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Vitreolysis for Vitreomacular Traction and Macular Holes Intravitreal injection of a modified protease that targets components of the vitreomacular interface resolved vitreomacular traction and closed macular holes more often than did placebo, albeit with associated, mainly transient, ocular adverse events. The human vitreous body is bounded posteriorly by the retina and is variably adherent to it. Collagen fibrils forming the posterior vitreous cortex are firmly attached at the macula, the central part of the retina where visual acuity is best, and are connected to its internal limiting membrane by means of a biochemical glue composed of proteoglycans, including laminin and fibrinectin. 1 – 4 With aging, the gel-like vitreous progressively liquefies and vitreoretinal adhesions weaken, leading to separation of the vitreous from the retina, or posterior vitreous detachment. 5 – 7 Vitreomacular adhesion is observed after partial posterior vitreous detachment, when a portion of . . .

Lactobacillus paracasei KW3110 (KW3110) has anti-inflammatory effects and mitigates retinal pigment epithelium (RPE) cell damage caused by blue-light exposure. We investigated whether KW3110 suppresses chronic inflammatory stress-induced RPE cell damage by modulating immune cell activity and whether it improves ocular disorders in healthy humans. First, we showed that KW3110 treatment of mouse macrophages (J774A.1) produced significantly higher levels of interleukin-10 as compared with other lactic acid bacterium strains (all p < 0.01). Transferring supernatant from KW3110- and E. coli 0111:B4 strain and adenosine 5′-triphosphate (LPS/ATP)-stimulated J774A.1 cells to human retinal pigment epithelium (ARPE-19) cells suppressed senescence-associated phenotypes, including proliferation arrest, abnormal appearance, cell cycle arrest, and upregulation of cytokines, and also suppressed expression of tight junction molecule claudin-1. A randomized, double-blind, placebo-controlled parallel-group study of healthy subjects (n = 88; 35 to below 50 years) ingesting placebo or KW3110-containing supplements for 8 weeks showed that changes in critical flicker frequency, an indicator of eye fatigue, from the week-0 value were significantly larger in the KW3110 group at weeks 4 (p = 0.040) and 8 (p = 0.036). These results suggest that KW3110 protects ARPE-19 cells against premature senescence and aberrant expression of tight junction molecules caused by chronic inflammatory stress, and may improve chronic eye disorders including eye fatigue.

Background and Objectives Nerve growth factor (NGF) is a neurotrophin with therapeutic possibilities that extend from the nervous system to the eye. We tested the safety, maximal tolerated dose, pharmacokinetics, and antigenicity of a novel human recombinant NGF (rhNGF) eye-drop formulation in a phase I study. Methods This prospective, randomized, double-masked, vehicle-controlled trial, sponsored by Dompé SpA (registered as NCT01744704 at ClinicalTrials.gov), enrolled 74 healthy volunteers (24 females, 50 males, age 40.2 ± 11.8 years). Subjects were randomized in three cohorts to receive (1) a single eye-drop containing 0.0175, 0.175, or 0.7 μg rhNGF; (2) a single ascending dose of rhNGF eye drops three times a day for 1 day (total daily dose 2.1, 6.3, or 18.9 μg), or vehicle; or (3) a multiple ascending dose of rhNGF eye drops three times a day for 5 days (total dose 10.5, 31.5, or 94.5 μg), or vehicle. Outcome measures included blood chemistry, urinalyses, vital signs, electrocardiograms (ECGs), serum NGF antibodies, ocular and systemic adverse events (AEs), visual acuity, tear function, intraocular pressure, fundus oculi, and ocular symptoms. Results Administration of rhNGF eye drops did not result in a significant increase of circulating NGF levels and no antidrug antibodies were detected in serum. No serious AEs were recorded, and a few mild, transient ocular AEs related to rhNGF administration were reported only at the highest concentration. Conclusions rhNGF eye drops were well tolerated, with no detectable clinical evidence of systemic AEs. These results pave the way for the development of clinical trials on rhNGF in ophthalmology.

Objective and design This double-blind cross-over study compared the potential of bilastine, cetirizine, and fexofenadine to relieve the symptoms of allergic rhinitis. Subjects and methods Seventy-five allergic volunteers were challenged with grass pollen in the Vienna Challenge Chamber (VCC) on two consecutive days of allergen provocation; 6 h on day 1 and 4 h day 2. Bilastine 20 mg, cetirizine 10 mg, fexofenadine 120 mg, or placebo were taken orally 2 h after the start of provocation on day 1 only. Total nasal symptom scores, the global symptom scores, nasal secretions, and eye symptoms were assessed on both day 1 and day 2. Results and conclusions Bilastine had a rapid onset of action, within 1 h, and a long duration of action, greater than 26 h. Cetirizine was similar. Fexofenadine was similar on day 1 but less effective on day 2, indicating a shorter duration of action. Bilastine, like cetirizine and fexofenadine, was safe and well tolerated in this study.

Superoxide dismutases (SODs) are metalloenzymes that play a major role in antioxidant defense against oxidative stress in the body. SOD supplementation may therefore trigger the endogenous antioxidant machinery for the neutralization of free-radical excess and be used in a variety of pathological settings. This paper aimed to provide an extensive review of the possible uses of SODs in a range of pathological settings, as well as describe the current pitfalls and the delivery strategies that are in development to solve bioavailability issues. We carried out a PubMed query, using the keywords “SOD”, “SOD mimetics”, “SOD supplementation”, which included papers published in the English language, between 2012 and 2020, on the potential therapeutic applications of SODs, including detoxification strategies. As highlighted in this paper, it can be argued that the generic antioxidant effects of SODs are beneficial under all tested conditions, from ocular and cardiovascular diseases to neurodegenerative disorders and metabolic diseases, including diabetes and its complications and obesity. However, it must be underlined that clinical evidence for its efficacy is limited and consequently, this efficacy is currently far from being demonstrated.

CK2 is a constitutively active Ser/Thr protein kinase, which phosphorylates hundreds of substrates, controls several signaling pathways, and is implicated in a plethora of human diseases. Its best documented role is in cancer, where it regulates practically all malignant hallmarks. Other well-known functions of CK2 are in human infections; in particular, several viruses exploit host cell CK2 for their life cycle. Very recently, also SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has been found to enhance CK2 activity and to induce the phosphorylation of several CK2 substrates (either viral and host proteins). CK2 is also considered an emerging target for neurological diseases, inflammation and autoimmune disorders, diverse ophthalmic pathologies, diabetes, and obesity. In addition, CK2 activity has been associated with cardiovascular diseases, as cardiac ischemia–reperfusion injury, atherosclerosis, and cardiac hypertrophy. The hypothesis of considering CK2 inhibition for cystic fibrosis therapies has been also entertained for many years. Moreover, psychiatric disorders and syndromes due to CK2 mutations have been recently identified. On these bases, CK2 is emerging as an increasingly attractive target in various fields of human medicine, with the advantage that several very specific and effective inhibitors are already available. Here, we review the literature on CK2 implication in different human pathologies and evaluate its potential as a pharmacological target in the light of the most recent findings.

RNA therapy for eye diseases has good clinical translation potential, benefiting from the eye’s immune privilege, local drug delivery, and minimal dosage needs.RNA therapeutics play a crucial role in the treatment of genetic ocular diseases, which are directly linked to gene regulation.Delivering RNA to the eye’s posterior segment necessitates combination of delivery carriers and technology for effective in situ therapy.RNA nanomedicines have been utilized to reach specific targets in clinical treatments for eye diseases.Sequencing technology can deepen our understanding of eye diseases, revealing new diagnostic markers and therapeutic targets. Ocular disorders remain a major global health challenge with unmet medical needs. RNA nanomedicine has shown significant therapeutic benefits and safety profiles in patients with complex eye disorders, already benefiting numerous patients with gene-related eye disorders. The effective delivery of RNA to the unique structure of the eye is challenging owing to RNA instability, off-target effects, and ocular physiological barriers. Specifically tailored RNA medication, coupled with sophisticated engineered delivery platforms, is crucial to guide and advance developments in treatments for oculopathy. Herein we review recent advances in RNA-based nanomedicine, innovative delivery strategies, and current clinical progress and present challenges in ocular disease therapy. Ocular disorders remain a major global health challenge with unmet medical needs. RNA nanomedicine has shown significant therapeutic benefits and safety profiles in patients with complex eye disorders, already benefiting numerous patients with gene-related eye disorders. The effective delivery of RNA to the unique structure of the eye is challenging owing to RNA instability, off-target effects, and ocular physiological barriers. Specifically tailored RNA medication, coupled with sophisticated engineered delivery platforms, is crucial to guide and advance developments in treatments for oculopathy. Herein we review recent advances in RNA-based nanomedicine, innovative delivery strategies, and current clinical progress and present challenges in ocular disease therapy.

This review describes the role of contact lenses as an innovative drug delivery system in treating eye diseases. Current ophthalmic drug delivery systems are inadequate, particularly eye drops, which allow about 95% of the active substance to be lost through tear drainage. According to the literature, many interdisciplinary studies have been carried out on the ability of contact lenses to increase the penetration of topical therapeutic agents. Contact lenses limit drug loss by releasing the medicine into two layers of tears on either side of the contact lens, eventually extending the time of contact with the ocular surface. Thanks to weighted soft contact lenses, a continuous release of the drug over an extended period is possible. This article reviewed the various techniques to deliver medications through contact lenses, examining their advantages and disadvantages. In addition, the potential of drug delivery systems based on contact lenses has been extensively studied.

The Wilcoxon rank sum test is widely used for two‐group comparisons for nonnormal data. An assumption of this test is independence of sampling units both between and within groups. In ophthalmology, data are often collected on two eyes of an individual, which are highly correlated. In ophthalmological clinical trials, randomization is usually performed at the subject level, but the unit of analysis is the eye. If the eye is used as the unit of analysis, then a modification to the usual Wilcoxon rank sum variance formula must be made to account for the within‐cluster dependence. For some clustered data designs, where the unit of analysis is the subunit, group membership may be defined at the subunit level. For example, in some randomized ophthalmologic clinical trials, different treatments may be applied to fellow eyes of some patients, while the same treatment may be applied to fellow eyes of other patients. In general, binary eye‐specific covariates may be present (scored as exposed or unexposed) and one wishes to compare nonnormally distributed outcomes between exposed and unexposed eyes using the Wilcoxon rank sum test while accounting for the clustering. In this article, we present a corrected variance formula for the Wilcoxon rank sum statistic in the setting of eye (subunit)‐specific covariates. We apply it to compare ocular itching scores in ocular allergy patients between eyes treated with active versus placebo eye drops, where some patients receive the same eye drop in both eyes, while other patients receive different eye drops in fellow eyes. We also present comparisons between the clustered Wilcoxon test and each of the signed rank tests and mixed model approaches and show dramatic differences in power in favor of the clustered Wilcoxon test for some designs.

Red eye is the cardinal sign of ocular inflammation. The condition is usually benign and can be managed by primary care physicians. Conjunctivitis is the most common cause of red eye. Other common causes include blepharitis, corneal abrasion, foreign body, subconjunctival hemorrhage, keratitis, iritis, glaucoma, chemical burn, and scleritis. Signs and symptoms of red eye include eye discharge, redness, pain, photophobia, itching, and visual changes. Generally, viral and bacterial conjunctivitis are self-limiting conditions, and serious complications are rare. Because there is no specific diagnostic test to differentiate viral from bacterial conjunctivitis, most cases are treated using broad-spectrum antibiotics. Allergies or irritants also may cause conjunctivitis. The cause of red eye can be diagnosed through a detailed patient history and careful eye examination, and treatment is based on the underlying etiology. Recognizing the need for emergent referral to an ophthalmologist is key in the primary care management of red eye. Referral is necessary when severe pain is not relieved with topical anesthetics; topical steroids are needed; or the patient has vision loss, copious purulent discharge, corneal involvement, traumatic eye injury, recent ocular surgery, distorted pupil, herpes infection, or recurrent infections.