Immunoproteasome-dependent neuronal ferroptosis in multiple sclerosis

多发性硬化症中免疫蛋白酶体依赖性神经元铁死亡

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Abstract

Presbyopia is a progressive, irreversible age-related decline in ocular accommodation caused by reduced lens elasticity, resulting in impaired near vision and a significant impact on daily activities and quality of life. Globally, presbyopia affects approximately 1.8 billion individuals, with projections rising to 2.1 billion by 2030. Current management options include spectacles, contact lenses, pharmacologic agents such as pilocarpine, and surgical interventions; however, each approach carries limitations related to convenience, adaptability, or visual compromise. Yuvezzi™ (carbachol 2.75% and brimonidine tartrate 0.1%) is a recently U.S. Food and Drug Administration (FDA)-approved dual-agent ophthalmic solution designed to improve near vision through pharmacologically induced miosis. Carbachol, a parasympathomimetic agent, stimulates muscarinic receptors to produce sustained pupillary constriction, while brimonidine, an α2-adrenergic agonist, inhibits iris dilator activity and prolongs the miotic effect, enhancing tolerability. Its approval was based on two Phase 3 randomized controlled trials, BRIO-I and BRIO-II, which demonstrated significant improvement in binocular uncorrected near visual acuity without compromising distance vision. Common adverse effects included ocular discomfort, irritation, visual disturbances, and headache. Yuvezzi™ offers a noninvasive, reversible alternative for presbyopia management; however, long-term safety and sustained efficacy require further evaluation.

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