Search Results (208)

Objectives: The aim of this study was to analyze the association between cardiovascular risk factors such as glycated hemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL-C), hypertension, overweight, and smoking and longitudinal anatomical and functional changes in diabetic macular edema (DME) during intravitreal therapy. Materials and Methods: This is a retrospective, observational, descriptive study conducted on a sample of 318 patients with DME associated with some degree of diabetic retinopathy (DR). They were treated with aflibercept, ranibizumab, and/or dexamethasone, assessing anatomical and functional outcomes through visual acuity, retinal thickness, and macular volume. Simultaneously, serum HbA1c and LDL-C levels, blood pressure, body mass index (BMI) and tobacco use were measured at baseline, 6, and 12 months to determine their association with treatment response using linear mixed models. Results: Of the variables analyzed in this study, HbA1c and degree of retinopathy were significantly associated with greater retinal thickness over time. Likewise, we found that, compared with aflibercept, dexamethasone intravitreal treatment was associated with greater retinal thickness over time. Concerning visual acuity, we found an inverse relationship with age, tobacco use and degree of retinopathy. Associations between outcomes and the initial intravitreal agent were observed; however, these findings should be interpreted cautiously. Conclusions: This study was consistent with previous research suggesting an association between glycemic control and DME response and progression. It also highlighted the importance of degree of retinopathy and intravitreal treatment in diabetic macular edema progression. Treatment-related findings represent exploratory associations and should not be interpreted as evidence of comparative effectiveness. Full article

This pharmacovigilance study drew upon the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS) database to compare the reporting patterns of ocular and systemic adverse events (AEs) for the 2 mg (standard-dose [SD]) and 8 mg (high-dose [HD]) formulations of aflibercept given for any ocular indication. Disproportionality analysis, including reporting odds ratios (ROR), was used to compare each dose individually to the background reporting rate for the AE. Statistical significance of the RORs was evaluated using Bonferroni correction, alongside signal detection based on Evans criteria, and Bayesian information components. The Breslow–Day test was used to conduct a head-to-head comparison of RORs between each dose. We identified 953 SD and 314 HD AE reports within the 750-day period after the approval of HD by the U.S. Food and Drug Administration (FDA; 8/18/2023). Compared to SD, HD had a higher ROR for endophthalmitis (HD: ROR 767.56 [95% CI, 466.11–1263.95]; SD: ROR 331.64 [95% CI, 216.71–507.51]), eye inflammation (HD: ROR 118.45 [95% CI, 55.85–251.20]; SD: 43.98 [95% CI, 21.87–88.44]), retinal vasculitis (HD: ROR 769.87 [95% CI, 337.13–1758.04]; SD: ROR 124.80 [95% CI, 39.67–392.63]), and systemic vasculitis (HD: ROR 28.40 [95% CI, 14.63–55.14]; SD: ROR 4.05 [1.52–10.82]). These results, based on FAERS, indicate associations rather than causal relationships. Further studies are needed to quantify the absolute risks and elucidate the mechanisms underlying differences in safety signals, if any. Full article

Neovascular age-related macular degeneration (nAMD) remains a major cause of visual morbidity worldwide, although its contribution to blindness in developed healthcare systems has declined in the era of anti-VEGF therapy. Although randomized clinical trials have consistently demonstrated meaningful visual gains under structured retreatment protocols, real-world outcomes frequently decline over time due to undertreatment, limited durability, and persistent disease activity. Recent therapeutic advances have shifted the focus from maximizing short-term efficacy to engineering sustained disease control. Faricimab, a bispecific antibody targeting both VEGF-A and angiopoietin-2, introduces dual-pathway vascular modulation, while high-dose aflibercept (8 mg) enhances VEGF suppression through pharmacokinetic intensification. This perspective critically examines the biological rationale, clinical evidence, real-world implications, and strategic positioning of these agents, proposing a durability-centered framework for next-generation management of nAMD. Full article

Background/Objectives: The PHOTON trial established the efficacy of aflibercept 8 mg using fixed-interval dosing in treatment-naïve patients; however, real-world evidence regarding pro re nata (PRN) regimens in switch cases remains limited. This pilot study evaluated the short-term efficacy and safety of switching to aflibercept 8 mg with PRN dosing in eyes with DME. Methods: This retrospective study included 20 eyes from 12 patients with DME who switched to aflibercept 8 mg and were followed for 6 months. Patients received initial induction doses (1–3 injections based on predetermined anatomical and functional criteria) followed by PRN dosing based on clinical findings. Primary outcomes were changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Treatment intervals and injection frequency were also analyzed. Results: Mean logMAR BCVA was maintained from baseline (0.242 ± 0.252) throughout the follow-up period: 0.164 ± 0.218 at 1 month, 0.138 ± 0.241 at 2 months, 0.145 ± 0.204 at 3 months, 0.143 ± 0.181 at 4 months, 0.149 ± 0.166 at 5 months, and 0.180 ± 0.224 at 6 months. No statistically significant changes in BCVA from baseline were observed at any time point. Mean CRT decreased from baseline (369.6 ± 138.3 μm) at all follow-up time points: 251.5 ± 82.1 μm at 1 month, 269.1 ± 104.5 μm at 2 months, 255.8 ± 67.8 μm at 3 months, 275.2 ± 76.6 μm at 4 months, 301.4 ± 81.2 μm at 5 months, and 302.7 ± 86.8 μm at 6 months. Statistically significant reductions in CRT were observed at 1 through 4 months (1 month: p = 0.000010; 2 months: p = 0.000243; 3 months: p = 0.000035; 4 months: p = 0.000597), whereas the reductions at 5 months (p = 0.0317) and 6 months (p = 0.0424) were not statistically significant. The mean number of injections over 6 months was 1.45 ± 1.05 (median 1; range 1–4), with 70% of eyes achieving treatment intervals ≥ 4 months. Five eyes (25%) required only the switching dose with no additional treatment during follow-up. No intraocular inflammation or retinal vasculitis was observed. Conclusions: Switching to aflibercept 8 mg with PRN dosing provided sustained anatomical improvement and maintained visual acuity in DME, with one quarter of the cases maintaining these outcomes with only a single additional injection. These real-world findings from a pilot study suggest that the PRN approach appears feasible and effective in real-world practice, offering a practical treatment option that may help reduce treatment burden while maintaining disease control. Full article

To investigate whether pretreatment serum endocan, platelet-derived growth factor (PDGF)-CC, and -DD levels are elevated in metastatic colorectal cancer (mCRC) patients compared to healthy controls, and to assess their independent associations with chemotherapy response and survival, along with their comparative predictive performance. Adult patients with mCRC receiving systemic chemotherapy combined with an anti-angiogenic agent (bevacizumab or aflibercept) were prospectively enrolled, along with healthy controls. Pretreatment serum samples were collected prior to therapy initiation. Endocan, PDGF-CC, and PDGF-DD levels were measured in duplicate using enzyme-linked immunosorbent assay. Treatment response was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and categorized as responders (complete or partial response) and non-responders (stable or progressive disease). Progression-free survival (PFS) and overall survival (OS) were recorded. Median serum levels of endocan (405.5 vs. 269.0 pg/mL), PDGF-DD (499.9 vs. 315.1 pg/mL), and PDGF-CC (2330 vs. 1118 pg/mL) were significantly higher in the mCRC group compared to controls (p < 0.001). In multivariable logistic regression, all three biomarkers were independently associated with non-response to chemotherapy [Odds ratio (ORs): 1.10 for endocan, 1.05 for PDGF-DD, 1.05 for PDGF-CC; all p < 0.05]. For disease progression, Cox regression showed that higher levels of endocan [Hazard ratio (HR) = 1.04], PDGF-DD (HR = 1.03), and PDGF-CC (HR = 1.04) were significant predictors (all p < 0.01). Similar associations were observed for overall mortality (HR = 1.04, 1.02, and 1.02, respectively; all p < 0.05). Endocan, PDGF-DD, and PDGF-CC are elevated in mCRC and independently predict poor treatment response and adverse survival outcomes, highlighting their potential as prognostic biomarkers. Full article

Background: Aflibercept is one of the anti-VEGF drugs used, among others, for the treatment of retinopathy of prematurity, alongside the widely used bevacizuab and ranibizumab. It is a recombinant fusion protein composed of the human VEGFR-1 and VEGFR-2 domains combined with the Fc part of human IgG, called VEGF-TRAP. The paper describes a group of premature infants treated with aflibercept due to retinopathy of prematurity at the Regional Specialized Children’s Hospital in Olsztyn, Poland, in the years 2017–2019. Methods: Eleven children (22 eyes) with extremely low birth weight and type 1 ROP and A-ROP qualified for treatment. The birth weight of the children was 460–940 g (average 677 g). Children were treated between 32 and 38 weeks of postconceptional age (on average in 33.3 week). We administered 1 mg (0.025 mL) of aflibercept intravitreal to each eye under local anesthesia. Results: In all cases, the retinopathy regressed. Between 2 and 7 weeks after treatment, the disease reactivated in five children (45%) in the form of ROP type 2, and these children underwent retinal laser photocoagulation. One child had a complication in the form of a cataract in one eye, while the remaining children had no complications after the injection and laser therapy. In all children, there was complete regression of ROP, and retinal vascularization was observed up to the end of zone III or up to the border of laser therapy. A child with cataract underwent lensectomy. All children are under the care of our center, and were examined ophthalmologically and strabologically; the results of these tests will be presented in a separate study. Conclusions: Aflibercept differs from other anti-VEGF drugs in its point of action and pharmacodynamics of action. In the literature, its effectiveness is estimated at over 80%, but there are also studies in which the reactivation of ROP after treatment reaches over 40%. In this study, the treated children were characterized by extremely low birth weight and, as a result, numerous complications related to prematurity occurred, such as bronchopulmonary dysplasia, sepsis, anemia, heart defects, and others. Many of them were in the intensive care unit. These factors may influence ROP reactivation and complications. The description compares studies in which aflibercept was administered at the same dose—1 mg. Currently, large studies (e.g., Firefleye and Butterfleye) describe the effects of a new aflibercept therapy at a dose of 0.4 mg. Studies on aflibercept obviously require further observations, so all reports, even from small groups, are important. Full article

Background/Objectives: Diabetic macular edema (DME) are major causes of visual impairment worldwide, with vascular endothelial growth factor (VEGF) playing a central role in disease pathogenesis. Intravitreal anti-VEGF therapy is the current standard of care for center-involving DME. Methods: This narrative review summarizes and compares the pharmacological properties, clinical efficacy, safety, and real-world performance of aflibercept and brolucizumab in the treatment of DME, based on randomized controlled trials and observational studies published between 2014 and 2025. Results: Both agents demonstrate significant improvements in visual acuity and retinal anatomy. Brolucizumab has shown non-inferior visual outcomes and, in several studies, greater reductions in central retinal thickness with the potential for extended dosing intervals, suggesting reduced treatment burden. However, post-marketing data have identified an increased risk of intraocular inflammation, including retinal vasculitis and retinal vascular occlusion, associated with brolucizumab, which has influenced its clinical use. Conclusions: Both aflibercept and brolucizumab are effective anti-VEGF therapies for diabetic macular edema, but they differ in durability and safety considerations. Aflibercept remains a reliable first-line option for many patients, while brolucizumab may be considered in carefully selected cases where treatment burden is a priority. Individualized treatment selection based on clinical characteristics, patient preferences, and safety considerations is essential for optimizing long-term outcomes. Full article

Background/Objectives: The influence of the vitreoretinal interface on neovascular age-related macular degeneration (nAMD) remains poorly characterized. Most previous studies relied solely on macular optical coherence tomography (OCT), which provides limited information about global posterior vitreous detachment (PVD). This study evaluated (1) whether ultrasonography-defined PVD status differs between nAMD eyes and healthy controls, and (2) whether baseline PVD influences macular neovascularization (MNV) phenotype and functional outcomes following anti-vascular endothelial growth factor (anti-VEGF) therapy. Methods: In this prospective longitudinal study, treatment-naïve nAMD eyes and population-based healthy controls underwent dynamic B-scan ultrasonography and spectral-domain OCT. PVD was categorized as absent, partial, or complete. nAMD eyes received intravitreal aflibercept according to a treat-and-extend protocol and were followed for 12 months. Structural parameters—including subretinal fluid (SRF), intraretinal fluid (IRF), and central foveal thickness—along with best-corrected visual acuity (BCVA) were recorded. A multivariable linear regression model was performed to assess whether PVD independently predicted BCVA gain after adjusting for age, baseline BCVA, MNV subtype, SRF, atrophy, and number of injections. Results: Absence of PVD was significantly more frequent in nAMD eyes than in controls (p < 0.001), whereas complete PVD prevalence was comparable. In nAMD, absence of PVD was associated with a higher prevalence of MNV type 2 (p = 0.032), while partial/complete PVD correlated with type 1 lesions. After 12 months, eyes without PVD achieved the greatest visual improvement (mean BCVA gain +0.34 ± 0.26), outperforming eyes with complete PVD (p = 0.026). A multivariable model confirmed that absence of PVD was an independent predictor of greater BCVA gain (β = −0.27; 95% CI −0.42 to −0.12; p = 0.0008). Eyes with complete PVD required more injections (p = 0.046). SRF and foveal-thickness reductions occurred across groups, whereas IRF changes were similar. Conclusions: Ultrasonography-defined PVD status differs markedly between nAMD and healthy eyes and independently influences neovascular phenotype and functional response to anti-VEGF therapy. These findings underscore the physiological importance of the vitreoretinal interface and support the use of ocular ultrasonography as an adjunct tool for assessing global vitreous status in selected nAMD settings. Full article

Purpose: We aimed to present the clinical outcomes of a combined pharmacological and gas-assisted treatment for sub-macular haemorrhage secondary to neovascular age-related macular degeneration (nAMD). Methods: This retrospective case series included ten eyes with sub-macular haemorrhage (SMH) treated between January 2024 and September 2025. All patients received intravitreal alteplase (100 µg) and C₃F₈ gas, followed by aflibercept (2 mg or 8 mg) within a treat-and-extend regimen. BCVA- and OCT-based anatomical changes were recorded at baseline, 7–14 days, 1 month, 3 months, and 6 months. BCVA changes were analysed using repeated-measures testing. Results: Mean BCVA improved from 0.99 ± 0.21 logMAR at baseline to 0.89 ± 0.20 at 7–14 days, 0.80 ± 0.20 at 1 month, 0.60 ± 0.18 at 3 months, and 0.53 ± 0.20 at 6 months (p < 0.05 for overall change). Eight eyes (80 percent) showed restoration of foveal contour, while two developed foveal atrophy. No major adverse events occurred. Conclusion: Combined intravitreal alteplase and C₃F₈, followed by aflibercept, may provide favourable short-term visual and anatomical improvement in SMH secondary to nAMD. Early intervention appears beneficial, but larger controlled studies are needed to confirm these findings. Full article

Background/Objectives: Different disease subtypes in neovascular age-related macular degeneration (nAMD) influence treatment burden, yet existing classifications such as the pachychoroid neovasculopathy (PNV)/non-PNV dichotomy may not fully capture clinical heterogeneity. This study aimed to compare the 12-month outcomes of intravitreal aflibercept (IVA) in treatment-naïve patients with unilateral nAMD stratified by the presence or absence of drusen and punctate hyperfluorescence (PH). Methods: This retrospective study included 130 eyes of 130 patients categorized into the Drusen−/PH−, Drusen+/PH−, Drusen−/PH+, and Drusen+/PH+ groups. Their best-corrected visual acuity, retinal thickness, choroidal thickness, number of injections, no-retinal fluid rate during the loading dose regimen, and 12-month retreatment rate following treatment initiation were determined. The primary outcome was 12-month retreatment rate for the four groups, which was determined using Kaplan–Meier curves and log-rank tests. Exploratory metric multidimensional scaling (MDS) was used to visualize the baseline profiles. Results: The 12-month retreatment rates of the groups were significantly different. The Drusen+/PH− group had a higher retreatment rate and required more injections than the Drusen−/PH+ and Drusen+/PH+ groups. The Drusen+/PH− group was older than the Drusen−/PH+ and Drusen−/PH− groups. The Drusen−/PH+ group had a thicker choroid than the Drusen+/PH− group. The MDS results clear separation of the groups, consistent with the older age of the Drusen+/PH− group and the thicker choroid of the Drusen−/PH+ group. Conclusions: nAMD stratified based on drusen and PH differed in age, choroidal thickness, and IVA outcomes. The four-category framework provides greater pathophysiologic and therapeutic resolution than the simple PNV/non-PNV dichotomy and may help anticipate injection demand to guide individualized dosing strategies. Full article

Background and Clinical Significance: To report a case of bilateral sterile intraocular inflammation following intravitreal aflibercept 8 mg (Eylea HD) injections. Case Presentation: An 89-year-old woman with bilateral neovascular age-related macular degeneration (nAMD) developed blurred vision and mild ocular pain in both eyes four days after receiving aflibercept 8 mg injections in both of her eyes. Examination revealed a marked anterior chamber reaction with Descemet’s folds, 2+ vitreous cells, and 3+ vitreous haze bilaterally. Intraocular pressures were normal, and B-scan ultrasonography confirmed attached retinas with bilateral vitreous opacities. The clinical presentation initially raised concern for infectious endophthalmitis; however, the bilateral presentation, quiet conjunctivae, and prior history of sterile inflammation after aflibercept 2 mg supported a diagnosis of sterile intraocular inflammation. The patient was hospitalized and treated with intensive topical corticosteroids, antibiotics, and cycloplegics, resulting in rapid improvement and complete resolution of symptoms within four days with recovery of baseline vision. Conclusions: Intravitreal aflibercept 8 mg can be associated with bilateral sterile intraocular inflammation, even in patients who previously tolerated standard-dose aflibercept. Awareness of this potential adverse event is essential to avoid unnecessary interventions and to guide appropriate management. Full article

Purpose: The aim was to compare the short-term outcomes of aflibercept 8 mg and brolucizumab for the treatment of polypoidal choroidal vasculopathy (PCV). Methods: This study included 48 eyes of 48 patients with PCV. Drug selection was based on the treatment period. Sixteen eyes received aflibercept 8 mg and thirty-two eyes received brolucizumab. All eyes underwent three consecutive monthly injections: aflibercept (114.3 mg/mL; 0.07 mL) or brolucizumab (120 mg/mL; 0.05 mL). Indocyanine green angiography was performed at baseline and at the 3-month visit to confirm the presence of polypoidal lesions. Results: In the aflibercept 8 mg group, best-corrected visual acuity (BCVA) significantly improved from 0.28 ± 0.26 at baseline to 0.18 ± 0.25 at the 3-month visit (p < 0.001). In the brolucizumab 6 mg group, BCVA improved from 0.35 ± 0.26 to 0.29 ± 0.27, although the change was not statistically significant (p = 0.08). Multivariate regression analysis showed that better BCVA at 3 months was associated with better baseline BCVA and lower central retinal thickness (CRT), independent of the drug used. CRT decreased from 382 ± 157 to 198 ± 98 in the brolucizumab 6 mg group and from 358 ± 152 to 192 ± 76 in the aflibercept 8 mg group at 3 months. Subfoveal choroidal thickness (SCT) decreased from 201 ± 78 to 167 ± 60 in the brolucizumab 6 mg group and from 186 ± 76 to 153 ± 67 in the aflibercept 8 mg group. The dry macula rate at 3 months was the same for aflibercept 8 mg and brolucizumab 6 mg at 93.8%. Complete regression of polypoidal lesions was observed in 62.5% and 75.0% of patients in the aflibercept and brolucizumab groups, respectively (p = 0.57). Conclusions: During the induction phase, aflibercept 8 mg demonstrated comparable outcomes to brolucizumab 6 mg in reducing CRT and SCT, achieving a dry macula, improving BCVA, and regressing polypoidal lesions in eyes with PCV. Full article

To address the shortcomings of existing anti-VEGF monotherapy in neovascular age-related macular degeneration (nAMD), we investigated the therapeutic capabilities of exosomes obtained from human induced pluripotent stem cell (hiPSC)-derived retinal organoids in a mouse model of laser-induced choroidal neovascularization (CNV). To evaluate Retinal Organoid-derived exosome (RO-Exo) distribution after intravitreal (IVT) injection, calcein-labeled RO-Exo was observed using confocal microscopy. CNV was induced in C57BL/6 J mice by laser photocoagulation. RO-Exo was isolated from retinal organoids (differentiation days 55–65) and injected 5 days post-laser. Therapeutic efficacy was evaluated on day 12. Vascular leakage and CNV size were assessed by angiography and CD31 immunostaining. We also examined HIF-1α/VEGF-A expression (Western blotting), Retinal Pigment Epithelium (RPE) integrity markers (immunofluorescence staining for α-SMA, fibronectin, and ZO-1), and the activation of the Mitogen-Activated Protein Kinase (MAPK) pathway (phospho-ERK, -p38, -JNK) in CNV lesions. After IVT injection, RO-Exo migrated to the RPE layer, showing high retinotropic distribution. In the CNV model, RO-Exo significantly reduced vascular leakage and CNV size, with greater suppression of HIF-1α and VEGFA expression than aflibercept, the standard-of-care anti-VEGF drug. CD31-positive vasculature was decreased, accompanied by downregulation of fibronectin (a fibrotic marker) and restoration of RPE hexagonality and integrity. Furthermore, RO-Exo inhibited the activation of ERK, P38, and JNK in CNV lesions. Our study results demonstrate that RO-Exo exhibits multi-target therapeutic effects—including anti-angiogenic, anti-fibrotic, and neuroprotective actions—offering a promising alternative to conventional anti-VEGF therapy for nAMD. Full article

This study aimed to determine the relative efficacy of bevacizumab gamma (an ophthalmic formulation of bevacizumab) versus alternative interventions relevant to the treatment of neovascular age-related macular degeneration (nAMD) in the United Kingdom (UK) via a systematic literature review (SLR) and network meta-analysis (NMA). An SLR was conducted to identify randomized controlled trials (RCTs) of anti-vascular endothelial growth factor (anti-VEGF) therapies for the treatment of nAMD in adult patients relevant to the UK context. The included anti-VEGF treatments were ranibizumab, aflibercept, faricimab, and bevacizumab gamma. Bayesian NMA models were used to estimate relative efficacy in terms of change from baseline (CFB) in best-corrected visual acuity (BCVA) at 12 months, the proportion of patients gaining 15 or more letters at 12 months, and the proportion of patients losing less than 15 letters at 12 months. Twenty-two relevant RCTs were included in the NMA. At 12 months, all anti-VEGF treatments were similarly efficacious to ranibizumab 0.5 mg every four weeks (Q4W) in terms of CFB in BCVA, the proportion of patients gaining 15 or more letters, and the proportion of patients losing less than 15 letters (except for ranibizumab 0.5 mg every 12 weeks [Q12W] and ranibizumab 0.5 mg pro re nata [PRN]). Bevacizumab gamma provided similar improvements in visual acuity to other anti-VEGF treatments. Full article

Background/Objectives: Currently, treatments for age-related macular degeneration (AMD) consist of regular intravitreal injections that exert significant pressure on healthcare systems via their high labor costs and economic burden. To address this, our study’s goal is to propose new treatment protocols by comparing the efficacy of bimonthly fixed dosing aflibercept injections versus the treat-and-extend (T&E) approach for wet AMD. Secondary objectives included categorical best-corrected visual acuity (BCVA) changes, anatomical outcomes, treatment intervals, and adverse events. Methods: This study is a 1-year randomized, open-label, prospective trial that included 44 eyes from 44 patients, 32 in the T&E arm and 12 in the bimonthly arm. Treatment-naïve AMD patients with neovascularization were randomized to a bimonthly fixed dosing group or a T&E group after receiving 3 consecutive monthly aflibercept injections. Following the induction doses, retreatment intervals for patients in the T&E arm were adjusted based on a predetermined algorithm. Results: Over 12 months, mean BCVA improvements were 5.0 letters in the bimonthly group and 4.1 in the T&E group (p = 0.096 for non-inferiority test). On average, T&E patients received 9.6 injections compared to 7.7 for those in the fixed dosing group (p < 0.001). Anatomical outcomes were comparable in both treatment arms. Conclusions: In our trial, the T&E approach provided significant visual improvements, but did not meet the threshold for non-inferiority when compared to fixed bimonthly dosing. It was also unable to minimize treatment burden over the course of the first year of injections. Further research is required to optimize the T&E algorithm with aflibercept. Full article