Successful Treatment of Hemi-Retinal Vein Occlusion with Macular Edema following Spinal Surgery Using Intravitreal Aflibercept and Retinal Photocoagulation: A Case Report.

Introduction: Perioperative visual loss (POVL) owing to hemi-retinal vein occlusion (HRVO) following prone positioning during spinal surgery is rare. Here, we report a case of HRVO with macular edema (ME) after spinal surgery that was successfully treated with intravitreal aflibercept (IVA) injections and retinal photocoagulation (RP). Case Presentation: A 63-year-old Japanese man underwent spinal surgery for lumbar spinal canal stenosis. Surgery was performed with the patient in the prone position under general anesthesia; the operation time was 305 min. No complications were associated with intraoperative anesthesia. On postoperative day 4, the patient noticed decreased visual acuity in his left eye and visited the Department of Ophthalmology on postoperative day 9. The best-corrected visual acuity (BCVA) in the left eye was 0.1. Fundus and optical coherence tomography revealed HRVO and ME in the left eye. IVA injections and RP were performed in the eye, which substantially decreased the ME and improved the patient's BCVA to 0.8. Conclusions: HRVO can cause POVL after prone positioning during spinal surgery. This is the first case of HRVO with ME after spinal surgery, which was successfully treated with IVA injections and RP.

Aflibercept or ranibizumab for diabetic macular edema.

Background: Vascular endothelial growth factor (VEGF) is the primary substance involved in retinal barrier breach. VEGF overexpression may cause diabetic macular edema (DME). Laser photocoagulation of the macula is the standard treatment for DME; however, recently, intravitreal anti-VEGF injections have surpassed laser treatment. Our aim was to evaluate the efficacy of intravitreal injections of aflibercept or ranibizumab for managing treatment-naive DME. Methods: This single-center, retrospective, interventional, comparative study included eyes with visual impairment due to treatment-naive DME that underwent intravitreal injection of either aflibercept 2 mg/0.05 mL or ranibizumab 0.5 mg/0.05 mL at Al-Azhar University Hospitals, Egypt between March 2023 and January 2024. Demographic data and full ophthalmological examination results at baseline and 1, 3, and 6 months post-injection were collected, including the best-corrected distance visual acuity (BCDVA) in logarithm of the minimum angle of resolution (logMAR) notation, slit-lamp biomicroscopy, dilated fundoscopy, and central subfield thickness (CST) measured using spectral-domain optical coherence tomography. Results: Overall, the 96 eyes of 96 patients with a median (interquartile range [IQR]) age of 57 (10) (range: 20-74) years and a male-to-female ratio of 1:2.7 were allocated to one of two groups with comparable age, sex, diabetes mellitus duration, and presence of other comorbidities (all P >0.05). There was no statistically significant difference in baseline diabetic retinopathy status or DME type between groups (both P >0.05). In both groups, the median (IQR) BCDVA significantly improved from 0.7 (0.8) logMAR at baseline to 0.4 (0.1) logMAR at 6 months post-injection (both P = 0.001), with no statistically significant difference between groups at all follow-up visits (all P >0.05). The median (IQR) CST significantly decreased in the aflibercept group from 347 (166) µm at baseline to 180 (233) µm at 6 months post-injection, and it decreased in the ranibizumab group from 360 (180) µm at baseline to 190 (224) µm at 6 months post-injection (both P = 0.001), with no statistically significant differences between groups at all follow-up visits (all P >0.05). No serious adverse effects were documented in either group. Conclusions: Ranibizumab and aflibercept were equally effective in achieving the desired anatomical and functional results in patients with treatment-naïve DME in short-term follow-up without significant differences in injection counts between both drugs. Larger prospective, randomized, double-blinded trials with longer follow-up periods are needed to confirm our preliminary results.

Transitioning from Aflibercept to Biosimilar Ranibizumab in Neovascular AMD (The TRANSFORM Trial): A Multicenter Observational Study.

Purpose: This study investigates the efficacy of transitioning patients with neovascular age-related macular degeneration (nAMD) from aflibercept (T1) to biosimilar ranibizumab (T2), an approach not previously documented in literature. Methods: In this multicenter observational study, patients over 50 years of age with nAMD were shifted from intravitreal aflibercept (IVI AFL) to biosimilar ranibizumab (B-RBZ) due to financial constraints. This study employed standardized ophthalmological methods to assess visual acuity (VA), central macular thickness (CMT), and subretinal and intraretinal fluid. Statistical analyses included paired t-tests, Wilcoxon signed-rank tests, and linear regression. Results: A total of 29 eyes (12 males and 17 females) were analyzed. Mean age was 72.55 ±6.43 years. VA improved significantly during T1, with a mean increase from 55.0 ± 10.2 to 70.0 ± 8.5 ETDRS letters at the switch time point (p < 0.01), then a slight decrease to 62.3 ± 8.9 at 12 months (p < 0.05) was noted during T2. The mean CMT decreased notably from 400 ± 50 to 290 ± 45 µm at the switch. The final CMT at 12 months after switching to B-RBZ was 280 ± 40 µm (p < 0.01). There was a significant decrease in the retinal and intra retinal fluid during T1, followed by a gradual increase during T2. A significant correlation (p < 0.05) was noted between the presence of intraretinal fluid and increased injection frequency of B-RBZ. Conclusion: The switch from IVI AFL to IVI B-RBZ in patients with nAMD demonstrated efficacy in maintaining the VA and macular anatomy, with some challenges in fluid management.

Subconjunctival aflibercept inhibits corneal angiogenesis and VEGFR-3+CD11b+ cells.

PURPOSE: This study aimed to investigate the effects of subconjunctival injection of aflibercept, a soluble protein decoy for VEGFR-1 and VEGFR-2, on corneal angiogenesis and VEGFR-expressing CD11b+ cells in a mouse model of suture-induced corneal neovascularization. METHODS: Corneal neovascularization was induced in BALB/c mice by placing three sutures on the cornea. Immediately after surgery, either 200 µg aflibercept (5 µL) or an equal volume of phosphate-buffered saline (PBS) was administered into the subconjunctival space. Seven days after later, corneal new vessels were quantified through clinical examination and measurement of the CD31-stained area in corneal flat mounts. The levels of pro-angiogenic and inflammatory markers in the cornea were evaluated using RT-qPCR. The percentages of VEGFR-2+CD11b+ cells and VEGFR-3+CD11b+ cells were analyzed in the cornea, blood, and draining cervical lymph nodes (DLNs) using flow cytometry. RESULTS: Subconjunctival injection of aflibercept significantly reduced the growth of corneal new vessels compared to subconjunctival PBS injection. The mRNA levels of Cd31, vascular growth factors (Vegfc and Angpt1), and pro-angiogenic/inflammatory markers (Tek/Tie2, Mrc1, Mrc2, and Il6) in the cornea were downregulated by subconjunctival aflibercept. Also, the percentage of VEGFR-3+CD11b+ cells in the cornea, blood, and DLNs was decreased by aflibercept, whereas that of VEGFR-2+CD11b+ cells was unaffected. CONCLUSION: Subconjunctival aflibercept administration inhibits inflammatory angiogenesis in the cornea and reduces the numbers of cornea-infiltrating and circulating VEGFR-3+CD11b+ cells.

[Aflibercept in a real-world setting: the AURIGA study : 24-month results of the German cohort of treatment-naïve patients with macular edema following retinal vein occlusion receiving intravitreal aflibercept]. / Aflibercept im klinischen Alltag: die AURIGA-Studie : 24-Monats-Ergebnisse der deutschen Kohorte behandlungsnaiver Patienten mit Makulaödem bei retinalem Venenverschluss unter Therapie mit intravitrealem Aflibercept.

BACKGROUND: AURIGA is the largest prospective real-world study to evaluate intravitreal aflibercept 2 mg (IVT-AFL) treatment of macular edema (ME) secondary to retinal vein occlusion (RVO) and diabetic macular edema. Here we present the 24-month data from the German cohort of treatment-naïve patients with ME due to RVO. METHODS: Treatment-naïve patients with ME secondary to RVO were treated with IVT-AFL 2 mg in the routine clinical practice. The primary endpoint was mean change in visual acuity (VA, early treatment diabetic retinopathy, ETDRS, letters) at month 12 compared to baseline. Analyses were descriptive. RESULTS: Analysis included 130 patients with RVO (n = 61, 46.9% with central RVO, n = 69, 53.1% with branch RVO). The mean (± SD) time the RVO patients remained in the study was 18.4 ± 7.4 months. The mean VA gain (95% confidence interval) in the overall cohort was +10.9 (7.5-14.2) letters at month 12 and +9.7 (6.1-13.3) at month 24 (baseline VA 56.5 ± 18.9 letters). At 24 months, 67% of RVO patients gained ≥5 letters and 40% gained ≥15 letters. The mean number of injections was 4.4 ± 1.3 up to month 6, 6.2 ± 2.7 up to month 12 and 8.2 ± 4.5 up to month 24. The mean central retinal thickness (CRT) reduction was -206µm (-252 to -160µm) at 12 months and -219µm (-263 to -175µm) at 24 months (baseline CRT 507 ± 177 µm). The safety profile was consistent with that of previous studies. DISCUSSION: In the German AURIGA cohort of treatment-naïve patients with ME secondary to RVO, IVT-AFL 2 mg treatment in clinical practice resulted in rapid and clinically relevant VA gains and a reduction in CRT. These results were largely maintained over 24 months despite the low injection frequency from month 6.

Long acting delivery and therapies for neovascular age-related macular degeneration.

INTRODUCTION: Neovascular age-related macular degeneration (nAMD) represents a leading cause of severe visual impairment in individuals over 50 years of age in developed nations. Intravitreal anti-vascular endothelial growth factor (VEGF) injections have become the standard of care for treating nAMD; however, monthly or bimonthly dosing represents significant time and cost burden due to the disease's chronic nature and limited medication half-life. AREAS COVERED: This review summarizes innovative therapeutics and delivery methods for nAMD. Emerging methods for extended drug delivery include high molar concentration anti-VEGF drugs, intravitreal sustained release devices, reservoirs for intravitreal delivery, and gene therapy biofactories. In addition to VEGF-A, therapies targeting inhibition of VEGF-C and D, the angiopoetin-2 (Ang-2)/Tie-2 pathway, tyrosine kinases, and integrins are reviewed. EXPERT OPINION: The evolving therapeutic landscape of nAMD is rapidly expanding our toolkit for effective and durable treatment. Recent FDA approvals of faricimab (Vabysmo) and high dose aflibercept (Eylea HD) for nAMD with potential extension of injection intervals up to four months have been promising developments for patients and providers alike. Further research and innovation, including novel delivery techniques and pharmacologic targets, is necessary to validate the efficacy of developing therapeutics and characterize real-world outcomes. demonstrating promise in expanding treatment durability.

Efficacy and safety of Brolucizumab for neovascular age-related macular degeneration: a systematic review and meta-analysis.

Background: To evaluate the efficacy and safety of Brolucizumab for neovascular age-related macular degeneration (n-AMD) through a systematic review and meta-analysis. Materials and Methods: Cochrane, PubMed, Embase, and Web of Science databases were comprehensively searched for relevant studies. Stata and RevMan5.4 were applied for meta-analysis and risk of bias assessment. Data on the best-corrected visual acuity (BCVA), central subfield thickness (CSFT), presence of intraretinal fluid (IRF) and/or subretinal fluid (SRF), participants with ≥1 serious adverse events, and participants with ≥1 adverse events were analyzed. Results: Six studies were finally included. Meta-analysis showed statistical differences in BCVA [SMD = -0.65, 95% CI [-0.17 to -0.23], P < 0.05], the presence of IRF and/or SRF [RR = 0.67, 95% CI [0.56-0.79], P < 0.05], and the safety of participants with ≥1 serious adverse events [RR = 0.57, 95% CI [0.39-0.84], P < 0.05] between the experimental group and the control group. However, no statistical differences were observed in CSFT [SMD = -1.16, 95% CI [-2.79 to 0.47], P > 0.05] or the safety of participants with ≥1 adverse events [RR = 1.07, 95% CI [0.97-1.17], P > 0.05]. Conclusions: Compared to other anti-VEGF drugs such as Aflibercept and Ranibizumab, intravitreal injection of 6 mg Brolucizumab is more effective and safer for n-AMD, especially in the presence of IRF and/or SRF, and for participants with ≥1 serious adverse events.

Efficacy of Faricimab vs Aflibercept in Diabetic Macular Edema in the 20/50 or Worse Vision Subgroup in Phase 3 YOSEMITE/RHINE Trials.

PURPOSE: DRCR.net Protocol T data suggest the response to treatment among patients with diabetic macular edema (DME) may vary depending on baseline best-corrected visual acuity (BCVA). We evaluated the efficacy of faricimab 6 mg versus aflibercept 2 mg over 2 years in patients with DME enrolled in faricimab phase 3 trials with baseline Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA ≤20/50. DESIGN: YOSEMITE/RHINE were identically designed, multicenter, randomized, double-masked, active comparator-controlled, noninferiority trials. PARTICIPANTS: Adults aged ≥18 years with center-involving macular edema secondary to type 1 or 2 diabetes. METHODS: Patients were randomized to faricimab every 8 weeks (Q8W), faricimab per a personalized treat-and-extend-based regimen (T&E), or aflibercept Q8W. Post hoc subgroup analyses were conducted using the intent-to-treat population with baseline BCVA ≤20/50 (ETDRS letters <69). MAIN OUTCOME MEASURES: Changes in ETDRS BCVA and central subfield thickness (CST) from baseline to years 1 and 2 were compared between treatment arms using mixed-model repeated measures analyses. RESULTS: In YOSEMITE/RHINE, 220/217 patients in the faricimab Q8W; 220/219, faricimab T&E; and 219/214, aflibercept Q8W arms had baseline BCVA ≤20/50. In both trials, mean change in ETDRS BCVA was comparable between treatments at years 1 and 2. In YOSEMITE, adjusted mean (95% CI) change from baseline in CST (µm) at year 1 was greater with faricimab Q8W (-232.8 [-243.5, -222.1]) and faricimab T&E (-217.4 [-227.9, -206.9]) versus aflibercept Q8W (-190.4 [-200.9, -179.8]; P<0.0001 and P=0.0004, respectively). The pattern was similar in RHINE: faricimab Q8W, -214.2 (-225.3, -203.1); faricimab T&E, -206.6 (-217.4, -195.7); aflibercept Q8W, -186.6 (-197.7, -175.5); P=0.0006 and P=0.0116 for faricimab arms versus aflibercept, respectively. In both trials, change from baseline in CST at year 2 was greater with faricimab Q8W versus aflibercept. Median time to first CST <325 µm and first absence of intraretinal fluid was shorter in the faricimab arms versus aflibercept, with fewer injections on average. CONCLUSIONS: In patients with DME and baseline ETDRS BCVA ≤20/50, faricimab treatment resulted in comparable visual acuity, greater reduction in retinal thickness, and fewer injections compared with aflibercept over 2 years of treatment.

Differences between pathologic and non-pathologic high myopia in 4-year outcomes of anti-VEGF therapy for macular neovascularization.

This retrospective observational study aimed to investigate the difference in 4-year outcomes of ranibizumab or aflibercept therapy for macular neovascularization (MNV) with high myopia between pathologic myopia (PM) and non-PM. This study was conducted at Kyoto University Hospital and included consecutive treatment-naïve eyes with active myopic MNV, in which a single intravitreal ranibizumab or aflibercept injection was administered, followed by a pro re nata (PRN) regimen for 4 years. Based on the META-PM study classification, eyes were assigned to the non-PM and PM groups. This study analyzed 118 eyes of 118 patients (non-PM group, 19 eyes; PM group, 99 eyes). Baseline, 1-year, and 2-year best-corrected visual acuity (BCVA) were significantly better in the non-PM group (P = 0.02, 0.01, and 0.02, respectively); however, the 3-year and 4-year BCVA were not. The 4-year BCVA course was similar in both groups. However, the total number of injections over 4 years was significantly higher in the non-PM than in the PM group (4.6 ± 2.6 vs. 2.9 ± 2.6, P = 0.001). Four-year BCVA significantly correlated only with baseline BCVA in both non-PM (P = 0.047, ß = 0.46) and PM groups (P < 0.001, ß = 0.59). In conclusion, over the 4-year observation period, the BCVA course after anti-VEGF therapy for myopic MNV was similar in the eyes with non-PM and those with PM; however, more additional injections in a PRN regimen were required in the eyes with non-PM compared to those with PM. Thus, more frequent and careful follow-up is required for the eyes with non-PM compared with those with PM to maintain long-term BCVA.

Prospective, Observational Study of Aflibercept Use in Combination with FOLFIRI in Patients with Metastatic Colorectal Cancer: A Real-World Effectiveness Study.

BACKGROUND: This was an observational study prospectively evaluating the effectiveness and safety of aflibercept/FOLFIRI administered in second-line mCRC per the reimbursement criteria in Poland. METHODS: Consecutive mCRC patients who progressed with first-line oxaliplatin-based chemotherapy received aflibercept (4 mg/kg IV) followed by FOLFIRI every 2 weeks until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS); overall survival (OS) and safety were the secondary endpoints. RESULTS: A total of 93 patients were treated at 17 Polish sites. A median of 10 cycles was administered. Over a median treatment duration of 5.3 months, median PFS and median OS were 8.4 months [95% CI, 6.9-9.9] and 27.0 months [95% CI, 23.9-30.1], respectively. There was no significant impact of primary tumor location, metastatic site, or KRAS status on PFS and OS. Main grade ≥ 3 adverse events were neutropenia (16%), hypertension (8%), diarrhea (4%), and stomatitis (4%). CONCLUSIONS: The benefits/risks of Aflibercept plus FOLFIRI administered per the Polish reimbursement criteria in second-line treatment of mCRC after failure of a prior oxaliplatin-based regimen is confirmed.

Biosimilar candidate CT-P42 in diabetic macular edema: 24-week results from a randomized, active-controlled, Phase III study.

OBJECTIVE: To demonstrate the therapeutic similarity of CT-P42 compared to reference aflibercept (Eylea®) in adult patients with diabetic macular edema (DME). DESIGN: Randomized, active-controlled, double-masked, Phase III clinical trial PARTICIPANTS: Patients with a diagnosis of either type 1 or 2 diabetes mellitus (DM) with DME involving the center of the macula. METHODS: Patients were randomized (1:1) to receive either CT-P42 or reference aflibercept (2 mg/0.05 mL) by intravitreal injection every 4 weeks (5 doses) then every 8 weeks (4 doses) in the main study period. Results up to Week 24 are reported herein. MAIN OUTCOME MEASURES: The primary endpoint was mean change from baseline at Week 8 in best corrected visual acuity (BCVA) using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Equivalence between CT-P42 and reference aflibercept was to be concluded if the two-sided 95% confidence interval (CI) (global assumptions) and two-sided 90% CI (US Food and Drug Administration [FDA] assumptions) for the treatment difference fell entirely within the equivalence margin of ±3 letters, as assessed in the full analysis set. RESULTS: Overall, 348 patients were randomized (CT-P42: 173; reference aflibercept: 175). BCVA improved from baseline to Week 8 in both groups, with a least squares mean (standard error) improvement of 9.43 (0.798) and 8.85 (0.775) letters in the CT-P42 and reference aflibercept groups, respectively. The estimated between-group treatment difference was 0.58 letters, with the CIs within the pre-defined equivalence margin of ±3 letters (95% CI -0.73, 1.88 [global]; 90% CI -0.52, 1.67 [FDA]). Through Week 24, other efficacy results for the two groups, in terms of change in BCVA and retinal central subfield thickness, as well as ETDRS Diabetic Retinopathy Severity Scale score, supported therapeutic similarity. Pharmacokinetics, usability, safety (including the proportions of patients experiencing at least one treatment-emergent adverse event [CT-P42: 50.3%; reference aflibercept: 53.7%]), and immunogenicity were also comparable between groups. CONCLUSIONS: This study in patients with DME demonstrated equivalence between CT-P42 and reference aflibercept (2 mg/0.05 mL) in terms of efficacy, with similar pharmacokinetic, usability, safety, and immunogenicity profiles.

Switching from a Fixed Monthly Aflibercept Regimen to Bi-Monthly Brolucizumab in Refractory Cases of Neovascular Age-Related Macular Degeneration.

Background/Objectives: This study aimed to assess the effectiveness of bi-monthly brolucimumab treatment in patients with neovascular age-related macular degeneration (nAMD) refractory to monthly aflibercept treatment. Methods: A retrospective chart review included 32 eyes of patients with refractory nAMD who switched from monthly intravitreal aflibercept treatment to bi-monthly intravitreal brolucizumab treatment. This study evaluated changes in visual acuity (VA), intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachment (PED), and central macular thickness (CMT), at specific times as follows: baseline before switching (T0), 2 months after switching (T1), 4 months after switching (T2), and 6 months after switching (T3). Results: The mean best-corrected visual acuity (BCVA) did not significantly change across all time points (0.52 ± 0.12, 0.48 ± 0.27, 0.48 ± 0.28, and 0.50 ± 0.27 logarithms of the minimum angle of resolution in T0, T1, T2, and T3, respectively). CMT significantly decreased after additional brolucizumab injections compared to the baseline (218.2 ± 48.6 and 207.9 ± 49.8 µm, respectively; p = 0.001). The PED height also significantly decreased from 251.0 ± 165.4 to 154.4 ± 115.65 µm (p < 0.001), with complete resolution in nine patients (28%). The mean subfoveal choroidal thickness (SFCT) before brolucizumab treatment was 262.8 ± 79.7 µm, which decreased to 233.0 ± 71.2 µm (p = 0.001) after the first injection. The final SFCT also significantly decreased after additional brolucizumab injections compared to the baseline SFCT (p = 0.012). Conclusions: Bi-monthly brolucizumab treatment proves effective for patients refractory to monthly fixed aflibercept, resulting in positive anatomical changes without significant deterioration in visual acuity. This approach provides a promising prognosis while reducing the treatment burden on refractory patients.

Short-Term Real-World Outcomes of Intensive Aflibercept Injection for Refractory Neovascular Age-Related Macular Degeneration.

Background: The aim of this study is to report short-term outcomes after the shortening of the treatment interval to 4 weeks with a treat-and-extend (TAE) regimen (Si4w) of aflibercept in patients with refractory neovascular age-related macular degeneration (nAMD). Methods: This retrospective study included 34 patients given aflibercept with a TAE regimen of a minimum of a 4-week interval when they had a limited response to bimonthly aflibercept. The best-corrected visual acuity (BCVA) and central macular thickness (CMT) were compared before and after Si4w. The resolution of subretinal and intraretinal fluid before and after Si4w was also examined. The risk factors associated with persistent fluid were analyzed. Results: The average treatment duration until initiation of Si4w was 57.82 ± 28.59 months, with an average of 23.64 ± 12.40 injections administered. The BCVA was not significantly improved after Si4w. The CMT decreased significantly from 427.91 ± 125.74 µm to 336.38 ± 121.67 µm at the third visit (p < 0.001). Eighteen eyes (52.9%) showed complete resolution, and twenty-three eyes (67.6%) experienced complete resolution at least once during the three visits. The duration of fluid before Si4w was significantly associated with complete resolution (p = 0.011). Conclusions: Si4w of aflibercept showed satisfactory anatomical outcomes with complete resolution of fluid in patients with a limited response to bimonthly aflibercept injections, and should be considered as a useful treatment option.

Association of Polyp Regression after Loading Phase with 12-Month Outcomes of Eyes with Polypoidal Choroidal Vasculopathy.

PURPOSE: We compared 12-month outcomes of eyes with polypoidal choroidal vasculopathy (PCV) with or without complete regression of polyps observed one month after three monthly intravitreal administrations (loading phase) of aflibercept (2.0 mg/0.05 mL) or brolucizumab (6.0 mg/0.05 mL). METHODS: All patients underwent indocyanine green angiography at both baseline and 3 months after initial injection and were followed up monthly with an as-needed regimen for up to 12 months. A total of 62 patients with PCV were included: 30 eyes were treated with brolucizumab, and 32 were treated with aflibercept. Eyes with complete regression of polyps (regression group) had significantly smaller maximum polyp diameter and were more frequently treated with brolucizumab than those without complete regression (non-regression) group. RESULTS: Best corrected visual acuity was comparable between the two groups at 12 months. Although the 12-month retreatment-free proportion was comparable between the two groups (33.0% versus 27.0%, p = 0.59), a retreatment-free period was significantly longer in the regression group than in the non-regression group (8.3 ± 3.3 versus 6.5 ± 3.6 months, p = 0.022), and the number of additional injections was significantly fewer in the regression group than in the non-regression group (1.2 ± 1.2 versus 3.0 ± 2.6, p = 0.007). CONCLUSIONS: Complete regression of polyps observed after the initial phase possibly prolongs the retreatment-free period and reduces the number of additional injections irrespective of aflibercept or brolucizumab.

Switch to faricimab after initial treatment with aflibercept in eyes with diabetic macular edema.

PURPOSE: To assess the effectiveness of a switch to faricimab in individuals affected by DME and previously treated with aflibercept. METHODS: In this retrospective, single-center study, DME patients previously treated with at least 3 injections of aflibercept then switched to faricimab were enrolled. Best corrected visual acuity (BCVA) and central subfield thickness (CST) were recorded at baseline, at the time of the switch and at 6 months follow-up. At transition to faricimab, patients were categorized as "good visual responders" (≥ 5 letters from baseline) or "poor visual responders" (< 5 letters), and as "good anatomical responders" (any reduction in edema compared to baseline) or "poor anatomical responders" (no reduction or worsening of edema). Changes in BCVA and CST were recorded at 6 months after the switch to faricimab. RESULTS: 100 eyes of 100 patients (61 female, 61%) were switched to faricimab after a mean of 6.8 ± 3.3 aflibercept injections. At the 6 months follow-up, only "poor visual responders" (N = 62) demonstrated a meaningful increase in BCVA (Δswitch-6M = + 5 letters; P = 0.007), coupled with a reduction in CST (Δswitch-6M = - 67.9 µm; P = 0.004); participants with "poor anatomical response" upon transitioning exhibited a significant functional gain (Δswitch-6M = + 4.5 letters; p = 0.05) but limited CST enhancements (Δswitch-6M = - 95.1 µm; p = 0.05). CONCLUSIONS: Faricimab shows a positive impact on anatomical and functional metrics in DME cases refractory to aflibercept.

Macular Ischemia Changes in Patients with Diabetic Macular Edema Treated with Aflibercept and Ranibizumab.

Τhis study aims to assess changes in the fovea avascular zone (FAZ) in treatment naïve patients receiving aflibercept or ranibizumab injections for diabetic macular edema (DME). Best corrected visual acuity (BCVA) testing, OCT, and OCT-angiography imaging were performed at baseline and 1 month after each injection. Injections of either aflibercept or ranibizumab were administered monthly for 6 consecutive months. FAZ in the superficial (SCP) and the deep capillary plexus (DCP) using OCT angiography was recorded for each visit. Fifty eyes from fifty patients with a mean age of 67.0 ± 10.7 years were included in the study. Twenty-five patients received aflibercept and twenty-five received ranibizumab. BCVA was 40.8 ± 10.0 and increased to 52.1 ± 7.9 ETDRS letters at the last visit (p < 0.001). CRT was 295.6 ± 34.0 at baseline and 247.9 ± 29.7 at the last study visit (p < 0.001). SCP FAZ was 350.6 ± 79.5 µm2 at baseline and 339.0 ± 71.3 µm2 after sox monthly injections (p = 0.132). DCP FAZ was 558.6 ± 199.0 µm2 at baseline and 459.5 ± 156.1 µm2 after six monthly injections (p < 0.001). There was no effect of the choice of ranibizumab or aflibercept on DCP FAZ change (p = 0.277). In conclusion, treatment with 6 monthly injections of ranibizumab and aflibercept led to an increase in BCVA and a decrease in CRT and DCP FAZ area. Both drugs led to an improvement in DCP ischemia.

Analytical Characterization for Similarity Assessment Between an Aflibercept Biosimilar SB15 and Reference Product (Eylea®).

INTRODUCTION: SB15 is a proposed biosimilar product of reference aflibercept (Eylea®), an approved biological drug product for retinal diseases including neovascular age-related macular degeneration (nAMD). This study aimed to assess the analytical similarity between SB15 and its commercially available reference product (RP) sourced from the United States (US-aflibercept) and European Union (EU-aflibercept) in terms of structural, physicochemical, and biological properties. METHODS: A panel of state-of-the-art analytical methods was used for the comprehensive characterization of SB15 and US/EU-aflibercept. In terms of the structural and physicochemical properties, primary structure; post-translational modifications (PTM); higher-order structure; purity and impurities; charge variants; and glycosylation were compared. In addition, biological characterization including mechanism of action (MoA)-related and Fc-related biological activities was conducted. RESULTS: Analytical similarity between SB15 and US/EU-aflibercept was demonstrated. The primary and higher-order structure of SB15 was confirmed to be comparable to that of US/EU-aflibercept. In addition, there were no meaningful differences in the physicochemical properties in terms of size and charge heterogeneity between SB15 and its RP. SB15 and RP were similar in biological activities including MoA-related binding activities, potencies, and Fc-related biological functions. Consequently, SB15 was confirmed to be highly similar to US/EU-aflibercept. CONCLUSIONS: Based on a comprehensive analytical similarity assessment of structural, physicochemical, and biological properties, SB15 was demonstrated to be highly similar to US/EU-aflibercept RP, supporting safe and effective use of SB15.

Near vision in patients with DME and RVO treated with aflibercept and correlation with NEI VFQ-25 questionnaire.

BACKGROUND: The aim of this study is to evaluate near and distance visual acuity (VA) and their correlation with the National Eye Institute Visual Function Questionnaire (NEI VFQ-25) outcomes in patients with diabetic macular edema (DME) and macular edema due to retinal vein occlusion (RVO) treated with aflibercept. METHODS: In this prospective study, we included 87 eyes of patients diagnosed with DME (n = 61) and RVO (n = 26), who received aflibercept treatment and were followed until the 8th injection. Near VA was examined on the 1st, 2nd, 3rd, 4th, 6th, and 8th injection, and patients completed the NEI VFQ-25 on the 1st, 4th, and 8th aflibercept injection. RESULTS: The mean near VA at baseline in all eyes was 0.89 ± 0.12 logMAR. With every administration, there was a statistically significant improvement; on the 4th (0.70 ± 0.19; p = 0.000) and the 8th application (0.60 ± 0.19; p = 0.000). At baseline, the mean NEI VFQ-25 total score was 71 ± 14%, and improved to 81 ± 13% (p = 0.000) on the 8th injection. The most significant score gain was recorded in the near VA subscale (+ 20 ± 14%, p = 0.000). There was no statistically significant difference between DME and RVO group in the questionnaire or near VA outcomes. CONCLUSION: Aflibercept treatment resulted in a remarkable improvement of near vision by 4 lines of logMAR optotype after the 8th application. The near vision questionnaire subscale, initially scoring the lowest, exhibited the greatest gain during the treatment period. This underscores the importance of near vision and reading ability for patients with DME and RVO.

Experience with the use of intravitreal bevacizumab in cases with type I retinopathy of prematurity in a Latin American country.

In retinopathy of prematurity (ROP) type I, the use of intravitreal bevacizumab (IVB), which is an inhibitor of endothelial growth factor (VEGF), has become popular despite not being a therapy approved by regulatory agencies. However, IVB has shown positive effects in halting disease progression at lower costs compared to other anti-VEGF therapies (ranibizumab or aflibercept). In this report, we present the experience during the treatment with IVB of 102 Colombian children with ROP type I, with a success rate of 98% (100). Complications occurred in 3.9% (4). Finally, we conclude that a single dose of IVB is an effective therapy for the management of ROP type I, with a lower risk of complications and retreatment.

Comparative study on the efficacy of Conbercept and Aflibercept in the treatment of neovascular age-related macular degeneration.

This study compares the effectiveness of Conbercept and Aflibercept in treating neovascular age-related macular degeneration (nAMD). Conducted at the First Affiliated Hospital of Chongqing Medical University's Ophthalmology Department (May 2020-May 2023), this prospective study enrolled 159 nAMD patients. Participants were randomly divided into two groups: one receiving 0.5 mg Conbercept and the other 2 mg Aflibercept intravitreal injections. Over 12 months, the study, employing a Treat-and-Extend (T&E) regimen, assessed Best-Corrected Visual Acuity (BCVA), Central Retinal Thickness (CRT) changes and injection frequency. Of the 159 patients, 137 (149 eyes) completed the study. No significant age difference was found between the groups (P = 0.331). After 12 months, BCVA improved similarly in both groups (Conbercept: 52.8 ± 18.9, Aflibercept: 52.0 ± 19.7 letters; P = 0.820). CRT reduction was also comparable (Conbercept: 246.3 ± 82.8 µm, Aflibercept: 275.9 ± 114.3 µm; P = 0.079). Injection frequencies averaged 6.9 ± 0.7 (Conbercept) and 6.7 ± 0.7 (Aflibercept; P = 0.255). Subtype analysis revealed Type 1 MNV had higher baseline BCVA and lower CRT, with more frequent injections compared to other types. Both Conbercept and Aflibercept are clinically similar in efficacy for nAMD, with the T&E regimen proving therapeutically effective and potentially reducing patient costs. Anti-VEGF treatment efficacy varies across nAMD subtypes, indicating a potential benefit in tailored treatments for specific subtypes.Clinical trial registration number NCT05539235 (Protocol Registration and Results System).