom control and reduce lesion growth. Orange: gain-of-function; Blue, circled with orange: enhanced signaling. [ABSTRACT FROM AUTHOR]

Purpose. Hypertension (HTN) is one of the most common adverse drug reactions to tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factor (VEGF), but little is known about its clinical risk factors. The aim of this study was to elucidate the association between baseline clinical characteristics and the occurrence of HTN in advanced gastric cancer (GC) patients prescribed apatinib, a commonly used VEGF-TKI in China, in a real-world setting. Patients and Methods. Fifty-five GC patients treated with apatinib from December 1st, 2016, to December 1st, 2020, were retrospectively included in electronic medical records. Adverse drug reactions were defined according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Univariate and multivariable logistic regression analyses were used to investigate potential clinical risk factors for apatinib-related HTN. Results. The incidence of apatinib-related HTN of all grades was 45.45%, and grade 3 HTN occurred in 16.36% of patients. The median maximal systolic blood pressure (SBP) during apatinib treatment was 153 mm·Hg, and the median time to event was 25 days. New-onset HTN occurred in 10/33 (30.30%) patients. Preexisting HTN (odds ratio [OR]: 4.155; 95% confidence interval [CI]: 1.252, 13.787; p = 0.020) was the key independent risk factor associated with apatinib-related HTN. Conclusion. The incidence of HTN was high in patients treated with apatinib, and preexisting HTN was an independent risk factor. It is important to provide thorough and close monitoring of patients during treatment with apatinib, especially for those with preexisting HTN. This trial is registered with ChiCTR1900024531. [ABSTRACT FROM AUTHOR]

Background: Combining immune checkpoint therapy (ICT) and vascular endothelial growth factor inhibitors (VEGFi) may result in increased treatmentrelated and immune-related adverse events (TRAEs and irAEs) compared to ICT alone. This metanalysis was conducted to identify prospective phase II or III clinical studies that evaluated the toxicity profile of ICT + VEGFi compared to ICT alone. Methods: A systematic search was performed across all cancer types and major databases until August 10, 2022, and screening was done by two independent investigators. Inclusion criteria included phase 2 or 3 studies with at least one arm of patients treated with combination therapy and one arm treated with monotherapy. Adverse event data were pooled using a restricted maximum likelihood fixed effects model, and heterogeneity using Cochran's Q (chi-square) test. Results: 7 out of 9366 studies met the inclusion criteria, and 808 and 927 patients were treated with ICT monotherapy and a combination of ICT with VEGFi, respectively. Only one study reported irAEs, so the analysis was restricted to TRAEs. The total number of TRAEs was significantly higher in the ICT + VEGFi group (RR:1.49; 95% CI 1.37 -1.62; p=1.5 x 10-21), and more frequent treatment withdrawals were attributed to TRAEs (RR:3.10; 95% CI 1.12-8.59; p=0.029). The highest TRAE effect size increases noted for rash (RR 6.50; 95% CI 3.76 -- 11.25; p=2.1 x 10-11), hypertension (RR:6.07; 95% CI 3.69--10.00; p=1.3 x 10-12), hypothyroidism (RR:5.02; 95% CI 3.08 -- 8.19; p=8.9 x 10-11), and diarrhea (RR:4.94; 95% CI 3.21--7.62; p=3.8 x 10-13). Other significantly more frequent TRAEs included nausea, anemia, anorexia, and proteinuria. Conclusion: Combination therapy with ICT and VEGFi carries a higher risk of certain TRAEs, such as rash, hypertension, hypothyroidism, diarrhea, nausea, anorexia, and proteinuria, compared to ICT monotherapy. More granular details on the cause of AEs, particularly irAEs, should be provided in future trials of such regimens. [ABSTRACT FROM AUTHOR]

Simple Summary: Vascular Endothelial Growth Factor inhibitors (VEGFi), commonly employed for diverse medical conditions such as advanced neoplasms and ocular diseases, pose potential adverse effects. This review delineates the principal VEGFi utilized in clinical practice and investigates the causes, recognition, management, and prevention of VEGFi toxicities. Its aim is to assist oncologists in both clinical practice and the design of clinical trials. The use of Vascular Endothelial Growth Factor inhibitors (VEGFi) has become prevalent in the field of medicine, given the high incidence of various pathological conditions necessitating VEGF inhibition within the general population. These conditions encompass a range of advanced neoplasms, such as colorectal cancer, non-small cell lung cancer, renal cancer, ovarian cancer, and others, along with ocular diseases. The utilization of VEGFi is not without potential risks and adverse effects, requiring healthcare providers to be well-prepared for identification and management. VEGFi can be broadly categorized into two groups: antibodies or chimeric proteins that specifically target VEGF (bevacizumab, ramucirumab, aflibercept, ranibizumab, and brolucizumab) and non-selective and selective small molecules (sunitinib, sorafenib, cabozantinib, lenvatinib, regorafenib, etc.) designed to impede intracellular signaling of the VEGF receptor (RTKi, receptor tyrosine kinase inhibitors). The presentation and mechanisms of adverse effects resulting from VEGFi depend primarily on this distinction and the route of drug administration (systemic or intra-vitreal). This review provides a thorough examination of the causes, recognition, management, and preventive strategies for VEGFi toxicities with the goal of offering support to oncologists in both clinical practice and the design of clinical trials. [ABSTRACT FROM AUTHOR]

Vascular endothelial growth factors (VEGF), Vascular endothelial growth factor receptors (VEGFR) and their downstream signaling pathways are promising targets in anti-angiogenic therapy. They constitute a crucial system to regulate physiological and pathological angiogenesis. In the last 20 years, many antiangiogenic drugs have been developed based on VEGF/VEGFR system to treat diverse cancers and retinopathies, and new drugs with improved properties continue to emerge at a fast rate. They consist of different molecular structures and characteristics, which enable them to inhibit the interaction of VEGF/VEGFR, to inhibit the activity of VEGFR tyrosine kinase (TK), or to inhibit VEGFR downstream signaling. In this paper, we reviewed the development of marketed anti-angiogenic drugs involved in the VEGF/VEGFR axis, as well as some important drug candidates in clinical trials. We discuss their mode of action, their clinical benefits, and the current challenges that will need to be addressed by the next-generation of anti-angiogenic drugs. We focus on the molecular structures and characteristics of each drug, including those approved only in China. [ABSTRACT FROM AUTHOR]

Background: Bevacizumab is a vascular endothelial growth factor (VEGF) inhibitor that is used off-label for select cases of recurrent respiratory papillomatosis (RRP) that are severe, involve the distal airway or lung parenchyma, and refractory to other forms of adjuvant therapy. However, there is limited safety data for the use of bevacizumab in children and VEGF inhibitors are reported to have a range of adverse renal effects, including hypertension, proteinuria, and thrombotic microangiopathy (TMA). Case-Diagnosis/Treatment: This report describes a case of severe juvenile-onset RRP that had an exceptionally high operative burden that was refractory to several adjuvant treatment strategies (including intralesional cidofovir and subcutaneous pegylated interferon). Bevacizumab treatment resulted in a dramatic and sustained improvement in disease control over a 5-year period. However, after 3 years of treatment, the patient developed hypertension and proteinuria and was found to have evidence of a glomerular TMA on kidney biopsy. These complications were successfully managed with a reduction in bevacizumab frequency and angiotensin-converting enzyme inhibitor initiation. Conclusions: Clinicians caring for children treated with VEGF inhibitors should be aware of the potential renal complications and their management. [ABSTRACT FROM AUTHOR]

This article provides a comprehensive review of the literature on biosimilars for retinal diseases. Biosimilars are laboratory-engineered proteins that offer a more affordable alternative to FDA-approved biologics. The article discusses the development process of biosimilars, their similarities to reference biologics, and the current biosimilar market and pipeline therapeutics for retinal diseases. It also addresses barriers to adopting the widespread use of biosimilar therapies, including limited data and concerns about adverse events. The article emphasizes the need for postmarketing surveillance and further research to address these concerns and maximize the potential benefits of biosimilars in retinal disease treatment. The document also contains a list of references related to the use of biosimilars for retinal diseases, including clinical trials, retrospective studies, and meta-analyses that evaluate the efficacy and safety of these drugs. It also discusses the regulatory and ethical considerations surrounding their use and provides insights into their cost-effectiveness. [Extracted from the article]

This article provides an overview of the management and treatment options for nonproliferative diabetic retinopathy (NPDR), a complication of diabetes that can lead to vision loss if left untreated. It discusses the classification and diagnosis of NPDR, as well as current treatment strategies including systemic management of diabetes and ophthalmic interventions like laser photocoagulation and anti-VEGF injections. The article also highlights the need for more effective and less invasive treatment options, and mentions ongoing clinical trials investigating new drugs and therapies. Additionally, the document includes a list of references to various studies and clinical trials exploring the effectiveness and safety of different medications and therapies for diabetic retinopathy and macular edema. [Extracted from the article]

Purpose: Diabetic macular edema (DME) is a significant cause of vision impairment, posing challenges in its management due to variable responses and patient diversity. While anti-vascular endothelial growth factor (anti-VEGF) agents have revolutionized DME treatment, some patients are not suitable candidates for this therapy. Intravitreal corticosteroid therapy, such as the dexamethasone implant (DEX), has emerged as an alternative. This study aimed to comprehensively investigate the role of intravitreal DEX in treatment-naive DME patients with systemic contraindications to anti-VEGF therapy, administered one month before cataract surgery. Patients and Methods: A single-center retrospective study included 20 eyes with controlled diabetes, visually significant cataracts, untreated DME, and systemic contraindications for anti-VEGF therapy. Patients underwent DEX treatment followed by cataract surgery after one month. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP) were assessed at multiple time points. Results: BCVA significantly improved on days 30, 90, and 180 post-DEX (P< 0.00001). CMT showed a significant decrease at day 30 (P< 0.00001), which was sustained through days 90 and 180 (P< 0.00001). Recurrent DME was observed in 25% of eyes on day 90. IOP increased significantly at days 30 (P< 0.00001) and 90 (P=0.0006), returning to baseline by day 180. However, only two eyes needed topical anti-glaucoma treatment. No other ocular or systemic adverse events were noted. Conclusion: Intravitreal DEX administered one month before cataract surgery offers a promising treatment strategy for treatment-naive DME patients with systemic contraindications to anti-VEGF therapy. The study's findings provide insights into improving visual acuity and reducing macular thickness, along with manageable IOP changes. This personalized approach is a valuable addition to DME management, especially for complex medical cases, warranting further research and consideration for clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: The goal of this case study and literature review is to assess whether anti-vascular endothelial growth factor (anti-VEGF) medication is effective in coping with branch retinal vein occlusion (BRVO). We present an in-depth examination of the patient's medical records, diagnostic accomplishments and therapy results utilizing data from a 61-year-old male patient. Methods: A case report with a brief literature review, which gives readers a better understanding of the current state of BRVO therapeutic choices, using data gathered from the Google Scholar and PubMed databases. Results: A 61-year-old male with blurred vision in the upper half of the visual field in his left eye, BCVA OD: 20/20; OS: 20/70, presented to an outpatient clinic in Stara Zagora, Bulgaria. The symptoms started three weeks ago. The patient reported a history of hypertension and hyperlipidemia. He denied any ocular diseases in his family. After an ophthalmology exam, he was recommended anti-VEGF therapy and antihypertensive and lipid lowering medications intake. Conclusion: Coping with BRVO as ophthalmologists is very important for us, because RVO is one of the most common eye diseases. Intravitreal therapy has revolutionized the treatment of retinal vascular diseases, including BRVO. Although these intravitreal agents are effective, our understanding of their specific indications and long -term roles is still evolving. Furthermore, until the underlying occlusive pathophysiology of RVO, our treatments will be limited to temporizing therapies against a chronic disease. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this guideline update is to reassess and update recommendations in the prior guideline from 2016 on the appropriate management of patients with uveal melanoma. Methods: In 2021, a multidisciplinary working group from the Provincial Cutaneous Tumour Team, Cancer Care Alberta, Alberta Health Services was convened to update the guideline. A comprehensive review of new research evidence in PubMed as well as new clinical practice guidelines from prominent oncology groups informed the update. An enhancement in methodology included adding levels of evidence and strength of recommendations. The updated guideline was circulated to all members of the Provincial Cutaneous Tumour Team for review and endorsement. Results: New and modified recommendations address provider training requirements, diagnostic imaging for the detection of metastases, neo-adjuvant pre-enucleation radiotherapy, intravitreal anti-vascular endothelial growth factor agents for radiation retinopathy, genetic prognostic testing, surveillance following definitive local therapy, and systemic therapy for patients with metastatic uveal melanoma. Discussion: The recommendations represent evidence-based standards of care agreed to by a large multidisciplinary group of healthcare professionals. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the correlation between time from diagnosis of treatment-naïve exudative age-related macular degeneration (AMD) to the introduction of anti-VEGF treatment and anatomical and functional outcomes. Design: Retrospective cohort study. Methods: Included were treatment-naïve exudative AMD patients who presented to a single tertiary medical center between 2012 and 2018. All patients were treated within the first 30 days of their diagnosis with three monthly intravitreal injections of bevacizumab. Patients were divided into three groups: group 1 (prompt anti-VEGF) were injected with bevacizumab within ten days, group 2 (intermediate anti-VEGF) within 11–20 days, and group 3 (delayed anti-VEGF) within 21–30 days from diagnosis. Baseline characteristics and clinical outcomes were compared up to two years from treatment. Results: 146 eyes of 146 patients were included. Sixty-eight patients were in the prompt anti-VEGF group, 31 in the intermediate anti-VEGF group, and 47 in the delayed anti-VEGF group. Following the induction phase of three intravitreal bevacizumab injections, the mean central subfield macular thickness (328.0 ± 115.4 µm vs. 364.6 ± 127.2 µm vs. 337.7 ± 150.1 µm, p = 0.432) and the best-corrected visual acuity (0.47 ± 0.38 vs. 0.59 ± 0.48 vs. 0.47 ± 0.44 logMAR units, p = 0.458) were comparable between the prompt, intermediate and delayed anti-VEGF groups. Anatomical and functional outcomes, treatment burden, number of relapses and eyes with second-line anti-VEGF therapy were comparable between the groups at both 1-year and 2-year timepoints. Conclusions: Our real-world evidence data emphasize that even if anti-VEGF induction cannot be initiated promptly within ten days from diagnosis of naïve exudative AMD, the visual and anatomical prognosis of the patients may not worsen if the treatment is started within one month of diagnosis. [ABSTRACT FROM AUTHOR]

To search the low dosage of anti-VEGF best for primary therapies on retinopathy of prematurity (ROP) in terms of success rate. We searched Medline(Pubmed), Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases only for randomized controlled trials that had been reported as of March 3, 2023. We included studies that used bevacizumab, aflibercept and conbercept for ROP with comparable cohorts and treatment criteria. This study was performed according the pre-specified protocol registered with PROSPERO (CRD42021270077) and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis checklist. Those with animal and cell experiments, non-randomized case-control, or single case report were excluded. Frequentist network meta-analyses determined the surface under the cumulative ranking (SUCRA) of the success rate of each dose range group and compared pairs of treatments via STATA 15. Since non-RCT research were excluded, aflflibercept and conbercept studies were excluded. Therefore, only 6 bevacizumab studies were included in final meta-analysis: Inconsistency was not detected in this study via global inconsistent model test, loop inconsistency and local inconsistent model test (p > 0.05). In addition, a consistent model test has been passed in this study (p > 0.05). Little bias was detected via funnel plot. Since bevacizumab adult standard dose of single-injection is 1.25 mg, the concentration groups were converted according to the proportion of adult standard dose, such as 1/2, [1/5, 1/6.25], [1/10, 1/12.5], [1/19.8, 1/78.1], [1/156.3, 1/625]. The SUCRA of [1/10, 1/12.5] dose group were the best of largest probability to achieve success. However, [1/156.3, 1/625] dose group was the worst dose to achieve success in the five dose groups. The success rate ranking of league chart in this study is that [1/10, 1/12.5] > [1/5, 1/6.25] > 1/2 ≈ [1/19.8, 1/78.1] > [1/156.3, 1/625]. [1/10, 1/12.5] were the best dosage ranges to achieve maximal medicine success. [1/156.3, 1/625] was the worst ineffective in the five dose ranges. [ABSTRACT FROM AUTHOR]

Introduction: The aims of the study were to investigate whether first-dose efficacy can predict third-dose anatomical response and analyze the risk factors for first-dose response of polypoidal choroidal vasculopathy (PCV) patients. Methods: We retrospectively reviewed patients' medical records from 27 centers of China PCV Research Alliance. PCV patients treated with intravitreal injections of conbercept (IVC) based on the 3+ pro re nata regimen (three initial monthly injections, followed by injections as needed) with complete 3-month injection data were included. Response correlations, risk factor associations, changes in central macular thickness (CMT) or best-corrected visual acuity (BCVA), and number of injections in the first year of follow-up were evaluated separately in the pachy-PCV and non-pachy-PCV phenotypes. Results: Overall, 165 eligible patients were included. There was a significant correlation between first-dose and third-dose anatomical response in pachy-PCV or non-pachy-PCV patients (rs = 0.611, p < 0.001; rs = 0.638, p < 0.001). Multivariate analysis revealed associations of good first-dose anatomical response in pachy-PCV patients with baseline CMT with a predicted area under the curve (AUC) of 0.847, while a good response in non-pachy-PCV patients was associated with baseline BCVA, baseline CMT, pigment epithelial detachment (PED) height, higher proportion of intraretinal fluid, and lower PED minimum diameter with a predicted AUC of 0.940. CMT in the good first-dose response group was significantly decreased from baseline at all first-year follow-up visits in both groups (p < 0.001), and mean BCVA was improved in the good versus poor first-dose anatomical response group (5.4 vs. 1.6 ETDRS letters in pachy-PCV, 10.6 vs. 7.4 letters in non-pachy-PCV) after the third injection. No significant difference was observed in the number of injections in the first year of follow-up between different response groups. Conclusion: In PCV patients receiving IVC, the first- and third-dose responses are significantly correlated, and different factors influence the first-dose response in different subtypes of PCV. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effects of switching between vascular endothelial growth factor inhibitors (anti-VEGF) treatments in patients with extensive serous pigment epithelial detachment (sPED) due to neovascular age-related macular degeneration (nAMD). Materials and Methods: This was a retrospective analysis of data where 38 patients (38 eyes) with fovea involving sPED of ≥200 μm measured manually using the caliper on the OCT due to AMD. The cases were divided into 2 groups. Group 1: included patients who were initially treated with intravitreal Ranibizumab (0.5 mg/0.05 ml) and then switched to intravitreal Aflibercept (2.0 mg/0.05ml). Group 2: included patients who were initially treated with intravitreal Aflibercept (2.0 mg/0.05ml) and then switched to intravitreal Ranibizumab (0.5 mg/0.05 ml). The outcome measures of best-corrected visual acuity (BCVA), PED height, PED width, the presence of subretinal fluid (SRF), intraretinal fluid (IRF), number of injections, and follow-up periods. Results: At baseline, all patients in Group 1 had SRF. At switch, Group 1:22(%100) eyes, Group 2:16(%100) eyes had SRF. After the switch last visit, Group 1:11(%50) eyes, Group 2:8(%50) eyes had SRF (p=1.00). At baseline, Group 1:13(%59) eyes, Group 2:5(%31) eyes had IRF. At switch, Group 1: 1(%4.5) eyes, Group 2:1(%6) eyes had IRF. After switching the last visit, Group 1:1(%4.5) eyes, Group 2:1(%6) eyes had IRF (p= 0.816). Conclusions: Our study found that both anti-VEGF switch treatments showed similar anatomical and functional effectiveness with a significant reduction in PED height and increases SRF, IRF absorption. [ABSTRACT FROM AUTHOR]

Proliferative diabetic retinopathy (PDR) poses a significant therapeutic problem that often results in severe visual loss. Panretinal photocoagulation (PRP) has long been a mainstay treatment for this condition. Conversely, intravitreal anti-VEGF therapy has served as an alternative treatment for PDR. This review aimed to evaluate the effects of PRP combined with anti-VEGF therapy on the regression of neovascularization (NV), including functional outcomes and incidence of complications. The MEDLINE database was searched for articles evaluating regression of NV using a combination of the following terms: "proliferative diabetic retinopathy", "anti-VEGF", "panretinal photocoagulation", and "combined treatment". The search yielded a total of 22 articles. The analysis of their results indicated PRP combined with ant-VEGF therapy as superior over PRP alone in the management of PDR. Combination treatment yields better and faster regression of NV and a lower incidence of serious complications, such as vitreous hemorrhage and the need for pars plana vitrectomy. Nevertheless, complete regression of NV is not achieved in a significant proportion of patients. Further research is needed to establish the most effective schedule for intravitreal injections as an adjunct to PRP. The current literature shows that in some cases, cessation of anti-VEGF injection in combination treatment for PDR can lead to relapse of NV. [ABSTRACT FROM AUTHOR]

Purpose: To identify the baseline predictors of anti-VEGF treatment response at 3 years in patients affected by choroidal neovascularization (CNV) secondary to central serous chorioretinopathy (CSCR). Methods: In this retrospective longitudinal study, medical records of patients diagnosed with CNV secondary to CSCR and treated using anti-VEGF injections between April 2015 and May 2020 were reviewed. The potential qualitative and quantitative predictors of treatment response were identified or measured based on the multimodal imaging examination available for each patient at the baseline, including structural OCT, fluorescein angiography (FA), indocyanine green angiography (ICGA), and OCT-angiography (OCT-A). Univariate and multivariate analyses were performed. Results: Twenty-nine eyes from 29 patients affected by CNV complicating CSCR were included in the study. At the end of the 3-year follow-up, the mean BCVA was 20/50 Snellen equivalent (0.38 ± 0.36 LogMAR), and no significant difference with baseline BCVA (0.37 ± 0.29 LogMAR) was found (p = 0.9). Twenty out of 29 eyes (69%) had active lesions at the end of the follow-up. At multivariate analysis, none of the included features was independently associated with the 3-year BCVA outcome. Pigment epithelium detachment (PED) height (ß = 0.017, p = 0.028) and outer limiting membrane (OLM) preservation at the fovea (ß = −5.637, p = 0.026) were independently associated with the CNV activity at 3 years. Conclusion: PED height and OLM obliteration at the fovea might be considered baseline predictors of lesion activity at 3-year follow-up in patients with CNV secondary to CSCR treated with anti-VEGF therapy. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the long-term safety and efficacy of adjuvant intravitreal anti-VEGF therapy in juvenile Coats disease. Methods: This retrospective, observational study included a total of 62 eyes in 62 pediatric patients with juvenile Coats disease treated with intravitreal anti-VEGF agents followed for a mean of 67.08 months (ranged from 60 to 93 months). All affected eyes were managed initially with one session of ablative treatment plus adjuvant intravitreal anti-VEGF agent (0.5 mg/0.05 ml ranibizumab or conbercept). Ablative treatment was repeated if telangiectatic retinal vessels were not completely regressed or recurred. Anti-VEGF therapy was repeated if subretinal fluid or macular edema still existed. Treatments above were repeated every 2 to 3 months. We reviewed clinical and photographic records of patients including the demographics, clinical characteristics and interventions. Results: At final visit, all 62 affected eyes had partially or completely disease resolution; none progressed to advanced stage namely neovascular glaucoma or phthisis bulbi, respectively. No ocular or systemic side effects related to intravitreal injections were observed during follow-up. In terms of 42 affected eyes that could cooperate with visual examination, best corrected visual acuity improved in 14 (14/42, 33.3%) eyes, stabled in 25 (25/42, 59.5%) eyes, and worsened in 3 (3/42, 7.1%) eyes. In the field of complications, 22 (22/62, 35.5%) eyes developed cataracts; 33 (33/62, 53.2%) eyes developed vitreoretinal fibrosis, of whom 14 (14/33, 42.4%) eyes in the subgroup of stage 3B developed progressive TRD; 40 (40/62, 64.5%) eyes developed subretinal fibrosis. Multivariate regression analysis showed increased clinical stage may be associated with the development of vitreo- and subretinal fibrosis (adjusted odds ratio:16.77,17.59; 95% CI:4.50–62.53, 3.98–77.86, respectively, all P < 0.001). Conclusion: Adjuvant intravitreal ranibizumab or conbercept combined with ablative therapies may be a long-term safe and effective treatment for juvenile Coats disease. [ABSTRACT FROM AUTHOR]

Background: Axitinib, a potent and selective inhibitor of vascular endothelial growth factor (VEGF) receptor (VEGFR) tyrosine kinase 1,2 and 3, is used in chemotherapy because it inhibits tumor angiogenesis by blocking the VEGF/VEGFR pathway. In veterinary medicine, attempts have been made to apply tyrosine kinase inhibitors with anti-angiogenic effects to tumor patients, but there are no studies on axitinib in canine mammary gland tumors (MGTs). Objectives: This study aimed to confirm the antitumor activity of axitinib in canine mammary gland cell lines. Methods: We treated canine MGT cell lines (CIPp and CIPm) with axitinib and conducted CCK, wound healing, apoptosis, and cell cycle assays. Additionally, we evaluated the expression levels of angiogenesis-associated factors, including VEGFs, PDGF-A, FGF-2, and TGF-β1, using quantitative real-time polymerase chain reaction. Furthermore, we collected canine peripheral blood mononuclear cells (PBMCs), activated them with concanavalin A (ConA) and lipopolysaccharide (LPS), and then treated them with axitinib to investigate changes in viability. Results: When axitinib was administered to CIPp and CIPm, cell viability significantly decreased at 24, 48, and 72 h ( p < 0.001), and migration was markedly reduced (6 h, p < 0.05; 12 h, p < 0.005). The apoptosis rate significantly increased ( p < 0.01), and the G2/M phase ratio showed a significant increase ( p < 0.001). Additionally, there was no significant change in the viability of canine PBMCs treated with LPS and ConA. Conclusion: In this study, we confirmed the antitumor activity of axitinib against canine MGT cell lines. Accordingly, we suggest that axitinib can be applied as a new treatment for patients with canine MGTs. [ABSTRACT FROM AUTHOR]

Background: In recent years, there has been rapid development in systemic therapeutic agents for advanced hepatocellular carcinoma. However, most treatment modalities lack head-to-head comparisons, and the distinctions in their efficacy and safety have yet to be elucidated. Consequently, the accurate selection of a treatment regimen poses a significant challenge for clinicians. Methods: This study incorporated twenty-three randomized controlled trials, encompassing fifteen first-line and eight second-line treatments, and involving a total of 14,703 patients with advanced hepatocellular carcinoma. Results: In the context of first-line treatment, it was observed that the combination of a PD-1 inhibitor with bevacizumab (1/15) significantly extended overall survival in patients with advanced HCC. Furthermore, PD-1 inhibitors combined with TKIs (1/15) and PD-1 inhibitors combined with bevacizumab (2/15) exhibited enhanced efficacy in reducing the risk of progression-free survival events. In second-line therapy, the network meta-analysis revealed that all investigational agents prolonged progression-free survival in patients with advanced hepatocellular carcinoma when compared to placebo. Cabozantinib ranked first (1/7) in this regard. However, this translated into an overall survival benefit only for cabozantinib, regorafenib, ramucirumab, and pembrolizumab, with regorafenib achieving the highest ranking (1/7). Conclusion: In the treatment of advanced HCC, the immune checkpoint inhibitor combined with bevacizumab regimen and the immune checkpoint inhibitor combined with TKI regimen stand out as the two most effective first-line treatment options. It is noteworthy that, for patients with absolute contraindications to VEGF inhibitors, dual immunotherapy is the preferred choice. For second-line treatment, regorafenib and cabozantinib are identified as the two most effective options. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the clinical effects and safety of immune checkpoint inhibitors (ICIs) combined with anti-VEGF therapy for the treatment of unresectable or advanced liver cancer. Method: Related databases were searched from inception to December 2022 to identify randomized controlled studies and clinical trials that evaluated the combination of ICIs and anti-VEGF therapy for the treatment of unresectable liver cancer. The outcome index was extracted and analyzed by RevMan5.4. Results A total of 8 clinical trials were included. In terms of efficacy, the intervention group had longer OS and PFS for unresectable or advanced liver cancer than the control group. In terms of safety, (1) Adverse events of all grades showed that the combination treatment led to significantly higher risks of urinary system disorders, cardiovascular system disorder, blood system disorders and liver dysfunction than the control treatment. Compared with monotherapy, the combination treatment led to lower risks of gastrointestinal disorders. (2) Adverse events above grade 3 showed that, compared with the control treatment, the combination treatment led to significantly higher risks of urinary system disorders, blood systeam disorders, cardiovascular system disorders and liver dysfunction. Additionally, compared with monotherapy, the combination treatment led to significantly lower risks of gastrointestinal disorders. Conclusions: ICIs combined with anti-VEGF therapy exerts significant clinical effects in patients with unresectable or advanced liver cancer, can prolong the survival of these patients and can improve their quality of life. However, clinical attention should be given to the occurrence of adverse reactions. [ABSTRACT FROM AUTHOR]

This investigation aims at evaluating the functional results 1-year following anti-VEGF therapy in macular pathology. Material and method: This is a retrospective examination that was carried out on 57 patients with macular pathology out of 108 at Sf. Spiridon Hospital in Iasi. 57 patients with macular pathology were included in the investigation, respectively 57 eyes, 24 eyes with diabetic macular edema and 33 with neovascular age-related macular degeneration. Eyes in which less than 6 intravitreous injections were performed (less than one-year of follow-up) as well as those without oct control examinations and without adequate controls were excluded. Results: Visual acuity improves considerably after the therapy was performed in both patients experiencing diabetic macular edema (370 vs 320 microns) and in those with age-related macular degeneration (320 vs 260 microns), while the average thickness of the central macula decreases considerably after therapy. Conclusions: In this study, the therapy with intravitreal Aflibercept was associated with improving the functional and anatomical outcomes, keeping the increasing trend up to one-year of therapy in those who received a minimum of three injections. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine the correlation between topographic vessel density (VD) and retinal thickness (RT) reductions induced by vascular endothelial growth factor inhibitors (anti-VEGF) in patients with diabetic macular edema (DME) using optical coherence tomography angiography (OCTA). This was a prospective, interventional case series. VD and RT measurements were separately taken in four parafoveal subfields at baseline and after six months of treatment. This correlation was statistically assessed using Spearman's rho correlation coefficient after adjustment for multiple comparisons. The study included a total of 48 eyes in the final analysis. Mean VD decreased from baseline to month 6 (from 45.2 (±3.5) to 44.6% (±3.2) in the superficial capillary plexus and from 50 (±3.3) to 49% (±3.9) in the deep capillary plexus). Statistically significant reductions in RT were observed in all ETDRS sectors (p < 0.0001). No significant association was found between RT and VD, even when analyzing responders and non-responders separately. After six months of anti-VEGF treatment, no significant correlation was observed between the topographic VD and RT values. These findings suggest that reductions in VD values may not solely result from a reduction in microaneurysms, also being affected by the repositioning of displaced vessels due to edema and a reduction in their caliber. Therefore, VD changes may not be a suitable indirect OCTA biomarker of microaneurysm turnover and treatment response. [ABSTRACT FROM AUTHOR]

Intraocular inflammations (IOIs) have been reported to occur after intravitreal injections of brolucizumab, and one of their causes has been suggested to be drug-specific features. We evaluated the anterior chamber by the aqueous flare value (AFV) and the retina by flicker electroretinography (ERG) after the initial intravitreal injection of aflibercept (IVA), brolucizumab (IVBr), or faricimab (IVF) for neovascular age-related macular degeneration (nAMD). The AFV and flicker ERGs were determined before, 2 weeks after, and 4 weeks after the injections in 14 eyes of 14 patients for each drug. After the injections, none of the patients had an IOI, but the AFV increased significantly in the IVA and IVF groups. The increase in the IVF group was +4.6 photon count/ms, which was significantly greater than in the other groups, but was not clinically significant. The implicit time was significantly prolonged in the IVBr group but unchanged in the IVA and IVF groups. These results suggest that brolucizumab, administered at high molar doses, may cause transient retinal disturbances that are not detectable by general ophthalmologic examinations but affect the implicit ERG times. [ABSTRACT FROM AUTHOR]

Diabetic macular edema (DME) is a common sight-threatening complication of diabetic retinopathy (DR) and the leading cause of severe visual impairment among the working-age population. Several therapeutic options are available for the management of DME, including intravitreal corticosteroids. They have been traditionally used as second-line treatment, due to the risk of intraocular pressure increase and cataract-related adverse events. However, attention has recently been focused on the primary or early use of intravitreal corticosteroids, due to growing evidence of the crucial role of inflammation in the pathogenesis of DME. Furthermore, intravitreal steroid implants offer the additional advantage of a longer duration of action compared to anti-vascular endothelial growth factor agents (anti-VEGF). This review aims to summarize the available evidence on the efficacy and safety profile of dexamethasone (DEX) intravitreal implant, with a specific focus on clinical scenarios in which it might be considered or even preferred as first-line treatment option by adequate selection of patients, considering both advantages and possible adverse events. Patients with contraindications to anti-VEGF, DME with high inflammatory OCT biomarkers, pseudophakic patients and phakic patients' candidates to cataract surgery as well as vitrectomized eyes may all benefit from first-line DEX implant. Additionally, DME not responders to anti-VEGF should be considered for a switch to DEX implant and a combination therapy of DEX implant and anti-VEGF could be a valid option in severe and persistent DME. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to report the demographic and clinical characteristics of diabetic macular edema (DME) patients treated with intravitreal injection (IVI) of anti-vascular endothelial growth factors (anti-VEGF) and provide an overview of outcomes during routine clinical practice in Türkiye. Materials and Methods: This retrospective, real-world study included 1,372 eyes (854 patients) treated with a pro re nata protocol by 21 ophthalmologists from 8 tertiary clinics on the Asian side of the Marmara region of Türkiye (MARMASIA Study Group). Five cohort groups were established by collecting the patients' baseline and 3, 6, 12, 24, and 36-month follow-up data, where each subsequent cohort may include the previous. Changes in best-corrected visual acuity (BCVA, approximate ETDRS letters) and central macular thickness (CMT, pm), number of visits and IVI, and rates of anti-VEGF switch and intravitreal dexamethasone implant (IDI) combination were evaluated. Results: The 3, 6, 12, 24, and 36-month cohorts included 1372 (854), 1352 (838), 1185 (722), 972 (581), and 623 (361) eyes (patients), respectively. The mean baseline BCVA and CMT were 51.4±21.4 letters and 482.6±180.3 pm. The mean changes from baseline in BCVA were + 7.6, +9.1, +8.0, +8.6, and +8.4 letters, and in CMT were -115.4, -140.0, -147.9, -167.3, and -215.4 pm at the 3, 6, 12, 24, and 36-month visits (p<0.001 for all). The median cumulative number of anti-VEGF IVI was 3.0, 3.0, 5.0, 7.0, and 9.0, respectively. The overall anti-VEGF switch and IDI combination rates were 18.5% (253/1372 eyes) and 35.0% (480/1372 eyes), respectively. Conclusion: This largest real-life study of DME from Türkiye demonstrated BCVA gains inferior to randomized controlled trials, mainly due to the lower number of IVI. However, with the lower baseline BCVA and higher IDI combination rates in our cohorts, these gains were relatively superior to other real-life study counterparts. [ABSTRACT FROM AUTHOR]

Introduction: To investigate the longitudinal changes in renal function and associated factors after intravitreal anti-vascular endothelial growth factor (VEGF) administration in diabetic macular edema (DME). Methods: A total of 108 patients who had received intravitreal ranibizumab or aflibercept for DME and had follow-up visits for at least 2 years in one hospital were retrospectively enrolled. The estimated glomerular filtration rate (eGFR) at baseline and during the follow-up period and receipt of any renal replacement therapy were recorded. Linear regression and Cox regression models were used to evaluate factors associated with eGFR decline and renal replacement therapy. Results: After intravitreal anti-VEGF treatment, eGFR showed a mean decline of −10.4 ± 23.2% and −16.5 ± 26.4% at months 12 and 24, respectively. Patients in the eGFR > 120 mL/min and 15–30 mL/min groups had the greatest decline (−32.0 ± 20.6% and −37.4 ± 30.9%, respectively) while those in the 61–90 mL/min group had the smallest decline (−4.3 ± 19.7%) in eGFR after the 2-year treatment. One out of 52 patients (1.9%) receiving ranibizumab and five out of 56 patients (8.9%) receiving aflibercept started hemodialysis or peritoneal dialysis within the 2-year follow-up period (P = 0.21). Baseline eGFR correlated with renal replacement therapy after intravitreal anti-VEGF treatment (hazard ratio = 0.879 per increase of 1 in eGFR, P = 0.018). Conclusions: In DME patients receiving intravitreal anti-VEGF treatment, a persistent decline in eGFR was observed during the 2-year treatment course. Patients with extremely high or low eGFR had greater eGFR decline, and those with poor baseline eGFR tended to require dialysis after intravitreal anti-VEGF treatment. [ABSTRACT FROM AUTHOR]

Introduction: Recurrent ovarian cancer is one of the most challenging issues in medical oncology. Being the fifth in the cancer mortality list among women, ovarian cancer is the reason of more deaths than any other cancer of the female reproductive system. A meta-analysis was conducted to investigate the optimal treatment options for recurrent platinum-sensitive and platinum-resistant ovarian cancer. Methods: Data for writing this article was collected from the publications in English, Russian and Italian from 2002 to 2023. PubMed and Web of Science were searched for the relevant articles. Survival rates, particularly overall survival (OS), progression-free survival (PFS), and adverse events (AEs) of the chemotherapy regimens were discussed. We analyzed the literature data comparing the effectiveness and safety of chemotherapy, antiangiogenic therapy, the use of poly-ADP ribose polymerase (PARP) inhibitors, and checkpoint inhibitors in the treatment of recurrent ovarian cancer. Results: An overview of the literature devoted to modern approaches to the systemic treatment of recurrent ovarian cancer is given in the article. General principles of classification and treatment of recurrent ovarian cancer are analyzed. The existing regimens of chemotherapy in combination with targeted therapy are given separately for various types of ovarian cancer relapses. Chemotherapy with doublet platinum compounds (carboplatin or cisplatin) continues to be the standard of care in platinum-sensitive relapsed ovarian cancer with or without targeted therapy. Treatment with poly-ADP ribose polymerase inhibitors, vascular endothelial growth factor inhibitors, immunotherapy with checkpoint inhibitors, and antibody-drug conjugate for patients with folate receptor alpha-positive, can be considered in platinum-resistant epithelial ovarian cancer. Conclusion: In summary, we can conclude that despite the success of the primary treatment of ovarian cancer, the majority of patients with a widespread tumor process develop a relapse of the disease over the next two years, which is the cause of death of these patients. The development of effective treatment regimens for recurrent ovarian/fallopian tube/primary peritoneal cancer remains particularly acute and important in gynecological oncology and requires further study. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the early effects of intravitreal anti–vascular endothelial growth factor (anti-VEGF) agents on the cornea and visual acuity in patients with diabetic retinopathy (DR). This retrospective study enrolled patients who were administered conbercept or ranibizumab to treat DR. Fundus photograph, fluorescein angiograph, and optical coherence tomography were preoperatively performed. The patients were classified into two groups: nonproliferative DR (NPDR) and PDR. Best-corrected visual acuity (BCVA), specular microscopy, central corneal thickness (CCT), and intraocular pressure were obtained before injection and at 1 day and 7 days after injection. The effects of anti-VEGF agents on BCVA and CCT were compared between the groups receiving conbercept and ranibizumab and between NPDR and PDR eyes. A total 38 eyes (30 patients) were enrolled in this study. Twenty-one eyes received conbercept, and 17 eyes received ranibizumab. Twenty eyes were classified as NPDR and 18 eyes as PDR. No significant differences were found between the groups receiving conbercept and ranibizumab in the increase in BCVA nor in the increase of CCT at 1 day and 7 days after injection. As compared with NPDR eyes, PDR eyes demonstrated a significantly greater increase in CCT (−5.3 ± 3.7 vs. 6.5 ± 2.9 μm, P = 0.02 < 0.05) but not in BCVA (P = 0.33) at 1 day after injection. At 7 days after injection, no significant differences were found in the increase in BCVA nor in the increase of CCT between NPDR eyes and PDR eyes. Intravitreal administration of anti-VEGF agents could cause a small but significant greater increase in CCT in PDR than in NPDR eyes in the early period. In patients with DR, no significant difference was found between conbercept and ranibizumab in the early effects on the visual acuity nor in the cornea. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to investigate retinal layers changes in patients with age-related macular degeneration (AMD) treated with anti-vascular endothelial growth factor (anti-VEGF) agents and to evaluate if these changes may affect treatment response. Methods: This study included 496 patients with AMD or PCV who were treated with anti-VEGF agents and followed up for at least 6 months. A comprehensive analysis of retinal layers affecting visual acuity was conducted. To eliminate the fact that the average thickness calculated may lead to differences tending to converge towards the mean, we proposed that the retinal layer was divided into different regions and the thickness of the retinal layer was analyzed at the same time. The labeled data will be publicly available for further research. Results: Compared to baseline, significant improvement in visual acuity was observed in patients at the 6-month follow-up. Statistically significant reduction in central retinal thickness and separate retinal layer thickness was also observed (p < 0.05). Among all retinal layers, the thickness of the external limiting membrane to retinal pigment epithelium/Bruch's membrane (ELM to RPE/BrM) showed the greatest reduction. Furthermore, the subregional assessment revealed that the ELM to RPE/BrM decreased greater than that of other layers in each region. Conclusion: Treatment with anti-VEGF agents effectively reduced retinal thickness in all separate retinal layers as well as the retina as a whole and anti-VEGF treatment may be more targeted at the edema site. These findings could have implications for the development of more precise and targeted therapies for AMD treatment. [ABSTRACT FROM AUTHOR]

Bevacizumab is a frequently used inhibitor of vascular endothelial growth factor (VEGF) in the management of macular edema in central retinal vein occlusion (CRVO). Studying retinal protein changes in bevacizumab intervention may provide insights into mechanisms of action. In nine Danish Landrace pigs, experimental CRVO was induced in both eyes with argon laser. The right eyes received an intravitreal injection of 0.05 mL bevacizumab (n = 9), while the left control eyes received 0.05 mL saline water (NaCl). Retinal samples were collected 15 days after induced CRVO. Label-free quantification nano-liquid chromatography–tandem mass spectrometry identified 59 proteins that were regulated following bevacizumab treatment. Following bevacizumab intervention, altered levels of bevacizumab components, including the Ig gamma-1 chain C region and the Ig kappa chain C region, were observed. Changes in other significantly regulated proteins ranged between 0.58–1.73, including for the NADH-ubiquinone oxidoreductase chain (fold change = 1.73), protein-transport protein Sec24B (fold change = 1.71), glycerol kinase (fold change = 1.61), guanine-nucleotide-binding protein G(T) subunit-gamma-T1 (fold change = 0.67), and prefoldin subunit 6 (fold change = 0.58). A high retinal concentration of bevacizumab was achieved within 15 days. Changes in the additional proteins were limited, suggesting a narrow mechanism of action. [ABSTRACT FROM AUTHOR]

Retrospective, real-world study to evaluate visual acuity (VA), anti-vascular endothelial growth factor (anti-VEGF) injection intervals, and central macular thickness (CMT) in neovascular age-related macular degeneration (nAMD) eyes switched to brolucizumab only or to brolucizumab alternating with another anti-VEGF.Methods: The overall study population comprised eyes that were given ≥ 1 brolucizumab injection between 1 October 2019 and 30 November 2021. The brolucizumab-only (BRO) cohort consisted of prior anti-VEGF-treated eyes treated exclusively with ≥ 3 brolucizumab injections over ≥ 12 or ≥ 18 months; the alternating brolucizumab (ALT) cohort comprised prior anti-VEGF-treated eyes treated with ≥ 2 brolucizumab injections and ≥ 1 other anti-VEGF over ≥ 12 or ≥ 18 months.Results: A total of 482 eyes received ≥ 1 brolucizumab injection during the study period. Mean VA changes from baseline were − 1.1± 15.1 letters (BRO cohort; n = 174) and 1.3± 13.0 letters (ALT cohort; n = 47) at Month 12, and 0.0± 13.5 letters (BRO cohort; n = 95) and − 7.3± 17.2 letters (ALT cohort; n = 29) at Month 18. Mean changes in injection intervals were +26.9± 48.1 days (BRO cohort) and +11.1± 17.3 days (ALT cohort) at Month 12 and +36.3± 52.3 days (BRO cohort) and +14.0± 19.9 days (ALT cohort) at Month 18. Mean changes in CMT were − 35.2± 108.1 μm (BRO cohort) and − 31.5± 91.2 μm (ALT cohort) at Month 12 and − 38.9± 75.0 μm (BRO cohort) and − 9.0± 59.9 μm (ALT cohort) at Month 18. Intraocular inflammation-related adverse events were recorded in 22/482 (4.6%) eyes.Conclusion: Treatment with either brolucizumab alone or brolucizumab alternating with another anti-VEGF can preserve vision, reduce CMT, and extend anti-VEGF injection intervals in patients with nAMD. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to investigate the factors influencing post-treatment visual acuity (VA) in patients with central retinal vein occlusion (CRVO) with macular edema (ME). Methods: The subjects of this study were patients who visited our clinic from May 2013 to July 2019 and who could be followed up with for at least 12 months. Cases with hemi CRVO were excluded from this study. Factors considered in the evaluation of visual prognosis at the 12 months included initial best-corrected VA, central subfoveal thickness, CRVO subtype (nonischemic, ischemic, or converted from nonischemic to ischemic), time taken for the first treatment, number of anti-vascular endothelial growth factor agent injections, structural changes in the inner and outer retinal layers, and the presence of macular ischemia in a multiple regression analysis. Results: There were 41 patients with 41 eyes, 27 males and 14 females. The mean age of the patients was 70.5 ± 12.2 (mean ± standard deviation) years. The mean VA was 0.544 ± 0.576, 0.456 ± 0.568, and 0.586 ± 0.665 at the initial visit, 12 months later, and time of last observation, respectively. There were no significant differences in VAs observed between the baseline, month 12, and final visit. Multiple regression analysis revealed that the external limiting membrane score at month 12 (p = 0.030), the VA at initial visit (p < 0.001), and the presence of severe macular ischemia (p < 0.001) were the key factors associated with VA at month 12. Moreover, severe macular ischemia was identified as the only factor affecting decimal VA less than 20/200 at the last observation (p = 0.0092). Conclusions: Severe macular ischemia is strongly linked to a poor visual prognosis in patients with ME associated with CRVO. [ABSTRACT FROM AUTHOR]