Search Results (685)

Background/Objectives: This study was conducted to analyze the associations between vascular endothelial growth factor (VEGF) serum concentrations and immunological biomarkers, inflammatory parameters, classical atherosclerosis risk factors, and cardiovascular manifestations in systemic lupus erythematosus (SLE) patients. Methods: The project included 83 individuals suffering from SLE, with 20 healthy individuals as controls. The serum levels of VEGF were determined through the ELISA method using R&D Systems tests. Laboratory markers, autoantibody profiles, traditional atherosclerotic risk factors, and organ manifestations were evaluated. Atherosclerotic changes were determined based on several indices including carotid intima-media thickness, ankle-brachial index and high resistance index assessments. Results: The reference range of serum VEGF concentrations was established based on the 25th and 75th percentiles obtained in the controls. High VEGF levels were significantly correlated with the presence of selected anti-phospholipid antibodies such as anti-prothrombin (OR = 10.7; 95%CI: 2.1–53.4) and anti-beta2 glycoprotein I (OR = 3.5; 95%CI: 1.1–10.8), as well as cardiac disorders (OR = 8.0; 95%CI: 1.6–39.5). On the other hand, low concentrations of VEGF were significantly related to lower frequencies of anti-double-stranded DNA antibodies (OR = 0.31; 95%CI: 0.11–0.91) and anti-endothelial cell antibodies (OR = 0.30; 95%CI: 0.11–0.85). Patients with low VEGF levels showed significantly reduced risks of atherosclerotic lesions (OR = 0.24; 95%CI: 0.04–0.99) and vasculitis development (OR = 0.17; 95%CI = 0.03–0.91). Conclusions: In conclusion, VEGF’s pathogenetic role in SLE and SLE-related atherothrombosis is manifested in close correlation with aPLs which may enhance their direct impact on endothelium. High VEGF levels are helpful for identifying cardiovascular risk in patients, while low concentrations indicate lower disease activity, as well as a lower risk of organ involvement. Full article

Retinal ischemia is implicated in ocular diseases involving aberrant neovessel proliferation that characterizes proliferative retinopathies. Their therapy still remains confined to the intravitreal administration of anti-vascular endothelial growth factor (VEGF) medication, which is limited by side effects and progressive reduction in efficacy. Mimicking neovascular diseases in rodents, although of great help for translating fundamental mechanistic findings and assessing therapeutic potential in humans, is limited by the rodent’s short life span, which prevents retinal vessel proliferation over time. However, the oxygen-induced retinopathy (OIR) model, which mimics retinopathy of prematurity, seems to meet some criteria that are common to proliferative retinopathies. The present review provides insight into preclinical models and their suitability to mimic proliferative retinopathies. Further considerations will be applied to emerging approaches and advanced methodologies for the management of proliferative retinopathies, leading to the identification of new therapeutic targets, including our contribution in the field. Major emphasis is given to the possibility of using systemic therapies either alone or in combination with intravitreal anti-VEGF administration to maximize clinical benefits by combining drugs with different modes of action. This review is concluded by an in-depth discussion on future advancements and a critical view of preclinical finding translatability. Despite the major effort of preclinical and clinical research to develop novel therapies, the blockade of VEGF activity still remains the only treatment for proliferative retinopathies for more than twenty years since its first therapeutic application. Full article

Tissue hypoxia is commonly observed in head cancers and contributes to both molecular and functional changes in tumour cells. It is known to stimulate erythropoiesis, angiogenesis, and metabolic alterations within tumour cells. Glioblastoma, a type of brain tumour, is characterized by rapid proliferation and aggressive growth. Recent studies have indicated that natural products may hold potential as components of cancer therapy. Among these, Polish propolis and its active compound, quercetin, have demonstrated promising anti-cancer properties. The aim of this study was to evaluate the concentrations of selected cytokines—specifically IL-6, IL-9, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF-BB), interferon gamma-induced protein 10 (IP-10), and monocyte chemoattractant protein-1 (MCP-1)—produced by astrocytes of the CCF-STTG1 cell line. The cytotoxic effects of ethanolic extract of propolis (EEP) and quercetin were assessed using the MTT assay. Astrocytes were stimulated with lipopolysaccharide (LPS, 200 ng/mL) and/or IFN-α (100 U/mL), followed by treatment with EEP or quercetin (25–50 µg/mL) under hypoxic conditions for two hours. Cytokine concentrations were measured using the xMAP Luminex Multiplex Immunoassay and the Multiplex Bead-Based Cytokine Kit. Our study demonstrated that Polish propolis and its component quercetin modulate the tumour microenvironment in vitro, primarily by altering the levels of specific cytokines. The HCA analysis revealed that IL-6 and MCP-1 formed a distinct cluster at the highest linkage distance (approximately 100% of Dmax), suggesting that their expression patterns are significantly different from those of the other cytokines and that they are more similar to each other than to the rest. PCA analysis showed that EEP-PL (50 μg/mL) with IFN-α and EEP-PL (50 μg/mL) with LPS exert similar activities on cytokine secretion by astrocytes. Similar effects were demonstrated for EEP-PL 50 μg/mL + LPS + IFN-α, EEP-PL 25 μg/mL + IFN-α and EEP-PL 25 μg/mL + LPS + IFN-α. Our findings suggest that Polish propolis and quercetin may serve as promising natural agents to support the treatment of stage IV malignant astrocytoma. Nonetheless, further research is needed to confirm these results. Full article

Diabetic retinopathy (DR), a leading cause of blindness in working-age adults, arises from chronic hyperglycemia-induced oxidative stress, inflammation, and vascular dysfunction. Current therapies such as laser photocoagulation, intravitreal anti-vascular endothelial growth factor (VEGF) agents, and steroids target advanced stages but fail to prevent early neuronal and microvascular damage. Emerging evidence highlights oxidative stress as a key driver of DR pathogenesis, disrupting the blood-retinal barrier (BRB), promoting neurodegeneration and angiogenesis. Advances in imaging, particularly optical coherence tomography angiography (OCTA), enable earlier detection of neurodegeneration and microvascular changes, underscoring DR as a neurovascular disorder. Polyphenols, such as resveratrol, curcumin, and pterostilbene, exhibit multitarget antioxidant, anti-inflammatory, and anti-angiogenic effects, showing promise in preclinical and limited clinical studies. However, their low bioavailability limits therapeutic efficacy. Nanotechnology-based delivery systems enhance drug stability, tissue targeting, and sustained release, offering potential for early intervention. Future strategies should integrate antioxidant therapies and precision diagnostics to prevent early irreversible retinal damage in diabetic patients. Full article

Rosacea is a chronic inflammatory skin condition characterized by persistent erythema and abnormal vascular response. Although current treatments focus on symptomatic relief, they often provide only temporary improvement and may be associated with side effects or recurrence. Cannabigerol (CBG), a non-psychoactive cannabinoid, has recently garnered attention for its pharmacological activities, including anti-inflammatory, antioxidant, neuroprotective, and skin barrier–supportive effects. However, its role in modulating pathological responses in rosacea remains unclear. In this study, we investigated the therapeutic potential of topically applied CBG in an LL-37-induced rosacea-like mouse model. Clinical and histological assessments revealed that CBG markedly reduced erythema, epidermal hyperplasia, and mast cell infiltration. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) showed downregulation of Il1b, Il4, Il6, Il13, Il22, Il31, Tlr2, Vegfa, and Mmp9. Immunohistochemistry and Western blot analyses further demonstrated suppression of CD31, vascular endothelial growth factor (VEGF), and Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), along with reduced activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, including decreased levels of JAK1, STAT3, and phosphorylated STAT3. These findings suggest that topical CBG alleviates rosacea-like skin inflammation by targeting inflammatory and vascular pathways, including JAK/STAT and YAP/TAZ signaling. Full article

This study aims to evaluate the real-world efficacy and safety of aflibercept 8 mg intravitreal injections (IVTs) in pretreated patients with neovascular age-related macular degeneration (nAMD) throughout the first three IVTs. Background: Established anti-vascular-endothelial-growth-factor (anti-VEGF) therapies positively impact the progression of nAMD but require frequent administration, thus burdening patients and the healthcare system. Pivotal trials of the recently approved aflibercept 8 mg have demonstrated extended dosing intervals with comparable safety to standard treatments. However, real-world data is still scarce. Methods: A retrospective, single-center single-arm analysis was conducted on 22 eyes from 18 pretreated nAMD patients. Eyes were switched from other anti-VEGF agents to aflibercept 8 mg injections continuing a treat-and-extend regimen (no loading dose after switching). Treatment intervals and structural (central subfield thickness (CST); disease activity) and functional (best corrected visual acuity (BCVA)) outcomes were assessed at baseline (date of first aflibercept 8 mg injection) and at follow-up examinations until follow-up 3. Safety data, including intraocular pressure changes, were recorded. Results: Over a median follow-up of 16.6 weeks (IQR 15.1–27.0), patients switched to aflibercept 8 mg showed prolonged intervals between injections (5.5 weeks vs. 7 weeks, p < 0.001, Wilcoxon signed-rank test), reduced disease activity, stable CST, and stable BCVA. One patient experienced transient intraocular pressure elevation, which resolved without intervention. No other adverse events were observed. Conclusions: Treatment with aflibercept 8 mg appears to provide effective disease control with prolonged treatment intervals in switched nAMD patients in routine clinical practice. These findings further indicate the potential for reducing treatment burden. Full article

Objectives: This study aimed to assess the initial anatomical and functional outcomes of switching to aflibercept 8 mg in patients with neovascular age-related macular degeneration (nAMD) previously treated with anti-vascular endothelial growth factor (VEGF) therapy. Methods: Patients with nAMD previously treated with anti-VEGF drugs were switched to aflibercept 8 mg. Patients with any exudative changes (subretinal fluid [SRF], intraretinal fluid [IRF] or serous pigment epithelial detachment [sPED]) at the time of the first aflibercept 8 mg injection and whose dosing interval before and after switching did not differ by more than ±7 days were included. Best-corrected visual acuity (BCVA), central foveal thickness (CFT), and the presence of SRF, IRF, and sPED were evaluated before and after switching to aflibercept 8 mg. Results: A total of 102 eyes from 98 patients were included in the analysis. The drugs used prior to switching were faricimab in five eyes, brolucizumab in six eyes, and aflibercept 2 mg in 91 eyes, with a mean interval of 63.7 ± 20.0 days from the last pre-switch injection and 64.9 ± 20.1 days to the first post-switch visit. The CFT was significantly reduced from 272 ± 85 µm to 246 ± 79 µm (p < 0.0001). The BCVA remained unchanged at 0.27 ± 0.35 logMAR. During switching, SRF, IRF, and sPED were observed in 70, 24, and 38 eyes, respectively. At the post-switch visit, complete resolution of exudative changes was observed in 44% of eyes with SRF, 55% with IRF, and 29% with sPED. No ocular or systemic adverse effects were observed. Conclusions: As an initial response to switching to aflibercept 8 mg in a real-world setting, SRF and IRF completely resolved in approximately half of the patients, and sPED resolved in about 30% of cases. Full article

Objectives: To evaluate the immediate and short-term changes in intraocular pressure (IOP) following intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) agents and to identify the clinical and procedural factors associated with IOP elevation after treatment. Methods: This retrospective study included 118 eyes from 115 patients who underwent IVI with anti-VEGF agents at Osaka Metropolitan University Hospital between September 2024 and January 2025. IOP was measured at three time points, namely before injection, within 1 min after injection, and at 30 min, in selected eyes with a post-injection IOP ≥ 25 mmHg. Differences in IOP elevation were analyzed according to the disease type and anti-VEGF agent. Univariate and multivariate linear regression analyses were performed to identify clinical factors associated with IOP elevation. Results: Mean IOP significantly increased from 13.9 ± 3.3 mmHg at baseline to 39.2 ± 12.4 mmHg immediately after injection (p < 0.001), with 79.7% of eyes showing an IOP ≥ 25 mmHg. Among those remeasured, IOP decreased to 17.7 ± 6.5 mmHg at 30 min. Significant differences in IOP elevation were observed among anti-VEGF agents (p < 0.001), with aflibercept at 2 mg and 8 mg showing greater increases than other agents. Multivariate analysis identified higher baseline IOP, history of glaucoma, absence of prior vitrectomy, and use of aflibercept (2 mg or 8 mg) as significant risk factors for greater post-injection IOP elevation. Conclusions: Transient IOP elevation ≥ 25 mmHg was observed in the majority of eyes after IVI but typically resolved within 30 min. Aflibercept use, high baseline IOP, glaucoma history, and absence of prior vitrectomy were associated with greater IOP elevation. Careful monitoring and attention to injection volume may be warranted, particularly in high-risk patients. Full article

Repairing and regenerating tissue barriers is a key challenge in regenerative medicine. Stem cells play a crucial role in restoring the structural and functional integrity of key epithelial barrier surfaces, including the skin and mucosa. This review analyzes the role of dental pulp stem cells (DPSCs) and their derivatives, including extracellular vesicles, conditioned medium, and intracellular factors, in accelerating skin wound healing. The key mechanisms include: (1) DPSCs regulating inflammatory microenvironments by promoting anti-inflammatory M2 macrophage polarization; (2) DPSCs activating vascular endothelial growth factor (VEGF) to drive angiogenesis; (3) DPSCs optimizing extracellular matrix (ECM) spatial structure through matrix metalloproteinase/tissue inhibitor of metalloproteinase (MMP/TIMP) balance; and (4) DPSCs enhancing transforming growth factor-β (TGF-β) secretion to accelerate granulation tissue formation. Collectively, these processes promote wound healing. In addition, we explored potential factors that accelerate wound healing in DPSCs, such as oxidative stress, mechanical stimulation, hypertension, electrical stimulation, and organoid modeling. In addition to demonstrating the great potential of DPSCs for skin repair, this review explores their translational prospects in mucosal regenerative medicine. It covers the oral cavity, esophagus, colon, and fallopian tube. Some studies have found that combining DPSCs and their derivatives with drugs can significantly enhance their biological effects. By integrating insights from skin and mucosal models, this review offers novel ideas and strategies for treating chronic wounds, inflammatory bowel disease, and mucosal injuries. It also lays the foundation for connecting basic research results with clinical practice. This represents a significant step forward in tackling these complex medical challenges and lays a solid scientific foundation for developing more targeted and efficient regenerative therapies. Full article

Advanced glycation end-products (AGEs) and oxidative stress are recognized as central contributors to the pathogenesis of age-related or diabetic cataracts, diabetic retinopathy (DR), and age-related macular degeneration (AMD). These glycation-related diseases are characterized by impaired redox balance and decreased glutathione (GSH) levels. This review aims to examine the mechanistic links between AGEs and GSH depletion across ocular tissues by integrating in vitro, ex vivo, in vivo, and clinical studies relevant to this topic. The multiple levels of evidence highlight GSH homeostasis as both a biomarker and therapeutic target in glycation-related ocular disorders. Therapeutic strategies aimed at restoring GSH homeostasis under glycation stress are categorized into four mechanistic domains: (I) promoting GSH supply and synthesis, (II) enhancing GSH recycling, (III) mitigating glycation stress, and (IV) reducing oxidative and nitrosative stress. Most of these strategies have been explored via different approaches, and experimental findings with various interventions have shown promise in restoring GSH balance and mitigating AGE-induced damage. A pathological link between GSH depletion and vascular endothelial growth factor (VEGF) overexpression is observed in DR and wet AMD. GSH-centered interventions act upstream to modulate redox homeostasis while anti-VEGF therapies target downstream angiogenesis. This study supports the rationale for a dual-targeting strategy that combines redox-based interventions with VEGF inhibition in glycation-related ocular diseases. Full article

Background/Objectives: To evaluate the potential of Optical Coherence Tomography (OCT) and OCT angiography parameters in predicting treatment requirements and visual outcomes after one year in therapy-naïve eyes with neovascular age-related macular degeneration (nAMD). Methods: A retrospective study of 96 therapy-naïve eyes newly diagnosed with nAMD was carried out. All eyes received baseline OCT and OCTA. Follow-up OCT after initial upload was then carried out, involving three intravitreal injections (IVIs) with anti-Vascular Endothelial Growth Factor (anti-VEGF) at four-week intervals. OCT parameters, including intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelium detachment (PED), and central retinal thickness (CRT), were assessed qualitatively and quantitatively. Macular Neovascularization (MNV) morphology at baseline was described in terms of area, total vessel length, flow density, and fractal dimension. OCT and OCTA parameters were correlated with best corrected visual acuity (BCVA) and number of administered IVIs after 1 year of treatment. Results: Eyes with persistent subretinal fluid (SRF) or both intraretinal fluid (IRF) and SRF after upload showed a significantly higher need for IVIs (p < 0.01). Also, pigment epithelium detachment (PED) presence at baseline (p < 0.05), PED height at baseline (p < 0.01), PED presence after upload (p < 0.01), and PED height after upload (p < 0.01) were each correlated with a greater number of IVIs. Decrease in PED height during upload was accompanied by a lower number of IVIs (p < 0.01). All the aforementioned parameters had no influence on BCVA after 1 year (p > 0.05). Baseline central retinal thickness (CRT) was linked to worse BCVA at 12 months (p < 0.05), but not the number of IVIs. Follow-up CRT correlated with worse BCVA (p < 0.01) and more IVIs (p < 0.01), while CRT decrease was associated with better BCVA (p < 0.05) and fewer IVIs (p < 0.01) at 1 year. In OCTA, area and total vessel length of MNVs were correlated with BCVA after 1 year (p < 0.01) but had no influence on number of IVIs (p > 0.05). Flow density had no influence on either outcome parameter (p > 0.05). Fractal dimension was associated with BCVA (p < 0.01) and number of IVIs (p < 0.05) after 1 year. Conclusions: MNV area, vessel length, and fractal dimension in OCTA, along with fluid distribution in OCT at baseline and after follow-up, may serve as indicators of treatment needs and visual outcomes after one year. Further studies with longer observation periods and the use of deep learning models are needed to improve analyses and to verify the applicability of these findings to clinical practice. Full article

Background: Colorectal cancer (CRC) is a significant global health burden, with liver metastases representing a key prognostic factor. Neoadjuvant chemotherapy (NAC) has improved outcomes in metastatic CRC (mCRC), and tumor regression is commonly assessed using the Rubbia–Brandt classification. The Poultsides classification defines ≥40% fibrosis as an independent prognostic factor, particularly in patients treated with cetuximab (45.71%). However, the predictive value of this threshold remains under debate, warranting further investigation. Methods: This study evaluates the extent of fibrosis (≥40%) induced by NAC plus anti-epidermal growth factor receptor (anti-EGFR) therapy vs. NAC plus anti-vascular endothelial growth factor (anti-VEGF) therapy in mCRC patients. It also examines the prognostic relevance of the Poultsides and Rubbia–Brandt classifications. A total of 108 patients undergoing liver resection for CRC metastases were included. Statistical analyses were performed using SPSS 28.0 version and R software 4.5 version to compare fibrosis rates and survival outcomes. Results: From September 2005 to January 2023, 108 patients were analyzed: 54 received chemotherapy plus anti-EGFR (Cohort 1), and 54 received chemotherapy plus anti-VEGF (Cohort 2). Fibrosis was significantly higher in Cohort 1 (median 40.0%, IQR: 25.4–53.2) than in Cohort 2 (median 20.6%, IQR: 8.07–36.9), p < 0.001. Overall survival was similar between both cohorts (p = 0.96), with a median follow-up of 41.6 months. Conclusions: Anti-EGFR therapy is associated with greater fibrosis than anti-VEGF, despite similar survival outcomes. The Poultsides classification may be a useful prognostic tool for resected liver metastases in mCRC. Full article

(1) Aim: To evaluate early real-world outcomes of switching to aflibercept 8 mg in eyes with neovascular age-related macular degeneration (nAMD) in the United Kingdom. (2) Methods: This retrospective, observational study included 59 eyes from 50 patients with treatment-refractory nAMD previously treated with multiple anti-vascular endothelial growth factor (anti-VEGF) agents. Eyes were switched to aflibercept 8 mg without loading doses and treated using a treat-and-extend regimen. Functional, anatomical, and safety outcomes were evaluated over a mean (SD) follow-up of 33.5 (10.4) weeks. (3) Results: The mean (SD) age was 80.2 (6.3) years, and 28 (56.0%) of 50 patients were male. At baseline, the mean (SD) best corrected visual acuity (BCVA) was 66.0 (14.4) letters, with 33 (55.9%) eyes achieving ≥70 letters. The mean (SD) baseline central subfield thickness (CST) was 367.2 (100.7) µm. Prior to switching to aflibercept 8 mg, the mean (SD) number of injections for each eye was 26.9 (19.0), with the most recent mean (SD) treatment interval of 7.7 (1.7) weeks. Switching to aflibercept 8 mg resulted in extension of the mean (SD) injection interval from 7.7 (1.7) weeks to 8.7 (2.2) weeks (p < 0.01). BCVA and CST remained stable, with a significant reduction in pigment epithelial detachment (PED) height (232.5 µm to 211.6 µm, p < 0.01). No serious ocular adverse events or intraocular pressure (IOP) elevations requiring treatment were reported. (4) Conclusion: Aflibercept 8 mg demonstrated early treatment durability, anatomical benefit, and a favourable short-term safety profile in eyes with treatment-refractory nAMD. Further prospective studies are warranted. Full article

Background/Objectives: Uncontrolled or long-standing diabetes can lead to proliferative diabetic retinopathy (PDR), a condition that significantly impairs vision. A subset of patients does not respond adequately to conventional therapies, such as intravitreal injections of anti-vascular endothelial growth factor (VEGF) or laser treatment. This study aims to identify potential biomarkers for alternative treatment pathways in the vitreous and blood of patients with severe PDR. Methods: Vitreous samples were collected from PDR patients (n = 3) undergoing vitrectomy for vitreous hemorrhage and from control patients (n = 9) undergoing ocular surgery for epiretinal membrane or macular holes. Blood samples were collected from a separate group of PDR patients (n = 13) and non-diabetic control patients without retinopathy (n = 13). Medical histories were obtained. Two-stage real-time quantitative polymerase chain reaction (qPCR) was used to evaluate mRNA expression levels of genes potentially implicated in PDR, including HIF2A, PAI-1, TIE1, TIE2, ANGPT2, and VEGFA. Molecular and statistical analyses were performed to compare PDR and control vitreous and blood samples. Results: The PDR vitrectomy group included two females and one male, aged 71–77 years (mean 74 years). All participants had undergone pan-retinal photocoagulation and two had received anti-VEGF injections before vitrectomy. These participants had elevated HbA1c levels. Targeted vitreous gene analysis revealed varying levels of increased expression of all genes examined as compared to the control group. A trend for increased median expression was demonstrated for all examined genes: HIF2A by 1.44-fold (PDR = 2.50, control = 1.74, p = 0.21), PAI-1 by 1.56-fold (PDR = 3.00, control = 1.93, p = 0.37), TIE1 by 1.36-fold (PDR = 2.33, control = 1.72, p = 0.66), TIE2 by 2.06-fold (PDR = 2.81, control = 1.36, p = 0.51), ANGPT2 by 2.93-fold (PDR = 6.32, control = 2.16, p = 0.1), and VEGFA by 3.53-fold (PDR = 3.51, control = 0.99, p = 0.08). PDR blood sample analysis as compared to controls showed a trend for increased expression of VEGFA by 1.2-fold (PDR = 0.88, control = 0.74, p = 0.57), whereas the other examined genes showed a trend of reduced expression; HIF2A decreased by 0.50-fold (PDR = 0.38, control = 0.75, p = 0.07), PAI by 0.51-fold (PDR = 0.35, control = 0.69, p = 0.09), TIE-1 by 0.79-fold (PDR = 0.79, control = 1.00, p = 0.54), TIE-2 by 0.70-fold (PDR = 0.58, control = 0.82, p = 0.34), and ANGPT2 by 0.45-fold (PDR = 0.51, control = 1.15, p = 0.11). Conclusions: Vitreous sample analysis revealed a trend of increased mRNA expression of ANGPT2 and VEGFA in patients with PDR. Blood sample analysis did not show a significant increase of VEGFA mRNA expression but a decreased trend of HIF2A, PAI-1, and ANGPT2 mRNA expression. These trends warrant validation in a larger cohort to explore alternative pathways for targeted treatment. Full article

Background: Diabetic macular edema (DME) is the leading cause of vision impairment in diabetic patients, with intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections being the first-line therapy. However, one-third of patients exhibit persistent DME despite treatment, suggesting additional pathogenic factors. This study aimed to evaluate the predictive value of complete blood count (CBC)-based inflammation indexes and optical coherence tomography (OCT) parameters in determining early anti-VEGF treatment effectiveness in DME. Methods: One hundred and four naïve patients with DME, treated with 0.05 mL of intravitreal aflibercept were retrospectively analyzed. Blood parameters analyzed included neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). Baseline OCT biomarkers included subretinal fluid (SRF), intraretinal cysts (IRC), hyperreflective retinal spots (HRS), and disorganization of retinal inner layers (DRIL). Treatment response was defined as a minimum 10% reduction in central macular thickness (CMT) at one month post-injection. Results: NLR, MLR, PLR, and SII were significantly higher in non-responders (p < 0.001), but their predictive value was fair, with an area under the ROC curve ranging between 0.704 (MLR) and 0.788 (SII). A multivariate model including SII, initial CMT, and the presence of IRC showed an excellent prediction value for early anatomical response (AUC ROC of 0.911). At the same time, lower PLR, DRIL, SRF, and the absence of HRF were correlated with early gain in BCVA. Conclusions: CBC-derived inflammation indices and OCT biomarkers have prognostic value in predicting early response to anti-VEGF therapy in DME in terms of functional and anatomical outcomes. These findings could help identify poor responders and guide personalized treatment strategies. Full article