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.
Bipolaris sorokiniana is a nectrophic fungal pathogen that causes foliar and root diseases on wheat and barley. Theose diseases are common in all wheat- and barley-growing regions with more severe outbreaks occurring in under warm and humid conditions. areas. The fungus B. sorokiniana can also infect a wide range of grass species in Poaceae and secrete ToxA, an important necrotrophic effector also identified other wheat leaf spotting pathogens. ToxA is an important effector gene that has been identified in several wheat fungal pathogens including B. sorokiniana. In this study, we investigated the prevalence and virulence role of ToxA were investigated in a collection of 278 B. sorokiniana populations isolates that were mainly collected from spring wheat and barley in the Upper Midwest of the United States or other places, including . A total of 278 B. sorokiniana isolates were evaluated including 169 from wheat leaves, 75 from wheat roots, 30 from barley leaves and four from wild quack grass leaves. ToxA was detected present in the isolates from wheat leaves, wheat roots and wild grass leaves, but was absent notfrom isolates collected in those 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 the ToxA-Tsn1 interaction plays an important role in spot blotch development. This work confirms the presence and importance of ToxA in B. sorokiniana populations from infecting wheat and thus, the need to eliminate breeding of Tsn1 out from spring wheat cultivars can to reduce susceptibility to spot blotch.
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.
Geographic atrophy (GA) secondary to age-related macular degeneration is the leading cause of permanent vision loss in patients over the age of 50 in developed countries. GA is characterized by the atrophy of retinal pigment epithelium and photoreceptors and can lead to central or peripheral vision loss, depending on the location of the atrophy. Currently, there are no US Food and Drug Administration-approved treatments for GA. Avacincaptad pegol (Zimura®; IVERIC Bio Inc, New York, NY, USA) is a C5-specific inhibitor that is being investigated as a potential treatment for GA. C5 is a key protein within the complement system, which maintains retina integrity and health under normal conditions. It is hypothesized that unregulated activation of the complement system (indicated by elevated levels of active proteins such as the membrane attack complex) can exacerbate the progression of GA. This article reviews the latest data regarding avacincaptad pegol as an investigational therapeutic for GA.
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