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17 pages, 537 KB  
Article
Ultrasound-Enhanced Assessment of Vitreous Status in Exudative AMD: Associations with Neovascular Phenotypes, Treatment Burden, and Functional Outcomes
by Cristina Rodriguez-Vidal, Lucía Galletero Pandelo, Nerea Martínez-Alday, Manuel Bande and María José Blanco Teijeiro
J. Clin. Med. 2026, 15(1), 167; https://doi.org/10.3390/jcm15010167 - 25 Dec 2025
Viewed by 291
Abstract
Background/Objectives: The influence of the vitreoretinal interface on neovascular age-related macular degeneration (nAMD) remains poorly characterized. Most previous studies relied solely on macular optical coherence tomography (OCT), which provides limited information about global posterior vitreous detachment (PVD). This study evaluated (1) whether ultrasonography-defined [...] Read more.
Background/Objectives: The influence of the vitreoretinal interface on neovascular age-related macular degeneration (nAMD) remains poorly characterized. Most previous studies relied solely on macular optical coherence tomography (OCT), which provides limited information about global posterior vitreous detachment (PVD). This study evaluated (1) whether ultrasonography-defined PVD status differs between nAMD eyes and healthy controls, and (2) whether baseline PVD influences macular neovascularization (MNV) phenotype and functional outcomes following anti-vascular endothelial growth factor (anti-VEGF) therapy. Methods: In this prospective longitudinal study, treatment-naïve nAMD eyes and population-based healthy controls underwent dynamic B-scan ultrasonography and spectral-domain OCT. PVD was categorized as absent, partial, or complete. nAMD eyes received intravitreal aflibercept according to a treat-and-extend protocol and were followed for 12 months. Structural parameters—including subretinal fluid (SRF), intraretinal fluid (IRF), and central foveal thickness—along with best-corrected visual acuity (BCVA) were recorded. A multivariable linear regression model was performed to assess whether PVD independently predicted BCVA gain after adjusting for age, baseline BCVA, MNV subtype, SRF, atrophy, and number of injections. Results: Absence of PVD was significantly more frequent in nAMD eyes than in controls (p < 0.001), whereas complete PVD prevalence was comparable. In nAMD, absence of PVD was associated with a higher prevalence of MNV type 2 (p = 0.032), while partial/complete PVD correlated with type 1 lesions. After 12 months, eyes without PVD achieved the greatest visual improvement (mean BCVA gain +0.34 ± 0.26), outperforming eyes with complete PVD (p = 0.026). A multivariable model confirmed that absence of PVD was an independent predictor of greater BCVA gain (β = −0.27; 95% CI −0.42 to −0.12; p = 0.0008). Eyes with complete PVD required more injections (p = 0.046). SRF and foveal-thickness reductions occurred across groups, whereas IRF changes were similar. Conclusions: Ultrasonography-defined PVD status differs markedly between nAMD and healthy eyes and independently influences neovascular phenotype and functional response to anti-VEGF therapy. These findings underscore the physiological importance of the vitreoretinal interface and support the use of ocular ultrasonography as an adjunct tool for assessing global vitreous status in selected nAMD settings. Full article
(This article belongs to the Section Ophthalmology)
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11 pages, 14078 KB  
Case Report
Combined Pharmacological and Pneumatic Displacement Therapy for Sub-Macular Haemorrhage Secondary to Age-Related Macular Degeneration: A Case Series and Review of the Literature
by Agnieszka Kudasiewicz-Kardaszewska, Małgorzata Anna Ozimek, Tomasz Urbański, Kinga Jamontt, Aleksander Tkaczenko, Karolina Bonińska and Sławomir Cisiecki
Life 2026, 16(1), 3; https://doi.org/10.3390/life16010003 - 19 Dec 2025
Viewed by 348
Abstract
Purpose: We aimed to present the clinical outcomes of a combined pharmacological and gas-assisted treatment for sub-macular haemorrhage secondary to neovascular age-related macular degeneration (nAMD). Methods: This retrospective case series included ten eyes with sub-macular haemorrhage (SMH) treated between January 2024 and September [...] Read more.
Purpose: We aimed to present the clinical outcomes of a combined pharmacological and gas-assisted treatment for sub-macular haemorrhage secondary to neovascular age-related macular degeneration (nAMD). Methods: This retrospective case series included ten eyes with sub-macular haemorrhage (SMH) treated between January 2024 and September 2025. All patients received intravitreal alteplase (100 µg) and C3F8 gas, followed by aflibercept (2 mg or 8 mg) within a treat-and-extend regimen. BCVA- and OCT-based anatomical changes were recorded at baseline, 7–14 days, 1 month, 3 months, and 6 months. BCVA changes were analysed using repeated-measures testing. Results: Mean BCVA improved from 0.99 ± 0.21 logMAR at baseline to 0.89 ± 0.20 at 7–14 days, 0.80 ± 0.20 at 1 month, 0.60 ± 0.18 at 3 months, and 0.53 ± 0.20 at 6 months (p < 0.05 for overall change). Eight eyes (80 percent) showed restoration of foveal contour, while two developed foveal atrophy. No major adverse events occurred. Conclusion: Combined intravitreal alteplase and C3F8, followed by aflibercept, may provide favourable short-term visual and anatomical improvement in SMH secondary to nAMD. Early intervention appears beneficial, but larger controlled studies are needed to confirm these findings. Full article
(This article belongs to the Special Issue Eye Diseases: Diagnosis and Treatment, 3rd Edition)
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12 pages, 1073 KB  
Article
Clinical Characteristics of Patients with Neovascular Age-Related Macular Degeneration and Responses to Anti-VEGF Therapy: Four-Group Stratification Based on Drusen and Punctate Hyperfluorescence
by Hiroyuki Kamao, Katsutoshi Goto, Kenichi Mizukawa, Ryutaro Hiraki, Atsushi Miki and Shuhei Kimura
J. Clin. Med. 2025, 14(23), 8593; https://doi.org/10.3390/jcm14238593 - 4 Dec 2025
Viewed by 357
Abstract
Background/Objectives: Different disease subtypes in neovascular age-related macular degeneration (nAMD) influence treatment burden, yet existing classifications such as the pachychoroid neovasculopathy (PNV)/non-PNV dichotomy may not fully capture clinical heterogeneity. This study aimed to compare the 12-month outcomes of intravitreal aflibercept (IVA) in [...] Read more.
Background/Objectives: Different disease subtypes in neovascular age-related macular degeneration (nAMD) influence treatment burden, yet existing classifications such as the pachychoroid neovasculopathy (PNV)/non-PNV dichotomy may not fully capture clinical heterogeneity. This study aimed to compare the 12-month outcomes of intravitreal aflibercept (IVA) in treatment-naïve patients with unilateral nAMD stratified by the presence or absence of drusen and punctate hyperfluorescence (PH). Methods: This retrospective study included 130 eyes of 130 patients categorized into the Drusen−/PH−, Drusen+/PH−, Drusen−/PH+, and Drusen+/PH+ groups. Their best-corrected visual acuity, retinal thickness, choroidal thickness, number of injections, no-retinal fluid rate during the loading dose regimen, and 12-month retreatment rate following treatment initiation were determined. The primary outcome was 12-month retreatment rate for the four groups, which was determined using Kaplan–Meier curves and log-rank tests. Exploratory metric multidimensional scaling (MDS) was used to visualize the baseline profiles. Results: The 12-month retreatment rates of the groups were significantly different. The Drusen+/PH− group had a higher retreatment rate and required more injections than the Drusen−/PH+ and Drusen+/PH+ groups. The Drusen+/PH− group was older than the Drusen−/PH+ and Drusen−/PH− groups. The Drusen−/PH+ group had a thicker choroid than the Drusen+/PH− group. The MDS results clear separation of the groups, consistent with the older age of the Drusen+/PH− group and the thicker choroid of the Drusen−/PH+ group. Conclusions: nAMD stratified based on drusen and PH differed in age, choroidal thickness, and IVA outcomes. The four-category framework provides greater pathophysiologic and therapeutic resolution than the simple PNV/non-PNV dichotomy and may help anticipate injection demand to guide individualized dosing strategies. Full article
(This article belongs to the Special Issue An Update on Retinal Diseases: From Diagnosis to Treatment)
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7 pages, 828 KB  
Case Report
Bilateral Sterile Intraocular Inflammation Following Intravitreal Aflibercept 8 mg Injections: A Case Report
by Ram Cohen, Tomer Kerman and Omer Trivizki
Reports 2025, 8(4), 249; https://doi.org/10.3390/reports8040249 - 28 Nov 2025
Viewed by 622
Abstract
Background and Clinical Significance: To report a case of bilateral sterile intraocular inflammation following intravitreal aflibercept 8 mg (Eylea HD) injections. Case Presentation: An 89-year-old woman with bilateral neovascular age-related macular degeneration (nAMD) developed blurred vision and mild ocular pain in [...] Read more.
Background and Clinical Significance: To report a case of bilateral sterile intraocular inflammation following intravitreal aflibercept 8 mg (Eylea HD) injections. Case Presentation: An 89-year-old woman with bilateral neovascular age-related macular degeneration (nAMD) developed blurred vision and mild ocular pain in both eyes four days after receiving aflibercept 8 mg injections in both of her eyes. Examination revealed a marked anterior chamber reaction with Descemet’s folds, 2+ vitreous cells, and 3+ vitreous haze bilaterally. Intraocular pressures were normal, and B-scan ultrasonography confirmed attached retinas with bilateral vitreous opacities. The clinical presentation initially raised concern for infectious endophthalmitis; however, the bilateral presentation, quiet conjunctivae, and prior history of sterile inflammation after aflibercept 2 mg supported a diagnosis of sterile intraocular inflammation. The patient was hospitalized and treated with intensive topical corticosteroids, antibiotics, and cycloplegics, resulting in rapid improvement and complete resolution of symptoms within four days with recovery of baseline vision. Conclusions: Intravitreal aflibercept 8 mg can be associated with bilateral sterile intraocular inflammation, even in patients who previously tolerated standard-dose aflibercept. Awareness of this potential adverse event is essential to avoid unnecessary interventions and to guide appropriate management. Full article
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12 pages, 1077 KB  
Article
Comparison of Three Consecutive Monthly Administrations Between Aflibercept 8 mg and Brolucizumab 6 mg in Polypoidal Choroidal Vasculopathy
by Yoshiko Fukuda, Yoichi Sakurada, Yumi Kotoda, Misa Kimura and Kenji Kashiwagi
Pharmaceuticals 2025, 18(12), 1811; https://doi.org/10.3390/ph18121811 - 27 Nov 2025
Viewed by 539
Abstract
Purpose: The aim was to compare the short-term outcomes of aflibercept 8 mg and brolucizumab for the treatment of polypoidal choroidal vasculopathy (PCV). Methods: This study included 48 eyes of 48 patients with PCV. Drug selection was based on the treatment period. Sixteen [...] Read more.
Purpose: The aim was to compare the short-term outcomes of aflibercept 8 mg and brolucizumab for the treatment of polypoidal choroidal vasculopathy (PCV). Methods: This study included 48 eyes of 48 patients with PCV. Drug selection was based on the treatment period. Sixteen eyes received aflibercept 8 mg and thirty-two eyes received brolucizumab. All eyes underwent three consecutive monthly injections: aflibercept (114.3 mg/mL; 0.07 mL) or brolucizumab (120 mg/mL; 0.05 mL). Indocyanine green angiography was performed at baseline and at the 3-month visit to confirm the presence of polypoidal lesions. Results: In the aflibercept 8 mg group, best-corrected visual acuity (BCVA) significantly improved from 0.28 ± 0.26 at baseline to 0.18 ± 0.25 at the 3-month visit (p < 0.001). In the brolucizumab 6 mg group, BCVA improved from 0.35 ± 0.26 to 0.29 ± 0.27, although the change was not statistically significant (p = 0.08). Multivariate regression analysis showed that better BCVA at 3 months was associated with better baseline BCVA and lower central retinal thickness (CRT), independent of the drug used. CRT decreased from 382 ± 157 to 198 ± 98 in the brolucizumab 6 mg group and from 358 ± 152 to 192 ± 76 in the aflibercept 8 mg group at 3 months. Subfoveal choroidal thickness (SCT) decreased from 201 ± 78 to 167 ± 60 in the brolucizumab 6 mg group and from 186 ± 76 to 153 ± 67 in the aflibercept 8 mg group. The dry macula rate at 3 months was the same for aflibercept 8 mg and brolucizumab 6 mg at 93.8%. Complete regression of polypoidal lesions was observed in 62.5% and 75.0% of patients in the aflibercept and brolucizumab groups, respectively (p = 0.57). Conclusions: During the induction phase, aflibercept 8 mg demonstrated comparable outcomes to brolucizumab 6 mg in reducing CRT and SCT, achieving a dry macula, improving BCVA, and regressing polypoidal lesions in eyes with PCV. Full article
(This article belongs to the Special Issue Pharmacotherapy of Macular Diseases)
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17 pages, 10642 KB  
Article
Retinal Organoid-Derived Exosomes Reduce CNV Lesion and Restore RPE Integrity in Mouse Laser-Induced Choroidal Neovascularization (CNV) Model
by Jin Young Yang, Yeji Kim, Sumin An, Jung Woo Han, Jun-Sub Choi and Tae Kwann Park
Int. J. Mol. Sci. 2025, 26(23), 11327; https://doi.org/10.3390/ijms262311327 - 24 Nov 2025
Viewed by 810
Abstract
To address the shortcomings of existing anti-VEGF monotherapy in neovascular age-related macular degeneration (nAMD), we investigated the therapeutic capabilities of exosomes obtained from human induced pluripotent stem cell (hiPSC)-derived retinal organoids in a mouse model of laser-induced choroidal neovascularization (CNV). To evaluate Retinal [...] Read more.
To address the shortcomings of existing anti-VEGF monotherapy in neovascular age-related macular degeneration (nAMD), we investigated the therapeutic capabilities of exosomes obtained from human induced pluripotent stem cell (hiPSC)-derived retinal organoids in a mouse model of laser-induced choroidal neovascularization (CNV). To evaluate Retinal Organoid-derived exosome (RO-Exo) distribution after intravitreal (IVT) injection, calcein-labeled RO-Exo was observed using confocal microscopy. CNV was induced in C57BL/6 J mice by laser photocoagulation. RO-Exo was isolated from retinal organoids (differentiation days 55–65) and injected 5 days post-laser. Therapeutic efficacy was evaluated on day 12. Vascular leakage and CNV size were assessed by angiography and CD31 immunostaining. We also examined HIF-1α/VEGF-A expression (Western blotting), Retinal Pigment Epithelium (RPE) integrity markers (immunofluorescence staining for α-SMA, fibronectin, and ZO-1), and the activation of the Mitogen-Activated Protein Kinase (MAPK) pathway (phospho-ERK, -p38, -JNK) in CNV lesions. After IVT injection, RO-Exo migrated to the RPE layer, showing high retinotropic distribution. In the CNV model, RO-Exo significantly reduced vascular leakage and CNV size, with greater suppression of HIF-1α and VEGFA expression than aflibercept, the standard-of-care anti-VEGF drug. CD31-positive vasculature was decreased, accompanied by downregulation of fibronectin (a fibrotic marker) and restoration of RPE hexagonality and integrity. Furthermore, RO-Exo inhibited the activation of ERK, P38, and JNK in CNV lesions. Our study results demonstrate that RO-Exo exhibits multi-target therapeutic effects—including anti-angiogenic, anti-fibrotic, and neuroprotective actions—offering a promising alternative to conventional anti-VEGF therapy for nAMD. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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14 pages, 857 KB  
Systematic Review
Network Meta-Analysis of Bevacizumab Gamma Versus Competing Interventions for Treating Neovascular Age-Related Macular Degeneration in the United Kingdom
by Maria Lorenzi, Stephen Ebohon, Jennifer Kissner, Jedd Comiskey, Mayke Paap, Christine Bouchet, Andy Garnham and Erika Wissinger
J. Mark. Access Health Policy 2025, 13(4), 58; https://doi.org/10.3390/jmahp13040058 - 19 Nov 2025
Viewed by 1057
Abstract
This study aimed to determine the relative efficacy of bevacizumab gamma (an ophthalmic formulation of bevacizumab) versus alternative interventions relevant to the treatment of neovascular age-related macular degeneration (nAMD) in the United Kingdom (UK) via a systematic literature review (SLR) and network meta-analysis [...] Read more.
This study aimed to determine the relative efficacy of bevacizumab gamma (an ophthalmic formulation of bevacizumab) versus alternative interventions relevant to the treatment of neovascular age-related macular degeneration (nAMD) in the United Kingdom (UK) via a systematic literature review (SLR) and network meta-analysis (NMA). An SLR was conducted to identify randomized controlled trials (RCTs) of anti-vascular endothelial growth factor (anti-VEGF) therapies for the treatment of nAMD in adult patients relevant to the UK context. The included anti-VEGF treatments were ranibizumab, aflibercept, faricimab, and bevacizumab gamma. Bayesian NMA models were used to estimate relative efficacy in terms of change from baseline (CFB) in best-corrected visual acuity (BCVA) at 12 months, the proportion of patients gaining 15 or more letters at 12 months, and the proportion of patients losing less than 15 letters at 12 months. Twenty-two relevant RCTs were included in the NMA. At 12 months, all anti-VEGF treatments were similarly efficacious to ranibizumab 0.5 mg every four weeks (Q4W) in terms of CFB in BCVA, the proportion of patients gaining 15 or more letters, and the proportion of patients losing less than 15 letters (except for ranibizumab 0.5 mg every 12 weeks [Q12W] and ranibizumab 0.5 mg pro re nata [PRN]). Bevacizumab gamma provided similar improvements in visual acuity to other anti-VEGF treatments. Full article
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15 pages, 1161 KB  
Article
Aflibercept for Wet Age-Related Macular Degeneration: A Prospective, Randomized Trial Comparing Treat-And-Extend and Fixed Bimonthly Dosing
by Kevin Y. Wu, Shu Yu Qian, Alexandre Camiré, David T. Kim and Michel Giunta
J. Clin. Med. 2025, 14(22), 8180; https://doi.org/10.3390/jcm14228180 - 18 Nov 2025
Viewed by 886
Abstract
Background/Objectives: Currently, treatments for age-related macular degeneration (AMD) consist of regular intravitreal injections that exert significant pressure on healthcare systems via their high labor costs and economic burden. To address this, our study’s goal is to propose new treatment protocols by comparing the [...] Read more.
Background/Objectives: Currently, treatments for age-related macular degeneration (AMD) consist of regular intravitreal injections that exert significant pressure on healthcare systems via their high labor costs and economic burden. To address this, our study’s goal is to propose new treatment protocols by comparing the efficacy of bimonthly fixed dosing aflibercept injections versus the treat-and-extend (T&E) approach for wet AMD. Secondary objectives included categorical best-corrected visual acuity (BCVA) changes, anatomical outcomes, treatment intervals, and adverse events. Methods: This study is a 1-year randomized, open-label, prospective trial that included 44 eyes from 44 patients, 32 in the T&E arm and 12 in the bimonthly arm. Treatment-naïve AMD patients with neovascularization were randomized to a bimonthly fixed dosing group or a T&E group after receiving 3 consecutive monthly aflibercept injections. Following the induction doses, retreatment intervals for patients in the T&E arm were adjusted based on a predetermined algorithm. Results: Over 12 months, mean BCVA improvements were 5.0 letters in the bimonthly group and 4.1 in the T&E group (p = 0.096 for non-inferiority test). On average, T&E patients received 9.6 injections compared to 7.7 for those in the fixed dosing group (p < 0.001). Anatomical outcomes were comparable in both treatment arms. Conclusions: In our trial, the T&E approach provided significant visual improvements, but did not meet the threshold for non-inferiority when compared to fixed bimonthly dosing. It was also unable to minimize treatment burden over the course of the first year of injections. Further research is required to optimize the T&E algorithm with aflibercept. Full article
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15 pages, 1320 KB  
Article
Intravitreal Aflibercept for the Treatment of Diabetic Retinopathy Among Patients Who Completed PANORAMA: 1-Year Outcomes from the VOYAGE Extension Study
by Avery W. Zhou, Gail M. Teagle, Liisa M. Baumann, Jessica A. Cao, Andres Emanuelli, Allen Y. Hu, Adam S. Berger, James C. Major, Seong Y. Lee, Stephen M. Huddleston, Victor H. Gonzalez, W. Lloyd Clark, David S. Liao, Ronald M. Kingsley, Howard S. Lazarus, John F. Payne, Eric G. Feinstein, Annal D. Meleth, Sagar B. Patel, Kenneth C. Fan, Alyson J. Berliner, Hadi Moini, Xiaomeng Niu, Michael S. Ip, SriniVas R. Sadda, Hasenin Al-khersan and Charles C. Wykoffadd Show full author list remove Hide full author list
J. Pers. Med. 2025, 15(11), 555; https://doi.org/10.3390/jpm15110555 - 14 Nov 2025
Viewed by 744
Abstract
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 [...] Read more.
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, corresponding to moderately severe non-proliferative diabetic retinopathy (NPDR). 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
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19 pages, 899 KB  
Article
Evaluation of the Duration of Good Visual Acuity During Anti-VEGF Therapy for Age-Related Macular Degeneration in Routine Clinical Practice
by Andrea Gyenes, Lilla István, András Papp, Miklós Resch, Zsuzsa Récsán, Mónika Ecsedy, Zsuzsanna Szepessy, Antal Szabó, Balázs Lesch, György Barcsay, Ágnes Borbándy, Gábor László Sándor, Zoltán Z. Nagy and Illés Kovács
Int. J. Mol. Sci. 2025, 26(22), 10927; https://doi.org/10.3390/ijms262210927 - 11 Nov 2025
Viewed by 1295
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Molecular Mechanisms and Treatment of Retinal Diseases)
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16 pages, 1621 KB  
Systematic Review
Effectiveness, Safety, and Real-World Experience of Brolucizumab: A Systematic Review
by Naif M. Alali, Abeer Aljahdali, Hani B. AlBalawi, Othman Jarallah Al Jarallah, Salem Mohammed AL Zaid, Ismail Abuallut, Faisal ALMarek, Ibrahim Shajry, Yousef A. Alotaibi, Mohammad A. Hazzazi and Moustafa S. Magliyah
Pharmaceuticals 2025, 18(11), 1620; https://doi.org/10.3390/ph18111620 - 27 Oct 2025
Viewed by 1767
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Recent Advances in Ocular Pharmacology)
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17 pages, 26217 KB  
Article
ZEB1 and Uveal Melanoma Invasiveness
by Maria Zhilnikova, Maria Balantaeva, Sofia Zvereva, Mikhail Biryukov, Vasiliy Atamanov, Julia Poletaeva, Elena Ryabchikova, Olga Stanishevskaya, Dmitryi Chernykh, Natalia Kononova and Olga Koval
Int. J. Mol. Sci. 2025, 26(21), 10346; https://doi.org/10.3390/ijms262110346 - 24 Oct 2025
Viewed by 611
Abstract
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 [...] Read more.
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 ZEB1low 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
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9 pages, 525 KB  
Article
High-Dose 8 mg Aflibercept for Neovascular Age-Related Macular Degeneration: Who Is Being Treated with This New Agent?
by Caspar Liesenhoff, Carolin Meyrl, Daniel Krause, Franziska Eckardt, Anna Lorger, Viktoria Deiters, Johannes Schiefelbein, Julian Elias Klaas, Benedikt Schworm, Siegfried G. Priglinger and Jakob Siedlecki
Life 2025, 15(11), 1657; https://doi.org/10.3390/life15111657 - 23 Oct 2025
Viewed by 1485
Abstract
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 [...] Read more.
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
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11 pages, 2587 KB  
Article
Switching from Aflibercept to Faricimab in the Treatment of Neovascular Age-Related Macular Degeneration: Short-Term Results from Real-Life Study
by Jan Kucharczuk, Hubert Kasprzak and Maciej Gawęcki
J. Clin. Med. 2025, 14(20), 7345; https://doi.org/10.3390/jcm14207345 - 17 Oct 2025
Viewed by 881
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue New Advances in Age-Related Macular Degeneration)
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15 pages, 2912 KB  
Article
Extended Real-World Efficacy of Faricimab in Therapy-Resistant Macular Edema Due to Retinal Vein Occlusion: 9-Month Follow-Up Results
by Michael Hafner, Tina R. Herold, Alexander Kufner, Franziska Eckardt, Ben Asani, Siegfried G. Priglinger and Johannes Schiefelbein
J. Clin. Med. 2025, 14(20), 7197; https://doi.org/10.3390/jcm14207197 - 13 Oct 2025
Viewed by 1587
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Causes and Advanced Treatments of Macular Edema)
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