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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.

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.

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.

AimTo quantify the areas of burden experienced by patients requiring repeated intravitreal injections (IVI) in the management of exudative retinal diseases.MethodsThe validated Questionnaire to Assess Life Impact of Treatment by Intravitreal Injections survey was administered to patients at four retina clinical practices across four US states. The primary outcome measure was Treatment Burden Score (TBS), a single score assessing overall burden.ResultsOf 1416 (n=657 age-related macular degeneration; n=360 diabetic macular oedema/diabetic retinopathy; n=221 retinal vein occlusion; n=178 other/uncertain) patients, 55% were women with an average age of 70 years. Patients most frequently reported receiving IVI every 4–5 weeks (40%). The mean TBS was 16.1±9.2 (range 1–48; scale of 1–54), and the TBS was higher in patients with diabetic macular oedema and/or diabetic retinopathy (DMO/DR) (17.1) compared with those with age-related macular degeneration (15.5) or retinal venous occlusive (15.3) (p=0.028). Though the mean level of discomfort was quite low (1.86) (scale 0–6), 50% of patients reported experiencing side effects more than half of the visits. Patients having received fewer than 5 IVI reported higher mean anxiety levels before (p=0.026), during (p=0.050) and after (p=0.016) treatment compared with patients having received more than 50 IVI. After the procedure, 42% of patients reported restrictions from usual activities due to discomfort. Patients reported a high mean satisfaction rating of 5.46 (scale 0–6) with the care of their diseases.ConclusionsThe mean TBS was moderate and highest among patients with DMO/DR. Patients with more total injections reported lower levels of discomfort and anxiety but higher disruption to daily life. Despite the challenges related to IVI, the overall satisfaction with treatment remained high.

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.

Gene therapies aim to deliver a therapeutic payload to specified tissues with underlying protein deficiency. Since the 1990s, gene therapies have been explored as potential treatments for chronic conditions requiring lifetime care and medical management. Ocular gene therapies target a range of ocular disorders, but retinal diseases are of particular importance due to the prevalence of retinal disease and the current treatment burden of such diseases on affected patients, as well as the challenge of properly delivering these therapies to the target tissue. The purpose of this review is to provide an update on the most current data available for five different retinal gene therapies currently undergoing clinical trials for use against age-related macular degeneration (AMD) and the development of novel delivery routes for the administration of such therapies. Research has been performed and compiled from PubMed and the select authors of this manuscript on the treatment and effectiveness of five current retinal gene therapies: Luxturna, ADVM-022, RGX-314, GT-005, and HMR59. We present the available data of current clinical trials for the treatment of neovascular and dry age-related macular degeneration with different AAV-based gene therapies. We also present current research on the progress of developing novel routes of administration for ocular gene therapies. Retinal gene therapies offer the potential for life-changing treatment for chronic conditions like age-related macular degeneration with a single administration. In doing so, gene therapies change the landscape of treatment options for these chronic conditions for both patient and provider.

To evaluate functional and anatomical outcomes of faricimab in treatment-naïve patients with neovascular age-related macular degeneration (nAMD) presenting with subretinal hemorrhage (SRH). A multicenter retrospective chart review was completed in retina practices in Canada and the United States from June 2022 to September 2025. Treatment-naïve nAMD patients with SRH receiving faricimab were evaluated. Standardized imaging protocols and treat-and-extend guidelines were employed. Primary outcome was visual acuity (VA) change; secondary outcomes included central subfield thickness (CST), pigment epithelial detachment (PED) height, and qualitative assessment of subretinal hyperreflective material (SHRM) and subretinal fibrosis. Outcomes were analyzed following three consecutive loading doses using Friedman statistics for repeated measures. Paired analysis was performed using Wilcoxon signed rank test. Detailed characterization of SRH included measurements of hemorrhage size in disc diameters (DD), location in terms of subfoveal versus extrafoveal, and duration from symptom onset to treatment initiation. Univariate regression analysis was performed to identify predictors of SRH resolution (effect ratio and 95% CI) and visual acuity improvement (odds ratio and 95% CI). This study included 63 treatment-naïve patients with nAMD and SRH (mean age was 81.6 ± 8.2 years; 58.2% females; n = 28 from Canada and n = 35 from United States; mean total follow-up duration was 17.5 ± 6.0 months). Significant VA improvement was observed (Friedman statistic: 26.3, p < 0.00001), with 42.6% of patients gaining ≥3 lines of vision after loading doses. CST decreased substantially from 391.8 µm to 249.4 µm (p < 0.00001, z = -5.48) and mean PED height reduced from 309.6 µm to 110.7 µm (p < 0.00001, z = -3.51). SHRM and subretinal fibrosis were noted in 81.6% and 25.4% of cases, respectively, at baseline. Of this, 70% had resolution of SHRM and 50% had improvement in fibrosis, at last follow up visit. Univariate analysis of predictors of faricimab injection account to achieve SRH resolution in n = 33 patients identified three significant predictors: SHRM-presence at baseline (effect ratio = 0.531, 95% CI 0.399-0.707, p < 0.0001), combined intraretinal fluid (IRF) and subretinal fluid (SRF) (effect ratio = 1.43, 95% CI 1.09-1.87, p = 0.011), and non-Caucasian ethnicity (effect ratio = 1.45, 95% CI 1.03-2.04, p = 0.031). Analysis of predictors of VA improvement >3 lines did not reveal any clinically meaningful associations. This study demonstrates faricimab's efficacy in nAMD with SRH, a challenging phenotype traditionally associated with poor visual prognosis. The dual-pathway inhibition of VEGF-A and Ang-2 achieved rapid hemorrhage clearance and meaningful vision gains, offering clinical hope for this high-risk population.

Background Investigate retinal fluid changes via a novel deep-learning algorithm in real-world patients receiving faricimab for the treatment of neovascular age-related macular degeneration (nAMD). Methods Multicenter, retrospective chart review and optical coherence tomography (OCT) image upload from participating sites was conducted on patients treated with faricimab for nAMD from February 2022 to January 2024. The Notal OCT Analyzer (NOA) algorithm provided intraretinal, subretinal and total retinal fluid for each scan. Results were segregated based on treatment history and fluid compartments, allowing for multiple cross-sections of evaluation. Results A total of 521 eyes were included at baseline. The previous treatments prior to faricimab were aflibercept, ranibizumab, bevacizumab, or treatment-naive for 52.3%, 21.0%, 13.3%, and 11.2% of the eyes, respectively. Of all 521 eyes, 49.9% demonstrated fluid reduction after one injection of faricimab. The mean fluid reduction after one injection was −60.7nL. The proportion of eyes that saw reduction in fluid compared to baseline after second, third, fourth and fifth faricimab injections were 54.4%, 51.9%, 51.4% and 52.2%, respectively. The mean (SD) retreatment interval after second, third, fourth and fifth faricimab injection were 53.4 (34.3), 56.6 (36.0), 57.1 (35.3) and 61.5 (40.2) days, respectively. Conclusion Deep-learning algorithms provide a novel tool for evaluating precise quantification of retinal fluid after treatment of nAMD with faricimab. Faricimab demonstrates reduction of retinal fluid in multiple groups after just one injection and sustains this response after multiple treatments, along with providing increases in treatment intervals between subsequent injections.

Pakistan falls significantly below the recommended forest coverage level of 20 to 30 percent of total area, with less than 6 percent of its land under forest cover. This deficiency is primarily attributed to illicit deforestation for wood and charcoal, coupled with a failure to embrace advanced techniques for forest estimation, monitoring, and supervision. Remote sensing techniques leveraging Sentinel-2 satellite images were employed. Both single-layer stacked images and temporal layer stacked images from various dates were utilized for forest classification. The application of an artificial neural network (ANN) supervised classification algorithm yielded notable results. Using a single-layer stacked image from Sentinel-2, an impressive 91.37% training overall accuracy and 0.865 kappa coefficient were achieved, along with 93.77% testing overall accuracy and a 0.902 kappa coefficient. Furthermore, the temporal layer stacked image approach demonstrated even better results. This method yielded 98.07% overall training accuracy, 97.75% overall testing accuracy, and kappa coefficients of 0.970 and 0.965, respectively. The random forest (RF) algorithm, when applied, achieved 99.12% overall training accuracy, 92.90% testing accuracy, and kappa coefficients of 0.986 and 0.882. Notably, with the temporal layer stacked image of the Sentinel-2 satellite, the RF algorithm reached exceptional performance with 99.79% training accuracy, 96.98% validation accuracy, and kappa coefficients of 0.996 and 0.954. In terms of forest cover estimation, the ANN algorithm identified 31.07% total forest coverage in the District Abbottabad region. In comparison, the RF algorithm recorded a slightly higher 31.17% of the total forested area. This research highlights the potential of advanced remote sensing techniques and machine learning algorithms in improving forest cover assessment and monitoring strategies.