Search Results (193)

Background/Objectives: Evaluate outcomes and treatment patterns with 2 mg intravitreal aflibercept injection among patients who completed the phase 3 PANORAMA trial and enrolled in the VOYAGE (ClinicalTrials.gov identifier, NCT04708145; 12 January 2021) long-term extension study. Methods: During VOYAGE, patients were evaluated every 16 weeks and treated with 2 mg intravitreal aflibercept injection as needed depending on ophthalmoscopic examination findings. Those with no history of panretinal photocoagulation (PRP) received aflibercept if their clinician-determined diabetic retinopathy severity scale (DRSS) level was ≥47. Patients with a history of PRP received aflibercept if active neovascularization was present. New or worsening diabetic retinopathy (DR) severity prompted more frequent treatment. Results: 320 patients (1 eye per patient) from 87 sites completed the PANORAMA trial. Of these, 41 patients (13% of PANORAMA completers) from 14 sites (16%) enrolled in VOYAGE after a mean interim period of 33.7 months, and 35 patients (85%) completed study visits through 1 year. At year 1 in VOYAGE, the mean number of anti-vascular endothelial growth factor (VEGF) injections increased from 1.1 per year during the interim period to 3.4 per year and was associated with stabilization or improvement in DRSS level in 81% (26/32) of patients. Mean best-corrected visual acuity (BCVA) remained relatively stable, and mean central subfield thickness (CST) improved by 24.4 µm to 269.5 μm through year 1 of VOYAGE. There were no unexpected safety events. Conclusions: Following a mean of 3 years of routine clinical care with associated declines in DRSS level, CST, and BCVA, stabilization of DRSS level and BCVA with reductions in CST was achieved through year 1 of the VOYAGE extension study, with a concurrent increase in aflibercept dosing frequency. Full article

The aim of this study was to analyse data from a clinical database using a novel visual acuity parameter to determine whether anti-VEGF molecules that target multiple domains involved in neovascularisation are more likely to achieve good visual acuity than agents that solely inhibit VEGF. This retrospective study analysed data from patients treated with anti-VEGF injections between 2015 and 2023. We set an ETDRS score threshold of 70 (equivalent to 20/40 Snellen acuity) to calculate ‘time in range’ (TIR). TIR is defined as ‘time spent with best-corrected visual acuity (BCVA) better than 20/40’ and can highlight significant variations in the time individuals spend above the threshold during their AMD treatment. Over nine years, 30,209 aflibercept and 10,876 ranibizumab injections were administered to 6043 patients. Patients received an average of 6.8 injections. The mean BCVA at the first injection was 57.00 ± 16.15 ETDRS letters for ranibizumab patients and 58.75 ± 15.82 for aflibercept patients, with a statistically significant difference (p < 0.001). Both groups showed significant improvement in visual acuity at follow-up (aflibercept: 60.21 ± 15.53; ranibizumab: 59.43 ± 15.81; both p < 0.001). The mean time between the two consecutive injections, including both the initial loading phase and the subsequent maintenance phase, was 67.22 ± 34.08 days for ranibizumab and 72.15 ± 31.00 days for aflibercept; the difference was statistically significant (p < 0.001). After controlling for the effect of initial BCVA and time between injections, patients who received aflibercept had a significantly higher average TIR (60.90 ± 36.27 days vs. 56.55 ± 38.78 days, p < 0.001), and significantly more likely to achieve >70 letters at the next visit (OR: 1.10; 95% CI: 1.05–1.15; p < 0.001) compared to patients receiving ranibizumab. Aflibercept treatment improves the likelihood of maintaining good BCVA by 10% compared to ranibizumab in patients receiving intravitreal anti-VEGF treatment for nAMD. Furthermore, the beneficial effects of aflibercept treatment are observed with less frequent dosing. Our results suggest that using anti-VEGF compounds that target multiple domains provides a detectable advantage in treating age-related macular degeneration, particularly when these agents have a longer duration of action. Full article

Background/Objectives: Brolucizumab is a humanized single-chain antibody fragment with a molecular weight of approximately 26 kilodaltons (scFv, ~26 kDa) targeting all VEGF-A isoforms. Intravitreal brolucizumab (6 mg) is FDA-approved for neovascular age-related macular degeneration (nAMD) (2019) and diabetic macular edema (DME) (2022). We systematically review the literature on brolucizumab for nAMD and DME, focusing on efficacy, safety, pharmacokinetics, real-world outcomes, and cost-effectiveness in adult and pediatric patients. Methods: Our method involves a comprehensive literature search of PubMed, Embase, Scopus, Cochrane, and related databases (through late 2024) using terms including “brolucizumab,” “Beovu,” “neovascular AMD,” “diabetic macular edema,” “safety,” “pharmacokinetics,” and “pediatric.” High-quality clinical trials, meta-analyses, regulatory documents, and real-world studies were prioritized. Results: In pivotal Phase III trials (HAWK/HARRIER for nAMD), brolucizumab 6 mg demonstrated non-inferior visual acuity (VA) gains to aflibercept, with >50% of eyes maintained on 12-week dosing and greater retinal fluid reduction. In DME trials (KESTREL/KITE), brolucizumab was similarly non-inferior to aflibercept for VA and showed superior anatomic drying, with 33–48% of eyes maintained on ≥12-week intervals. However, brolucizumab use has been associated with intraocular inflammation (IOI), retinal vasculitis, and vascular occlusion: clinical trials and post hoc analyses reported higher rates of these events than comparator agents. Real-world cohorts found IOI in ~4–10% of treated eyes, often occurring early (within 3 months) after initiation. Conclusions: In conclusion, Brolucizumab is an effective anti-VEGF option for nAMD and DME, providing durable anatomic control with fewer injections. Non-inferior vision outcomes and superior fluid resolution have been demonstrated. However, it carries a distinct risk of IOI and occlusive vasculitis, necessitating careful patient selection, dosing, and monitoring. Full article

Uveal melanoma (UM) is the most prevalent primary intraocular tumor in adults. Transcription factor ZEB1 is one of the potential master regulators of melanocytes plasticity, because it is recognized as a “driver” of epithelial-to-mesenchymal transitions (EMTs) in carcinomas. We studied the correlation of tumor invasiveness with ZEB1 status and vascular endothelial growth factor/its receptor (VEGF-A/VEGFR2) in UM cells, and also with melanocyte’s differentiation rate. Eight UM cell cultures were characterized by melanosomes content using an ETM. ZEB1, VEGF-A and VEGFR2 levels in UM cells were detected by RT-PCR, Western blot, ELISA and flow cytometry. Effects of siRNA-dependent ZEB1 knockdown on UM cell proliferation and their sensitivity to the VEGF-A inhibitor Eylea (aflibercept) were tested by MTT and in a real-time proliferation assay. UMs with an invasive growth type can maintain a high degree of melanocyte differentiation. All ZEB1^low cells were obtained from spindle cell tumors. The sensitivity of UM cells to Eylea inversely correlated with the level of the VEGFR2 receptor. ZEB1 knockdown completely blocked VEGF-A production while anti-VEGF treatment stimulated ZEB1 increase. In UM cell cultures, ZEB1 is a positive regulator of VEGF-A expression. In addition, there is probably a ZEB1 feedback loop that is sensitive to a drop in VEGF-A concentration. The data obtained allow us to consider ZEB1 silencing as an auxiliary link for a combined strategy of killing UM cells. Full article

Purpose: To describe the indication spectrum for high-dose 8 mg aflibercept for neovascular age-related macular degeneration (nAMD) in a real-world cohort in a tertiary referral center. Methods: The database of the University Eye Hospital Munich, Ludwig Maximilians-University was screened for eyes with nAMD treated with 8 mg aflibercept. Demographic data, multimodal imaging and treatment parameters were recorded. Reasons for treatment with 8 mg aflibercept were analyzed. Results: Thirty-four consecutive eyes of 31 patients (mean age 78.6 ± 8.9 years) were identified. There were 22 women (70.1%) and 9 men (29.9%). In all eyes (100%), 8 mg Aflibercept was applied as switching therapy. Prior to switching, the mean anti-vascular endothelial growth factor (VEGF) treatment duration for nAMD was 3.9 ± 2.9 years, pretreatment amounted to a mean of 34.5 ± 26.3 injections, equaling 9.2 ± 2.4 injections/year, and the mean visual acuity (VA) was 0.4 ± 0.4 logMAR. The last treatment before switching was 2 mg aflibercept in 76%, faricimab in 18%, ranibizumab in 3% and bevacizumab in 3% of cases. Reasons for switching included (A) recalcitrant nAMD with persistent fluid despite q4w dosing (17 eyes, 50%), (B) the wish for interval extension (15 eyes, 44%) and (C) macular hemorrhage (2 eyes, 6%). In group B, two-thirds of eyes (10/15, 66.7%) were maintained at ≤q6w prior to switching. Conclusions: In this study, high-dose 8 mg aflibercept was exclusively used as a switch therapy. Most eyes (76%) switched were from pretreatment with 2 mg aflibercept. The main reasons for switching were recalcitrant nAMD with persistent fluid despite q4w dosing (50%) or the wish for treatment extension beyond 6 weeks (32%). In the future, these data will aid in the design of prospective real-world studies comparing the efficacy of high-dose 8 mg aflibercept with older generation treatment options, especially 2 mg aflibercept. Full article

Purpose: To evaluate anatomical and functional outcomes after switching from aflibercept to faricimab in patients with neovascular age-related macular degeneration (nAMD) with suboptimal response. Methods: This retrospective study included 72 eyes of 66 patients with nAMD previously treated with intravitreal aflibercept using a treat-and-extend regimen. Indications for switching included persistent retinal fluid, pigment epithelial detachment (PED), lack of best-corrected visual acuity (BCVA) improvement, or inability to extend treatment intervals beyond four weeks. Patients received three monthly loading doses of faricimab followed by individualized 8- to 16-week dosing. Follow-up comprised six visits over a mean of 8.5 ± 1.4 months. Outcomes included BCVA (logMAR), retinal morphology (subretinal fluid—SRF; intraretinal fluid—IRF; pigment epithelial detachment—PED), central subfoveal thickness (CST), and treatment interval changes. Results: Switching to faricimab led to significant short-term anatomical improvement, primarily reduction in subretinal fluid (p < 0.0001), with maximal effect during the loading phase. Resolution of SRF was significant at the end of the follow up; however, IRF changes were transient and not sustained beyond three months. PED reduction reached borderline significance (p = 0.0455). CST decreased during the loading phase (p < 0.0001) but returned to baseline thereafter. BCVA improved only after loading (p = 0.0287) but not at final follow-up. Treatment intervals were extended by a mean of ~2 weeks (p < 0.0001), increasing in 80% of eyes. Eyes with fewer prior injections and better baseline BCVA achieved superior final visual outcomes. Conclusions: Switching to faricimab provides short-term anatomical benefits and treatment-interval extension without sustained visual gain. Functional improvements tended to be greater in patients with fewer injections and shorter treatment duration prior to switch. Full article

Background: Macular edema (ME) secondary to retinal vein occlusion (RVO) is a significant cause of vision impairment. Many patients show suboptimal responses to anti-vascular endothelial growth factor (anti-VEGF) monotherapy, prompting the exploration of alternative treatments. Faricimab is a bispecific antibody that targets VEGF-A and angiopoietin-2. We report 9-month real-world outcomes of switching to faricimab in therapy-resistant RVO-associated ME. Methods: In this retrospective study at a single tertiary center, patients with persistent or recurrent ME despite prior treatments (ranibizumab, aflibercept, or dexamethasone implant) were switched to faricimab. All eyes received a loading phase of four monthly faricimab injections, followed by a treat-and-extend regimen individualized per response. Key outcomes included best-corrected visual acuity (BCVA, logMAR), the central subfield thickness (CST, μm), and the intraretinal fluid (IRF) status on optical coherence tomography, assessed from the baseline (month 0, mo0) through the loading phase (mo1–mo3) and at month 9 (mo9). Results: Nineteen eyes (19 patients, mean age 64.8 years) were analyzed. The median BCVA improved from 0.20 to 0.00 logMAR by month 3 (p < 0.01) and was maintained at month 9. The median CST decreased from 325 μm at the baseline to 285 μm at month 3 (p < 0.01) and remained at 285 μm at month 9. IRF was present in 100% of eyes at the baseline, 26% at month 3, and 26% at month 9 (p < 0.01 for the baseline vs. month 9). Among eyes previously on anti-VEGF therapy (n = 14), the median treatment interval increased from 45.50 days at the baseline to 56.50 days at month 9 (p = 0.01; δ = 0.86). No intraocular inflammation or other adverse events were observed in this cohort over nine months. Conclusions: In this retrospective series, switching to faricimab was associated with improvements in vision and retinal anatomy that were maintained over 9 months; injection intervals were extended in a subset of eyes. These exploratory findings warrant confirmation in larger, controlled studies to define long-term effectiveness, safety, and dosing strategies. Full article

Background/Objectives: Real-world registries of neovascular age-related macular degeneration (nAMD) treatments provide critical insights for optimizing patient care and resource allocation. This study evaluates one-year outcomes of anti-VEGF therapy with aflibercept, ranibizumab, and brolucizumab in the Polish Therapeutic Program Monitoring System between 1 January 2016 and 31 October 2023. Methods: We analyzed data from 51,902 treatment-naïve patients with nAMD, comparing baseline characteristics and outcomes across drugs, as well as between those who discontinued therapy early and those treated for at least one year. Results: No significant baseline differences were found between drug groups. One-year follow-up was available for 40,396 eyes; 3184 were lost to follow-up, and 8322 discontinued treatment: 14.4% for those receiving aflibercept, 24.1% for those receiving brolucizumab, and 20.1% for those receiving ranibizumab. Early discontinuers were older and had higher baseline visual acuity (aflibercept, ranibizumab). Twelve-month treatment outcomes, particularly visual acuity gains and injection frequency (~6–7/year), were similar across agents. Only ~22% achieved at least 0.3 logMAR improvement, underscoring real-world treatment challenges. Conclusions: System-level support, appropriate treatment intensification, and strategic use of newer, durable agents like brolucizumab are crucial to narrowing the gap between clinical trial efficacy and real-world effectiveness, ultimately improving long-term outcomes in nAMD care. Full article

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

Background/Objectives: To compare the treatment outcomes of intravitreal faricimab (IVF) and intravitreal aflibercept (IVA) in treatment-naïve patients with neovascular age-related macular degeneration (nAMD), stratified by the presence or absence of punctate hyperfluorescence (PH). Methods: This retrospective study included 301 treatment-naïve patients with nAMD who underwent either IVF or IVA. After 1:1 propensity score matching based on baseline best-corrected visual acuity (BCVA), age, and PH status, 56 eyes (28 per group) were analyzed within each PH subgroup. Outcome measures included BCVA, central retinal thickness (CRT), subfoveal choroidal thickness (SFCT), and no retinal fluid rate during the loading dose regimen, and the retreatment rate after the loading dose regimen. The prespecified primary endpoint was the 1-year retreatment rate after completion of the loading dose regimen, analyzed by Kaplan–Meier curves with log-rank tests. Comparisons were performed separately between the PH and non-PH groups. Results: In the PH group, no significant differences were observed between IVF and IVA groups in terms of BCVA, CRT, SFCT, no retinal fluid rate, or retreatment rate at any time point. In the non-PH group, IVF and IVA groups showed no significant differences in BCVA, CRT, or SFCT at any time point; however, the IVF group achieved a significantly higher no retinal fluid rate (100.0% vs. 64.3%, p < 0.001) and a lower retreatment rate at 1 year (71.4% vs. 92.9%, p = 0.004) than the IVA group. Conclusions: IVF and IVA showed comparable efficacy in nAMD with PH. In contrast, IVF demonstrated superior anatomical outcomes in nAMD without PH. These retrospective findings suggest distinct pathophysiological mechanisms between PH and non-PH subtypes. 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

Objectives: This study aimed to evaluate the 6-month real-world outcomes of switching to faricimab in patients with aflibercept-resistant neovascular age-related macular degeneration (nAMD). Methods: A retrospective review was conducted on the eyes of 60 patients with aflibercept-resistant nAMD that were switched to faricimab. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) parameters, including central subfield thickness (CST), subfoveal choroidal thickness (SFCT), and both the maximum height and width of pigment epithelial detachment (PED), at baseline and 1, 3, and 6 months after switching were evaluated. The type of PED and retinal fluid were also analyzed. Results: The results showed that BCVA remained stable at month 6 (p = 0.150), while CST significantly decreased (p = 0.020), and SFCT remained unchanged (p = 0.072). The maximum PED height significantly decreased (p = 0.030), while the maximum PED width did not change (p = 0.07). The mean injection interval significantly increased from 6.8 ± 2.4 weeks before switching to 11.2 ± 1.7 weeks after switching (p = 0.068). Furthermore, the dry macula rate was 43.3% at month 6. Conclusions: Switching to faricimab in aflibercept-resistant nAMD patients showed stable visual outcomes, significant anatomical improvements, and reduced treatment burden over 6 months in real-world clinical settings. 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

Background/Objectives: To identify the predictive biomarkers of treatment response following a switch to brolucizumab in patients with aflibercept-refractory neovascular age-related macular degeneration (nAMD). Methods: This retrospective study included 47 eyes of 44 patients with nAMD who were switched to brolucizumab; a two-year follow-up was completed for 37 eyes of 34 patients after the switch. The patients were classified into two groups based on the presence (fluid group) or absence (dry group) of retinal fluid at one and two years after switching, and their visual acuity, central retinal thickness, subfoveal choroidal thickness, injection interval, and dry macular rate were evaluated. Results: A dry macula was achieved for approximately 80% of patients at two years after the switch (p < 0.001), and the mean injection interval was significantly extended from 6.4 ± 1.8 weeks to 10.5 ± 2.6 weeks during the same period (p < 0.001). Both the mean central retinal thickness and subfoveal choroidal thickness showed a significant decrease at two years after the switch (p < 0.001 for both). A significantly higher proportion of patients in the Dry group exhibited punctate hyperfluorescence in the fellow eye (p < 0.001), and all patients in the dry group achieved a dry macula at two years. Conclusions: Switching to brolucizumab may be an effective treatment option for patients with aflibercept-refractory nAMD. Punctate hyperfluorescence may serve as a favorable prognostic factor following a switch to brolucizumab. Full article