Where are the next drug targets for myopia control? A review charts new directions from atropine to molecular pathways

Myopia has become a major global public health concern. It is not simply a matter of blurred distance vision: as the eye continues to elongate, high myopia can increase the risk of macular lesions, choroidal neovascularization, retinal degeneration, and retinal detachment. With myopia rising among children and adolescents, current management increasingly combines behavioral measures, optical interventions, and pharmacological treatment. While atropine has long been the best-known option, uncovering how these medications work to slow myopia progression is far more complex than expected.

A review titled Pharmacological Management of Myopia: Emerging Agents and Novel Molecular Targets published in Eye Discovery brings together current and emerging pharmacological approaches for myopia control. Written by Tong Zhao of Nanjing Medical University and Meiyan Li of the Eye & ENT Hospital of Fudan University, the article reviews established and investigational agents, including atropine, pirenzepine, 7-methylxanthine (7-MX), and intraocular pressure-lowering drugs. It also discusses emerging molecular targets linked to endoplasmic reticulum stress, ferroptosis, signaling pathway modulation, and epidermal growth factor receptor (EGFR) blockade.

“Myopia drug research is no longer only about whether atropine works,” said Dr. Meiyan Li of the Eye & ENT Hospital of Fudan University. “The field is moving deeper into the molecular processes behind axial elongation. Atropine remains one of the most important pharmacological options, but newer studies suggest that scleral remodeling, choroidal perfusion and oxidative stress may also become important breakthrough points for future drug development. We hope this review helps readers see how myopia pharmacotherapy is moving from clinical use toward mechanism-based target discovery.”

Atropine takes central stage in the review. As a nonselective muscarinic cholinergic receptor antagonist, it has been used in myopia control. Yet the review emphasizes that atropine’s effects may not be limited to muscarinic receptor blockade. It may also influence retinal dopamine release, adrenergic receptors, choroidal blood flow, scleral hypoxia, extracellular matrix remodeling, and intracellular pathways such as Wnt/β-catenin, HIF, and mTOR signaling. The review’s mechanism diagrams place atropine activity across the sclera, choroid, ciliary muscle, and retina, illustrating that pharmacological myopia control is likely mediated by a network of ocular tissues and molecular pathways rather than a single target.

In clinical practice, combining low-dose atropine with optical interventions is one of the most developed strategies. The review notes that atropine used together with orthokeratology, defocus-incorporated multiple segments spectacle lenses, or dual-focus soft contact lenses has shown additive effects in some studies. For example, compared with atropine plus single-vision spectacles, atropine combined with orthokeratology further suppressed axial elongation by 0.19 mm, while atropine combined with DIMS lenses produced an additional 0.24 mm restriction in axial elongation after 12 months. These findings suggest that drug and optical approaches  aren’t competing options. Instead, for children with rapidly progressing myopia, combination therapy may offer a more tailored management route.

The review also discusses several drugs beyond atropine that have attracted sustained interest. Pirenzepine, a selective muscarinic receptor antagonist, showed approximately 50% efficacy in slowing childhood myopia progression in some placebo-controlled trials, but a phase II trial in the United States was halted because of a low success rate and apparent gastric complications. 7-MX, a nonselective adenosine receptor antagonist, has drawn attention as an oral candidate for myopia control. Following encouraging trial results in Danish children, the Danish Medicines Agency cleared it for use. Intraocular pressure-lowering agents such as brimonidine and latanoprost are also discussed, although the review notes that their potential anti-myopic effects may not be explained by pressure reduction alone and may involve choroidal perfusion or scleral remodeling.

The more forward-looking part of the review focuses on molecular targets that are still under investigation. Endoplasmic reticulum stress is one such direction, with pathways including PERK-EIF2, IRE1-XBP1, and ATF6 implicated in axial elongation and scleral change. In mouse models, 4-phenylbutyric acid eye drops reduced axial elongation through ER stress-related pathways, while quercetin has also been reported to affect myopia models by suppressing ER stress. Ferroptosis has emerged as another research focus in ophthalmic disease, with PIEZO1, HIF-1α, and DNA methyltransferase 3A discussed as key mediators connecting oxidative stress, scleral cell changes, and myopia development. Other promising candidates target distinct cellular mechanisms, including everolimus for mTOR/HIF signaling, doxycycline for matrix metalloproteinase regulation, α-ketoglutarate for mitochondrial metabolism, and EGFR antibodies. These emerging directions, however, are not yet ready to be treated as routine clinical options. Much of the evidence for newer candidate drugs still comes from cellular studies, animal models, or early observational work. EGFR antibodies, for instance, raise questions about intraocular delivery, immune reactions, and long-term safety, even though early studies have reported no obvious treatment-emergent systemic adverse events or intraocular inflammatory reactions over limited follow-up. Similarly, ER stress inhibitors, ferroptosis-related agents, and mTOR pathway drugs should be understood as drug-development leads rather than established treatments for childhood myopia control.

The value of the review lies in broadening the discussion of myopia pharmacology from “one drug” to a map of mechanisms. Low-dose atropine remains the most established pharmacological approach, while research on scleral remodeling, choroidal perfusion, cellular stress, ferroptosis, and EGFR signaling is unlocking new avenues  for next-generation therapies. For clinicians and researchers, the next frontier isn't finding a single universal drug, but tailoring therapies to the specific molecular drivers while safeguarding children’s long-term eye health.

Article information:

Title：Pharmacological Management of Myopia: Emerging Agents and Novel Molecular Targets.

Read the full article:https://doi.org/10.1016/j.edisc.2026.100055

About Eye Discovery

Eye Discovery is an open-access, peer-reviewed international academic journal, with ISSN 3117-4167. It is published quarterly by Elsevier and serves as the official journal of Eye & ENT Hospital of Fudan University, China. 

Eye Discovery  is dedicated to creating a high-end platform for ophthalmologists, scientists, and scholars worldwide to focus on innovative achievements in ophthalmology and interdisciplinary fields, and to promote academic dissemination and exchange.

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