Search Results (91)

Neovascular age-related macular degeneration (nAMD) is a significant cause of vision loss globally, with intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents forming the cornerstone of treatment. Despite advances, the considerable treatment burden associated with frequent injections and the occurrence of suboptimal responses in some patients highlight an ongoing need for more effective and durable therapeutic options. Faricimab, a bispecific antibody that targets both VEGF-A and angiopoietin-2 (Ang-2), has been developed to address these challenges by promoting greater vascular stability and potentially offering extended treatment intervals. This review synthesizes current evidence from pivotal clinical trials (TENAYA/LUCERNE), real-world studies, meta-analyses, and case reports on the efficacy, durability, and safety of intravitreal faricimab for nAMD. Key efficacy outcomes, such as changes in best-corrected visual acuity and anatomical parameters (e.g., central subfield thickness, retinal fluid dynamics, pigment epithelial detachment morphology), are evaluated in both treatment-naïve and previously treated/treatment-resistant nAMD populations. The safety profile, including intraocular inflammation, retinal vasculitis, retinal pigment epithelium tears, and systemic adverse events, is also comprehensively addressed. Faricimab has demonstrated non-inferior visual outcomes compared to aflibercept 2 mg, alongside robust anatomical improvements and a significant potential for reduced treatment frequency, thereby lessening patient and healthcare system burden. While generally well-tolerated, ongoing monitoring for adverse events remains essential. Full article

Age-related macular degeneration (AMD) represents a leading cause of irreversible blindness in the elderly, primarily by choroidal neovascularization (CNV) leakage. While intravitreal injections of anti-angiogenic antibodies (e.g., aflibercept) provide clinical benefits, their short half-life necessitates frequent administrations, potentially causing ocular infections or retinal detachment. There is an urgent need for effective antibody delivery systems. Mesoporous silica nanoparticles (MSN) have emerged as promising nanocarriers due to their tunable porosity, surface modifiability, and biocompatibility, though their application in ophthalmology for antibody delivery remains underexplored. We developed two MSN carries: spiky mesoporous silica nanospheres (S-MSN) without amino groups and amine-functionalized hollow dendritic mesoporous silica nanospheres (A-HDMSN). Characterization revealed that A-HDMSN exhibited superior properties, including a larger surface area (550.32 vs. 257.72 m²/g), larger mesoporous pore size (17 vs. <10 nm), and 5.28 times higher drug loading capacity (286.31 ± 8.14 vs. 54.26 ± 3.61 μg/mg) compared to S-MSN (n = 3, p < 0.001), attributable to pore size effects and hydrogen bonding. FITC-labeled A-HDMSN demonstrated efficient uptake by retinal pigment epithelial cells (ARPE-19). Notably, A-HDMSN loaded with Aflibercept (A-HDMSN@Afl) showed significant inhibitory effect on VEGF-induced cell migration even 10 days after drug release in vitro, indicating a favorable sustained-release effect of the drug. These findings highlight A-HDMSN as a promising antibody delivery platform that could extend clinical dosing intervals, offering potential for improved AMD management. Full article

Background/Objectives: The relative efficacy of 8 mg aflibercept compared to 2 mg in treating neovascular age-related macular degeneration (nAMD) has not been fully established. This study aims to compare the visual and anatomical outcomes of aflibercept 8 mg versus 2 mg in patients with nAMD in both treatment-naïve individuals with no history of anti-VEGF treatment and those previously treated with intravitreal injections. Methods: This retrospective study included 13 eyes treated with aflibercept 8 mg and 14 eyes with aflibercept 2 mg in treatment-naïve patients, along with 15 eyes switched to aflibercept 8 mg previously treated with other intravitreal injections and 15 eyes continued on aflibercept 2 mg in patients. Baseline and one-month post-injection changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT) were assessed. Results: In treatment-naïve patients, the aflibercept 8 mg group showed a significant improvement in BCVA (logMAR 0.19 ± 0.23 to 0.13 ± 0.20, p = 0.0156), while the 2 mg group did not. Both doses reduced CMT significantly, with a greater reduction in the 8 mg group (dCMT 28.60% vs. 24.08%, p = 0.0220). In previously treated patients, no significant changes in BCVA were noted in either group; however, both groups showed significant reductions in CMT. Conclusions: Real-world data demonstrated that aflibercept 8 mg led to substantial improvements in anatomical outcomes one month after injection, irrespective of previous intravitreal injection history. However, significant improvements in visual outcomes were observed exclusively in treatment-naïve patients. Further large-scale, long-term studies are required to determine the proportion of patients who experience improvement and to assess whether these improvements are maintained over time. Full article

Background: In clinical practice, visual outcomes with anti-VEGF therapy may be worse than those observed in clinical trials. In this study, we aim to investigate the long-term outcomes of neovascularization treated with intravitreal aflibercept injections (IAI) in a teaching hospital setting. Methods: This is a retrospective, single-center study including 81 nAMD patients (116 eyes), those both newly diagnosed and switched from ranibizumab. All patients had a follow-up duration of at least seven years. Treatment involved three monthly injections followed by either a pro re nata (PRN) or treat and extend regimen. Follow-up care was primarily conducted by training physicians. The primary endpoint was the change in best-corrected visual acuity (BCVA) over seven years. Secondary endpoints included central retinal thickness changes, qualitative OCT parameters, macular atrophy progression, injection frequency, and treatment adherence. Results: Among the 116 eyes, 52 (44.8%) completed the seven-year follow-up. Visual acuity improved by +2.1 letters in the overall population (+6.3 letters in treatment-naive eyes) after the loading phase but gradually declined, resulting in a loss of −12.3 letters at seven years. BCVA remained stable (a loss of fewer than 15 letters) in 57.7% of eyes. Central retinal thickness (CRT) decreased significantly during follow-up in both naive and switcher eyes. Macular atrophy occurred in 94.2% of eyes, progressing from 1.42 mm² to 8.55 mm² over seven years (p < 0.001). The mean number of injections was 4.1 ± 1.8 during the first year and 3.7 per year thereafter. Advanced age at diagnosis was a risk factor for loss to follow-up, with bilaterality being a protective factor against loss to follow-up (p < 0.05). Conclusions: This study highlights the challenges faced by a retina clinic in a teaching hospital. Suboptimal functional and anatomical outcomes in real life may derive from insufficient patient information and inconsistent monitoring, which contributes to undertreatment and affects long-term visual outcomes. It also raises concerns about supervision in a teaching hospital which needs to be improved. 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: 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

This case report describes a unique ocular finding in a 64-year-old male with a history of central serous chorioretinopathy with choroidal neovascular membrane, treated with intravitreal injections of Aflibercept. The patient was found to have an iatrogenic retro-lenticular non-pigmented cystic formation in the left eye, an anomaly not previously documented in the literature. Comprehensive imaging included ultrasound biomicroscopy and anterior segment optical coherence tomography. This report emphasises a rare ocular finding and the significance of recognising iatrogenic cataracts following intravitreal injections. It also highlights the necessity of individualised patient management and preoperative evaluations to prevent surgical complications. 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

Background: Bacterial endophthalmitis is a rare but serious complication of intravitreal injections (IVIs). Prefilled syringes have been introduced to reduce contamination risk during drug preparation. However, whether they lower the incidence of bacterial endophthalmitis compared to vials remains unclear. Methods: This retrospective cohort study analyzed aflibercept IVIs performed at 17 clinical centers in Japan between 2015 and 2022. Patients aged ≥20 years who received aflibercept IVIs (vial or prefilled syringe) for age-related macular degeneration, diabetic macular edema, retinal vein occlusion, or myopic choroidal neovascularization were included. Bacterial endophthalmitis was diagnosed based on clinical signs (e.g., rapid vision loss, pain, hypopyon, vitreous opacity). Incidence rates were compared using Fisher’s exact test. Results: Among 152,039 injections (43,684 prefilled syringes; 108,355 vials), 12 cases of bacterial endophthalmitis were identified (0.0046% vs. 0.0092%, p = 0.53). Poor visual outcomes were associated with Enterococcus faecalis, Streptococcus spp., and diabetes. Conclusions: Although incidence was lower in the prefilled syringe group, the difference was not statistically significant. Detecting a significant difference requires a larger sample. Further studies are needed to confirm the potential benefits of prefilled syringes in reducing endophthalmitis risk. Full article

Background/Objectives: Macular edema (ME), due to retinal vein occlusion (RVO), is a major cause of vision impairment. Many patients experience suboptimal responses to anti-vascular endothelial growth factor (anti-VEGF) monotherapy, necessitating alternative treatment approaches. Faricimab, a bispecific antibody targeting VEGF-A and angiopoietin-2 (Ang-2), introduces a novel dual-mechanism therapy. This study evaluates the short-term real-world efficacy of switching to Faricimab in patients with treatment-resistant ME secondary to RVO. Methods: This retrospective study included patients from LMU University Hospital who were switched to Faricimab due to an inadequate response or adverse events related to prior intravitreal therapy (Ranibizumab, Aflibercept, or Ozurdex^TM). All patients completed a structured loading phase of four monthly injections. Key outcome measures included changes in best-corrected visual acuity (BCVA, logMAR), central subfield thickness (CST, µm), and intraretinal fluid (IRF) presence on optical coherence tomography (OCT). Changes were assessed from baseline (mo0) to three months (mo3). Results: The study included 19 eyes from 19 patients (mean age 63.0 ± 14.2 years). BCVA improved from 0.20 logMAR at baseline to 0.00 logMAR at mo3 (p < 0.01). CST decreased from 325 µm to 280 µm (p < 0.01). The proportion of eyes with IRF reduced from 100% to 32% (p < 0.01). Significant reductions in retinal volume within the 1 mm and 6 mm (both p < 0.01) circles of the ETDRS grid were observed. Conclusions: Switching to Faricimab in patients resulted in significant short-term improvements in BCVA, CST, and IRF resolution. Given the small sample size and retrospective design, these findings should be interpreted as exploratory and hypothesis-generating. Further studies are needed to evaluate long-term efficacy and optimal treatment regimens. Full article

Background/Objectives: XTEND is the largest global, prospective, observational study of treatment-naïve patients with neovascular age-related macular degeneration (nAMD) receiving 2 mg of intravitreal aflibercept (IVT-AFL) in routine clinical practice designed to examine the real-world effectiveness of IVT-AFL proactive treatment regimens. The outcomes from the Switzerland cohort are reported here. Methods: Patients aged ≥50 years were eligible if they planned to receive IVT-AFL 2 mg. After three initial monthly IVT-AFL injections, treatment intervals could be extended (4-week minimum treatment interval). Visual and anatomic outcomes, treatment exposure, and safety were assessed. Statistics were descriptive. Results: Fifty-one patients were treated. At baseline, the mean ± standard deviation (SD) best-corrected visual acuity (BCVA) was 64.9 ± 17.9 letters, and central subfield thickness (CST) was 402 ± 106 µm. At month (M) 12 and M24, the mean (95% confidence interval [CI]) change from baseline in BCVA was +5.7 (1.9, 9.4) and +5.6 (1.3, 9.8) letters, respectively. In patients with a high baseline BCVA (≥70 letters [n = 28; mean ± SD: 77.5 ± 4.8 letters]), BCVA was maintained at ≥70 letters at M12 and M24 (mean change from baseline [range] +1.0 [−15.0, 11.0] and +1.1 [–10.0, 14.0], respectively). At M12 and M24, the mean (95% CI) change in CST was −125 (−161, −90) µm and −127 (−162, −93) µm, respectively. Patients received a mean ± SD of 9.5 ± 3.2 and 13.7 ± 6.0 injections by M12 and M24, respectively. No safety concerns were identified. Conclusions: In Swiss routine clinical practice, functional and anatomic improvements were achieved with IVT-AFL 2 mg proactive treatment in patients with nAMD over 24 months despite a relatively high baseline BCVA. Full article

Objectives: To compare the 1-year visual outcomes of patients treated with intravitreal anti-vascular endothelial growth factor (VEGF) monotherapy or vitrectomy for large submacular hemorrhages (SMHs) due to neovascular age-related macular degeneration (nAMD). Methods: We retrospectively studied 31 eyes with severe SMHs exceeding 3 disc areas (DAs) secondary to nAMD treated with anti-VEGF agents or a vitrectomy. Patients undergoing anti-VEGF monotherapy received three monthly loading doses of intravitreal injections of aflibercept or brolucizumab followed by as-needed injections or proactive treatment (anti-VEGF group); those undergoing vitrectomies underwent a 25-gauge vitrectomy and a submacular injection of tissue plasminogen activator (25 μg) and 0.4 mL of air with a microneedle having an outer diameter of 50 μm. The best-corrected visual acuities (BCVAs) were compared before and 6 and 12 months after initial treatment. Factors affecting the visual acuity (VA) at 12 months and VA improvements were determined. Results: A total of 17 eyes from 16 patients (54.8%) received anti-VEGF treatment and 14 eyes from 14 patients (45.2%) underwent vitrectomy. The baseline and 12-month mean logarithm of the minimum angle of resolution BCVAs in all eyes after treatment were 0.78 and 0.82, respectively, which were not significantly different (p = 0.661). The lens status, central foveal thickness (CFT) height, and baseline VA were associated significantly with the 12-month BCVA (p = 0.028, p = 0.008, and p = 0.021, respectively) and VA improvement (p = 0.015, p = 0.002, and p = 0.003, respectively). Conclusions: Anti-VEGF monotherapy and vitrectomy maintained functionality in patients with large SMHs due to nAMD. Greater CFT was associated with worse 12-month BCVA and less BCVA improvement despite the treatment modality. Full article

Anti-vascular endothelial growth factor (VEGF) treatment with intravitreal brolucizumab (IVBr) was launched as a novel treatment for neovascular age-related macular degeneration (AMD), but the incidence of intraocular inflammation (IOI) as a specific adverse effect of brolucizumab has been reported. We evaluated the dynamics of inflammatory factors in AMD in patients with or without IOI before and after anti-VEGF treatment with IVBr. We describe three patients who did not develop inflammation after three consecutive administrations of IVBr and three in whom inflammation occurred after the first IVBr treatment. The presence or absence of inflammation was determined by slit-lamp examination and a laser flare meter. Aqueous humor was obtained during anti-VEGF treatment with IVBr. Levels of VEGF, platelet-derived growth factor (PDGF)-AA, monocyte chemoattractant protein 1 (MCP-1), interleukin (IL)-6, IL-8, interferon-inducible 10 kDa protein (IP-10), Fms-related tyrosine kinase 3 ligands (Flt-3L), and fractalkine were measured. Vision worsened in one patient who developed IOI after initial IVBr, so IVBr was discontinued and the patient was switched to intravitreal aflibercept with sub-tenon injection of triamcinolone acetonide. IVBr was continued in the two other patients with IOI. VEGF decreased after IVBr in all patients with and without IOI. On the other hand, at 1 month IL-6, IL-8, MCP-1, IP-10, and Flt-3L were higher in the three patients with IOI compared with baseline and with the three patients without IOI. In two patients with IOI, not only flares but also IL-8, IP-10, and Flt-3L decreased from 1 to 2 months after IVBr despite continued IVBr. This case series might lead to a better understanding of the pathogenesis of IOI after IVBr. Full article

Aflibercept and brolucizumab, two anti-VEGF agents used as intravitreal injections in ophthalmology, differ significantly in molecular weight (aflibercept—115 kDa and brolucizumab—26 kDa). Using aqueous humor samples collected after drug administration, we measured and performed a comparative analysis of pharmacokinetics and half-lives of these drugs in the human eye. Since the quantification of monoclonal antibodies (mAbs) using antigen–antibody reactions, such as ELISA, is influenced by endogenous ligands or anti-drug antibodies, we employed nano-surface and molecular-orientation limited proteolysis (nSMOL), combined with liquid chromatography–tandem mass spectrometry (LC-MS/MS), for accurate measurements. Aqueous humor samples were collected from 59 eyes of 59 patients treated with aflibercept and 52 eyes of 52 patients treated with brolucizumab. Samples were obtained with a median post-injection period of 30 (range, 2–49) days for aflibercept and 28 (range, 4–60) days for brolucizumab. A population pharmacokinetic (PPK) analysis revealed that the half-life of aflibercept in human aqueous humor was significantly shorter than that of brolucizumab, 2.88 days versus 9.00 days, respectively (p = 1.16 × 10⁻⁷). Using the same mass spectrometry conditions, we calculated the half-lives of the two drugs. These results may be useful for optimizing the efficacy of these drugs in clinical practice. Full article

The abnormal growth of irregular new blood vessels into the subretinal or intraretinal space is known as macular neovascularization (MNV). People over 50 are often affected by this disorder, which is typically brought on by age-related macular degeneration. In addition, MNV can be found in people under 50 years of age, who may present primary ophthalmic diseases such as pathological myopia, angioid streaks, traumatic choroidal rupture, or suspected ocular histoplasmosis syndrome. However, it is important to consider a specific set of young individuals who may develop MNV even in the absence of pathological myopia or other identifiable inflammatory, peripapillary, post-traumatic, or degenerative fundus abnormalities. This latter condition is classified as idiopathic MNV. After a literature review focused on young patients affected by one of these two clinical entities, we report the case of a Caucasian young woman suffering for four years from an idiopathic and quiescent MNV that started exuding after childbirth, probably due to the induction with oxytocin, and was treated with intravitreal Aflibercept 2 mg injections. Full article