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J. Su, Y. Liu, K. E. Healy, C. F. Wildsoet; Effect of in vivo Atropine Delivery at Posterior Sclera Using Biomimetic Extracellular Matrix for Myopia Control. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1619.
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To synthesize and test the suitability of a synthetic extracellular matrix (ECM) hydrogel as an atropine delivery vehicle that allows localized site of action at the posterior sclera for the control of myopia progression. We previously reported that the same ECM-hydrogel supports in vitro scleral fibroblast growth.1
A synthetic ECM hydrogel composed of a thermo-responsive semi-interpenetrating polymer network (sIPN) was synthesized by redox radical addition polymerization.1 The sIPN was lyophilized and allowed to soak overnight in 1% w/v atropine sulfate solution. Eighteen 12 day-old chicks (3 groups of 6) wore monocular -10 D lenses for 1 wk to induce myopia, then the lens power was increased to -15 D and the treated eyes subjected for 2 weeks to either: 1) daily topical atropine ointment (4 µl, 10 mg/ml); 2) retrobulbar hydrogel-saline (sham) injection (100 µl); or 3) retrobulbar hydrogel-atropine injection (100 µl, 10 mg/ml). Ocular dimensions were measured by high frequency A-scan ultrasonography and refractions by retinoscopy at 0, 1, 2, and 3 wks (means & SDs given below). Statistical significance was computed by ANOVA, followed by Tukey/Kramer post-hoc test.
Treated eyes were significantly longer than their fellows (p < 0.05). However, anterior chamber depth was significantly less by day 21 in both eyes treated with atropine ointment (2.01 ± 0.06 mm; p < 0.05) and hydrogel-atropine (2.045 ± 0.12 mm; p < 0.05) compared to sham-treated eyes (2.35 ± 0.11 mm). The axial lengths of the treated eyes of both atropine groups also tended to be shorter than the sham-treated group from days 7 to 21, although this difference was not statistically significant, and the 3 groups of treated eyes recorded similar vitreous chamber depths (hydrogel atropine: 7.50 ± 0.18 mm; atropine ointment: 7.40 ± 0.14 mm; sham: 7.28 ± 0.18 mm). Endpoint refractions (mean spherical equivalent) of treated eyes in each group were: 1) -4.88, 1.85 D (daily atropine); 2) -6.79, 1.91 D (sham); and, 3) -7.46, 4.12 D (hydrogel-atropine).
This study proved the feasibility of using a synthetic ECM hydrogel to deliver atropine to the posterior sclera for myopia control, with the main advantage of being a single intraorbital injection rather than daily topical dosing. The lack of control over vitreous chamber elongation suggests that both atropine doses used were too low. The inhibitory effect on anterior chamber expansion of both atropine treatments was unexpected and implies a specific atropine effect.1Su J, Healy KE, Wildsoet CF, 2007. IOVS, ARVO E-abstract 5939.
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