Search Results (133)

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

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

This study aims to evaluate the real-world efficacy and safety of aflibercept 8 mg intravitreal injections (IVTs) in pretreated patients with neovascular age-related macular degeneration (nAMD) throughout the first three IVTs. Background: Established anti-vascular-endothelial-growth-factor (anti-VEGF) therapies positively impact the progression of nAMD but require frequent administration, thus burdening patients and the healthcare system. Pivotal trials of the recently approved aflibercept 8 mg have demonstrated extended dosing intervals with comparable safety to standard treatments. However, real-world data is still scarce. Methods: A retrospective, single-center single-arm analysis was conducted on 22 eyes from 18 pretreated nAMD patients. Eyes were switched from other anti-VEGF agents to aflibercept 8 mg injections continuing a treat-and-extend regimen (no loading dose after switching). Treatment intervals and structural (central subfield thickness (CST); disease activity) and functional (best corrected visual acuity (BCVA)) outcomes were assessed at baseline (date of first aflibercept 8 mg injection) and at follow-up examinations until follow-up 3. Safety data, including intraocular pressure changes, were recorded. Results: Over a median follow-up of 16.6 weeks (IQR 15.1–27.0), patients switched to aflibercept 8 mg showed prolonged intervals between injections (5.5 weeks vs. 7 weeks, p < 0.001, Wilcoxon signed-rank test), reduced disease activity, stable CST, and stable BCVA. One patient experienced transient intraocular pressure elevation, which resolved without intervention. No other adverse events were observed. Conclusions: Treatment with aflibercept 8 mg appears to provide effective disease control with prolonged treatment intervals in switched nAMD patients in routine clinical practice. These findings further indicate the potential for reducing treatment burden. Full article

Objectives: This study aimed to assess the initial anatomical and functional outcomes of switching to aflibercept 8 mg in patients with neovascular age-related macular degeneration (nAMD) previously treated with anti-vascular endothelial growth factor (VEGF) therapy. Methods: Patients with nAMD previously treated with anti-VEGF drugs were switched to aflibercept 8 mg. Patients with any exudative changes (subretinal fluid [SRF], intraretinal fluid [IRF] or serous pigment epithelial detachment [sPED]) at the time of the first aflibercept 8 mg injection and whose dosing interval before and after switching did not differ by more than ±7 days were included. Best-corrected visual acuity (BCVA), central foveal thickness (CFT), and the presence of SRF, IRF, and sPED were evaluated before and after switching to aflibercept 8 mg. Results: A total of 102 eyes from 98 patients were included in the analysis. The drugs used prior to switching were faricimab in five eyes, brolucizumab in six eyes, and aflibercept 2 mg in 91 eyes, with a mean interval of 63.7 ± 20.0 days from the last pre-switch injection and 64.9 ± 20.1 days to the first post-switch visit. The CFT was significantly reduced from 272 ± 85 µm to 246 ± 79 µm (p < 0.0001). The BCVA remained unchanged at 0.27 ± 0.35 logMAR. During switching, SRF, IRF, and sPED were observed in 70, 24, and 38 eyes, respectively. At the post-switch visit, complete resolution of exudative changes was observed in 44% of eyes with SRF, 55% with IRF, and 29% with sPED. No ocular or systemic adverse effects were observed. Conclusions: As an initial response to switching to aflibercept 8 mg in a real-world setting, SRF and IRF completely resolved in approximately half of the patients, and sPED resolved in about 30% of cases. Full article

Background/Objectives: To evaluate the potential of Optical Coherence Tomography (OCT) and OCT angiography parameters in predicting treatment requirements and visual outcomes after one year in therapy-naïve eyes with neovascular age-related macular degeneration (nAMD). Methods: A retrospective study of 96 therapy-naïve eyes newly diagnosed with nAMD was carried out. All eyes received baseline OCT and OCTA. Follow-up OCT after initial upload was then carried out, involving three intravitreal injections (IVIs) with anti-Vascular Endothelial Growth Factor (anti-VEGF) at four-week intervals. OCT parameters, including intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelium detachment (PED), and central retinal thickness (CRT), were assessed qualitatively and quantitatively. Macular Neovascularization (MNV) morphology at baseline was described in terms of area, total vessel length, flow density, and fractal dimension. OCT and OCTA parameters were correlated with best corrected visual acuity (BCVA) and number of administered IVIs after 1 year of treatment. Results: Eyes with persistent subretinal fluid (SRF) or both intraretinal fluid (IRF) and SRF after upload showed a significantly higher need for IVIs (p < 0.01). Also, pigment epithelium detachment (PED) presence at baseline (p < 0.05), PED height at baseline (p < 0.01), PED presence after upload (p < 0.01), and PED height after upload (p < 0.01) were each correlated with a greater number of IVIs. Decrease in PED height during upload was accompanied by a lower number of IVIs (p < 0.01). All the aforementioned parameters had no influence on BCVA after 1 year (p > 0.05). Baseline central retinal thickness (CRT) was linked to worse BCVA at 12 months (p < 0.05), but not the number of IVIs. Follow-up CRT correlated with worse BCVA (p < 0.01) and more IVIs (p < 0.01), while CRT decrease was associated with better BCVA (p < 0.05) and fewer IVIs (p < 0.01) at 1 year. In OCTA, area and total vessel length of MNVs were correlated with BCVA after 1 year (p < 0.01) but had no influence on number of IVIs (p > 0.05). Flow density had no influence on either outcome parameter (p > 0.05). Fractal dimension was associated with BCVA (p < 0.01) and number of IVIs (p < 0.05) after 1 year. Conclusions: MNV area, vessel length, and fractal dimension in OCTA, along with fluid distribution in OCT at baseline and after follow-up, may serve as indicators of treatment needs and visual outcomes after one year. Further studies with longer observation periods and the use of deep learning models are needed to improve analyses and to verify the applicability of these findings to clinical practice. Full article

(1) Aim: To evaluate early real-world outcomes of switching to aflibercept 8 mg in eyes with neovascular age-related macular degeneration (nAMD) in the United Kingdom. (2) Methods: This retrospective, observational study included 59 eyes from 50 patients with treatment-refractory nAMD previously treated with multiple anti-vascular endothelial growth factor (anti-VEGF) agents. Eyes were switched to aflibercept 8 mg without loading doses and treated using a treat-and-extend regimen. Functional, anatomical, and safety outcomes were evaluated over a mean (SD) follow-up of 33.5 (10.4) weeks. (3) Results: The mean (SD) age was 80.2 (6.3) years, and 28 (56.0%) of 50 patients were male. At baseline, the mean (SD) best corrected visual acuity (BCVA) was 66.0 (14.4) letters, with 33 (55.9%) eyes achieving ≥70 letters. The mean (SD) baseline central subfield thickness (CST) was 367.2 (100.7) µm. Prior to switching to aflibercept 8 mg, the mean (SD) number of injections for each eye was 26.9 (19.0), with the most recent mean (SD) treatment interval of 7.7 (1.7) weeks. Switching to aflibercept 8 mg resulted in extension of the mean (SD) injection interval from 7.7 (1.7) weeks to 8.7 (2.2) weeks (p < 0.01). BCVA and CST remained stable, with a significant reduction in pigment epithelial detachment (PED) height (232.5 µm to 211.6 µm, p < 0.01). No serious ocular adverse events or intraocular pressure (IOP) elevations requiring treatment were reported. (4) Conclusion: Aflibercept 8 mg demonstrated early treatment durability, anatomical benefit, and a favourable short-term safety profile in eyes with treatment-refractory nAMD. Further prospective studies are warranted. Full article

The increasing prevalence of age-related macular degeneration (AMD), a disease that can result in the loss of central vision, is an emerging problem worldwide due to aging societies. Growing patient numbers create a challenge for the healthcare system. Understanding the mechanisms of AMD pathogenesis will aid in early, personalized, and efficient intervention, helping to mitigate this issue. Current diagnostic methods rely on optical coherence tomography and angiography imaging, which identify existing damages, but do not provide information on the mechanisms behind them. In the present work, we demonstrate a difference in the serum RNA profile between neovascular AMD (nAMD) patients and controls. Moreover, the RNA profile of nAMD patients corresponded with anatomical changes in the retinal fluid compartments as well as atrophic changes of the retina. We followed two independent ways to control false positive leads, and when these approaches were combined, thioredoxin-related transmembrane protein 4 (TMX4) was observed to be differentially expressed by both approaches. This finding opens a new pathway in AMD studies, which are limited due to restricted access to live human target material and the limited value of animal models of human AMD. Full article

The process of evaluation and selection of drugs in Spain is currently changing, with hospital pharmacists (HPs) having a growing relevance. This cross-sectional observational study aimed to assess HPs’ preferences for different hypothetical intravitreal treatments for neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Best corrected visual acuity (BCVA), ocular adverse events (AE), annual drug cost, available presentation, and mechanisms of action (MoA) were the selected attributes. A conjoint analysis was used. Ninety-one HPs completed the study. The mean (SD) age was 39.2 (10.2) years, 60.4% were female, and the mean (SD) time of experience as HP was 12.6 (8.3) years. For nAMD treatments, BCVA (38.6%) and ocular AE (27.3%) were the most important attributes, while annual drug cost (16.3%), available presentation (11.1%), and MoA (6.7%) were not as important. For DME drugs, BCVA (44.6%) and ocular AE (25.5%) were the most significant factors; annual drug cost (17.9%), the drug’s available presentation (7.3%), and MoA (4.8%) were not considered to be as crucial. Preferences were comparable independent of HP experience. Effectiveness and safety were the most important attributes when choosing a drug. Comprehending the significant characteristics for HPs could potentially improve their collaborative function within multidisciplinary teams involved in intravitreal treatments. Full article

Background/Objectives: To investigate the impact of pachychoroid on the clinical features of neovascular age-related macular degeneration (nAMD) in Japan using the deep learning-based Hokkaido University pachychoroid index (HUPI), which has a high discriminative ability for pachychoroid. Methods: This retrospective observational study examined 124 eyes of 111 treatment-naïve nAMD patients, including 44 eyes with type 1 macular neovascularization (MNV), 26 eyes with type 2 MNV, and 54 eyes with polypoidal choroidal vasculopathy (PCV). HUPI was calculated for each eye from EDI-OCT choroidal images using our modified LeNet that had learned the image patterns of pachychoroid. Differences in HUPI between nAMD types and inter-relationships between nAMD parameters, including HUPI, were evaluated. Results: The mean HUPI was 0.53 ± 0.30 for type 1 MNV, 0.33 ± 0.23 for type 2 MNV, and 0.61 ± 0.3 for PCV, with significant differences between any two of the three groups (p < 0.05, for each). Round-robin multiple regression analysis for nAMD parameters showed the close associations of the HUPI with choroidal vascular hyperpermeability (CVH) and subretinal fluid (SRF) (p = 0.017 and p < 0.001 for each) and the clear division of nAMD parameters into the following two groups: one including intraretinal fluid and type 1 and type 2 MNV and the other including SRF, CVH, polypoidal lesions, and HUPI. Conclusions: HUPI revealed that eyes with type 1 MNV and PCV had more pachychoroid-like features than eyes with type 2 MNV. HUPI was tightly associated with CVH and SRF but not MNV per se in nAMD parameters, reinforcing the pathoetiological concept of differentiating pachychoroid from typical nAMD. Full article

Objectives: To evaluate the efficacy of faricimab in patients with neovascular age-related macular degeneration (nAMD) that did not respond to other VEGF inhibitors. Methods: This retrospective study included the eyes of patients diagnosed with nAMD who had been switched to faricimab treatment due to the persistence of intraretinal fluid (IRF) and/or subretinal fluid (SRF), despite monthly anti-VEGF treatment with aflibercept, bevacizumab, or ranibizumab using the treat and extend regimen, and who had received at least three faricimab injections following the switch. Best-corrected visual acuity (BCVA) measurement and optical coherence tomography (OCT) analysis were performed at each visit, and the OCT results were graded by two independent readers. Results: We included 41 eyes of 39 patients (21 male, 18 female) with a mean age of 80.5 ± 8.1 years. The median duration of anti-VEGF treatment prior to the switch to faricimab was 5.0 years, with a median of 53 injections. Complete resolution of IRF and SRF was observed after the first dose of faricimab in 12 eyes (29.3%) and after the third dose in 15 eyes (36.6%). Twenty-eight eyes reached a follow-up time after a switch of at least 12 months, with a median of 10 faricimab injections. Of these 28 eyes, 10 eyes (35.7%) exhibited complete IRF/SRF resolution; treatment intervals were extended beyond 4 weeks in 21 eyes (80.7%), and 8 eyes (28.6%) presented complete IRF/SRF resolution under extended treatment intervals at month 12. Central retinal thickness after 12 months was reduced from a median of 368.0 µm to 297.5 µm (p < 0.001), and the BCVA remained stable (p = 0.057). No adverse events were reported throughout the entire treatment period. Conclusions: In nAMD patients with poor anti-VEGF treatment response, complete and fast fluid resolution and the extension of treatment intervals can be reached by switching to faricimab, even after years of prior unsuccessful therapy. Full article

Background/Objectives: Submacular hemorrhage (SMH) associated with neovascular age-related macular degeneration (nAMD) can lead to significant vision loss, and the optimal management strategy remains uncertain. This study aimed to evaluate the efficacy and safety of pneumatic displacement (PD) without tissue plasminogen activator (t-PA) for SMH secondary to nAMD. Methods: A retrospective analysis was conducted on 22 eyes with SMH secondary to nAMD treated with PD without t-PA. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), number of intravitreal injections, and postoperative complications were assessed at baseline and follow-up. Multiple logistic regression analyses were used to identify factors associated with visual outcomes. Results: In the 22 eyes that completed the 6-month follow-up, BCVA (logMAR) was 0.88 ± 0.46 at baseline and 0.76 ± 0.63 at 6 months (p = 0.24). In the 15 eyes with 12-month follow-up, BCVA improved significantly from 0.92 ± 0.47 at baseline to 0.56 ± 0.51 at 12 months (p = 0.01). CRT significantly decreased at 3 months (p < 0.01). During this period, patients received an average of 8.13 ± 2.90 intravitreal anti-vascular endothelial growth factor (VEGF) injections. A shorter duration from symptom onset to treatment was associated with better visual outcomes (p = 0.02). Postoperative vitreous hemorrhage occurred in 31.8% of cases. Conclusions: PD without t-PA, in combination with anti-VEGF therapy, improved visual outcomes over 12 months. Early intervention and continuous anti-VEGF administration appear to be key factors in optimizing treatment outcomes. Further studies are needed to establish standardized treatment protocols for SMH associated with nAMD. Full article

Vascular endothelial growth factor (VEGF) is a key mediator of exudative age-related macular degeneration (eAMD), yet non-invasive biomarkers for disease monitoring remain limited. This study evaluates VEGF levels in human tear fluid as a potential biomarker for eAMD and investigates the molecular dynamics of VEGF in a laser-induced choroidal neovascularization (lCNV) mouse model. Tear VEGF levels were quantified using proximity qPCR immunoassays in eAMD patients (n = 29) and healthy controls (n = 21) and correlated with optical coherence tomography (OCT) findings. Molecular analyses, including immunohistochemistry, gene expression profiling, and phosphorylation assays, were conducted on choroid–retinal pigment epithelium (RPE) and lacrimal gland (LG) tissues from lCNV mice (n = 25). Tear VEGF levels were significantly elevated in eAMD patients, correlating with disease severity. Females exhibited higher VEGF levels, a pattern not replicated in the mouse model. In lCNV mice, VEGF overexpression originated from the choroid–RPE, driven by hypoxic and inflammatory signaling, with no significant LG contribution. Increased VEGF, IL-6, and vimentin expression, along with NF-κB and STAT3 activation, were observed. These findings suggest that tear VEGF is a promising non-invasive biomarker for eAMD, warranting further validation for clinical application in disease monitoring and treatment optimization. Full article

Background: Anti-Vascular Endothelial Growth Factor (VEGF) therapy is an effective therapy for improving and stabilizing the vision of patients with neovascular age-related macular degeneration (nAMD). However, the treatment requirements, particularly the number of intraocular injections, can vary significantly among patients. This study aimed to analyze the vascular characteristics of macular neovascularizations (MNVs) to identify potential biomarkers that could predict the required injection frequency throughout the disease course. Methods: In all patients, the initial diagnosis of nAMD was confirmed using optic coherence tomography (OCT), fluorescein angiography, and OCT angiography (OCTA). MNVs detected using OCTA were subjected to quantitative vascular analysis of their area, total vascular length (sumL), fractal dimension (FD), and flow density. These results were then correlated with the number of intravitreal anti-VEGF treatments administered during the first 3 years of treatment. Additionally, the relationship between the parameters and visual acuity progression was analyzed. Results: A total of 68 treatment-naïve eyes were included in the study, comprising 31 eyes with type 1 MNV, 19 eyes with type 2 MNV, and 18 eyes with type 3 MNV. The average MNV area at baseline was 1.11 mm² ± 1.18 mm², the mean total vascular length was 12.95 mm ± 14.24 mm, the mean fractal dimension was 1.26 ± 0.14, and the mean flow density was 41.19 ± 5.87. On average, patients in our cohort received 19.8 ± 8.5 intravitreal injections (IVIs). A significant correlation was found between the number of administered IVIs in the first 3 treatment years and the MNV area (p < 0.005), sumL (p < 0.005), and FD (p < 0.05), while no correlation was found with flow density. Additionally, there was no significant association between MNV type and treatment requirements, nor between MNV vascular architecture and visual acuity progression. Conclusions: The results suggest that the specific vascular structure of untreated MNV may serve as a predictor of long-term treatment demand. With the emergence of new drug classes and advancements in imaging techniques, these parameters could offer valuable insights for forecasting treatment requirements. Full article

Background/Objectives: XTEND is the largest global, prospective, observational study of treatment-naïve patients with neovascular age-related macular degeneration (nAMD) receiving 2 mg of intravitreal aflibercept (IVT-AFL) in routine clinical practice designed to examine the real-world effectiveness of IVT-AFL proactive treatment regimens. The outcomes from the Switzerland cohort are reported here. Methods: Patients aged ≥50 years were eligible if they planned to receive IVT-AFL 2 mg. After three initial monthly IVT-AFL injections, treatment intervals could be extended (4-week minimum treatment interval). Visual and anatomic outcomes, treatment exposure, and safety were assessed. Statistics were descriptive. Results: Fifty-one patients were treated. At baseline, the mean ± standard deviation (SD) best-corrected visual acuity (BCVA) was 64.9 ± 17.9 letters, and central subfield thickness (CST) was 402 ± 106 µm. At month (M) 12 and M24, the mean (95% confidence interval [CI]) change from baseline in BCVA was +5.7 (1.9, 9.4) and +5.6 (1.3, 9.8) letters, respectively. In patients with a high baseline BCVA (≥70 letters [n = 28; mean ± SD: 77.5 ± 4.8 letters]), BCVA was maintained at ≥70 letters at M12 and M24 (mean change from baseline [range] +1.0 [−15.0, 11.0] and +1.1 [–10.0, 14.0], respectively). At M12 and M24, the mean (95% CI) change in CST was −125 (−161, −90) µm and −127 (−162, −93) µm, respectively. Patients received a mean ± SD of 9.5 ± 3.2 and 13.7 ± 6.0 injections by M12 and M24, respectively. No safety concerns were identified. Conclusions: In Swiss routine clinical practice, functional and anatomic improvements were achieved with IVT-AFL 2 mg proactive treatment in patients with nAMD over 24 months despite a relatively high baseline BCVA. Full article

Background/Objectives: In a recent study, we investigated anti-VEGF treatment strategies for three subtypes of neovascular age-related macular degeneration (nAMD)—typical AMD (tAMD), polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP)—among a large cohort of Japanese patients. To further explore these findings, we conducted a post hoc analysis of this cohort to identify factors associated with the discontinuation of anti-VEGF therapy for nAMD in a real-world clinical setting. Methods: We collected medical records of patients newly diagnosed with nAMD who initiated intravitreal anti-VEGF antibody injection therapy. Patients were divided into two groups: those who continued anti-VEGF therapy for one year and those who discontinued treatment. Baseline best-corrected visual acuity, optical coherence tomography (OCT) findings, injection regimen, and the type of anti-VEGF antibody drug used were analyzed using univariate and multivariate analyses. Results: A total of 667 treatment-naïve nAMD patients initiated anti-VEGF agents and followed the therapy for 1 year. The one-year dropout rate in this study was 13%. Logistic regression analysis revealed that poor initial visual acuity and a PRN treatment regimen were significantly associated with higher odds of dropout. Age, gender, systemic factors, and the choice of intravitreal injection did not show any significant differences. Conclusions: Poor initial visual acuity and PRN treatment regimens may increase the risk of treatment dropout and should be carefully monitored. Full article