Search Results (1,011)

Objective: To purpose of this study was to retrospectively evaluate the 1-year outcomes and factors associated with the treatment responsiveness of switching to intravitreal brolucizumab (IVBR) for neovascular age-related macular degeneration (nAMD) in Japanese patients refractory to ranibizumab or aflibercept using a treat and extend (TAE) regimen. Methods: A total of 48 eyes of 47 nAMD patients were switched to IVBR, and 36 eyes of 35 patients (27 males and 8 females) underwent 1-year treatment after the switch. Results: The rate of dry macula was significantly higher 12 months after the switch to IVBR (p < 0.001), with a significant decrease in the mean central macular thickness (CMT) and the mean central choroidal thickness (CCT) (p < 0.01 and p < 0.01, respectively). The injection interval was significantly extended from 7.0 ± 1.7 weeks to 10.3 ± 2.5 weeks 12 months after the switch (p < 0.001). In the multivariate analysis, a smaller number of prior anti-VEGF injections (p = 0.025; odds ratio: 0.947; 95% confidence interval: 0.903–0.994) and a pre-switching CCT of less than 250 µm (p = 0.023; odds ratio: 0.099; 95% confidence interval: 0.013–0.731) were associated with the good response group. Conclusions: These results suggest that IVBR may suppress disease activity and prolong the injection interval by switching for AMD patients with an insufficient response to treatment with ranibizumab and aflibercept. Full article

MicroRNAs (miRs) regulate physiological and pathological processes, including ischemia-induced angiogenesis and neovascularization. They can be transferred between cells by extracellular vesicles (EVs). However, the specific miRs that are packaged in EVs released from skeletal muscles, and how this process is modulated by ischemia, remain to be determined. We used a mouse model of hindlimb ischemia and next generation sequencing (NGS) to perform a complete profiling of miR expression and determine the effect of ischemia in skeletal muscles, and in EVs of different sizes (microvesicles (MVs) and exosomes) released from these muscles. Ischemia significantly modulated miR expression in whole muscles and EVs, increasing the levels of several miRs that can have pro-angiogenic effects (angiomiRs). We found that specific angiomiRs are selectively enriched in MVs and/or exosomes in response to ischemia. In silico approaches indicate that these miRs modulate pathways that play key roles in angiogenesis and neovascularization, including HIF1/VEGF signaling, regulation of actin cytoskeleton and focal adhesion, NOTCH, PI3K/AKT, RAS/MAPK, JAK/STAT, TGFb/SMAD signaling and the NO/cGMP/PKG pathway. Thus, we show for the first time that angiomiRs are selectively enriched in MVs and exosomes released from ischemic muscles. These angiomiRs could be targeted in order to improve the angiogenic function of EVs for potential novel therapeutic applications in patients with severe ischemic vascular diseases. Full article

Purpose: To determine the recurrence rate of neovascular age-related macular degeneration (nAMD) during a 5-year period after the suspension of anti-vascular endothelial growth factor (anti-VEGF) treatments. Methods: Thirty-four eyes of 34 nAMD patients who met the inclusion criteria and were treated by anti-VEGF drugs were studied. All met the treatment suspension criteria and were followed for 5 years after the suspension of the anti-VEGF treatment. Patients with a recurrence within one year were placed in Group A, and patients with a recurrence between 1 and 5 years were placed in Group B. The rate and time of a recurrence were analyzed using the Kaplan–Meier method. We also examined whether there were differences in the baseline factors of age, sex, subtype, treatment period, and treatment interval between Groups A and B. Results: Twenty-five of 34 eyes (73.5%) had a recurrence within 5 years of stopping the anti-VEGF treatments. Thirteen (52.0%) of the 25 eyes had a recurrence within 1 year, 4 (16.0%) eyes between 1 and 2 years, 4 (16.0%) eyes between 2 and 3 years, 2 (8%) between 3 and 4 years, and 2 eyes (8%) between 4 and 5 years. The baseline factors were not significantly different between Groups A and B. Conclusions: The results showed that the recurrence rate was highest within one year after the suspension of the anti-VEGF treatments, with a number of recurrences one year after the suspension. Clinicians should remember that nAMD may recur several years after the suspension of anti-VEGF treatments. Full article

The objective of this paper was to determine how different types of posterior staphyloma (PS) may affect the appearance and degree of myopic maculopathy. A cross-sectional study was conducted, in which 467 eyes from 246 highly myopic patients [axial length (AL) ≥ 26 mm] were studied. A complete ophthalmic exploration was carried out on all patients, including imaging tests. The presence of macular PS was established as the main comparison variable between groups (macular PS vs. non-macular PS vs. non-PS). The variables analyzed included age, AL, decimal best-corrected visual acuity (BCVA), Atrophy (A)/Traction (T)/Neovascularization (N) components according to the ATN grading system, and the presence of severe pathologic myopia (PM). Out of the total, 179 eyes (38.3%) presented macular PS, 146 eyes presented non-macular PS (31.2%), and 142 eyes showed no PS (30.4%). The group without PS was significantly younger than macular PS and non-macular PS groups (53.85 vs. 66.57 vs. 65.20 years; p < 0.001 each, respectively). There were no age differences between PS groups. Eyes with macular PS (31.47 ± 2.30 mm) were significantly longer than those with non-macular PS (28.68 ± 1.78 mm, p < 0.001) and those without PS (27.47 ± 1.34 mm, p < 0.001). BCVA was significantly better in the non-PS group (0.75 ± 0.27) compared to the non-macular PS (0.56 ± 0.31) and macular PS groups (0.43 ± 0.33), with p < 0.001 each. Eyes without PS showed significantly lower A and T components (1.31 ± 0.96 and 0.30 ± 0.53, respectively) than non-macular PS (2.21 ± 0.75 and 0.71 ± 0.99, respectively, p < 0.001 each) and macular PS eyes (2.83 ± 0.64 and 1.11 ± 1.10, respectively, p < 0.001 each). The N component was lower in non-PS eyes vs. non-macular PS eyes (0.20 ± 0.59 vs. 0.47 ± 0.83, p < 0.001) and as compared to the macular PS group (0.68 ± 0.90, p < 0.01). Additionally, the N component was significantly lower in the non-macular PS group than in the macular PS one (p < 0.05). The prevalence of severe PM was different between groups (p < 0.001). It was higher among macular PS eyes (138/179) when compared to other groups (p < 0.001, each), followed by the non-macular PS eyes (40/146) and being the lowest in the non-PS group (20/142). To conclude, macular PS is associated with a more advanced maculopathy, worse vision, and higher rates of severe PM. Full article

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness worldwide and a severe medical and social problem. The steadily increasing number of patients is related to the aging of the population. So far, many factors affecting the development of AMD have been identified, which can be divided into non-modifiable, including genetic factors, age, and sex, and modifiable or environmental factors, such as smoking, poor diet, and hypertension. Early stages of age-related macular degeneration are characterized by fundus drusen and abnormalities in the retinal pigment epithelium. In late stages, geographic atrophy and choroidal neovascularization (CNV) are observed. The treatment of AMD, especially its advanced forms, is very challenging. Intensive research has made it possible to treat advanced stages of the dry form of AMD with pegcetacoplan and avacincaptad pegol, new drugs approved for use in the US. Pegcetacoplan targets the C3 and avacincaptad pegol targets the C5, the pivotal proteins of the complement cascade. The drugs are administered by intravitreal injection. The gold standard for neovascular AMD (nAMD) consists of intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) drugs such as bevacizumab, ranibizumab, aflibercept, brolucizumab, and faricimab. Treatment can be administered according to the fixed, pro-re-nata, and treat-and-extend regimens. The latter seems to have the best effect on improving visual acuity (VA) and the maximum therapeutic benefit. The search continues for the best ways to deliver intravitreal drugs. Current methods include sustained-release implants and hydrogel platforms for drug release, while the most promising future pathways for treating dry and nAMD are stem cell and gene therapy. Full article

Background and Objectives: In this study, our objective was to assess and compare the changes in visual and structural outcomes among patients with neovascular age-related macular degeneration (nAMD) who were switched from intravitreal aflibercept (IVA) to either intravitreal brolucizumab (IVBr) or intravitreal faricimab (IVF) injections in a clinical setting. Materials and Methods: This observational clinical study included 20 eyes of 20 patients switched to brolucizumab and 15 eyes of 14 patients switched to faricimab from aflibercept in eyes with nAMD. We measured the structural outcome (central macular thickness (CMT)) and the visual outcome (best-corrected visual acuity (BCVA); logMAR) as follows: just before the most recent IVA injection (B0), one month after the most recent IVA injection (B1), just before the first IVBr or IVF injection (A0), one month after (A1) and three months after (A3) the first IVBr or IVF injection. Results: BCVA showed significant improvement at A1 (0.25 ± 0.34) and at A3 (0.19 ± 0.24) compared to A0 (0.38 ± 0.35) in the IVBr group (p = 0.0156, p = 0.0166, respectively). CMT (μm) was significantly thinner at A1 (IVBr: 240.55 ± 51.82, IVF: 234.91 ± 47.29) and at A3 (IVBr: 243.21 ± 76.15, IVF: 250.50 ± 72.61) compared to at A0 (IVBr: 303.55 ± 79.18, IVF: 270.33 ± 77.62) in the IVBr group (A1: p = 0.0093, A3: p = 0.0026) and in the IVF group (A1: p = 0.0161, A3: p = 0.0093). There was no significant difference in BCVA and CMT improvement observed between two groups at any time point (p > 0.05 for all). Conclusions: Switching from aflibercept to either brolucizumab or faricimab has a significant anatomical effect in eyes with nAMD and both treatments appear to be effective short-term treatment options. There is a trend towards greater visual improvements and reductions in CMT with brolucizumab. Full article

Hypoxia-inducible factor (HIF) plays a crucial role in regulating oxygen sensing and adaptation at the cellular level, overseeing cellular oxygen homeostasis, erythrocyte production, angiogenesis, and mitochondrial metabolism. The hypoxia-sensitive HIF-1α subunit facilitates tissue adaptation to hypoxic conditions, including the stimulation of proangiogenic factors. Retinopathy of prematurity (ROP) is a proliferative vascular disease of the retina that poses a significant risk to prematurely born children. If untreated, ROP can lead to retinal detachment, severe visual impairment, and even blindness. The pathogenesis of ROP is not fully understood; however, reports suggest that premature birth leads to the exposure of immature ocular tissues to high levels of exogenous oxygen and hyperoxia, which increase the synthesis of reactive oxygen species and inhibit HIF expression. During the ischemic phase, HIF-1α expression is stimulated in the hypoxia-sensitive retina, causing an overproduction of proangiogenic factors and the development of pathological neovascularization. Given the significant role of HIF-1α in the development of ROP, considering it as a potential molecular target for therapeutic strategies appears justified. This review synthesizes information from the last six years (2018–2024) using databases such as PubMed, Google Scholar, and BASE, focusing on the role of HIF-1α in the pathogenesis of ROP and its potential as a target for new therapies. Full article

Corneal neovascularization is a significant cause of vision loss, often resulting in corneal clouding and chronic inflammation. Shark cartilage is widely recognized as a significant natural source of anti-angiogenic compounds. Our previous studies have shown that a polypeptide from white-spotted catshark (Chiloscyllium plagiosum Bonnet) has the potential to inhibit the angiogenesis of breast tumors. This study applied this peptide (SAIF) to a corneal alkali injury model to assess its effect on corneal neovascularization. Results revealed that SAIF inhibits endothelial cell proliferation, migration, and tube formation. SAIF inhibited VEGF-induced angiogenesis in the matrigel plug. Using the corneal alkali injury model, SAIF significantly inhibited corneal vascular neovascularization in mice. We found that SAIF not only significantly inhibited the upregulation of pro-angiogenic factors such as VEGF, bFGF, and PDGF expression induced by alkali injury, but also promoted the expression of anti-angiogenesis factor PEDF. Moreover, we also analyzed the MMPs and TIMPs involved in extracellular matrix (ECM) remodeling, angiogenesis, and lymphangiogenesis. We found that SAIF treatment inhibited the expression of pro-angiogenic factors like MMP1, MMP2, MMP3, MMP9, MMP13, and MMP14, and promoted the expression of anti-angiogenesis factors such as MMP7, TIMP1, TIMP2, and TIMP3. In conclusion, SAIF acts as an anti-angiogenic factor to inhibit the proliferation, migration, and tube formation of endothelial cells, inhibit pro-angiogenic factors, promote anti-angiogenic factors, and regulate the expression of MMPs, ultimately inhibiting corneal neovascularization. Full article

Uveal melanoma (UM) represents a rare tumor of the uveal tract and is associated with a poor prognosis due to the high risk of metastasis. Despite advances in the treatment of UM, the mortality rate remains high, dictating an urgent need for novel therapeutic strategies. The current study introduces the first in vivo analysis of the therapeutic potential of calcium electroporation (CaEP) compared with electrochemotherapy (ECT) with bleomycin in a patient-derived xenograft (PDX) model based on the chorioallantoic membrane (CAM) assay. The experiments were conducted as monotherapy with either 5 or 10 mM calcium chloride or 1 or 2.5 µg/mL bleomycin in combination with EP or EP alone. CaEP and ECT induced a similar reduction in proliferative activity, neovascularization, and melanocytic expansion. A dose-dependent effect of CaEP triggered a significant induction of necrosis, whereas ECT application of 1 µg/mL bleomycin resulted in a significantly increased apoptotic response compared with untreated tumor grafts. Our results outline the prospective use of CaEP and ECT with bleomycin as an adjuvant treatment of UM, facilitating adequate local tumor control and potentially an improvement in metastatic and overall survival rates. Full article

It is acknowledged that conventional renal cell carcinoma (cRCC), which makes up 85% of renal malignancies, is a highly vascular tumor. Humanized monoclonal antibodies were developed to inhibit tumor neo-angiogenesis, which is driven by VEGFA/KDR signaling. The results largely met our expectations, and in several cases, adverse events occurred. Our study aimed to analyze the expression of VEGFA and its receptor KDR by immunohistochemistry in tissue multi-array containing 811 cRCC and find a correlation between VEGFA/KDR signaling and new vessel formation. None of the 811 cRCC displayed VEGFA-positive immunostaining. However, each glomerulus in normal kidney showed VEGFA-positive endothelial cells. KDR expression in endothelial meshwork was found in only 9% of cRCC, whereas 2% of the cRCC displayed positive KDR reaction in the cytoplasm of tumor cells. Our results disclose the involvement of VEGFA/KDR signaling in the neo-vascularization of cRCC and explain the frequent resistance to drugs targeting the VEGFA/KDR signaling and the high frequency of adverse events. Full article

One of the major causes of vision impairment among elderly people in developed nations is age-related macular degeneration (AMD). The distinctive features of AMD are the accumulation of extracellular deposits called drusen and the gradual deterioration of photoreceptors and nearby tissues in the macula. AMD is a complex and multifaceted disease influenced by several factors such as aging, environmental risk factors, and a person’s genetic susceptibility to the condition. The interaction among these factors leads to the initiation and advancement of AMD, where genetic predisposition plays a crucial role. With the advent of high-throughput genotyping technologies, many novel genetic loci associated with AMD have been identified, enhancing our knowledge of its genetic architecture. The common genetic variants linked to AMD are found on chromosome 1q32 (in the complement factor H gene) and 10q26 (age-related maculopathy susceptibility 2 and high-temperature requirement A serine peptidase 1 genes) loci, along with several other risk variants. This review summarizes the common genetic variants of complement pathways, lipid metabolism, and extracellular matrix proteins associated with AMD risk, highlighting the intricate pathways contributing to AMD pathogenesis. Knowledge of the genetic underpinnings of AMD will allow for the future development of personalized diagnostics and targeted therapeutic interventions, paving the way for more effective management of AMD and improved outcomes for affected individuals. Full article

Background: To evaluate functional and anatomical outcomesof cataract surgery in neovascular age-related macular neovascularization (nAMD) eyes receiving anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections in modified pro re nata (PRN) regimen. Materials and Methods: Sixty eyes of 60 nAMD patients, including 41 women (68.3%) and 19 men (31.7%) in an average age of 77.35 ± 6.41 years, under treatment with intravitreal aflibercept injections in modified PRN regimen with no signs of macular neovascularization (MNV) activity during two consecutive visits were included in this prospective, observational study. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), as well as the number of anti-VEGF injections were monitored six months before and after phacoemulsification with intraocular lens (IOL) implantation. Further, the change of the abovementioned parameters was assessed during the six-month follow-up period for CRT and the number of injections, while the BCVA was monitored for 54 months. Results: BCVA measured on the first day after surgery (0.17 ± 0.19 logMAR) as well as in the six-month post-surgery (0.13 ± 0.16 logMAR) significantly improved compared to preop values (0.42 ± 0.20 logMAR). BCVA remains stable during the observational period. We found that both differences were statistically significant (p < 0.01). The mean CRT and the mean number of injections did not differ between the six-month pre- and post-surgical periods. Conclusions: We showed the beneficial effect of phacoemulsification in nAMD patients treated with anti-VEGF agents on visual outcomes in the short and long term. Cataract surgery in nAMD eyes treated with anti-VEGF injections does not increase the frequency of anti-VEGF injections and does not cause deterioration of the macular status. Full article

Background/Aims: To investigate the effectiveness of an accelerated high-fluence peripheral crosslinking (pCXL) treatment protocol for corneal neovascularization (cNV) and the viability of optical coherence tomography angiography (OCTA) to monitor cNV dynamics. Methods: This pilot study included six eyes of six adult patients with cNV in at least one corneal quadrant who were treated with pCXL (7.2 J/cm², 9 mW). The degree of cNV regression was monitored with slit lamp photography and anterior segment OCTA. The main outcome measure was total vessel area one and four weeks after treatment. Results: OCTA allowed for the objective monitoring of vascular metrics: The total vessel area declined from an average of 1025.4 mm² (min: 0.13 mm²; max: 3637 mm²) at the baseline evaluation to 382.4 mm² (min: 0.08 mm²; max: 1528 mm²) (p = 0.096). The total vessel length lessened from an average of 107.1 mm (min: 2.8 mm; max: 321.1 mm) to 47 mm (min: 2.6 mm; max: 156.5 mm) (p= 0.27). The average number of junctions at baseline decreased from 46.67 (min: 3; max: 166) to 26.5 (min: 0; max: 50) (p = 0.23). The junction density decreased from an average of 10.75/mm² (min: 0.0002 /mm²; max: 36.5056/mm²) to 7.37/mm² (avg.) (min: 0; max 18.7356/mm²) (p = 0.24). PCXL was performed safely without adverse effects, but vascular occlusion was not complete in all eyes. Conclusions: High-fluence pCXL may represent a valuable treatment option to achieve cNV regression, whilst the optimal fluence dose still remains to be defined. Anterior segment OCTA is an innovative tool for non-invasive, objective, and quantitative cNV monitoring. Full article

Background/Objectives: To approach the clinical properties of pachydrusen that differ from conventional drusen, we investigated the incidence of macular neovascularization (MNV) in fellow eyes and the treatment outcomes of intravitreal aflibercept (IVA) in MNV eyes of unilateral MNV patients with pachydrusen in the fellow eye. Methods: We retrospectively studied 261 consecutive patients with treatment-naïve unilateral MNV. Patients were classified into four groups according to the type of drusen in the fellow eye: the pachydrusen group (n = 49), the soft drusen group (n = 63), the subretinal drusenoid deposit (SDD) group (n = 24), and the no drusen group (n = 125). The development of the MNV in the fellow eye was evaluated for five years, and the retreatment proportion after three monthly aflibercept injections was evaluated for one year. Results: The choroidal thickness in the fellow eyes and MNV eyes was the greatest in the pachydrusen group (all p < 0.001). The 5-year incidence of MNV in the pachydrusen group was similar to that in the soft drusen group and no drusen group. The pachydrusen group had a lower retreatment rate than the other groups did (pachydrusen group: 46.4%; soft drusen group: 78.1%; SDDs: 87.5%; no drusen group: 83.3%). Conclusions: Unilateral MNV patients with pachydrusen in the fellow eye had a lower retreatment rate (46.4%/1 year); therefore, aflibercept monotherapy using the PRN regimen is one of the preferred treatment methods for MNV patients with pachydrusen in the fellow eye. Full article

Osteoarthritis (OA) of the knee is a prevalent cause of chronic pain and disability, particularly affecting women. While traditionally attributed to chronic wear and tear, recent evidence highlights multifactorial pathogenesis involving low-grade inflammation and neoangiogenesis. Current therapeutic options include physical therapy, pharmacotherapy, and total knee arthroplasty (TKA). However, a subset of patients remain symptomatic despite conservative measures, necessitating the development of minimally invasive interventions. Genicular artery embolization (GAE) emerges as a promising option, targeting neovascularization and inflammatory processes in OA. This paper reviews the pathophysiological basis, patient selection criteria, procedural details, and outcomes of GAE. Notably, GAE demonstrates efficacy in relieving knee pain and improving function in patients refractory to conventional therapy. While further research is warranted to elucidate its long-term outcomes and compare it with existing modalities, GAE represents a novel approach in the management of symptomatic knee OA, potentially delaying or obviating the need for surgical intervention. Here, we synthesize the relevant literature, technical details of the procedure, and future perspectives. Moreover, the success of GAE prompts the exploration of transarterial embolization in other musculoskeletal conditions, underscoring the evolving role of interventional radiology in personalized pain management strategies. Full article