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This study investigated the one-year real-world clinical outcomes of intravitreal faricimab (IVF) in treatment-naïve neovascular age-related macular degeneration (nAMD) and its association with aqueous humor cytokine profiles. Thirty-four eyes of 32 nAMD patients, who received initial IVF at Jichi Medical University were included. These eyes showed significant improvements in central retinal subfield thickness (CST), central choroidal thickness (CCT), and best-corrected visual acuity (BCVA) one year post-IVF (all P  < 0.01). Among 24 measurable cytokines, only VEGF-A was significantly higher in eyes with a dry macula at week 16 ( P  = 0.0030). Three cytokines were significantly higher in eyes with longer injection interval. Higher levels of galectin-1 and VCAM-1, and lower levels of P-selectin, were correlated with greater CST reduction ( P  = 0.020, 0.0061, and 0.012, respectively). Conversely, five cytokines including Ang-1 were correlated with greater BCVA improvement (all P  < 0.05). In conclusion, an anatomical perspective faricimab demonstrated anatomical efficacy for VEGF-driven nAMD in the loading phase, while multiple cytokines associated with vascular instability or fibrosis appear to contribute to its durability. Notably, Ang-1 may be linked to visual improvement, suggesting that the neurotrophic effects of Ang-1 could be enhanced by Ang-2 inhibition.

Purpose To assess 6-month outcomes of switching from aflibercept to faricimab in eyes with refractory neovascular age-related macular degeneration (nAMD) previously requiring monthly injections. Methods This multicenter retrospective study examined nAMD eyes receiving monthly aflibercept injections switched to faricimab administered monthly up to 4 injections followed by injections at a minimum of 2-month intervals as per drug labeling. Data regarding age, sex, number of previous injections, treatment intervals, and best-corrected visual acuity (BCVA) were collected. Central retinal thickness (CRT), subfoveal choroidal thickness (SFCT), and maximal pigment epithelial detachment (PED) height were measured by optical coherence tomography. Results The study included 130 eyes of 124 patients. At 6 months, 53 eyes (40.8%) continued on faricimab treatment (Group 1), while 77 eyes (59.2%) discontinued faricimab for various reasons (Group 2) the most common being worse exudation. There were no significant differences between the two groups at baseline. In Group 1, CRT and SFCT significantly decreased at 1 month ( P = 0.013 and 0.008), although statistical significance was lost at 6 months ( P = 0.689 and 0.052). BCVA and maximal PED height showed no significant changes; however, mean treatment intervals were extended from 4.4 ± 0.5 weeks at baseline to 8.7 ± 1.7 weeks at 6 months ( P < 0.001) in Group 1. No clear predictors of response were identified. Conclusion Switching from aflibercept to faricimab allowed for extension of treatment intervals from monthly to bimonthly in roughly 40% of eyes, suggesting that faricimab may be considered in refractory nAMD cases.

PurposeTo investigate the efficacy and safety of loading phase treatment with 3 monthly intravitreal injections of faricimab for neovascular age-related macular degeneration (nAMD).MethodsWe retrospectively analyzed 16-week outcomes of 40 consecutive eyes of 38 patients with treatment-naïve nAMD. Three monthly injections of faricimab were administered to all eyes as a loading phase treatment. Best-corrected visual acuity (BCVA), foveal thickness, central choroidal thickness (CCT), and dry macula achievement were all assessed every 4 weeks. Moreover, the regression of polypoidal lesions was evaluated after the loading phase.ResultsBCVA was 0.33 ± 0.41 at baseline and showed significant improvement to 0.22 ± 0.36 at week 16 (P < 0.01). Foveal thickness was 278 ± 116 µm at baseline, decreasing significantly to 173 ± 48 µm at week 16 (P < 0.01). CCT was 214 ± 98 µm at baseline, decreasing significantly to 192 ± 89 µm at week 16 (P < 0.01). Dry macula was achieved in 31 eyes (79.5%) at week 16. Indocyanine green angiography after the loading phase revealed complete regression of polypoidal lesions in 11 of 18 eyes (61.1%) with polypoidal lesions. One eye (2.5%) developed vitritis without visual loss at week 16.ConclusionLoading phase treatment with intravitreal faricimab appears to generally be safe and effective for improving visual acuity and reducing exudative changes in eyes with nAMD.

To evaluate the initial efficacy and safety of intravitreal faricimab in eyes previously treated for neovascular age-related macular degeneration (nARMD). A retrospective review of all patients with nARMD previously treated with anti-vascular endothelial growth factor (anti-VEGF) injections who received at least 3 intravitreal faricimab injections with at least 3 months of follow-up. A total of 190 eyes were included. Patients received a mean of 34.2±23 anti-VEGF injections over 182.41±128 weeks prior to switching to faricimab. Patients then received a mean of 6.99±2.3 faricimab injections with an average 34.88±8.2 weeks of follow-up. The mean best corrected visual acuities improved from 0.33±0.32 logMAR ≈20/43 to 0.27±0.32 logMAR ≈20/37 ( =0.0022). The central subfield thickness (CST) improved from 312±87μm to 287±71μm ( <0.0001). At the last clinical visit, 24% had no subretinal fluid or intraretinal fluid on optical coherence tomography. The mean dosing interval between the last two consecutive faricimab injections (7.64±6.2 weeks) was significantly longer than that for ranibizumab (5.16±2.0 weeks, <0.001) or aflibercept (5.57±3.6 weeks, <0.001). No patients developed idiopathic intraocular inflammation. Intravitreal faricimab was associated with improved vision and CSTs, even in treatment-resistant nARMD eyes. The mean last dosing interval for faricimab was longer than for ranibizumab or aflibercept. No significant adverse events were directly attributed to faricimab during the study.

Background and Objectives: Faricimab is the first intravitreal injection of vascular endothelial growth factor-A and angiopoietin-2 bispecific monoclonal antibody. Here, we evaluate the functional and anatomical outcomes of faricimab treatment in patients with diabetic macular edema (DME) that was refractory to ranibizumab or aflibercept. Materials and Methods: We performed a retrospective, observational, consecutive-case study of patients who had DME that was refractory to treatment with ranibizumab or aflibercept and were treated with faricimab between July 2022 and January 2023 under a pro re nata regimen. All the participants were followed for ≥4 months after the initiation of faricimab. The primary outcome was a recurrence interval of ≥12 weeks, and the secondary outcomes were the changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT). Results: We analyzed 18 eyes of 18 patients. The mean recurrence interval of previous anti-VEGF injection was 5.8 ± 2.5 weeks, which was significantly extended to 10.8 ± 4.9 weeks (p = 0.0005) by the switch to faricimab. Eight patients (44.4%) achieved a recurrence interval of ≥12 weeks. A history of subtenon injection of triamcinolone acetonide (p = 0.0034) and the presence of disorganization of the retinal inner layers (p = 0.0326) were found to be significantly associated with a recurrence interval of <12 weeks. The mean BCVAs were 0.23 ± 0.28 logMAR and 0.19 ± 0.23 logMAR, and the mean CMTs were 473.8 ± 222.0 µm and 381.3 ± 219.4 µm at baseline and 4 months, respectively, but these changes were not statistically significant. None of the patients experienced serious adverse events. Conclusions: Faricimab may extend the treatment interval for patients with DME that is refractory to ranibizumab or aflibercept. DME previously treated with the subtenon injection of triamcinolone acetonide or associated with disorganization of the retinal inner layers may be less likely to be associated with a longer recurrence interval after switching to faricimab.

To assess the 12 month outcomes of intravitreal faricimab (IVF) in treatment-resistant diabetic macular edema (DME) recalcitrant to intravitreal aflibercept (IVA).PurposeTo assess the 12 month outcomes of intravitreal faricimab (IVF) in treatment-resistant diabetic macular edema (DME) recalcitrant to intravitreal aflibercept (IVA).This study was undertaken as a retrospective interventional case series of DME subjects receiving care at a single private practice facility. Subjects at baseline had undergone ≥8 IVA injections over the previous 12 months, ≥4 IVA injections over the previous 6 months, had an optical coherence tomography (OCT)-measured central macular thickness (CMT) of ≥320 microns, and had observable edema on OCT. The baseline visit for this study's purpose was considered the examination in which the subject was changed from IVA to IVF. Subjects were managed with a treat-and-extend (TAE) protocol and followed over 12 months from baseline.MethodsThis study was undertaken as a retrospective interventional case series of DME subjects receiving care at a single private practice facility. Subjects at baseline had undergone ≥8 IVA injections over the previous 12 months, ≥4 IVA injections over the previous 6 months, had an optical coherence tomography (OCT)-measured central macular thickness (CMT) of ≥320 microns, and had observable edema on OCT. The baseline visit for this study's purpose was considered the examination in which the subject was changed from IVA to IVF. Subjects were managed with a treat-and-extend (TAE) protocol and followed over 12 months from baseline.A total of 51 eyes of 51 subjects were analyzed. There were 39.2% (20/51) of patients who reached a treatment interval of ≥8 weeks and had a fluid-free macula on OCT at 12 months. The CMT on OCT of the patient population reduced from 400.2 (385.3-415.3) microns at baseline to 340.6 (324.3-356.9) microns at 12 months (p<0.01). There were 21.6% (11/51) of patients who improved ≥3 lines of Snellen visual acuity at 12 months. The visual acuity of the overall study population improved from 0.60 (0.54-0.66) logMAR (Snellen 20/80) at baseline to 0.47 (0.41-0.53) logMAR (Snellen 20/59) at 12 months (p<0.01).ResultsA total of 51 eyes of 51 subjects were analyzed. There were 39.2% (20/51) of patients who reached a treatment interval of ≥8 weeks and had a fluid-free macula on OCT at 12 months. The CMT on OCT of the patient population reduced from 400.2 (385.3-415.3) microns at baseline to 340.6 (324.3-356.9) microns at 12 months (p<0.01). There were 21.6% (11/51) of patients who improved ≥3 lines of Snellen visual acuity at 12 months. The visual acuity of the overall study population improved from 0.60 (0.54-0.66) logMAR (Snellen 20/80) at baseline to 0.47 (0.41-0.53) logMAR (Snellen 20/59) at 12 months (p<0.01).A longer treatment interval and improved functional and anatomical outcomes at 12 months may be attained in a clinically significant minority of aflibercept-resistant DME patients after changing to IVF when a TAE protocol is employed. Specialists may consider IVF whenever resistance to IVA is experienced in this patient population.ConclusionA longer treatment interval and improved functional and anatomical outcomes at 12 months may be attained in a clinically significant minority of aflibercept-resistant DME patients after changing to IVF when a TAE protocol is employed. Specialists may consider IVF whenever resistance to IVA is experienced in this patient population.

To compare real-world outcomes in treatment-naïve neovascular age-related macular degeneration (nAMD) patients initiated on Faricimab at early (<0.3 logMAR) versus late (0.6-0.7 logMAR) visual thresholds. Retrospective, single-centre cohort study of 97 patients (53 early, 44 late) treated at a UK centre, with three monthly loading doses followed by treat-and-extend. Outcomes: BCVA change, vision loss (≥5 letters), stable vision at 6/12/18 months, injection intervals, extension >8 weeks, dry macula. Baseline VA was 74 ± 3.5 letters (early) vs 54 ± 2.0 letters (late), p<0.001. No early patient experienced sustained vision loss at 6, 12, or 18 months compared with 76.7%, 73.3%, and 75.0% of late patients, respectively (p<0.05 for all). At the 7th injection, 67.6% of late patients lost ≥5 letters vs 14.9% of early patients (ARR 52.7%, p<0.001). Cumulatively, 81.8% of late patients experienced ≥5-letter loss vs 41.5% of early patients (ARR 40.3%, NNT 3, p<0.001). Mean injection intervals were similar, but the early cohort sustained extension beyond 8 weeks in >50% of eyes from the 4th-5th interval onward. In contrast, the late cohort exhibited a biphasic collapse, with extension rates declining from 62.2% at 6th-7th to only 35.0% by 9th-10th. Despite a significant baseline anatomical disadvantage (18.9% vs 50.0% dry macula, p=0.001), the early cohort achieved 100% dryness by 18 months compared with 96.7% in the late cohort, with crossover occurring by 12 months (95.8% vs 89.7%, p=0.269). In this retrospective, single-centre study, early faricimab initiation was associated with preservation of high-function vision, a lower risk of clinically significant vision loss, and high rates of anatomical quiescence and durable treatment extension. These findings suggest that proactive early intervention may offer advantages over reactive treatment paradigms, although confirmation in larger, prospective, and multi-centre studies is needed.

Diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD) are common retinal vascular diseases responsible for most blindness in the working-age and older population in developed countries. Currently, anti-VEGF agents that block VEGF family ligands, including ranibizumab, bevacizumab (off-label use), brolucizumab, and aflibercept, are the first-line treatment for nAMD and DME. However, due to the complex pathophysiological background of nAMD and DME, non-response, resistance during anti-VEGF therapy, and relapses of the disease are still observed. Moreover, frequent injections are a psychological and economic burden for patients, leading to inadequate adhesion to therapy and a higher risk of complications. Therefore, therapeutic methods are strongly needed to develop and improve, allowing for more satisfactory disease management and lower treatment burden. Currently, the Ang/Tie-2 pathway is a promising therapeutic target for retinal vascular diseases. Faricimab is the first bispecific monoclonal antibody for intravitreal use that can neutralize VEGF and Ang-2. Due to the prolonged activity, faricimab allows extending the interval between successive injections up to three or four months in nAMD and DME patients, which can be a significant benefit for patients and an alternative to implanted drug delivery systems.

To assess the 12-month outcomes of intravitreal faricimab (IVF) in treatment-resistant neovascular age-related macular degeneration (nAMD) subjects recalcitrant to intravitreal aflibercept (IVA). This study was conducted as a retrospective interventional case series of nAMD patients receiving treatment at a single private practice institution. All included patients at baseline had undergone six or more IVA injections over the previous 12 months, four or more IVA injections over the previous 6 months, had a central macular thickness (CMT) ≥320 µm on optical coherence tomography (OCT), and were observed to have intraretinal and/or subretinal fluid on OCT assessment. The baseline exam for the purpose of this study was considered the visit in which the patient was switched from IVA to IVF. Patients were managed with a real-world treat-and-extend protocol and followed over a 12-month study period. A total of 54 eyes of 54 subjects were analyzed. Overall, 31.5% (17/54) of subjects attained a treatment interval ≥8 weeks and had a fluid-free macula on OCT at 12 months. The CMT on OCT decreased from 395.4 (383.5-407.3) µm at baseline to 350.0 (335.1-364.8) µm at the end of the 12-month study interval ( <0.01). There were 16.7% (9/54) of subjects who gained three or more lines of Snellen visual acuity at the end of the study. Visual acuity improved from 0.72 (0.67-0.77) logMAR (Snellen 20/105) at baseline to 0.59 (0.55-0.64) logMAR (Snellen 20/78) at the end of the study ( <0.01). A clinically significant minority of aflibercept-resistant nAMD subjects may attain longer treatment intervals and improved outcomes at 12 months after switching to IVF when a treat-and-extend treatment protocol is utilized. IVF use may be considered whenever resistance to IVA is encountered in this patient population.

Neovascular age-related macular degeneration (nAMD) is a major cause of visual impairment and blindness. Anti-vascular endothelial growth factor (VEGF) agents, such as ranibizumab, bevacizumab, aflibercept, brolucizumab and faricimab have revolutionized the clinical management of nAMD. However, there remains an unmet clinical need for new and improved therapies for nAMD, since many patients do not respond optimally, may lose response over time or exhibit sub-optimal durability, impacting on real world effectiveness. Evidence is emerging that targeting VEGF-A alone, as most agents have done until recently, may be insufficient and agents that target multiple pathways (e.g., aflibercept, faricimab and others in development) may be more efficacious. This article reviews issues and limitations that have arisen from the use of existing anti-VEGF agents, and argues that the future may lie in multi-targeted therapies including alternative agents and modalities that target both the VEGF ligand/receptor system as well as other pathways.