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Background/Objective Investigate real-world patients receiving faricimab for the treatment of neovascular age-related macular degeneration (nAMD). Subjects/Methods Multicenter, retrospective chart review was conducted on patients treated with faricimab for nAMD from February 2022 to September 2022. Collected data includes background demographics, treatment history, best-corrected visual acuity (BCVA), anatomic changes, and adverse events as safety markers. The main outcome measures are changes in BCVA, changes in central subfield thickness (CST) and adverse events. Secondary outcome measures included treatment intervals and presence of retinal fluid. Results After one injection of faricimab, all eyes ( n  = 376), previously-treated ( n  = 337) and treatment-naïve ( n  = 39) eyes demonstrated a + 1.1 letter ( p  = 0.035), a + 0.7 letter ( p  = 0.196) and a + 4.9 letter ( p  = 0.076) improvement in BCVA, respectively, and a − 31.3 μM ( p  < 0.001), a − 25.3 μM ( p  < 0.001) and a − 84.5 μM ( p  < 0.001) reduction in CST, respectively. After three injections of faricimab, all eyes ( n  = 94), previously-treated ( n  = 81) and treatment-naïve ( n  = 13) eyes demonstrated a + 3.4 letter ( p  = 0.03), a + 2.7 letter ( p  = 0.045) and a + 8.1 letter ( p  = 0.437) improvement in BCVA, and a − 43.4 μM ( p  < 0.001), a − 38.1 μM ( p  < 0.001) and a − 80.1 μM ( p  < 0.204) reduction in CST, respectively. One case of intraocular inflammation was observed after four injections of faricimab and resolved with topical steroids. One case of infectious endophthalmitis was treated with intravitreal antibiotics and resolved. Conclusions Faricimab has demonstrated improvement or maintenance of visual acuity for patients with nAMD, along with rapid improvement of anatomical parameters. It has been well-tolerated with low incidence of treatable intraocular inflammation. Future data will continue to investigate faricimab for real-world patients with nAMD.

Age-related macular degeneration (AMD) is characterized as a chronic, multifactorial disease and is the leading cause of irreversible blindness. Advanced AMD is classified as neovascular (wet) AMD and non-neovascular (dry) AMD. Dry AMD can progress to a more advanced form that manifests as geographic atrophy (GA), which significantly threatens vision, leading to progressive and irreversible loss of visual function. There are currently no approved therapeutics commercially available for GA patients. However, data from various clinical trials have demonstrated favorable results with significant reduction in GA lesion growth. This review furthers the understanding of the pathophysiology of GA, as well as current clinical trial data on investigational therapeutics.

Management of vitreoretinal disorders (e.g., neovascular age-related macular degeneration [nAMD] and diabetic macular edema [DME]) have assumed the standard therapy of lifelong anti-VEGF injections with drugs like aflibercept, brolucizumab, ranibizumab and bevacizumab. However, the burden imposed on patients is a major deterrent for continual therapy and recovery. Faricimab, a bispecific antibody, blocking both VEGF-A and Ang-2 molecules, produces a comparable functional and anatomical results, with less injections, significantly reducing patient burden. Visual acuity, safety, adverse effects, and anatomical outcomes are discussed in the pivotal clinical trials (YOSEMITE/RHINE and TENAYA/LUCERNE), and early data from real-world studies (TRUCKEE, TAHOE, FARWIDE-DME, FARETINA and others). In YOSEMITE and RHINE, faricimab demonstrated non-inferior vision gains, better anatomical outcomes compared to aflibercept every 8 weeks. Faricimab in the personalized treatment interval (PTI), after week 96, achieved 12-week interval in 78.1% of the patients and 16-week interval in 62.3%. TENAYA and LUCERNE reported comparable best corrected visual acuity (BCVA) improvement and better anatomic outcomes during head-to-head phase, parallel to aflibercept, at its 8-week treatment schedule. Faricimab in the PTI regimen, after week 96 achieved 12-week interval in 77.8% of the patients and 16-week interval in 63.1%. Safety of faricimab has been comparable to aflibercept in these pivotal trials. Real-world data supports the data from the pivotal studies regarding the efficacy and safety profile of faricimab in heterogenous real world patient population. Moreover, in previously treated patients, it also demonstrated a faster fluid resolution, good safety profile. Considering faricimab has demonstrated anatomic and durability benefit in the treatment of nAMD and DME, additional data from ongoing extension clinical trials, AVONELLE-X and RHONE-X will help understand longer term outcomes for patients treated with faricimab as well as patients switching from aflibercept to faricimab after finishing the pivotal trials. Longer term data from the real-world studies will also continue to contribute to our understanding of long-term efficacy, safety and durability in the real world patient population.

This review summarizes the latest findings in the literature of Angiopoietin-2 (Ang-2), Tyrosine-protein kinase receptor (Tie-2) complex, and faricimab along with their involvement for the treatment of retinal vascular diseases in various clinical trials. In ischemic diseases, such as diabetic retinopathy, Ang-2 is upregulated, deactivating Tie-2, resulting in vascular leakage, pericyte loss, and inflammation. Recombinant Angiopeotin-1 (Ang-1), Ang-2-blocking molecules, and inhibitors of vascular endothelial protein tyrosine phosphatase (VE-PTP) decrease inflammation-associated vascular leakage, showing therapeutic effects in diabetes, atherosclerosis, and ocular neovascular diseases. In addition, novel studies show that angiopoietin-like proteins may play an important role in cellular metabolism leading to retinal vascular diseases. Current therapeutic focus combines Ang-Tie targeted drugs with other anti-angiogenic or immune therapies. Clinical studies have identified faricimab, a novel bispecific antibody designed for intravitreal use, to simultaneously bind and neutralize Ang-2 and VEGF-A for treatment of diabetic eye disease. By targeting both Ang-2 and vascular endothelial growth factor-A (VEGF-A), faricimab displays an improved and sustained efficacy over longer treatment intervals, delivering superior vision outcomes for patients with diabetic macular edema and reducing the treatment burden for patients with neovascular age-related macular degeneration and diabetic macular edema. Phase 2 results have produced promising outcomes with regard to efficacy and durability. Faricimab is currently being evaluated in global Phase 3 studies.

Macular telangiectasia Type 2 (MacTel) is a gradually progressive disease that affects the quality of life by impairing both distant and near vision. It had previously been considered a vascular condition, but recent evidence suggests a neurodegenerative etiology, with primary involvement of Muller cells. Retinal pigment epithelium (RPE) hyperplasia and subretinal neovascularization (SNV) are responsible for most of the vision loss in advanced cases. Neurotrophic factors in the non-proliferative phase and intravitreal anti-Vascular Endothelial growth factor (VEGF) in the proliferative phase have shown to retard the progression of the disease. This review will discuss the pathophysiology, clinical features, important diagnostic imaging studies and available treatment options for MacTel. Keywords: macular telangiectasia type 2, MacTel, CNTF, ciliary neurotrophic factor

Port delivery system (PDS) with ranibizumab (Susvimo, Genentech, USA) was approved by the U.S. Food and Drug Administration (FDA) on 22nd October 2021 for the management of neovascular age-related macular degeneration (n-AMD) in eyes with at least two prior anti-vascular endothelial growth factor (VEGF) injections [1, 2]. [...]it did not include the Susvimo (ranibizumab injection) 100 mg/ml drug vial for a refill-exchange solution and refill needles in order to allow for continued refill-exchange procedures in eligible patients in clinical trials as well as in the commercial setting who already have an implant. The control arm in phase 2 and 3 studies was monthly ranibizumab and data from both studies show that PDS significantly reduces the treatment burden compared to monthly injections. [...]PDS can be clinically beneficial by decreasing treatment burden for patients with nAMD, especially the high need patients requiring frequent injections.

The Ang/Tie2 pathway complements VEGF-mediated activity in retinal vascular diseases such as DME, AMD, and RVO by decreasing vascular integrity, increasing neovascularization, and increasing inflammatory signaling. Faricimab is a bispecific antibody that has been developed as an inhibitor of both VEGF and Ang2 that has shown positive results in phase I, II and III trials. Recent Year 1 data from phase III clinical trials YOSEMITE, RHINE, TENAYA, and LUCERNE have confirmed the efficacy, safety, durability, and superiority of faricimab in patients with DME and nAMD. Faricimab, if approved, may significantly decrease treatment burden in patients with retinal vascular diseases to a greater extent than would current standard of care anti-VEGF injections.

BackgroundUnresolved retinal fluid and high injection burden are major challenges for patients with neovascular age-related macular degeneration. Brolucizumab addresses these challenges by providing robust vision gains and superior fluid resolution, with the potential for longer treatment intervals.Brolucizumab has been associated with adverse events of retinal vasculitis and retinal vascular occlusion typically in the presence of intraocular inflammation (IOI). To define the incidence of the adverse events, Novartis convened an external safety review committee, which found a rate of 4.6% for definite or probable IOI, 3.3% for retinal vasculitis, and 2.1% for retinal vascular occlusion in the HAWK and HARRIER trials. Novartis also established a coalition to explore 4 areas regarding the adverse events: root cause, patient characterization, event mitigation and vigilance, and treatment protocols for the adverse events. Based on the coalition findings, a risk mitigation framework was developed. Prior to initiating treatment with brolucizumab, it is important to weigh the potential benefit against risk of adverse events and to consider patient risk factors such as prior history of IOI and/or retinal vascular occlusion. To mitigate the potential for IOI-related adverse events, it is important to conduct a thorough dilated eye examination before each injection and closely monitor patients throughout treatment. Patients should be educated on symptoms of IOI to monitor for. Brolucizumab should not be injected in the presence of active IOI. If an adverse event is identified, prompt and intensive treatment should be considered.ConclusionProgress has been made in understanding how to mitigate IOI-related adverse events following treatment with brolucizumab.

The approval of Syfovre® (pegcetacoplan) and Iverzay® (avacincaptad pegol) for the treatment of geographic atrophy (GA) marks a significant advancement in retinal disease therapy, offering both complement 3 and complement 5 inhibitors. With this breakthrough, an increase in intravitreal injections (IVI) is expected to treat GA, raising questions about potential effects on intraocular pressure (IOP). This concern is exacerbated by the larger injection volume required for GA treatment, potentially impacting IOP. Previous studies have shown that IVI can lead to a temporary increase in IOP with a 0.05 ml injection. This transient elevation is challenging to manage with glaucoma drops, and a preventive approach, such as paracentesis immediately before IVIs, may be more effective. Despite concerns, clinical significance and long-term effects of IOP changes with a 0.05 ml injection remain uncertain. To address these concerns, routine evaluations including macular optical coherence tomography (OCT), fundus autofluorescence, IOP measurements, and retinal nerve fiber layer OCT before the first IVI with avacincaptad pegol and pegcetacoplan are recommended to detect potential changes early. Further research is needed to determine the extent to which IOP changes impact GA patients and whether cumulative effects occur with repeated IVIs, especially in those with additional eye conditions.

Intravitreal (IVT) injections are the most common procedure performed in retinal clinics today. It has revolutionized the treatment of neovascular age-related macular degeneration (nAMD), diabetic macular edema, macular edema due to veinous occlusive disease and other forms of exudative maculopathy. Though IVT injections prevent vision loss, the discomfort at the time of the injection has been troublesome to patients. This has led to patients missing their regular and routine dosage of treatment. Various modes of pre-injection anesthetic methods have been tried but in vain. Lidocaine-based topical anesthesia, in the form of pledgets, topical gel or subconjunctival lidocaine injection, has been the standard of care (SOC) for IVT injections worldwide. This article highlights the role of cooling anesthesia in reducing pain, anxiety and discomfort associated with needle penetration at the time of injection. PubMed and MedLine search were related to anesthesia for intravitreal injections, cooling anesthesia, mechanism of cooling anesthesia, COOL-1 trial, COOL-2 trial, results of COOL-1 trial and ultrarapid cooling anesthesia.