Myopia control in Mendelian forms of myopia

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Abstract

Purpose: To study the effectiveness of high-dose atropine for reducing eye growth in Mendelian myopia in children and mice. Methods: We studied the effect of high-dose atropine in children with progressive myopia with and without a monogenetic cause. Children were matched for age and axial length (AL) in their first year of treatment. We considered annual AL progression rate as the outcome and compared rates with percentile charts of an untreated general population. We treated C57BL/6J mice featuring the myopic phenotype of Donnai–Barrow syndrome by selective inactivation of Lrp2 knock out (KO) and control mice (CTRL) daily with 1% atropine in the left eye and saline in the right eye, from postnatal days 30–56. Ocular biometry was measured using spectral-domain optical coherence tomography. Retinal dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were measured using high-performance liquid chromatography. Results: Children with a Mendelian form of myopia had average baseline spherical equivalent (SE) –7.6 ± 2.5D and AL 25.8 ± 0.3 mm; children with non-Mendelian myopia had average SE −7.3 ± 2.9 D and AL 25.6 ± 0.9 mm. During atropine treatment, the annual AL progression rate was 0.37 ± 0.08 and 0.39 ± 0.05 mm in the Mendelian myopes and non-Mendelian myopes, respectively. Compared with progression rates of untreated general population (0.47 mm/year), atropine reduced AL progression with 27% in Mendelian myopes and 23% in non-Mendelian myopes. Atropine significantly reduced AL growth in both KO and CTRL mice (male, KO: −40 ± 15; CTRL: −42 ± 10; female, KO: −53 ± 15; CTRL: −62 ± 3 μm). The DA and DOPAC levels 2 and 24 h after atropine treatment were slightly, albeit non-significantly, elevated. Conclusions: High-dose atropine had the same effect on AL in high myopic children with and without a known monogenetic cause. In mice featuring a severe form of Mendelian myopia, atropine reduced AL progression. This suggests that atropine can reduce myopia progression even in the presence of a strong monogenic driver.

Original languageEnglish
Pages (from-to)494-504
Number of pages11
JournalOphthalmic and Physiological Optics
Volume43
Issue number3
Early online date7 Mar 2023
DOIs
Publication statusPublished - May 2023

Bibliographical note

Funding Information:
This work was supported by the Netherlands Organisation for Scientific Research (NWO; 91815655; C.C.W. Klaver; NWO‐ALW 824.02.001; C.I. de Zeeuw), the Dutch Organization for Medical Sciences (ZonMW 91120067; C.I. de Zeeuw), Medical Neuro‐Delta (MD 01092019–31082023; C.I. de Zeeuw), INTENSE LSH‐NWO (TTW/00798883; C.I. de Zeeuw, B.W. Winkelman), European Research Council (ERC) under the European Union's Horizon 2020 Research and Innovation Programme (648268; C.C.W. Klaver), ERC‐adv (GA‐294775; C.I. de Zeeuw) and ERC‐POC (737619 and 768914; C.I. de Zeeuw) as well as the Dutch NWO Gravitation Program (DBI2; C.C.I. de Zeeuw).

Funding Information:
We would like to thank all participating patients and the medical staff of the Department of Ophthalmology at Erasmus MC. We also thank Tamara van der Meer (University of Applied Science, Utrecht, Dept. Optometry and Orthoptics) for helping with the myopia database and Cynthia Geelen (Netherlands Institute for Neuroscience) for helping with the atropine application and genotyping of the mice.

Publisher Copyright:
© 2023 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists.

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