Myopia, also known as nearsightedness, is one of the prime reasons for vision impairment worldwide. Atropine in topical ophthalmic solutions (e.g., 0.01% atropine sulfate eye drops) is the primary medical treatment for controlling myopia, especially for pseudomyopia or true myopia in rapid progress. However, aqueous atropine solution is unstable and easily breaks down to tropic acid, which will result in vision blur. Drug-eluting contact lenses (CLs) have been explored as a potentially superior alternative to effectively control the drug release and improve the drug efficacy. In this work, an atropine-eluting contact lens was developed by encapsulating an atropine implant in a silicon-based contact lens, towards functioning in vision correction and controlling myopia. The safety and effectiveness of this atropine-eluting contact lens were verified with rabbit and guinea pig models. The results showed that the lenses reduced the side effects like mydriasis and no other adverse events were observed in rabbit eyes. More importantly, atropine-loaded lenses could effectively delay the progress of form-deprivation myopia with guinea pig eyes as the model. Thus, we concluded that atropine-eluting CLs prepared by implantation technology may be an option for the treatment of myopia.
FlitcroftDIHeMJonasJB, et al.IMI - defining and classifying myopia: a proposed set of standards for clinical and epidemiologic studies. Invest Ophthalmol Vis Sci2019; 60: M20–M30. DOI: 10.1167/iovs.18-25957.
2.
MorganIGFrenchANAshbyRS, et al.The epidemics of myopia: aetiology and prevention. Prog Retin Eye Res2018; 62: 134–149. DOI: 10.1016/j.preteyeres.2017.09.004.
3.
HughesRPVincentSJReadSA, et al.Higher order aberrations, refractive error development and myopia control: a review. Clin Exp Optom2020; 103: 68–85. DOI: 10.1111/cxo.12960.
4.
FlitcroftDI. The complex interactions of retinal, optical and environmental factors in myopia aetiology. Prog Retin Eye Res2012; 31: 622–660. DOI: 10.1016/j.preteyeres.2012.06.004.
5.
Ohno-MatsuiKLaiTYYLaiCC, et al.Updates of pathologic myopia. Prog Retin Eye Res2016; 52: 156–187. DOI: 10.1016/j.preteyeres.2015.12.001.
6.
PanCWRamamurthyDSawSM. Worldwide prevalence and risk factors for myopia. Ophthalmic Physiol Opt2012; 32: 3–16. DOI: 10.1111/j.1475-1313.2011.00884.x.
7.
CooperJTkatchenkoAV. A review of current concepts of the etiology and treatment of myopia. Eye Contact Lens2018; 44: 231–247. DOI: 10.1097/icl.0000000000000499.
8.
VutipongsatornKYokoiTOhno-MatsuiK. Current and emerging pharmaceutical interventions for myopia. Br J Ophthalmol2019; 103: 1539–1548. DOI: 10.1136/bjophthalmol-2018-313798.
9.
NovackGD. A drug to prevent pediatric myopia-what would it take?Eye Contact Lens2018; 44: 220–223. DOI: 10.1097/icl.0000000000000498.
10.
TranHDMTranYHTranTD, et al.A review of myopia control with atropine. J Ocul Pharmacol Ther2018; 34: 374–379. DOI: 10.1089/jop.2017.0144.
11.
McBrienNAStellWKCarrB. How does atropine exert its anti-myopia effects?Ophthalmic Physiol Opt2013; 33: 373–378. DOI: 10.1111/opo.12052.
12.
GrynkiewiczGGadzikowskaM. Tropane alkaloids as medicinally useful natural products and their synthetic derivatives as new drugs. Pharmacol Rep2008; 60: 439–463.
13.
ShihKCChanTCYNgALK, et al.Use of atropine for prevention of childhood myopia progression in clinical practice. Eye Contact Lens2016; 42: 16–23. DOI: 10.1097/icl.0000000000000189.
14.
JiMLiuHMaS, et al.Stable atropine loaded film as a potential ocular delivery system for treatment of myopia. Pharm Res2021; 38: 1931–1946. DOI: 10.1007/s11095-021-03135-4.
15.
UpadhyayABeuermanRW. Biological mechanisms of atropine control of myopia. Eye Contact Lens2020; 46: 129–135. DOI: 10.1097/icl.0000000000000677.
16.
SchwahnHNKaymakHSchaeffelF. Effects of atropine on refractive development, dopamine release, and slow retinal potentials in the chick. Vis Neurosci2000; 17: 165–176. DOI: 10.1017/s0952523800171184.
17.
García Del ValleIAlvarez-LorenzoC. Atropine in topical formulations for the management of anterior and posterior segment ocular diseases. Expert Opin Drug Deliv2021; 18: 1245–1260. DOI: 10.1080/17425247.2021.1909568.
18.
LindGJChewSJMarzaniD, et al.Muscarinic acetylcholine receptor antagonists inhibit chick scleral chondrocytes. Invest Ophthalmol Vis Sci1998; 39: 2217–2231.
19.
AddoRTYeboahKGSiwaleRC, et al.Formulation and characterization of atropine sulfate in albumin-chitosan microparticles for in vivo ocular drug delivery. J Pharm Sci2015; 104: 1677–1690. DOI: 10.1002/jps.24380.
20.
DonnellyRFCormanC. Physical compatibility and chemical stability of a concentrated solution of atropine sulfate (2 mg/mL) for use as an antidote in nerve agent casualties. Int J Pharm Compd2008; 12: 550–552.
21.
VerestiucLNastasescuOBarbuE, et al.Functionalized chitosan/NIPAM (HEMA) hybrid polymer networks as inserts for ocular drug delivery: synthesis, in vitro assessment, and in vivo evaluation. J Biomed Mater Res A2006; 77: 726–735. DOI: 10.1002/jbm.a.30668.
22.
LasowskiFSheardownH. Atropine and roscovitine release from model silicone hydrogels. Optom Vis Sci2016; 93: 404–411. DOI: 10.1097/opx.0000000000000807.
23.
González-ChomónCConcheiroAAlvarez-LorenzoC. Soft contact lenses for controlled ocular delivery: 50 years in the making. Ther Deliv2013; 4: 1141–1161. DOI: 10.4155/tde.13.81.
24.
Alvarez-LorenzoCAnguiano-IgeaSVarela-GarcíaA, et al.Bioinspired hydrogels for drug-eluting contact lenses. Acta Biomater2019; 84: 49–62. DOI: 10.1016/j.actbio.2018.11.020.
25.
LanierOLChristopherKGMacoonRM, et al.Commercialization challenges for drug eluting contact lenses. Expert Opin Drug Deliv2020; 17: 1133–1149. DOI: 10.1080/17425247.2020.1787983.
26.
GauseSHsuKHShaforC, et al.Mechanistic modeling of ophthalmic drug delivery to the anterior chamber by eye drops and contact lenses. Adv Colloid Interface Sci2016; 233: 139–154. DOI: 10.1016/j.cis.2015.08.002.
27.
XuJXueYHuG, et al.A comprehensive review on contact lens for ophthalmic drug delivery. J Control Release2018; 281: 97–118. DOI: 10.1016/j.jconrel.2018.05.020.
28.
MaulviFALakdawalaDHShaikhAA, et al.In vitro and in vivo evaluation of novel implantation technology in hydrogel contact lenses for controlled drug delivery. J Control Release2016; 226: 47–56. DOI: 10.1016/j.jconrel.2016.02.012.
29.
DesaiARMaulviFADesaiDM, et al.Multiple drug delivery from the drug-implants-laden silicone contact lens: addressing the issue of burst drug release. Mater Sci Eng C Mater Biol Appl2020; 112: 110885. DOI: 10.1016/j.msec.2020.110885.
30.
WeinmüllerCLangelCFornasieroF, et al.Sorption kinetics and equilibrium uptake for water vapor in soft-contact-lens hydrogels. J Biomed Mater Res A2006; 77: 230–241. DOI: 10.1002/jbm.a.30598.
31.
IlechieAADanquahDNtodieM, et al.Contact lens- and patient-related factors associated with contact lens discomfort among contact lens wearers in an african cohort. Optom Vis Sci2021; 98: 1056–1062. DOI: 10.1097/opx.0000000000001765.
EfronNMorganPCameronI, et al.Oxygen permeability and water content of silicone hydrogel contact lens materials. Optom Vis Sci2007; 84: 328–337. DOI: 10.1097/OPX.0b013e31804375ed.
34.
LuensmannDJonesL. Protein deposition on contact lenses: the past, the present, and the future. Cont Lens Anterior Eye2012; 35: 53–64. DOI: 10.1016/j.clae.2011.12.005.
35.
SilvaDFernandesACNunesTG, et al.The effect of albumin and cholesterol on the biotribological behavior of hydrogels for contact lenses. Acta Biomater2015; 26: 184–194. DOI: 10.1016/j.actbio.2015.08.011.
36.
XuJLiXSunF. In vitro and in vivo evaluation of ketotifen fumarate-loaded silicone hydrogel contact lenses for ocular drug delivery. Drug Deliv2011; 18: 150–158. DOI: 10.3109/10717544.2010.522612.
CurtinBJIwamotoTRenaldoDP. Normal and staphylomatous sclera of high myopia: an electron microscopic study. Arch Ophthalmol 19601979; 97: 912–915. DOI: 10.1001/archopht.1979.01020010470017.
40.
LiuSLiSWangB, et al.Scleral cross-linking using riboflavin UVA irradiation for the prevention of myopia progression in a guinea pig model: blocked axial extension and altered scleral microstructure. PLoS One2016; 11: e0165792. DOI: 10.1371/journal.pone.0165792.
41.
NieHHHuoLJYangX, et al.Effects of 7-methylxanthine on form-deprivation myopia in pigmented rabbits. Int J Ophthalmol2012; 5: 133–137. DOI: 10.3980/j.issn.2222-3959.2012.02.03.
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