Approved treatments for neovascular age-related macular degeneration: current safety and future directions.

INTRODUCTION: Age-related macular degeneration (AMD) is a progressive retinal degenerative disease that is implicated as one of the leading causes of visual impairment in the elderly population. Vascular endothelial growth factor (VEGF) has been identified as the main driver of AMD, and various therapeutics have revolutionized the treatment and management of neovascular AMD (nAMD) with favorable visual and anatomical outcomes. AREAS COVERED: Physicians have a variety of approved therapeutics in their arsenal for patients with varying disease progression and patient-specific needs, with the ultimate goal of achieving optimal visual and anatomic outcomes. The literature search was conducted using PubMed, Google Scholar, and sources from companies' websites, allowing us to locate findings recently presented at conferences. EXPERT OPINION: Scientific advancements in the field have led to newly approved therapeutics and devices, such as the port-delivery system with ranibizumab (PDS), and further investigation is ongoing in the realm of gene therapy for retinal diseases. In addition to efficacy and durability, newer agents must have comparable safety profiles to older agents in order to be used broadly. These options introduce a level of complexity in nAMD treatment; however, physicians to personalize treatment to improve vision in nAMD patients and reduce treatment burden overall.

Infiltrative Basal Cell Carcinoma (iBCC) Adjacent to a Desmoplastic Trichoepithelioma (DTE): A Case Report and Literature Review of iBCCs and DTEs.

The co-existence of an infiltrative basal cell carcinoma (iBCC) and a desmoplastic trichoepithelioma (DTE) within the same cutaneous lesion is a rare occurrence. iBCCs are relatively common malignant skin neoplasms that pose a risk for local tissue destruction and recurrence. DTEs are cutaneous neoplasms originating from hair follicles that may clinically and histologically appear similar to iBCCs but are ultimately benign. Distinguishing between these two entities is important given their differing destructive potential. Herein, we describe the case of a 36-year-old female with a single skin lesion on her left cheek that was comprised of both an iBCC distinct from a DTE, as verified by histopathologic analysis. A literature review highlights the rarity of such collision tumors and discusses the potential genetic links between these two histologically similar cutaneous neoplasms.

Exudation in Patients With Neovascular Age-Related Macular Degeneration Treated With the Port Delivery System or Monthly Injections.

PURPOSE: To evaluate for the presence, severity, and type of exudation at each study visit for a subgroup of patients with neovascular age-related macular degeneration from the Archway and Portal trials. DESIGN: Retrospective analysis of prospectively obtained data. METHODS: Spectral-domain optical coherence tomography scans from each study visit of 44 patients from the Port Delivery System (PDS) arm and 32 patients from the monthly injection arm of Archway were evaluated, and composites of horizontal scans through the fovea were created. Each composite was graded for the presence, type, and severity of exudation and impact on best-corrected visual acuity. RESULTS: After PDS implantation, 20 of 44 eyes (45%) never showed any exudation in the fovea, 2 (5%) never showed exudation in the fovea but had several missed visits, whereas 15 (34%), 3 (7%), and 4 (9%) showed mild, moderate, or severe exudation at 1 or more study visits, respectively. When exudation was present, it was most commonly subretinal fluid (50%). Of 32 patients randomized to monthly injections, 15 (47%) had no exudation in the fovea during monthly injections or after PDS implantation. Fluctuation of exudation in the fovea over time was seen in some patients after PDS implantation or during monthly injections with little or no identifiable impact on best-corrected visual acuity. In the 7 eyes with moderate or severe exudation in the fovea after PDS implantation, final vision was good in 5 (20/25 in 3, 20/40 in 1, and 20/50 in 1) and 2 had reduced vision from submacular hemorrhage. CONCLUSIONS: The PDS provides excellent control of exudation in the fovea in patients with neovascular age-related macular degeneration, and when exudation occurs, it often resolves without a negative impact on vision.

The real-world efficacy and safety of faricimab in neovascular age-related macular degeneration: the TRUCKEE study - 6 month results.

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.

Emerging Treatment Options for Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration.

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.

Prevalence and Importance of the Necrotrophic Effector Gene ToxA in Bipolaris sorokiniana Populations Collected from Spring Wheat and Barley.

Bipolaris sorokiniana is a necrotrophic fungal pathogen that causes foliar and root diseases on wheat and barley. These diseases are common in all wheat- and barley-growing regions, with more severe outbreaks occurring under warm and humid conditions. B. sorokiniana can also infect a wide range of grass species in the family Poaceae and secrete ToxA, an important necrotrophic effector also identified other wheat leaf spotting pathogens. In this study, the prevalence and virulence role of ToxA were investigated in a collection of 278 B. sorokiniana isolates collected from spring wheat and barley in the Upper Midwest of the United States or other places, including 169 from wheat leaves, 75 from wheat roots, 30 from barley leaves, and 4 from wild quack grass leaves. ToxA was present in the isolates from wheat leaves, wheat roots, and wild grass leaves but was absent from isolates collected from barley leaves. Prevalence of ToxA in wheat leaf isolates (34.3%) was much higher than that in wheat root isolates (16%). Sequencing analysis revealed the presence of two haplotypes, with the majority being BsH2. All ToxA+ isolates produced the functional effector in liquid cultures. Pathogenicity assays revealed that ToxA+ isolates caused significantly more disease on spring wheat lines harboring Tsn1 than their tsn1 mutants, suggesting that the ToxA-Tsn1 interaction plays an important role in spot blotch development. This work confirms the importance of ToxA in B. sorokiniana populations infecting wheat and, thus, the need to eliminate Tsn1 from spring wheat cultivars to reduce susceptibility to spot blotch.

Cooling Anesthesia for Intravitreal Injections - A Review.

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.