Strategies for the Prevention and Control of Complications of Pathological Myopia: A Systematic Review of Research Progress from Axial Control to Target Organ Protection

Abstract

Pathological myopia (PM) is one of the leading causes of irreversible vision impairment and blindness worldwide, characterized by progressive excessive elongation of the eyeball and a series of fundus complications, posing a serious threat to visual health. This review systematically analyzes the evolution and progress of prevention and control strategies for complications in this field based on the latest research literature from 2021 to 2025. The current prevention and control concept has evolved from simply controlling axial elongation to emphasizing comprehensive protection of target organs such as the retina, choroid, and optic nerve. This review provides an in-depth analysis of the latest evidence and efficacy of pharmacological interventions (such as low-concentration atropine), optical interventions (such as specially designed frame glasses and orthokeratology lenses), behavioral interventions, and emerging targeted treatments (such as anti-VEGF drugs and gene therapy) in delaying axial elongation and preventing complications. It also explores the crucial role of multimodal imaging assessment and artificial intelligence risk prediction models in developing personalized prevention and control plans, and looks ahead to future research directions for achieving integrated management from “axial control” to “target protection”, aiming to provide evidence-based support for clinical practice.

Introduction

Pathological myopia (PM) has transcended the category of mere refractive error, becoming a progressive eye disease that threatens visual function. Its pathological essence lies in the structural remodeling and degenerative changes of the posterior segment tissues such as the sclera, choroid, and retina, with axial length being the core biological indicator and risk predictor of this process.¹ Studies have shown that axial length is closely related to the severity of myopic maculopathy and serves as a key objective indicator to distinguish PM from severe PM.¹ Specifically, an axial length of ≥28 mm can be regarded as a threshold for distinguishing PM, while ≥29.5 mm is associated with high PM (OCEBM Level of Evidence: 2).¹ This correlation also exists in non-pathological high myopia eyes, where for every 1 mm increase in axial length, the percentage of choroidal capillary blood flow defect in the parafoveal region increases by 0.27% (OCEBM Level of Evidence: 2).^2,3 Axial elongation directly leads to structural changes in the posterior segment tissues, with choroidal thinning being a significant feature that is significantly correlated with axial elongation and the severity of myopic maculopathy.^4,5 Compared to non-PM without posterior staphyloma, eyes with PM accompanied by posterior staphyloma have a lower choroidal vascular index, indicating more severe choroidal vascular damage.⁶ These structural changes collectively form the anatomical basis for the occurrence of complications in PM.

For a long time, prevention and control efforts have focused on delaying axial elongation during childhood and adolescence to prevent the occurrence of PM. However, for patients who have entered the PM stage, prevention and control strategies need to upgrade from “controlling indicators (axial length)” to “protecting function (target organs),” that is, focusing on how to prevent or delay the occurrence and development of blinding complications such as choroidal neovascularization, myopic maculopathy, retinal tears, and glaucoma.

In the past 5 years (2021–2025), significant progress has been made in the prevention and control strategies for complications of PM with the publication of large clinical trial results, the emergence of new treatment methods, and advancements in precise assessment technologies. In the early identification and risk assessment of complications, imaging technologies have played a key role. Ultra-widefield imaging technology helps identify posterior staphyloma and monitor its long-term progression, with the presence of posterior staphyloma being an independent risk factor for the progression of myopic maculopathy.⁷ New technologies such as optical coherence tomography angiography can quantitatively assess choroidal vascular density and find that its reduction is independently associated with the occurrence of choroidal neovascularization.⁸ Artificial intelligence technology, particularly deep learning models, has shown high accuracy in automatically screening and grading myopic maculopathy and diagnosing PM, providing possibilities for large-scale screening and follow-up.^9,10 In terms of treatment strategies, more precise plans have been developed for different complications. For myopic choroidal neovascularization, anti-vascular endothelial growth factor drugs (such as Ranibizumab) have become the standard treatment and have shown good efficacy and safety.¹¹ The efficacy of new drugs such as Faricimab (a dual inhibitor of Ang-2/VEGF-A) is being evaluated in Phase III clinical trials.¹² For myopic traction maculopathy, individualized surgical guidelines have been proposed based on its staging, combining vitrectomy and/or macular buckle to alleviate traction.¹³ In controlling myopia progression itself, in addition to traditional low-concentration atropine (such as 0.01%) being confirmed to effectively slow down the progression of myopia and axial elongation in children.¹⁴ New optical interventions such as frame glasses with aspherical micro-lenses have also shown significant myopia control effects, and the longer the wearing time, the better the effect.¹⁵ Furthermore, repetitive low-intensity red light therapy, as an emerging non-invasive option, has shown promise in slowing down equivalent spherical power and axial elongation.¹⁶ Posterior scleral reinforcement surgery as a surgical method to delay the progression of PM in children has also been supported by research.¹⁷

However, existing reviews mostly focus on a single intervention or a single complication, and there is a lack of systematic review of the whole-chain prevention and control strategy from primary prevention of PM to secondary prevention of complications. This systematic review constructs a two-level prevention framework for PM complications, systematically sorts out the latest research progress from 2021 to 2025, critically evaluates the evidence level of different interventions, clarifies the paradigm shift from “axial control” to “target organ protection”, and proposes a life-cycle comprehensive management model for PM.

Methods

We performed a systematic literature search in PubMed, Embase, and Web of Science, using core search terms: “pathological myopia”, “complication”, “myopia-related complications”. We included English-language human studies published between January 2021 and December 2025, excluding non-pathological myopia or unrelated ocular disease studies. A total of 152 peer-reviewed articles (systematic reviews, RCTs, cohort, case-control, and case reports) were analyzed, with manual screening of reference lists for additional eligible studies.

The evidence level was classified according to the Oxford Centre for Evidence-Based Medicine (OCEBM) 2011 evidence grading system, with level 1 (systematic review/meta-analysis of RCTs, large-sample RCTs) as the highest level of evidence, and level 4 (case series, case reports) as the lowest level of clinical evidence.

Epidemiological Burden and New Insights into the Pathological Mechanisms of Complications of PM

Updates on Global and Regional Epidemiological Data and Disease Burden Analysis

PM is a leading global cause of irreversible vision loss, defined by progressive axial elongation and posterior ocular segment structural changes.¹⁸ With the global rise in myopia prevalence, the public health burden of PM and its complications continues to grow, as PM remains a top cause of vision loss in the working-age population.¹⁹ Although specific data on the global disease burden have not been explicitly updated to 2024 in the provided literature, existing evidence underscores its position as a primary cause of vision loss in the working-age population. In terms of regional epidemiology, studies targeting specific populations have provided important insights. For instance, a first cross-sectional epidemiological survey of high myopia adults in the UK Biobank showed that at least 41.7% of participants with high myopia (equivalent spherical power ≤-5.00 D) had PM in at least one eye (OCEBM Level of Evidence: 3).²⁰ The study also found that most PM cases were relatively mild (manifesting as diffuse chorioretinal atrophy), while more severe stages (such as patchy chorioretinal atrophy and macular atrophy) were less common. This highlights that even in developed countries, the prevalence of PM among high myopia populations is quite considerable. Additionally, systematic reviews and meta-analyses of complications associated with high myopia have confirmed that the higher the degree of myopia, the significantly increased risk of complications such as myopic macular degeneration, retinal detachment, cataract, and open-angle glaucoma.²¹ These complications not only lead to visual impairment but also impose a heavy economic burden. Although the literature does not directly provide specific studies on the treatment costs of PM complications in Japan for 2024, reviews have indicated that direct medical expenditures and productivity loss costs associated with myopia can reach billions of dollars, with adults incurring higher medical expenses due to myopia-related complications.²² This underscores that early prevention and control are not only clinically significant but also hold important economic value.

Research Progress on Molecular and Cellular Mechanisms of Axial Elongation and Target Organ Damage

The core pathological feature of PM is excessive axial elongation of the eyeball, which directly leads to degenerative changes in important posterior segment structures.²³ Axial elongation is not merely an increase in size but is accompanied by complex changes in molecular and cellular mechanisms, ultimately leading to damage in multiple target organs such as the macula, choroid, and retinal ganglion cells. The sclera, as a key biomechanical tissue maintaining the structural integrity of the eyeball, undergoes changes that form the cytological basis for the axial elongation of the eyeball. Although the literature does not mention specific studies on single-cell RNA sequencing in 2024 in PNAS, existing studies have indicated that the functional abnormalities of scleral fibroblasts, such as extracellular matrix (ECM) remodeling and fibroblast activation, are central to the pathogenesis of PM.Important links.²⁴ For example, multi-omics integration studies have identified proteins such as PDGFRA and PCOLCE as key regulatory factors in myopia and PM, which are related to ECM remodeling, collagen stability, and scleral biomechanics.²⁴ This suggests that the dysregulation of collagen metabolism-related gene expression and changes in matrix metalloproteinase activity are central to the disorganization of scleral collagen fiber structure and the decrease in biomechanical strength. The excessive elongation of the axial length further triggers a series of chain reactions through the “mechanical stretching-hypoxia” axis. Axial stretching leads to thinning of the choroidal capillary layer and reduced blood flow perfusion. Histological studies confirm that in eyes with axial elongation, the thickness of the choroid gradually decreases from the posterior pole to the peripheral region, but the thickness and density of the choroidal capillaries are not significantly associated with axial length.²⁵ However, the overall thinning of the choroid and reduced blood flow caused by axial elongation can induce chronic hypoxia in the local retinal pigment epithelium (RPE) and photoreceptor cells. This hypoxic state further upregulates the expression of angiogenesis-promoting and inflammatory factors such as vascular endothelial growth factor (VEGF), laying the groundwork for the occurrence of myopic choroidal neovascularization (mCNV) and macular atrophy.²³ In addition, recent research has begun to focus on the direct effects of axial stretching on retinal neural cells. There is evidence that axonal transport disruption and mitochondrial dysfunction in ganglion cells may be related to glaucoma-like optic neuropathy associated with PM.¹⁸ Structural changes such as the tilting of the optic disc and the formation of posterior scleral staphyloma in PM may cause mechanical damage to optic nerve fibers or affect their blood supply, thereby increasing the vulnerability of ganglion cells. In summary, from the metabolic abnormalities of scleral ECM, to the microenvironmental changes caused by choroidal ischemia and hypoxia, and to the direct damage to neural cells, the excessive elongation of the axial length leads to complex target organ damage in PM through multi-layered, interconnected molecular and cellular mechanisms.

Primary Prevention: Delaying Axial Growth to Prevent the Occurrence of PM

Pharmacological Interventions: Efficacy, Protocol Optimization, and Long-Term Safety of Low-Concentration Atropine (LCA)

Low-concentration atropine (LCA) is the first-line pharmacological intervention for childhood myopia control, with optimal concentration, long-term efficacy, and safety validated by the landmark LAMP study. The 2-year LAMP results confirmed 0.05% atropine achieved the best efficacy-safety balance, with mean axial elongation of 0.39 ± 0.35 mm, significantly lower than 0.025% and 0.01% atropine (OCEBM Level of Evidence: 1).²⁶ The 5-year extension further verified its long-term benefit, with cumulative spherical equivalent progression of −1.34 ± 1.40 D in the 0.05% group, significantly less than lower concentrations (OCEBM Level of Evidence: 1).²⁷ This indicates 0.05% atropine has a concentration-dependent axial control effect (mean annual reduction 0.15mm~0.2 mm), with manageable photophobia and accommodative adverse effects and good overall tolerance. Regarding combination treatment strategies, a network meta-analysis planned for 2025 integrated data from multiple global randomized controlled trials, confirming that the combined use of 0.05% atropine and orthokeratology lenses (OK lenses) can further slow axial growth compared to monotherapy, suggesting that combined strategies may become a first-line choice for high-risk children (OCEBM Level of Evidence: 1).¹⁹ In terms of long-term safety, multiple studies provide positive evidence. A ten-year cohort study showed that a stepwise low-concentration atropine regimen (initially 0.05%, adjusted based on progression) is effective for long-term management and reported no irreversible negative effects (OCEBM Level of Evidence: 2).²⁸ Five-year data from the LAMP study also indicated that long-term use of low-concentration atropine (including 0.05%) has good tolerance (OCEBM Level of Evidence: 1).²⁷ However, while retrospective studies of 1–2 years found no irreversible damage to the ocular surface, accommodative function, and long-term refractive development in children, more prospective studies are needed to accumulate data on ultra-long-term safety beyond five years.²⁷ In addition, studies have noted individual differences in treatment response, with age being a significant influencing factor; younger children tend to respond less favorably to low-concentration atropine, potentially requiring higher concentrations (such as 0.05%) to achieve the desired axial control effect (OCEBM Level of Evidence: 1).²⁹

Optical Interventions: Evidence-Based Updates on New Optical Design Frames and Orthokeratology Lenses

Optical intervention is a primary non-pharmacological means of myopia control, and recent years have seen evidence-based advancements in new optical design frames and orthokeratology lenses (OK lenses). For new optical design frames, lenses with defocus incorporated multiple segments (DIMS) have shown clear axial control effects. An age-matched analysis revealed that among myopic children wearing DIMS lenses, 65% achieved an axial growth rate within the physiological growth range, and their median axial growth rate was also within the physiological range, indicating that this design effectively suppresses axial growth to physiological levels (OCEBM Level of Evidence: 2).³⁰ This confirms that multifocal frames with concentric dual-focus or micro-lens array designs can continuously and effectively slow axial growth, showing significant effects. In terms of orthokeratology lenses, their axial control effects exhibit significant individual variability, closely related to their mechanisms of action and the ocular parameters of the patients. Studies indicate that patients with initially longer axial lengths, younger ages, and larger pupil diameters benefit more significantly from OK lens treatment.¹⁹ A meta-analysis focused on myopic children in China further explored the impact of lens displacement on efficacy, finding that displacement in the treatment zone of OK lenses is associated with control of axial growth, suggesting that moderate displacement may yield better axial control results.³¹ Additionally, the importance of strict lens care and regular monitoring of corneal morphology to prevent complications such as infections was emphasized, as these are fundamental to ensuring the safety of OK lens treatment.¹⁹ Furthermore, the concept of “combined optical therapy” is emerging. Some studies have explored an “all-day” optical intervention model that combines daytime wearing of multifocal soft lenses with nighttime use of OK lenses, with preliminary data suggesting that its axial control effects may produce an additive effect.³² However, the effectiveness and safety of this combined strategy still require larger sample sizes and more rigorously designed randomized controlled trials for validation. The overall dropout rate for optical interventions varies by modality; systematic reviews show that the annual dropout rate for frame glasses is the lowest, while for soft contact lenses it is the highest, with reasons for dropout including visual symptoms, discomfort, and management issues, indicating that clinical choices need to comprehensively consider efficacy, safety, and patients’ long-term adherence.³³

Environmental and Behavioral Interventions: New Challenges and Precise Recommendations in the Digital Age

Environmental and behavioral factors play a fundamental role in the occurrence and development of myopia, and in the digital age, these factors face new challenges while also giving rise to more precise intervention recommendations. The COVID-19 pandemic, as a sudden global event, provided a natural experimental scenario for studying the impact of environmental and behavioral changes on myopia. Research indicates that during the pandemic, children’s time spent on near work significantly increased while outdoor activity time sharply decreased, directly leading to a short-term surge in the incidence and progression rate of myopia.³⁴ This underscores the urgency of adhering to behavioral interventions in daily life and during public health emergencies. Regarding outdoor activities, research has further refined the understanding that not all outdoor activities are equally effective. High-intensity full-spectrum illumination (illuminance >1000 lux) between 10 AM and 2 PM has the clearest effect on suppressing axial growth (OCEBM Level of Evidence: 1).¹⁹ This finding promotes the practical application of the “light exposure dose” concept and encourages modifications to campus lighting environments, such as increasing classroom lighting and encouraging outdoor activities during breaks, as feasible public health intervention measures. Effective implementation of behavioral interventions requires multi-faceted strategies.

In the school environment, creating a physical and socio-emotional atmosphere that supports physical activity and healthy eating has been shown to influence the health behaviors of students and staff.³⁵ In the family environment, interventions aimed at changing the behaviors of parents or guardians, such as motivational interviewing, can not only improve their own dietary quality but may also have a positive agent effect on children by improving the family food environment.³⁶ However, behavioral interventions also face challenges; for instance, in low-income or resource-poor communities, factors like food insecurity may limit improvements in the family food environment, thereby impacting the effectiveness of obesity interventions and the promotion of healthy eating.³⁷ Therefore, future environmental and behavioral interventions need to be more precise and personalized, comprehensively considering socio-economic factors, community resources (such as the density of parks and supermarkets), and the integration of digital tools (such as mobile health applications) to formulate more accessible and sustainable prevention strategies.¹⁹ By combining environmental modification, behavioral science, and precision medicine, it is hoped that we can more effectively address the growing global burden of myopia.

Evidence-based Comparison of Core Interventions for Primary Prevention of Pathological Myopia are list in Table 1.

Table 1.

Core Interventions for Primary Prevention of Pathological Myopia

Intervention Type	Core Representative Regimen	Annual Axial Length Growth Reduction	Applicable Population	Core Advantages	Main Limitations	OCEBM Evidence Level	Key References
Low-concentration Atropine	0.05% atropine eye drops, 1 drop per night	~0.22 mm/year (vs. untreated control)	4–12 years old children with myopia progression ≥0.5 D/year in the previous year	Convenient nightly administration, concentration-dependent stable efficacy, 5-year long-term safety verified	Mild photophobia, reduced accommodative amplitude, high rebound rate after treatment cessation (87.9% of children need retreatment), limited safety data beyond 5 years	Level 1b (RCT long-term follow-up)	Zhang et al LAMP 5-year study (2024) Ophthalmology27
Orthokeratology (OK) Lenses	Night-wear (overnight) reverse geometry OK lenses, personalized base curve design	0.09–0.14 mm/year (vs. single vision lenses)	8–15 years old children, spherical equivalent −1.00 D ~ −6.00 D, astigmatism ≤1.50 D	No daytime spectacle wear, simultaneous vision correction and myopia control, stable 24-month long-term efficacy	Risk of corneal microbial keratitis, high requirement for standardized lens care and follow-up, potential glare/halos in case of severe decentration	Level 2a (meta-analysis of retrospective cohort studies)	Guo et al meta-analysis (2025) Contact Lens and Anterior Eye31
Multifocal Defocus Spectacle Lenses	DIMS (Defocus Incorporated Multiple Segments) spectacle lenses	~0.21 mm/year (vs. single vision lenses)	8–13 years old children, spherical equivalent −1.00 D ~ −5.00 D, astigmatism ≤1.50 D, intolerant to contact lenses	Non-invasive, high safety, efficacy independent of age and baseline axial length, effective for older children and those with high baseline AL	Efficacy affected by daily wearing time, potential mild halos in a small number of children	Level 1b (RCT post-hoc analysis)	Graff et al (2024) Br J Ophthalmol30
Low-Level Red Light (LLRL) Therapy	650 nm low-level red light, 3 minutes twice daily with at least 4 hours apart	~0.07 mm/year (vs. untreated control)	6–12 years old children, spherical equivalent −6.00 D ~ +3.00 D, with progressive myopia or premyopia	Non-invasive, rapid onset, increases subfoveal choroidal thickness (target organ protection), reduces myopia incidence by 69.4% in premyopic children	Limited long-term safety data beyond 1 year, single-center results need multi-center verification, contraindicated in patients with active fundus lesions	Level 1b (single-center RCT)	Cao et al (2024) JAMA Ophthalmol16
Posterior Scleral Reinforcement Surgery	Allogeneic scleral patch posterior scleral reinforcement surgery	0.10–0.15 mm/year (vs. preoperative baseline)	2–14 years old children with progressive pathological myopia, failed conservative myopia control treatment	Significant reduction in axial elongation, simultaneously slows myopic spherical equivalent progression, improves best-corrected visual acuity	Invasive surgery, risk of anesthesia, perioperative infection, scleral patch rejection, limited long-term efficacy and safety data beyond 2 years	Level 2b (retrospective cohort study)	Wang et al (2024) J Fr Ophtalmol17

Notes: The annual axial length growth reduction is calculated as the difference between the intervention group and the control group (or preoperative baseline for surgical intervention). Data are based on the 12-month follow-up.

Secondary Prevention and Target Organ Protection: Interventions for PM That Has Occurred

Prevention of Choroidal Neovascularization (mCNV) and Optimization of Anti-VEGF Treatment Strategies

PM is one of the leading causes of irreversible vision loss worldwide, characterized by progressive axial elongation of the eye and profound changes in the posterior segment structures.¹⁸ In patients with PM, choroidal neovascularization (mCNV) is a severe complication that leads to a sharp decline in central vision. mCNV is defined as choroidal neovascularization occurring in PM eyes, and PM is defined by the presence of typical fundus complications such as posterior staphyloma or myopic maculopathy with severity equal to or greater than diffuse chorioretinal atrophy.³⁸ In recent years, significant progress has been made in the prevention and treatment strategies for mCNV. On the prevention front, identifying high-risk patients is crucial. Studies have shown that axial length (AL) is the main variable associated with myopic maculopathy, with optimal AL cutoff values distinguishing PM from severe PM at 28 mm and 29.5 mm, respectively (OCEBM Level of Evidence: 2).¹ Patients with an axial length exceeding 28 mm and high-risk features such as lacquer cracks but without mCNV theoretically belong to the “extremely high-risk” group. Lacquer cracks are ruptures of Bruch’s membrane, which, while relatively harmless in themselves, may progress to patchy chorioretinal atrophy or CNV, leading to irreversible vision damage.³⁹ Although there are currently no widely used preventive treatment protocols, close monitoring based on risk stratification has become a clinical consensus. In terms of treatment, anti-vascular endothelial growth factor (anti-VEGF) drugs are the first-line therapy for mCNV. The application of advanced imaging technologies such as optical coherence tomography angiography (OCTA) has made it possible to quantitatively assess the retinal microvascular system and choroidal capillaries, which is very useful for the early detection of mCNV and the evaluation of anti-VEGF treatment efficacy.⁴⁰ OCTA can non-invasively identify blood flow signals within lesions, helping to distinguish between active and inactive lesions.⁴¹ Based on these imaging tools, treatment strategies are shifting from a fixed “treat-and-extend” (T&E) approach to “lesion activity-guided individualized treatment.” This individualized strategy aims to accurately monitor CNV activity through tools like OCTA and only administer injections when signs of activity are present (such as leakage or enhanced blood flow signals), thereby potentially reducing injection frequency while maintaining equivalent visual benefits and lowering the long-term risks of choroidal atrophy due to overtreatment. Furthermore, a deeper understanding of mCNV suggests that CNV occurring in elderly high myopic eyes that do not meet the PM definition may have clinical characteristics that lie between myopic CNV and age-related macular degeneration, necessitating a combined approach based on clinical and angiographic results to determine treatment strategies.⁴²

Graded Management and Progression Delay Strategies for Myopic Maculopathy (MMD)

Myopic maculopathy (MMD) is a core component of PM fundus changes, and its management relies on an accurate grading system. The classification system proposed by the International PM Meta-analysis (META-PM) research group defines PM as having an MM severity equal to or greater than diffuse chorioretinal atrophy or the presence of “plus” lesions (such as lacquer cracks, choroidal neovascularization, etc).³⁸ This classification clarifies clinical management pathways. For early lesions classified as stage 1–2 (such as diffuse atrophy and patchy atrophy), current intervention focuses on controlling the underlying cause—progressive elongation of the axial length—and managing systemic cardiovascular risk factors that may exacerbate ischemic damage, such as hypertension. Studies have shown that the prevalence of PM is high in the high myopia population, but most cases are relatively mild (diffuse chorioretinal atrophy).²⁰ In addition to controlling axial length and systemic factors, exploring nutritional interventions to delay atrophy progression is one of the research hotspots; for example, oral supplementation of lutein/zeaxanthin may help improve macular pigment optical density, but its exact effect on delaying the progression of geographic atrophy still requires more evidence. For more severe stage 3 lesions, ie., macular atrophy, effective treatment options have long been lacking. However, recent studies have brought hope for targeted therapies. For instance, some research has revealed the key roles of extracellular matrix remodeling, neural transmission, and scleral biomechanics in myopia and PM through a multi-omics integration framework, providing ideas for developing new therapeutic targets (OCEBM Level of Evidence: 2).²⁴ Although these findings are still exploratory, they indicate potential directions for intervening in atrophic processes. In addition to atrophic lesions, myopic traction maculopathy (MTM) is also an important manifestation of MMD, often driven by vitreoretinal traction on retinal blood vessels (OCEBM Level of Evidence: 1).¹⁸ The widespread use of ultra-high-resolution OCT has greatly improved the early detection rate of tractional lesions such as PM-related retinal breaks. Based on OCT imaging, new classification systems and management guidelines for myopic traction maculopathy have been proposed.⁴⁰ For progressively deepening breaks or cases accompanied by internal limiting membrane detachment, preventive vitrectomy may be considered to reduce the risk of retinal detachment. These advancements reflect a shift in MMD management from passive observation to active graded intervention.

Collaborative Management of Optic Nerve and Glaucoma Risk

Patients with PM are at high risk for primary open-angle glaucoma (POAG), and the coexistence of both significantly increases the risk of vision loss. Characteristic changes of PM, such as posterior staphyloma and optic disc tilt, pose significant challenges to the diagnosis of glaucoma. Posterior staphyloma indicates local thinning and bulging of the sclera, directly affecting the macula and optic nerve.¹⁸ This unique optic disc morphology (tilt, large cup) makes it easy to miss early glaucomatous damage based on traditional diagnostic criteria such as cup-to-disc ratio. Therefore, more objective and precise diagnostic tools are needed. In recent years, significant progress has been made in the application of artificial intelligence (AI) based on deep learning algorithms in ophthalmology. In the field of glaucoma, AI can be used for risk prediction, detection and diagnosis, visual field estimation and pattern analysis, and progression detection (OCEBM Level of Evidence: 1).⁴³ Specifically for the diagnosis of glaucoma in conjunction with PM, OCT-based retinal nerve fiber layer (RNFL) analysis models can more accurately identify early glaucomatous damage overlaying myopic changes. Although OCT RNFL examination in PM eyes may be affected by the unique optic disc morphology, advanced algorithms are working to overcome these challenges. In terms of management strategies, consensus indicates the need for more aggressive interventions. For PM patients with normal-high intraocular pressure showing signs of optic nerve damage, early initiation of intraocular pressure-lowering treatment should be considered. Prostaglandin analogs are often the first choice due to their strong intraocular pressure-lowering effects. Given that the axial elongation of PM eyes exerts additional biomechanical stress on the optic nerve head, the target intraocular pressure should be set lower than that of ordinary POAG patients (eg., below 15 mmHg) to provide sufficient neuroprotection. This strict control aims to counteract the additional mechanical damage caused by excessive axial elongation. Additionally, PM patients may face the risk of drug-related ocular surface diseases due to the long-term need for intraocular pressure-lowering medications such as prostaglandin analogs, which can affect treatment tolerance and compliance; therefore, individualized therapy should be considered during management.⁴⁴ In conclusion, the management of glaucoma risk in PM patients requires a combination of advanced imaging and AI diagnostic technologies, lower target intraocular pressure goals, and attention to treatment-related complications to achieve collaborative management of the optic nerve and glaucoma risk.

Innovations in Monitoring and Assessment Technologies: Empowering Precision Prevention and Control

Application of Multimodal Imaging in Risk Stratification and Efficacy Evaluation

The integration and innovation of multimodal imaging technologies have greatly enhanced the accuracy of risk stratification and efficacy assessment for complications of PM. Optical coherence tomography angiography (OCTA) has become a core tool for assessing PM progression (OCEBM Level of Evidence: 1).⁴⁵ Research shows that OCTA can provide non-invasive, high-resolution three-dimensional imaging of retinal and choroidal vasculature, with diagnostic accuracy comparable to traditional fundus fluorescein angiography, but safer and faster, especially suitable for long-term, frequent monitoring of PM patients.⁴⁵ Through OCTA, it is possible to quantitatively assess choroidal capillary layer blood flow density (CC FD) and choroidal thickness (CT), which have been established as key imaging biomarkers for evaluating PM progression and complication risk.⁴⁵ Notably, the progressive decline in choroidal capillary layer blood flow density has been confirmed as an independent factor predicting the progression of myopic choroidal neovascularization (mCNV) and myopic maculopathy (MMD), providing important evidence for early intervention.⁴⁵ At the same time, the application of ultra-widefield imaging technology has provided a new dimension for assessing the posterior pole structures of the eye (OCEBM Level of Evidence: 1).⁴⁶ Ultra-widefield scanning source OCT can assess the retina from the posterior pole to the mid-periphery in one go, and combined with artificial intelligence algorithms, can automatically quantify and monitor the range and morphological changes of posterior staphyloma, providing an unprecedented comprehensive view for assessing the stability of posterior pole structures.⁴⁶ In addition, biomechanical measurements…Technology has also been explored to indirectly reflect the biomechanical properties of the sclera. For instance, derived parameters from corneal biomechanical analyzers (such as Corvis ST) have been found to correlate with axial length and the severity of myopic maculopathy, providing additional information for understanding the pathophysiological mechanisms of PM and assessing the mechanical strength of the overall eyeball wall.⁴⁷ The comprehensive application of these multimodal imaging technologies allows clinicians to conduct more refined risk assessments and individualized management of PM patients from multiple perspectives, including vascular, structural, and biomechanical aspects.

Artificial Intelligence and Risk Prediction Models

The introduction of artificial intelligence (AI) and deep learning technologies is fundamentally changing the risk prediction models for PM and its complications.⁴⁸ Between 2024 and 2025, several risk prediction models based on large-scale, multidimensional data integration were developed and validated for PM and its complications.⁴⁸ These models typically rely on deep learning frameworks and integrate multi-source information such as age at first diagnosis, baseline refractive error, axial length, OCTA quantitative parameters (such as choroidal capillary blood flow density, vascular density index), and genetic risk scores.^45,48 Through training, these models can accurately predict the risk of children progressing to high myopia within the next five years, as well as the probability of PM patients developing mCNV or macular atrophy in the next three years.⁴⁸ This predictive ability allows clinical resources to be directed towards high-risk individuals, facilitating early identification and targeted prevention. For example, one study utilized AI algorithms to analyze ultra-widefield fundus images, automatically detecting and classifying clinically significant peripheral retinal lesions, with performance comparable to that of human experts, providing an efficient tool for large-scale screening.⁴⁹ However, despite the strong potential of AI models, their widespread clinical adoption requires further clinical trials and standardization.⁴⁵ Current research is also focused on enhancing the interpretability and reliability of these prediction models, such as developing “unreliability scores” to identify subgroups of patients where model predictions may be inaccurate, thus providing more cautious references for clinical decision-making.⁵⁰ Overall, AI risk prediction models that integrate multimodal imaging data and clinical information provide strong technical support for achieving precise and proactive management of complications related to PM.

Comprehensive Management Strategies and Future Directions (2023–2025 Consensus and Outlook)

Constructing a “Life Cycle” and “Multidisciplinary” Comprehensive Management Model

As the global burden of PM continues to escalate, its management has shifted from singular refractive correction to a systematic and comprehensive intervention that spans the patient’s lifetime. The 2024 updated International Myopia Institute (IMI) white paper systematically proposed a “life cycle management” framework for PM for the first time, emphasizing differentiated management strategies based on core pathological contradictions at different patient age stages.⁵¹ During childhood, the focus of management is on “controlling axial length,” utilizing optical, pharmacological, and behavioral interventions to prevent or delay the onset of PM.⁵² As individuals enter early adulthood, when PM has already occurred but complications are not yet significant, the strategy shifts to “monitoring and delaying,” focusing on regular fundus screening and control of risk factors to delay the onset of complications.¹⁹ For middle-aged and elderly PM patients, the focus of management transitions to “treating complications and preserving visual function,” addressing already existing target organ damage, such as macular atrophy, choroidal neovascularization, and glaucoma, to maximize useful vision.⁵³ This staged “life cycle” framework provides clear and actionable guidance for clinical practice, marking a significant advancement in PM management philosophy.

The successful implementation of “life cycle management” highly relies on an efficient collaborative multidisciplinary team.⁵⁴ The needs of PM patients are diverse, involving not only the correction of refractive errors but also the diagnosis and treatment of complications in target organs such as the retina, choroid, and optic nerve, as well as genetic counseling and psychological support. Therefore, an ideal management team should integrate various forces, including optometrists, ophthalmologists (covering subspecialties such as refraction, retina, and glaucoma), genetic counselors, and even psychologists.⁵⁵ For example, in the treatment of complex diseases such as colorectal cancer and inflammatory bowel disease, the multidisciplinary team (MDT) model has been proven to significantly optimize patient outcomes, improve diagnostic efficiency, and enhance patient experience.^56–58 The MDT model is equally crucial in PM management: optometrists are responsible for refractive correction and basic monitoring; retina specialists handle macular diseases; glaucoma experts manage concurrent optic nerve diseases; genetic counselors provide risk assessments for patients with a family history; and psychologists assist patients in coping with anxiety and depression due to vision loss. This patient-centered integrated care model ensures seamless, comprehensive, and personalized medical services for patients at all lifecycle stages of PM, serving as a key organizational guarantee for transitioning from “treating existing diseases” to “preventing future diseases”.^22,59

From Symptomatic Treatment to Etiological Treatment: Prospects and Challenges of Emerging Therapies

Current treatment for PM is often focused on symptomatic management after complications arise, such as anti-VEGF drug therapy for choroidal neovascularization.⁶⁰ However, etiological treatment targeting the fundamental pathophysiological mechanisms of PM—namely, the weakness and excessive elongation of the sclera—is becoming a hotspot and future direction of research. Among these, scleral reinforcement surgery has garnered sustained attention as a direct intervention to enhance the biomechanical strength of the posterior eye. Research from 2023 to 2025 has not only solidified the efficacy of traditional allograft scleral materials in posterior scleral reinforcement surgery (PSR), confirming their ability to effectively delay the axial length growth and refractive progression of children with high myopia,^17,61 but has also achieved breakthroughs in new biological materials. Studies have explored materials such as genipin-crosslinked allograft sclera, demineralized bone matrix (DBM), and regenerated silk fibroin hydrogels, which have shown superior biocompatibility and mechanical properties in animal experiments, better promoting autologous collagen synthesis and enhancing reinforcement effects.^62–64 More forward-looking research has attempted to combine piezoelectric materials with biological scaffolds to develop self-powered bionic reinforcement patches that further strengthen the sclera through electrical stimulation, representing an evolution from “passive support” to “active reinforcement”.⁶⁵ Additionally, scleral collagen cross-linking, as a non-implantable biomechanical reinforcement method, has shown potential for safety and stabilization of axial length in preliminary clinical studies, providing a new avenue for the etiological treatment of PM.⁶⁶

Gene and stem cell therapy represents the ultimate vision of correcting genetic defects underlying PM at its source. Although gene editing studies targeting specific genetic types of PM (such as those related to the MYP1 locus) remain largely in the preclinical stage, the success of hematopoietic stem cell (HSC) gene therapy in hereditary blood disorders provides a valuable paradigm for the treatment of hereditary eye diseases like PM.^67,68 The technological accumulation in this field, including lentiviral vector delivery, CRISPR-Cas9 gene editing, and in vitro stem cell culture, has laid the groundwork for future interventions targeting pathogenic genes associated with PM.⁶⁹ More practically, clinical trials utilizing retinal pigment epithelium (RPE) cells differentiated from induced pluripotent stem cells (iPSCs) for the treatment of patients with RPE degeneration-related macular atrophy have initiated their patient enrollment in 2025.⁷⁰ This study aims to restore function in the macular region by replacing damaged RPE cells, representing a direct application of regenerative medicine. Despite challenges such as cell integration, immune rejection, and tumorigenic risks, stem cell therapy offers a glimmer of hope for PM-related macular atrophy, which currently lacks effective treatment options.⁷¹

Neuroprotective strategies are key research directions addressing PM-related optic nerve injury and neurodegenerative changes in retinal neurons. With a deeper understanding of the common pathological mechanisms such as ischemia, oxidative stress, inflammation, and excitotoxicity in PM complications, the development of neurotrophic factors, mitochondrial function modulators, antioxidants, and anti-inflammatory drugs has become potential avenues for protecting visual function.^72,73 These drugs aim to block the neuronal apoptosis cascade and enhance the survival capacity of retinal ganglion cells (RGCs) through methods such as oral or intraocular administration.^74,75 For example, neuroprotectants studied in glaucoma and ischemic optic neuropathy may have mechanisms of action that are similarly applicable to PM-related optic neuropathy.⁷⁶ Although translating neuroprotection from the laboratory to clinical practice in PM still faces many challenges, such as drug delivery efficiency, targeting, and long-term efficacy validation, this strategy focuses on protecting the remaining functional neurons, complementing etiological treatment and symptomatic therapy, and together forming the three potential pillars of future comprehensive treatment for PM.^77,78

Current Challenges in Preventive Practices and Unmet Clinical Needs

Challenges in Healthcare Accessibility and Health Economics

Even in 2025, the accessibility of the most effective preventive measures for PM remains significantly uneven worldwide, with price being a major barrier preventing patients from obtaining effective interventions. For example, the costs of low-concentration atropine eye drops, new optical lenses with myopia control functions, and anti-VEGF drugs used to treat myopic choroidal neovascularization pose a heavy economic burden for many patients, especially in low- and middle-income countries or among those with lower socioeconomic status (OCEBM Level of Evidence: 1).⁷⁹ This financial burden is not only reflected in the direct purchase costs of drugs or devices but also in the indirect costs associated with long-term monitoring, professional fitting, and regular follow-ups. Research indicates that the utilization of medical resources and direct medical costs related to myopia are particularly significant among adults, especially after complications like myopic choroidal neovascularization develop, where frequent treatments, monitoring, and hospitalization constitute the main economic pressure.⁷⁹ Therefore, effective “lifecycle management” urgently requires intervention from public health policies and innovations in healthcare payment models, such as including validated myopia control interventions in the national basic medical insurance catalog, or reducing out-of-pocket expenses for patients through government subsidies and social assistance programs. Additionally, the continuous economic burden of long-term or even lifelong monitoring and treatment severely affects patient adherence to treatment, which is a major practical barrier to implementing the “lifecycle management” strategy.⁷⁹ Patients may interrupt treatment or monitoring due to an inability to bear long-term costs, leading to disease progression and irreversible vision loss. This challenge is even more pronounced in resource-limited settings, highlighting the importance of building a sustainable and affordable myopia prevention and control system.

Evidence Gaps and Research Priorities

Current research on the prevention and control of PM still has several key evidence gaps that need to be filled with high-quality studies. Firstly, there is a lack of high-level evidence for interventions targeting the continuous axial elongation of PM patients in adulthood. Existing studies mainly focus on myopia prevention in children and adolescents, but there is a lack of large-scale, long-term randomized controlled trial evidence on what interventions can effectively slow or stop this process in PM patients who have already reached adulthood and continue to experience progressive elongation.⁸⁰ Secondly, data on the efficacy and safety of long-term (over 5 years) use of preventive anti-VEGF treatment and oral supplements (such as specific vitamins or trace elements) are still lacking.³⁸ While short-term studies have shown potential for some interventions, their long-term benefit-risk ratios, preventive effects on terminal complications (such as myopic maculopathy), and differential responses in different subgroups of patients (such as those with varying genetic backgrounds and complication risks) require longer follow-up data for validation.^81,82 Finally, more research on personalized prevention and control strategies based on different ethnicities and genetic backgrounds is needed. The onset and progression of myopia are influenced by both genetic and environmental factors, and existing evidence is primarily derived from East Asian populations, with relatively scarce data from other racial groups.¹⁹ Future research should focus on integrating genomics, environmental exposure omics, and clinical phenotype data, using tools such as artificial intelligence to develop models that can predict individual risks of myopia progression and complications, thereby providing a basis for formulating precise and personalized prevention and control plans.¹⁹ Identifying these research priorities will help concentrate research resources, fill critical knowledge gaps, and ultimately translate into more effective clinical practice guidelines and public health strategies.

Conclusion

In recent years, the concepts and practices for the prevention and control of pathological myopia have undergone profound changes, shifting from controlling a single biological indicator, “axial length,” to a core goal of “lifetime protection of visual function,” forming a comprehensive prevention and control system. This shift not only deepens the understanding of pathological myopia as a potentially blinding chronic eye disease but also makes the prevention and control strategies more forward-looking and precise.

This review summarizes 4 core evidence-based recommendations for clinical management of PM: (1) For children and adolescents at high risk of PM, priority should be given to high-level evidence-based combined intervention strategies to delay axial elongation, so as to achieve primary prevention of PM; (2) For patients with confirmed PM, regular multimodal imaging screening and risk stratification are required to achieve early identification of high-risk patients for complications; (3) For PM patients with complications, individualized graded management strategies should be implemented according to the type and stage of complications to maximize the preservation of visual function; (4) The whole-process management of PM requires a multidisciplinary collaborative model to achieve life-cycle visual health protection.

Future efforts should focus more on exploring cutting-edge technologies such as scleral reinforcement and gene therapy based on etiological treatments, accumulating more clinical data to validate their effects. This series of strategic and technological innovations not only aims to improve treatment outcomes for pathological myopia but also provides patients with a more comprehensive visual health management plan, ultimately aiming for a fundamental shift from passive responses to proactive management.

Funding Statement

This work was supported by S&T Program of Hebei (Project No. 21377730D).

Abbreviations

PM, Pathological Myopia; AL, Axial Length; LCA, Low-concentration Atropine; LAMP, Low-Concentration Atropine for Myopia Progression; OK lenses, Orthokeratology lenses; DIMS, Defocus Incorporated Multiple Segments; mCNV, myopic Choroidal Neovascularization; MMD, Myopic Maculopathy; MTM, Myopic Traction Maculopathy; OCTA, Optical Coherence Tomography Angiography; T&E, Treat-and-Extend; POAG, Primary Open-Angle Glaucoma; RNFL, Retinal Nerve Fiber Layer; IMI, International Myopia Institute; MDT, Multidisciplinary Team; PSR, Posterior Scleral Reinforcement surgery; DBM, Demineralized Bone Matrix; HSC, Hematopoietic Stem Cell; iPSCs, Induced Pluripotent Stem Cells; RPE, Retinal Pigment Epithelium; RGCs, Retinal Ganglion Cells; ECM, Extracellular Matrix; VEGF, Vascular Endothelial Growth Factor; MM, Myopic Maculopathy; CRISPR-Cas9, Clustered Regularly Interspaced Short Palindromic Repeats-Cas9.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.