BACKGROUND: The aim of this study was to investigate the predictive factors for persistent disease activity following anti-vascular endothelial growth factors (anti-VEGF) and their long-term effects in patients to be treated for neovascular age-related macular degeneration (nAMD) under real-world conditions.
METHODS: Retrospective data analysis of the PROOF study, a multi-center real-world retrospective chart review conducted across Korea in patients with nAMD included treatment-naive patients with nAMD who received first anti-VEGF (ranibizumab, bevacizumab, or aflibercept) between January 2017 and March 2019 was performed. All 600 patients (cohort 1) had a minimum follow-up of 12 months of which 453 patients (cohort 2) were followed-up for 24 months from baseline.
RESULTS: At month 12 after anti-VEGF therapy, 58.10% (95% confidence interval [CI]: 54.09, 62.12) of patients and at month 24, 66.02% of patients continued to have persistent retinal fluid. At both months 12 and 24, predictive factors for persistent disease activity were fibrovascular pigment epithelial detachments (PED) (P = 0.0494) and retinal fluid at month 3 after loading phase (P = 0.0082). The mean changes in visual acuity were + 6.2, + 10.1, and + 13.3 letters and in the central subfield thickness were - 79.1 µm, - 96.3 µm, and - 134.4 µm at 12 months from baseline, in the bevacizumab, aflibercept, and ranibizumab groups, respectively.
CONCLUSIONS: The presence of retinal fluid after loading phase and fibrovascular PED were predictors of persistent disease activity after at least 1 year of anti-VEGF treatment.

OBJECTIVE: To investigate the efficacy and outcomes of switching neovascular age-related macular degeneration (nAMD) patients from aflibercept to faricimab, focusing on visual acuity, retinal fluid management, and treatment intervals. The primary aim was to assess the early outcomes in nAMD patients refractory to aflibercept and explore faricimab\'s potential as a longer-lasting therapeutic alternative.
METHODS: A single-center retrospective study was conducted on 50 refractory nAMD patients at Cleveland Clinic Abu Dhabi from September 2022-May 2023. Patients were switched from aflibercept to faricimab, having met specific criteria for refractory nAMD. The study analyzed best-corrected visual acuity (BCVA), central subfield thickness (CST), and fluid changes post-switch, using Optical Coherence Tomography (OCT).
RESULTS: After three faricimab injections, significant reductions in CST were observed, with a notable decrease in retinal fluid. The mean BCVA remained stable throughout the study period. Although there was a decrease in the maximum pigment epithelial detachment (PED) height, it was not statistically significant. Treatment intervals post-switch showed that the majority of patients maintained or extended their treatment intervals, with a significant proportion achieving resolution of intraretinal fluid (IRF) and subretinal fluid (SRF).
CONCLUSIONS: Switching to faricimab from aflibercept in refractory nAMD patients led to significant improvements in retinal fluid management and CST, with stable BCVA outcomes. Faricimab presents a promising alternative for patients requiring frequent aflibercept injections, potentially offering a more manageable treatment regimen with extended dosing intervals. This study highlights the need for personalized therapeutic strategies in nAMD treatment, though further research is necessary to optimize treatment switches.

OBJECTIVE: This study aimed to compare the effect of intravitreal aflibercept (IVA) and ranibizumab (IVR) on the maximal diameter of the largest intraretinal cyst (mdIRC), indicating chronicity in patients with diabetic cystoid macular edema (CME).
METHODS: This retrospective, comparative study included a subgroup of patients from the MARMASIA Study with treatment-naïve diabetic CME who had IVA (IVA group) or IVR (IVR group) on a pro re nata regimen after a loading dose of 3-monthly injections and followed-up for 24 months. Best-corrected visual acuity (logMAR), central macular thickness (CMT, µm), and mdIRC (µm) and their changes during the study period in the IVA and IVR groups were compared.
RESULTS: A total of 175 eyes (65 [37.1%] in IVA and 110 [62.9%] in IVR group) of 113 patients were included in the study analysis. Both groups had statistically significant improvements in BCVA and CMT during the follow-up (p < 0.05 for all), which were comparable between the groups at each time point. However, the mean reduction in mdIRCs was consistently and significantly higher in the IVA group compared to the IVR group at each follow-up examination (F[1, 3.52] = 6.93, p = 0.009).
CONCLUSIONS: IVA seems to have a greater impact in reducing cyst sizes than IVR in diabetic CME.

BACKGROUND: This study aimed to compare the regressive effects of aflibercept and faricimab on pigment epithelial detachment (PED) in patients with neovascular age-related macular degeneration.
METHODS: In total, 41 eyes of 40 patients diagnosed with type 1 macular neovascularization were retrospectively analyzed using multimodal imaging. Of these, 23 eyes were treated with intravitreal aflibercept injections (IVA group), and 18 eyes were treated with intravitreal faricimab (IVFa group), with 3 consecutive injections administered as loading dose therapy. Before treatment and at 1, 2, and 3 months after the first treatment, the maximum height (MH) and maximum diameter (MD) of the PED were measured using optical coherence tomography in each treatment group.
RESULTS: In the IVA group, the MH at baseline (215 ± 177 μm) was reduced to 141 ± 150 (P = 0.06), 119 ± 150 (P < 0.01), and 107 ± 150 µm (P < 0.0001) at 1, 2, and 3 months after treatment, respectively. Similarly, in the IVFa group, the MH decreased from 240 ± 195 µm before treatment to 165 ± 170 µm (P = 0.24), 139 ± 142 µm (P < 0.05), and 117 ± 112 µm (P < 0.01) at 1, 2, and 3 months after treatment, respectively. The reduction at 2 and 3 months was significant in both treatments. The mean changes of MH from baseline were -108 ± 142 µm in the IVA group and -124 ± 112 µm in the IVFa group, with no significant difference (P = 0.21). In both groups, the MD did not regress significantly.
CONCLUSIONS: The results suggested that the MH of the PED between the IVA and IVFa groups regressed similarly after each loading therapy.

The objective of this study was to analyze the effectiveness of two intravitreal antiangiogenic drugs, ranibizumab and aflibercept, in a Mexican population over a period of 5 years, evaluating the improvement in visual acuity (VA) and central retinal thickness (CRT) in a real-world scenario. This is a retrospective study with subjects diagnosed with diabetic retinopathy (DR), proliferative diabetic retinopathy (PDR), and diabetic macular edema (DME) receiving intravitreal injections of ranibizumab and/or aflibercept. In this study, we analyzed 588 eyes of 294 patients who received intravitreal antiangiogenic injections. The results showed an improvement regardless of antiangiogenic treatment or diagnosis in both VA and CRT. We found that both aflibercept and ranibizumab improved VA, while subjects with DME responded less to antiangiogenic treatment (p < 0.05), and that this difference did not correspond to the CRT measured by OCT. These results support evidence that intravitreal antiangiogenic medications are effective for ophthalmic complications of diabetes in our population; however, damage to visual structures is not reversed in most patients. And that the perception by the patient (VA) and that of the ophthalmologist (CRT) do not completely correlate in our study.

Background and Objectives: Our study compared the visual and anatomical outcomes of polypoidal choroidal vasculopathy (PCV) patients receiving intravitreal aflibercept (IVA) with or without photodynamic therapy (PDT) over 12 months. Materials and Methods: This retrospective study was performed for 60 eyes from 60 patients with treatment-naïve PCV. Thirty eyes were treated using IVA monotherapy (IVA group), and thirty eyes were treated using a combination of IVA with PDT (IVA/PDT group). The baseline characteristics, treatment outcomes, and retreatment rates were compared between the two groups over a one-year follow-up period. Results: The best-corrected visual acuity (BCVA) was found to have improved significantly in the IVA/PDT group at every 3-month visit. However, no significant BCVA improvement was observed in the IVA group. A significantly lower retreatment rate and higher dry macula rate were found in the IVA/PDT group than that in the IVA group. In the entire population of the study, a better baseline vision and younger age were associated with better final visual outcomes. Retreatment was associated with poor baseline BCVA and IVA monotherapy. Conclusions: The combination of IVA and PDT may offer superior visual improvement and a higher dry macula rate compared to IVA monotherapy in the treatment of PCV patients while requiring fewer retreatments over 12 months.

UNASSIGNED: To evaluate two-year outcomes of intravitreal aflibercept injection for neovascular age-related macular degeneration (nAMD) treated with \'observe before treat-and-extend\' (O-TAE) strategy in the real-world setting.
UNASSIGNED: This retrospective study included treatment-naïve nAMD patients treated with aflibercept using O-TAE regimen and followed up for more than 2 years. Patients were observed bimonthly to check recurrence after 3 monthly loading injections. In case of recurrence, treatment was resumed using the treat-and-extend (TAE) regimen starting from the 4th injection. In case of non-recurrence, observation was continued. Best-corrected visual acuity (BCVA), central macular thickness (CMT), number of injections, TAE intervals, and proportion of recurrence after dry-up following 3 loadings were analyzed.
UNASSIGNED: 38 eyes of 34 patients were included. Follow-up period was 37.0 ± 11.0 months. BCVA by logMAR improved from 0.33 ± 0.29 at baseline to 0.24 ± 0.23 in the 1st year (p = 0.01), and 0.25 ± 0.22 in the 2nd year (p = 0.054). CMT decreased significantly from 357.4 ± 74.5 at baseline to 269.6 ± 48.1 in the 1st year (p < 0.001), and 279.1 ± 54.6 in the 2nd year (p < 0.001). Numbers of injections were 5.1 ± 1.7 in the first year and 3.8 ± 2.4 in the second year. The percentage of eyes with a TAE interval of ≥12 weeks was 37.0% in the first year and 34.4% in the second year. Of the 36 eyes that dried up after 3 loadings, 28 eyes (78%) recurred, and the average period of recurrence was 6.5 months. The remaining 8 eyes (22%) had no recurrence during the mean follow-up period of 29.7 months.
UNASSIGNED: This study showed that the newly suggested O-TAE strategy can reduce the treatment burden significantly reducing the number of injections while improving BCVA and CMT in the first and second year.

Aflibercept (AFL) plus FOLFIRI prolongs overall survival (OS) in patients with metastatic colorectal cancer (mCRC). However, there is limited evidence on the efficacy and safety of AFL plus FOLFIRI previously treated with anti-epidermal growth factor receptor (EGFR) agents. Therefore, we conducted a prospective open-label phase II trial evaluating the efficacy and safety of AFL plus FOLFIRI in Japanese patients with mCRC failing a prior oxaliplatin-based chemotherapy plus an anti-EGFR agent. AFL (4 mg/kg iv) followed by FOLFIRI (irinotecan 180 mg/m2, leucovorin 200 mg/m2 iv, bolus 5-fluorouracil [5-FU] 400 mg/m2, and infusional 5-FU 2400 mg/m2/46 h) was given every 2 weeks until progression or unacceptable toxicities. The primary endpoint was progression-free survival (PFS) rate at 6 months. Forty three patients were enrolled between November 2019 and October 2022. The primary endpoint was met: 6-month PFS rate was 58.8% (90% confidence interval [CI], 45.7%-72.0%). Median PFS and OS were 7.3 months (95% CI, 5.5-11.0 months) and 18.8 months (95% CI, 12.9-26.6 months), respectively. The overall response rate was 20.9% (95% CI, 10.0-36.0%) and disease control rate was 88.4% (95% CI, 74.9-96.1%). The main grade ≥3 adverse events included hypertension (62.8%), neutropenia (55.8%), leukopenia (25.6%), febrile neutropenia (11.6%), fatigue (9.3%), anorexia (9.3%), proteinuria (9.3%), and diarrhea (7.0%). No deaths and no new safety signals with a causal relation to the study treatment were observed. This study suggests that AFL plus FOLFIRI shows a high response rate and a manageable safety profile in Japanese patients with mCRC who failed prior oxaliplatin-based chemotherapy plus an anti-EGFR agent.

OBJECTIVE: This study aimed to compare the treatment outcomes of patients with neovascular age-related macular degeneration (nAMD) who initially received faricimab or aflibercept treatment using propensity score matching (PSM) to align patient backgrounds.
METHODS: Patients with treatment-naïve nAMD who received either faricimab or aflibercept for three consecutive monthly injections as the loading phase were enrolled in this study. In the 1:1 PSM, sex, age, best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), and AMD subtypes in the pre-treatment state were selected as covariates. We examined the BCVA, CMT, CCT, and remaining fluid at 1-, 2-, and 3-month after the first injection.
RESULTS: After PSM, 43 eyes were included in the faricimab and aflibercept group each. Both groups showed significant improvements in BCVA, CMT, and CCT at 1-, 2-, and 3-month after the initial injection compared with baseline. Meanwhile, no significant differences were observed between the two groups at any time point regarding BCVA, CMT, and CCT. At 1-month, 18.6% of patients in the faricimab group and 41.9% in the aflibercept group demonstrated residual subretinal fluid or intraretinal fluid, with a significant difference between the groups (P = 0.03).
CONCLUSIONS: The BCVA improved after three loading injections of both faricimab and aflibercept. Faricimab may provide a favorable early treatment response in reducing subretinal fluid in a Japanese cohort.

BACKGROUND: Anti-vascular endothelial growth factor (VEGF) agents have been the standard treatment for retinal diseases for almost two decades. These treatments are administered via intravitreal injection using single-use vials or prefilled syringes (PFS). In this systematic review, we evaluate health care resource use and clinical outcomes and experiences with PFS for intravitreal injection of anti-VEGF treatments.
METHODS: MEDLINE, EMBASE, and The Cochrane Library were searched from January 1, 2015 to February 8, 2024 to identify literature reporting outcomes regarding procedural efficiency, health care resource use, patient and clinician experiences, and safety for currently approved anti-VEGFs (ranibizumab, aflibercept, brolucizumab) administered using PFS. Comparators were vial-based injections of the same anti-VEGFs.
RESULTS: A total of 36 publications met the criteria for inclusion in the systematic literature review; the majority were non-randomized studies, with a small number of reviews, case series, survey studies, and opinion articles. Publications reported that preparation times were significantly shorter for PFS (40.3-57.9 s) versus vials (ranibizumab, 62.8-98.0 s; aflibercept, 71.9-79.5 s), with no differences in product stability between PFS and vials. Clinicians expressed a preference for PFS and thought PFS were faster, easier to use, and had increased safety versus vials. Publications consistently reported significantly lower rates of endophthalmitis per injection with PFS versus vials (ranibizumab PFS, 0-0.02%; aflibercept PFS, 0.01-0.02%; ranibizumab vial, 0.02-0.05%; aflibercept vial, 0.02-0.06%). Four publications reported increased rates of transient vision loss after aflibercept PFS injection versus vial-based injection. No publications reported outcomes regarding health care resource use or patient experiences.
CONCLUSIONS: The available literature supports the increased procedural efficiency of PFS versus vial-based intravitreal injection of anti-VEGFs. PFS are positively perceived by clinicians and have a safety benefit in the form of a decreased risk of endophthalmitis versus vials.
Anti-vascular endothelial growth factor (VEGF) drugs, given by injection into the eye, are commonly used to treat diseases that affect the back of the eye (the retina). Anti-VEGF drugs are provided in small containers (vials) or in syringes that are already filled with the drug (prefilled syringes). When someone is treated with an anti-VEGF drug from a vial, the drug must first be taken from the vial using a needle and syringe, and then injected. When someone is treated with an anti-VEGF drug from a prefilled syringe, the drug is injected directly from the prefilled syringe, i.e., there are fewer steps involved when a prefilled syringe is used. We searched the medical literature to see if there were differences in clinical outcomes and experiences between prefilled syringes and vials when used to inject anti-VEGF drugs. Clinicians spent about 50% less time getting ready for injections when prefilled syringes were used than when vials were used. Clinicians also preferred to use prefilled syringes than vials for injecting anti-VEGF drugs. Clinicians reported that prefilled syringes were easier to use, faster, and safer than vials. Patients who were given injections from prefilled syringes had a lower rate of infection of the inside of the eye (endophthalmitis) than patients who were given injections from vials. These results indicate that using prefilled syringes for injecting drugs into the eye can improve efficiency at ophthalmology clinics and improve safety for patients.