Pharmaceutical intervention for myopia control

Abstract

Myopia is the result of a mismatch between the optical power and the length of the eye, with the latter being too long. Driving the research in this field is the need to develop myopia treatments that can limit axial elongation. When axial elongation is excessive, as in high myopia, there is an increased risk of visual impairment and blindness due to ensuing pathologies such as retinal detachments. This article covers both clinical studies involving myopic children, and studies involving animal models for myopia. Atropine, a nonselective muscarinic antagonist, has been studied most extensively in both contexts. Because it remains the only drug used in a clinical setting, it is a major focus of the first part of this article, which also covers the many shortcomings of topical ophthalmic atropine. The second part of this article focuses on in vitro and animal-based drug studies, which encompass a range of drug targets including the retina, retinal pigment epithelium and sclera. While the latter studies have contributed to a better understanding of how eye growth is regulated, no new antimyopia drug treatments have reached the clinical setting. Less conservative approaches in research, and in particular, the exploration of new bioengineering approaches for drug delivery, are needed to advance this field. Keywordsanimal models; atropine; clinical trials; dopamine; eye growth; growth factors; myopia Myopia describes the refractive error in which light entering the eye from distant objects is focused in front of the retina, leading to blurred vision. The condition is most commonly the result of excessive elongation of the posterior vitreous chamber of the eye, increasing the risk of retinal detachment and some degenerative retinal conditions, and rendering high myopia a major cause of visual impairment and blindness [1][2][3][4][5][6]. Myopia has become a major public health concern owing to rapid rises in the prevalence of myopia, first noted in East Asian populations. For example, as of the year 2000, the prevalence of myopia had reached 84% for Taiwanese adolescents between 16 and 18 years of age. Of the 18-yearolds, 21% were highly myopic, putting them at high risk for pathologic conditions in the future [7]. Similar trends are evident in recently published myopia prevalence figures for the USA, although they are not as high as East Asian figures [8][9][10][11].The management of myopia has been mostly directed at correcting the mismatch between the eye's optical power and its length using either optical means, such as single-vision spectacles and contact lenses, or refractive surgeries, such as photorefractive keratectomy (PRK) and laser-assisted in situ keratomileusis (LASIK), which both involve reshaping and thus modifying the optical power of the cornea. While these options restore sharp distance vision in myopes, they do nothing to control myopia progression. On the other hand, the © 2010 Expert Reviews Ltd † Author for correspondence: prema@berkeley.edu. NIH Public Access Author ManuscriptExpert Rev O...

Atropine 0.01% Eyedrops Significantly Reduce the Progression of Childhood Myopia

“…Antimuscarinic medications have been shown to inhibit cell proliferation in human scleral fibroblasts. 34 The identification of a potential site of action for atropine, the M4 subtype of muscarinic receptor, 35 may allow a more targeted therapy with fewer side effects, although it will be difficult to demonstrate fewer side effects than has been documented with atropine 0.01%.…”

Molecular and Biochemical Aspects of the Retina on Refraction

“…Both non-selective (such as atropine) and partially selective (such as pirenzepine) muscarinic antagonists have been shown to have inhibitory effects on experimental myopia in chickens and mammals (see review, [60, 64]). Clinically, atropine [65–67] and pirenzepine [68–70] has been used to slow myopia progression in children.…”

The effect of intravitreal injection of vehicle solutions on form deprivation myopia in tree shrews

“…Intravitreal injection, in which a substance, dissolved in a vehicle solution, is placed into the vitreous chamber, is a frequently used tool in both clinical and basic research studies (Avery, Pieramici, Rabena, Castellarin, Nasir and Giust, 2006; Brown, Kaiser, Michels, Soubrane, Heier, Kim, Sy and Schneider, 2006; Feldkaemper, Neacsu and Schaeffel, 2009; Ganesan and Wildsoet, 2010; Haritoglou, Kook, Neubauer, Wolf, Priglinger, Strauss, Gandorfer, Ulbig and Kampik, 2006; Iturralde, Spaide, Meyerle, Klancnik, Yannuzzi, Fisher, Sorenson, Slakter, Freund, Cooney and Fine, 2006; Norton, Essinger and McBrien, 1994; Pickett-Seltner and Stell, 1995; Rohrer, Iuvone and Stell, 1995; Rohrer, Spira and Stell, 1993; Stone, Lin, Laties and Iuvone, 1989; Zhu and Wallman, 2009). This approach is often used to deliver neurotransmitter agonists and antagonists to the vicinity of the retina so as to observe their impact on retinal function.…”