Neovascular Age-related Macular Degeneration Research Articles

Full thickness macular hole after intravitreal brolucizumab injection in neovascular age-related macular degeneration.

To describe a case of full thickness macular hole after intravitreal brolucizumab injection in neovascular age-related macular degeneration, which has not been reported to date. A 65-year-old male patient received brolucizumab intravitreal injection therapy for neovascular macular degeneration of the right eye. He received multiple intravitreal anti-VEGF injections on a pro re nata regimen and developed a full thickness macular hole. Surgical treatment was performed with pars plana vitrectomy of the right eye. Full thickness macular hole was successfully treated. Although a full thickness macular hole following intravitreal brolucizumab injection is an uncommon complication, it requires caution.

Intravitreal therapy in neovascular age-related macular degeneration-adapting to increasing demand and changing times.

To report the outcomes of patients with neovascular age-related macular degeneration (nAMD) at Palmerston North Eye Clinic (PNEC) during 2020 and 2021, comparing time to treatment initiation based on nurse-injector availability and during COVID-19 restrictions. Data were recorded from a prospective database for patients with nAMD at PNEC. Each patient's electronic health record was reviewed to ensure the accuracy of the database and to fill in missing data points. Statistics were done using Microsoft Excel and R. One hundred and fifty-six eyes were diagnosed with nAMD during the study. Mean time from referral triage to first injection was 13.08 days across the study period. Time to treatment initiation was not statistically different by level of COVID-19 restriction but there was a significant difference in first specialist appointment to injection interval when three nurse-injectors were available compared to four. The effect seemed most evident in subsequent months after reduced nurse-injector availability began. Despite an increase in nAMD diagnoses each year, PNEC continues to meet national guidelines for interval from referral to treatment initiation through innovations in practice. As demand for intravitreal injections continues to increase, further resourcing and research into newer agents will be required to keep wait times compliant with guidelines.

Dysfunction of Endothelial Cell-Mediated Intercellular Communication and Metabolic Pathways in Age-Related Macular Degeneration

Purpose Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, but the therapies are not satisfactory. This study aimed to find AMD specific features through the analysis of high-throughput sequencing. Methods In this study, we integrated six projects containing single-cell RNA sequencing (scRNA-seq) data to perform a comprehensive analysis for AMD samples in the tissues of retina and retinal pigment epithelium/choroid, and in the positions of macula and periphery. Differentially expressed genes (DEGs) were analyzed and crucial signaling pathways were identified across cell types and between the macula and periphery. The intercellular signaling transduction among cell types were inferred by "CellChat" to build cell–cell communication network under normal and AMD conditions, and verified at the transcriptional level. The CD31+ endothelial cells were obtained to evaluate the enrichment of KEGG pathways in atrophic and neovascular AMD, and GSVA was adopted to discover differential metabolic signals in each AMD type. Results Thirteen major cell types were identified in the integrated scRNA-seq data. Although no disease-specific cell type or differential cell proportion was found, DEGs and enriched pathways were shown in cell-type- and position-dependent manners. Severe impairment of endothelial cell-mediated cell interactions was found in the signaling transduction network of the macula, and compromised cell interactions were observed in the periphery. Furthermore, distinct signaling pathways and metabolic states were uncovered in atrophic and neovascular AMD. Striking reduction in energy metabolism, lipid metabolism, and oxidative stress was indicated in the atrophic AMD. Conclusion Conclusively, we discover aberrant signals and metabolic pathways in AMD samples, providing insight into mechanisms and potential therapeutic targets for the AMD treatment.

Subretinal fibrosis occurrence according to macular neovascularisation subtypes in neovascular age-related macular degeneration.

To assess subretinal fibrosis (SF) occurrence in neovascular age-related macular degeneration (nAMD), according to macular neovascularisation (MNV) subtypes. A Retrospective national multi centre cohort study included eyes with naive nAMD. Main outcome measures were, according to MNV subtypes, cumulative incidence for SF, risk factors, and best corrected visual acuity (BCVA) for 36 months. Four hundred and twenty eyes were included. Cumulative incidence of SF was 34.3% at 1 year, 39.0% at 2 years and 50.6% at 3 years. In multivariable analysis, Type 2 and mixed type 1 and 2 MNV were associated (p < 0.001) with a more frequent and rapid development of SF (respectively 85.5% and 81.0% at 1 year, then 95.8% and 93.1% at 3 years) than Types 1 and 3 (respectively 11.3% and 3.6% at 1 year, then 22.9% and 12.7% at 3 years). In Type 2 and mixed type 1 and 2 MNV combined, at baseline a worse BCVA (p = 0.02) and a higher maximal subretinal hyperreflective material (SHRM) thickness (p = 0.005) were associated with SF development at 3 years. In Type 1 MNV, the presence at baseline of intraretinal fluid (IRF) (p = 0.007) or SHRM (p < 0.001) and a higher percentage of visits with IRF (p < 0.001) or with SHRM (p < 0.001) were associated with SF occurrence. For Type 3 MNV, only a higher percentage of visits with SHRM (p = 0.001) was associated with SF. Including all MNV subtypes, eyes with a worse BCVA at baseline were associated with SF development (p < 0.001). Conversely, presence of SF at 3 years was associated with a worse baseline BCVA (p < 0.001). Occurrence of SF differs when considering apart MNV subtypes.

A cost-minimization analysis of anti-VEGFs for the treatment of neovascular age-related macular degeneration in the Netherlands.

Age-related macular degeneration (AMD) is the main cause of severe vision loss globally. Neovascular AMD (nAMD) is an advanced stage of AMD treated with anti-vascular endothelial growth factors (anti-VEGFs). Although anti-VEGF treatment is effective, the frequent intravitreal injections place a burden on patients, (in)formal caregivers, and clinics. This study assesses the health-economic impact of anti-VEGF agents with lower injection frequency that have the potential to reduce treatment burden and compares it to the standard of care. We developed a cost-minimization model to evaluate the direct medical costs associated with first-line unilateral anti-VEGF treatment across a 3-year time horizon in the Netherlands. The analysis compared aflibercept 8mg, aflibercept 2mg, bevacizumab, faricimab, and ranibizumab. Our model adopted a treat-and-extend (T&E) regimen for aflibercept 2mg, bevacizumab, and ranibizumab. For aflibercept 8mg, a flexible regimen that was extendable up to 24weeks was applied, while faricimab followed a flexible regimen that was extendable up to 16weeks. Additionally, since list prices may vary from net prices, we calculated the break-even price for each anti-VEGF in comparison to bevacizumab, which is the recommended first-line treatment due to its low medication price. Based on list prices, aflibercept 8mg led to the lowest treatment costs (€16,251 per patient over a 3-year time horizon), closely followed by bevacizumab (€17,616 per patient over a 3-year time horizon). Ranibizumab led to the highest per-patient costs (€31,746 over a 3-year time horizon). For bevacizumab, most costs were attributable to administration, while for the other anti-VEGFs, most were attributable to medication. Aflibercept 8mg is cost-saving compared to bevacizumab at their medication prices at the time of writing. Aflibercept 2mg, faricimab, and ranibizumab should be priced below €488, €591, and €75, respectively. To be cost-equal to bevacizumab with current list prices, anti-VEGFs should be administered with a maximum of 12.7 to 13.8 injections over a 3-year time horizon. According to the injection frequency observed in clinical trials, aflibercept 8mg would be the anti-VEGF that generates the lowest per-patient healthcare costs for the treatment of nAMD in the Netherlands after a treatment period of three years. Our study indicates that anti-VEGF drugs with a lower injection frequency might provide a cost-saving solution to the increasing burden of anti-VEGF treatment on the healthcare system.

Identification and Activity Study of an Impurity Band Observed in the nrSDS-PAGE of Aflibercept.

Aflibercept is a biopharmaceutical targeting vascular endothelial growth factor (VEGF) that has shown promise in the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) in adults. Quality control studies of aflibercept employing non-reduced SDS-PAGE (nrSDS-PAGE) have shown that a significant variant band (IM1) is consistently present below the main band. Considering the quality control strategy of biopharmaceuticals, structural elucidation and functional studies are required. In this study, the variant bands in nrSDS-PAGE were collected through electroelution and identified by peptide mass fingerprinting based on liquid chromatography-tandem MS (LC-MS/MS). This variant was expressed using knob-into-hole (KIH) design transient transfection for the detection of ligand affinity, binding activity and biological activity. The variant band was formed by C-terminal truncation at position N99 of one chain in the aflibercept homodimer. Then, this variant was successfully expressed using KIH design transient transfection. The ligand affinity of the IM1 truncated variant was reduced by 18-fold, and neither binding activity nor biological activity were detected. The efficacy of aflibercept is influenced by the loss of biological activity of the variant. Therefore, this study supports the development of a quality control strategy for aflibercept.

Review of Guideline Recommendations for Optimal Anti-VEGF Therapy in Age-Related Macular Degeneration.

Neovascular age-related macular degeneration is a progressive, blinding macular disease that has become a burden both in healthcare systems and the global economy. The vascular endothelial growth factor (VEGF) is the main agent involved in the pathogenic process of the disease. The main goal of the age-related macular degeneration treatment is to maintain and improve visual acuity by injecting intravitreal anti-VEGF agents in either a reactive or proactive manner. Subretinal and intraretinal fluids are the main biomarkers that should be considered when managing the frequency of the therapy. This review discusses both functional and morphological treatment criteria according to current recommendations as opposed to real-life situations encountered during day-to-day clinical practice and highlights situations in which the benefits of continuing therapy are arguable in terms of improving patients' quality of life. Optimizing the treatment regimen represents an important aim of current clinical ophthalmological practice, as age-related macular degeneration patients usually have a long follow-up period.

Inflammasome activation aggravates choroidal neovascularization.

Inflammasome activation is implicated in diseases of aberrant angiogenesis such as age-related macular degeneration (AMD), though its precise role in choroidal neovascularization (CNV), a characteristic pathology of advanced AMD, is ill-defined. Reports on inhibition of inflammasome constituents on CNV are variable and the precise role of inflammasome in mediating pathological angiogenesis is unclear. Historically, subretinal injection of inflammasome agonists alone has been used to investigate retinal pigmented epithelium (RPE) degeneration, while the laser photocoagulation model has been used to study pathological angiogenesis in a model of CNV. Here, we report that the simultaneous introduction of any of several disease-relevant inflammasome agonists (Alu or B2 RNA, Alu cDNA, or oligomerized amyloid β (1-40)) exacerbates laser-induced CNV. These activities were diminished or abrogated by genetic or pharmacological targeting of inflammasome signaling constituents including P2rx7, Nlrp3, caspase-1, caspase-11, and Myd88, as well as in myeloid-specific caspase-1 knockout mice. Alu RNA treatment induced inflammasome activation in macrophages within the CNV lesion, and increased accumulation of macrophages in an inflammasome-dependent manner. Finally, IL-1β neutralization prevented inflammasome agonist-induced chemotaxis, macrophage trafficking, and angiogenesis. Collectively, these observations support a model wherein inflammasome stimulation promotes and exacerbates CNV and may be a therapeutic target for diseases of angiogenesis such as neovascular AMD.

Clinical Observation of Micropulse Laser Combined with Conbercept in the Treatment of Neovascular Age-related Macular Degeneration with Pigment Epithelial Detachment (PED)

The aim of this study is to observe the efficacy of micropulse laser combined with Conbercept in the treatment of neovascular age-related macular degeneration (nAMD) complicated with PED. Thirty patients (30 eyes) diagnosed with nAMD and PED at our hospital in 2023 were randomly divided into two groups: the Conbercept treatment (IVC) group with 15 cases (15 eyes) and the Conbercept combined with 577 nm threshold micropulse laser treatment (IVC+SMLP) group with 15 cases (15 eyes). Anti-VEGF treatment was administered according to the 3+PRN regimen, and the combined treatment group received 577 nm threshold micropulse laser treatment within 2 weeks after anti-VEGF injection. Follow-up observed the best-corrected visual acuity (BCVA), central macular thickness (CMT), PED height (PEDH), number of injections, and related complications at 1 month, 3 months, 6 months, and 12 months after Conbercept intravitreal injection. The average BCVA, CMT, and PEDH in both groups improved significantly from baseline at all time points (P &lt; 0.05). At 12 months of follow-up, PEDH in the IVC+SMLP group decreased significantly from baseline (293.57±82.59 vs 184.84±33.95) and was significantly lower than in the IVC group (P &lt; 0.05). The number of IVC injections in the IVC group was significantly higher than in the IVC+SMLP group (8.04±0.3 vs 5.29±1.26) with a significant difference (t=4.290, P=0.016). No treatment-related adverse events were observed during the study. The 577 nm threshold micropulse laser combined with Conbercept effectively improves or stabilizes visual function and anatomical morphology in nAMD with PED, reduces the number of intravitreal injections, and alleviates the patient's economic burden to some extent.

Fight Retinal Blindness SPAIN. Report 3: clinical outcomes of vascular endothelial growth factor inhibitors in low vision eyes with neovascular age-related macular degeneration. A national database study

Fight Retinal Blindness SPAIN. Report 3: clinical outcomes of vascular endothelial growth factor inhibitors in low vision eyes with neovascular age-related macular degeneration. A national database study

Pneumatic displacement of submacular haemorrhage secondary to neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.

To compare the visual and anatomical outcomes of pneumatic displacement (PD) combined with anti-vascular endothelial growth factor (VEGF) therapy versus anti-VEGF monotherapy in treatment-naive eyes with submacular haemorrhage (SMH) secondary to neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. In a retrospective comparative interventional study of 57 eyes, the changes in logMAR visual acuity (VA), and SMH height and area at baseline at months 1, 3 and 12 were compared between the PD and non-PD groups. There was no significant difference in mean VA in the PD versus non-PD group at month 12 (1.1 versus 0.7, p = 0.09). At baseline, the PD group, compared to the non-PD group, had significantly larger SMH area (35.9 versus 26.9 mm2, p = 0.04) and SMH height at the fovea (733.7 versus 503.6 µm, p < 0.01). The greatest reduction in SMH height and area occurred between baseline and month 1 in the PD group, which was faster than between month 1 and month 3 in the non-PD group, with similar findings in the matched pair analysis matched for SMH height and area. In the multivariable analysis, only baseline VA was associated with VA outcomes (month 1: β = -0.46, 95% [confidence interval] CI = -0.78 to -0.14, p = 0.006; month 3: β = -0.52, 95% CI = -0.86 to -0.18, p = 0.004; and month 12: β = -0.78, 95% CI = -1.16 to -0.39, p < 0.001). The visual outcome of SMH at month 12 in nAMD and PCV is poor regardless of whether PD is performed in addition to anti-VEGF therapy, although a more rapid resolution of SMH can be expected.

Infographic: The port delivery system with ranibizumab for neovascular age-related macular degeneration: LADDER trial.

Infographic: The port delivery system with ranibizumab for neovascular age-related macular degeneration: LADDER trial.

Complement Inhibitors for Geographic Atrophy in Age-Related Macular Degeneration-A Systematic Review.

Age-related macular degeneration (AMD) is one of the main causes of blindness and visual impairment worldwide. Intravitreal complement inhibitors are an emergent approach in the treatment of AMD, which have had encouraging results. This systematic review analyzes the outcomes and safety of complement inhibitor therapies for GA in AMD cases. A comprehensive search on the PubMed and Web of Science databases returned 18 studies involving various complement inhibitor agents, with a total of 4272 patients and a mean follow-up of 68.2 ± 20.4 weeks. Most treated patients were white (96.8%) and female (55.8%), with a mean age of 78.3 ± 7.8 years and a mean GA area of 8.0 ± 3.9 mm2. There were no differences in visual function change between treated and control participants. The mean GA area change was 2.4 ± 0.7 mm2 in treated participants vs. 2.7 ± 0.8 mm2 in control groups (p < 0.001). The ocular and systemic side effects were similar to those of intravitreal anti-VEGF. A less-understood effect was that of the onset of choroidal neovascularization (CNV) in 1.1-13% of patients; this effect was found to be more frequent in patients with neovascular AMD in the fellow eye or nonexudative CNV in the study eye at baseline. Complement inhibitors may represent a useful therapy for GA in AMD, but a personalized approach to patient selection is necessary to optimize the outcomes.

The I-OPTA Questionnaire: A National Assessment of Patients with Neovascular Age-Related Macular Degeneration.

Neovascular age-related macular degeneration (nAMD) is the leading cause of irreversible vision loss in developed countries. However, a significant gap persists in understanding this population, exacerbated by their advanced age and visual impairments, which can hinder research participation and access to healthcare. The purpose of this study was to describe the content of the questionnaire and the participating patients with nAMD. The survey includes patients diagnosed with nAMD who had previously received treatment or were currently undergoing intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections. Participants were recruited using various methods, as reaching out to patients who are no longer receiving treatment poses a particular challenge. A patient and public advisory board assisted throughout the study period. Of the 713 electronic invitations sent out, 494 (69.3%) patients responded to the questionnaire, with an additional 57 responses obtained through e-mail or telephone interviews. Due to the exclusion of 16 responses, there were a total of 535 valid responses, including 176 from patients previously treated and 359 from those currently undergoing treatment for nAMD. The median age of respondents was 79.9years (interquartile range [IQR] 75.5-84.7), with 59.8% being women. Among them, 53.2% were married, while 43.1% lived alone. Data from the I-OPTA (Identification of Patient-Reported Barriers in Treatment for nAMD) questionnaire allows future exploration of patients who are no longer receiving treatment, patients' knowledge about preventive measures, and the impact of nAMD on visual function and quality of life. Future research, including studies that integrate data from corresponding retinal images and Danish national registers, has the potential to generate invaluable knowledge, providing benefits to both patients and healthcare professionals.

A Nanogel Formulation of Anti-VEGF Peptide for Ocular Neovascularization Treatment.

Age-related macular degeneration (AMD) is an eye disorder that can lead to visual impairment in elder patients, and current treatments include repeated injections of monoclonal antibody-based antivascular endothelial growth factor (anti-VEGF) agents. This study investigates the potential of a nanoformulation of a peptide anti-VEGF molecule for neovascular AMD. Anti-VEGF peptide HRHTKQRHTALH (HRH), which has high affinity to VEGF-Fc receptor, was used as the bioactive agent to control neovascularization of the retina. The nanoformulation consisting of hyaluronic acid nanogel was generated by incorporating divinyl sulfone and cholesterol to increase the stability and control the size of the nanodrug. The encapsulation efficacy of nanogel was 65%, and drug release was 34.72% at the end of 192 h. Obtained nanogels were efficiently internalized in 15 min by human umbilical vascular endothelial cells (HUVECs) and ARPE-19 cells, and results indicate that nanoformulation is not toxic to ARPE-19 cells, whereas it inhibits HUVEC proliferation owing to anti-VEGF peptide in the nanogel structure. In the coculture experiment in which retinal penetration was modeled, it was observed that the nanogel reached HUVECs and negatively affected their proliferation without disturbing the monolayer of ARPE-19 cells. In vivo experiments with chick chorioallantoic membrane revealed that nanogel formulation has higher antiangiogenesis activity compared to free HRH. Additionally, in an oxygen-induced retinopathy model, the excessive growth of blood vessels was notably suppressed in mice treated with HRH-loaded nanogel. This research indicates that nanogels formulated in this study are promising candidates as a topical treatment for AMD.

Clinical Outcomes of Intravitreal Brolucizumab Injection for Refractory Neovascular Age-related Macular Degeneration

Purpose: To investigate the clinical outcomes and intraocular inflammation (IOI) following intravitreal brolucizumab injection for the treatment of refractory neovascular age-related macular degeneration (nAMD).Methods: This retrospective study reviewed the medical records of nAMD patients who received intravitreal brolucizumab injection that was switched from other anti-vascular endothelial growth factor (anti-VEGF) agents due to limited responses. The changes in subretinal/intraretinal fluid (SRF/IRF) and development of IOI were evaluated using slit lamp examination, fundoscopy, and optical coherence tomography.Results: The study included 76 eyes of 75 patients (56 males, 19 females). SRF and IRF disappeared in 55.3% (42/76 eyes) after the first injection and in 52.3% (23/44 eyes) of the remaining eyes after the third injection. The mean treatment interval increased from 5.6 to 9.6 weeks (&lt;i&gt;p&lt;/i&gt; &lt; 0.001). Visual acuity did not change. Eleven eyes (14.5%) developed IOI: an anterior chamber reaction in two eyes, vitritis in nine eyes, retinal vasculitis in one eye, and no retinal vascular occlusion. All IOI was treated with steroid eye solution or oral medication and recovered within 3.8 weeks. Three eyes also underwent subtenon steroid injection. Early recovery from IOI was observed in the subtenon steroid injection group (1.67 ± 0.58 vs. 4.63 ± 2.97 weeks, &lt;i&gt;p&lt;/i&gt; = 0.048). Visual acuity (logMAR) decreased from 0.51 to 0.67 when IOI developed (&lt;i&gt;p&lt;/i&gt; = 0.018), but increased to 0.52 after recovery from IOI.Conclusions: Approximately half of the eyes with refractory nAMD showed complete resolution of SRF/IRF when receiving brolucizumab. IOI had a high incidence, but recovery was successful, with careful monitoring and intensive steroid treatment.

Relationship between hypertransmission defect size and progression in eyes with intermediate age-related macular degeneration.

To determine the associations between the presence of various-sized hypertransmission defects (hyperTDs) and progression to incomplete retinal pigment epithelial (RPE) and outer retinal atrophy (iRORA) and complete RORA (cRORA) in eyes with intermediate age-related macular degeneration (iAMD). Optical coherence tomography (OCT) data from consecutive iAMD patients, were retrospectively reviewed. All of iAMD eyes with or without iRORA (but not cRORA) at baseline were included. Graders evaluated the presence of hyperTDs at baseline (small: 63-124 µm; medium: 125-249 µm; large: ≥250 µm in diameter on choroidal en face OCT) and the progression two years later. Of the 145 eyes that not developed neovascular AMD at two years, the eyes that progressed to or developed iRORA or cRORA included 13 eyes (10.7%), 5 eyes (83.3%), 9 eyes (81.8%), and 6 eyes (85.7%) in the groups with no, small, medium, and large hyperTDs at baseline, respectively (P-value < 0.001). The odds ratios (95% CI) for progression were 41.6 (4.5-383.6), 37.4 (7.3-192.0), and 49.9 (5.6-447.1) in the small, medium, and large hyperTDs groups, compared to no hyperTDs (P-value ≤ 0.001). Eyes with ≥2 hyperTDs also showed more frequent progression than eyes with one or no hyperTDs (100% vs. 16.4%; P-value < 0.001). While most iAMD eyes with no hyperTDs remained stable on OCT over two years, eyes with hyperTDs of any size appeared to be at a higher risk for progression. HyperTDs may provide an important OCT biomarker for identifying high-risk iAMD patients.

PROSPECTIVE TRIAL OF HOME OPTICAL COHERENCE TOMOGRAPHY-GUIDED MANAGEMENT OF TREATMENT EXPERIENCED NEOVASCULAR AGE-RELATED MACULAR DEGENERATION PATIENTS.

To evaluate the impact of home optical coherence tomography (OCT)-guided patient management on treatment burden and visual outcomes. An interventional trial was conducted to compare frequency of treatment and visual acuity for the neovascular age-related macular degeneration patients before and during use of home optical coherence tomography over a period of 6 months. Patient adherence to regular scanning was measured by the number of scans performed per week. The characteristics of episodes of fluid recurrence and classification of typical fluid volume trajectories were performed. Twenty-seven eyes (21 with diagnosis of neovascular age-related macular degeneration and one converted during the study), of 15 patients were monitored for 6 months, scanning at 6.2 times/week per eye and yielding 4,435 scans of which 91.2% were eligible for artificial intelligence-based fluid volume quantification. Total number of monitoring weeks before and during the study were 1,555 and 509. The mean (SD) number of weeks per injection before and during home OCT management were 8.0 (4.7) and 15.3 (8.5) (P = 0.004), respectively. The mean (SD) visual acuity change before and during home OCT-based management was 3.5 (12.0) letters and 0.0 (9.5) letters (P = 0.45), respectively, showing no significant impact on visual acuity. For the first time, remote patient monitoring with a home OCT allowed personalized management of neovascular age-related macular degeneration. This study showed significant reduction in treatment burden while maintaining stable visual acuity.

EFFICACY AND SAFETY OF THE PROPOSED BIOSIMILAR AFLIBERCEPT, SDZ-AFL, IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: 52-Week Results From the Phase 3 Mylight Study.

The Phase 3 Mylight study was designed to confirm clinical equivalence of proposed biosimilar aflibercept (SOK583A1; Sandoz [proposed biosimilar aflibercept, SDZ-AFL]) to its reference biologic (Eylea; Regeneron Pharmaceuticals, Inc; Bayer AG [reference aflibercept, Ref-AFL]). Mylight was a prospective, double-masked, 2-arm, parallel Phase 3 study. Participants with neovascular age-related macular degeneration were randomized 1:1 to receive eight injections of SDZ-AFL (n = 244) or Ref-AFL (n = 240) over 48 weeks. The primary endpoint was mean change in best-corrected visual acuity score from baseline to Week 8. Secondary endpoints included anatomical outcomes, best-corrected visual acuity at Weeks 24 and 52, safety, and pharmacokinetics. Similarity in mean change in best-corrected visual acuity score was established between SDZ-AFL (n = 235) and Ref-AFL (n = 226) at Week 8 (difference: -0.3 [90% CI, -1.5 to 1.0]) and Week 52. No clinically meaningful differences occurred between groups in anatomical outcomes. Safety profiles were similar, with comparable incidences of treatment-related adverse events (SDZ-AFL: 2.5%; Ref-AFL: 2.9%). The incidence of anti-drug antibodies was similar between groups. Systemic free aflibercept concentrations 24 hours postdose were low and comparable between SDZ-AFL and Ref-AFL. Proposed biosimilar aflibercept matched reference aflibercept in efficacy, safety, and pharmacokinetics in participants with neovascular age-related macular degeneration. Therefore, this Phase 3 study confirmed biosimilarity of SDZ-AFL to Ref-AFL.

Artificial Intelligence in neovascular age-related macular degeneration

Artificial Intelligence in neovascular age-related macular degeneration