Introduction

Glaucoma encompasses various conditions, including progressive optic nerve damage marked by excavation of the optic disc (cupping). Globally, it is a primary cause of permanent blindness [1]. Primary open-angle glaucoma (POAG) is prevalent and has a multifaceted origin. Typically, glaucoma remains symptom-free during its early stages, and the sole established method to prevent its progression is lowering intraocular pressure (IOP), which can be achieved via medicinal, laser, or surgical procedures [2]. The primary risk factors for POAG include older age, increased IOP, sub-Saharan African ancestry, familial history, and significant myopia. Moreover, advanced age, hyperopia, and East Asian descent are primary risk factors associated with primary angle-closure glaucoma (PACG) [3].

The risk of glaucoma increases with age and is often intertwined with other age-related conditions such as macular degeneration, vascular diseases, and obstructive sleep apnea [4]. Although these associations exist, they do not create direct links between most age-related diseases and glaucoma. Studies, such as the Ocular Hypertension Treatment Study, suggest that male sex might predict the onset of POAG [5]. However, the influence of sex on the incidence of glaucoma varies according to the definition. Although some studies have indicated a greater risk of angle-closure glaucoma in women, there is no explicit sex inclination in patients with open-angle glaucoma. Notably, women’s longer life expectancy increases their susceptibility to glaucoma and, eventually, glaucoma-related vision loss [6].

In recent years, the global incidence of myopia has increased. The link between myopia and POAG is widely acknowledged. Extensive studies involving large populations have consistently shown an increase in the POAG rate with increasing myopia. Moreover, this connection is notably stronger in patients with severe myopia [7]. Individuals with myopia commonly exhibit a reduced circumpapillary retinal nerve fiber layer (pRNFL) thickness [8].

Optical correction methods such as glasses, contact lenses, and refractive surgery can address myopia. However, this condition is associated with potential complications such as myopic macular degeneration, retinal detachment, cataracts, and open-angle glaucoma. These complications lead to permanent vision loss in later stages of life [9, 10]. In patients with mild-to-moderate myopia, whose axial length is less than 26.0 mm, the size of the optic disc remains comparable to that in nonmyopic eyes [6].

Photographs aid in tracking optic disc changes, whereas optical coherence tomography (OCT) has transformed glaucoma monitoring capabilities. OCT, a noninvasive imaging method that uses Michelson interferometry, decodes light interference patterns from intraocular tissues. It quantitatively measures the optic nerve, the retinal ganglion cell axon layer (retinal nerve fiber layer), and the ganglion cell body layer [11, 12]. These structural changes, such as thinning of the pRNFL, often precede functional losses that can be detected in standard visual field tests [1]. Examining the ganglion cell complex (GCC) layer is more sensitive than examining pRNFL; however, the pRNFL thickness is the most commonly used parameter for evaluating glaucoma. The primary segment affected in ganglion cells is the inner plexiform layer, followed by the macular retinal nerve fiber layer (mRNFL) and ganglion cell layers [11, 12].

This systematic review and meta-analysis aimed to evaluate the relationship between high myopia and POAG risk, focusing on structural and functional assessment modalities such as OCT. Specifically, we aimed to identify the critical risk factors associated with glaucoma in highly myopic populations and to assess the diagnostic accuracy of OCT in detecting early glaucomatous changes. The outcomes measured included the prevalence and severity of glaucoma in patients with high myopia, structural changes in the pRNFL and GCC layers, and the effectiveness of OCT as a diagnostic tool.

Materials and methods

Study design

This study was meticulously designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A Participant, Intervention, Comparison, Outcomes (PICO) framework was employed to investigate the association between high myopia and POAG. High myopia was defined as a refractive error of less than -6.0 diopters or an axial length exceeding 26.0 mm. The primary objective of this study was to assess the diagnostic accuracy and reliability of OCT for detecting early glaucomatous changes in highly myopic eyes.


PICO framework

Component

Description

Population (P)

Individuals with highly myopic eyes

Intervention (I)

Use of OCT imaging to detect glaucomatous changes

Comparison (C)

Alternative imaging modalities used in chronic glaucoma assessment within the highly myopic population

Outcomes (O)

Prevalence of POAG in high myopia patients

Severity of glaucomatous changes detected via structural imaging (pRNFL, GCC complex thickness)

Functional assessments, including visual field defects and their correlation with structural changes

Study selection criteria

This study included randomized controlled trials (RCTs), prospective cohort studies, network meta-analyses, and observational studies that examined the association between high myopia and POAG. It prioritized original research articles published in English. The inclusion criteria were as follows.

Criteria

Description

Inclusion criteria

Adults aged 18 years or older

High myopia (refractive error of less than  -6.0 diopters or axial length > 26.0 mm)

 

Diagnosed with chronic glaucoma (e.g., POAG, pigmentary glaucoma, myopic glaucoma)

Including phakic and pseudophakic patients diagnosed with chronic glaucoma

Study scope with articles from January 2012 to June 2024 prioritizing original studies in English using OCT for structural assessment

Exclusion criteria

Studies published before 2012

Non-English publications

Studies involving optic injuries without a report of glaucoma

Studies focusing on imaging assessment tools unrelated to glaucoma diagnosis

Case reports, systematic reviews, and review articles

Literature search strategy

A comprehensive literature search was conducted across multiple databases, including Web of Science, MEDLINE, Embase, Lilacs, PubMed, PubMed Central, Scopus, the Cochrane Library, and Google Scholar. The search strategy combined Medical Subject Headings (MeSH) and relevant text words and used Boolean operators (“AND,” “OR,” and “NOT”) to refine the search. The search strings used were as follows:

  • “(high myopia) AND (pigmentary glaucoma OR primary open-angle glaucoma OR myopic glaucoma OR glaucoma) AND (imaging assessment) AND (optical coherence tomography)”

  • “(high myopia OR pigmentary glaucoma OR primary open-angle glaucoma OR myopic glaucoma OR glaucoma) AND (imaging assessment tool OR optical coherence tomography)”

These search strategies were adapted for each database to ensure the exhaustive retrieval of relevant studies. Appendix 1 of the Supplementary Information file presents the detailed search strategy.

Assessment of the quality of literature

Robust measures were taken to assess the quality of the literature through meticulous evaluation of the risk of bias and meta-analysis when applicable. Each included study was scrutinized based on its design, methodology, and risk of bias. This study focused on synthesizing evidence concerning the efficacy and safety of imaging diagnostic modalities compared with OCT in individuals with glaucoma and high myopia. The quality of the included studies was carefully evaluated using the Jadad scale, which rates studies on a scale from 0 (poor quality) to 5 (high quality). Additionally, the risk of bias was assessed using the Robivis tool (ROBINS-I), which focuses on the effectiveness and safety of diagnostic imaging methods, especially OCT, in individuals with glaucoma and high myopia.

Meta-analysis

Descriptive methodologies were employed to summarize the characteristics of the selected studies, including patient demographics, features of myopia, glaucoma types, imaging tools used, observed outcomes, associated complications, and inherent limitations. When data were available, a meta-analysis was performed to compare the interventions and outcomes across studies. Statistical analyses were conducted using IBM SPSS Statistics for Windows, version 26.0 (IBM Corp., Armonk, NY, USA). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, and forest plots were constructed to represent the data visually.

Results

Literature selection

After the initial screening process, 350 articles were extracted from nine databases (PubMed, PubMed Central, Scopus, Cochrane Library, Google Scholar, MEDLINE, EMBASE, LILACS, and Web of Science). After eliminating duplicates, non-English articles, and articles lacking full text, 163 articles were considered eligible. Fifty-six articles that did not align with the focus of the study and required more information on the imaging assessment used (n = 41) or had incomplete data (n = 15) were excluded. Fifteen studies were included in this review. These studies were published between 2012 and 2024. The PRISMA chart delineating the comprehensive process of literature collection and screening is shown in Fig. 1. Among these, retrospective studies emerged as the most prevalent study type, constituting six out of 15 studies. Among the remaining nine studies, four were cross-sectional, three were prospective, and two were observational.

Fig. 1
figure 1

PRISMA flow diagram of the systematic screening process

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Study characteristics

Patient demographics

These 15 studies included 3078 patients, and the number of females (n = 1557) was slightly greater than the number of males (n = 1521), excluding one study [13] that did not disclose the sex distribution. The patients included in the studies were between 20 and 84 years old, with the majority being over 50 years of age. All patients had highly myopic eyes, with an axial length of 26.0 mm or greater and a refractive error of less than − 6 diopters.

Imaging technology used

Twelve of the 14 studies used different OCT assessments, including enhanced depth imaging OCT (EDI-OCT), optical nerve head OCT, OCT angiography, stratus OCT, and swept-source OCT. However, one study [14] used color fundus images. When using OCT for assessing glaucoma in highly myopic eyes, interpreting the results is challenging because of the greater likelihood of false-positive diagnoses. Myopic eyes often show structural changes such as pRNFL thinning, which can be mistaken for glaucomatous damage. This becomes more difficult when standard normative databases not considering myopic eyes are used. Including a myopic normative database has been found to improve diagnostic specificity and reduce false positives without compromising sensitivity [15]. This is crucial for accurate diagnosis and management, especially in populations with a high prevalence of myopia.

Risk factors, structural findings, and functional findings

Outcomes of the study

Among the included studies, four discussed different diagnostic assessment tools [4, 5, 14, 16], four discussed glaucomatous damage [17,18,19,20], six reported the use of OCT assessments [5, 8, 21,22,23,24], three discussed associations with myopia [2, 4, 5], and three reported visual field progressions and microstructure, such as the distribution of lamina cribrosa defects (LCDs) in the optic disc and the proportion of abnormal clusters. Segmentation errors in OCT scans have been reported [2, 8, 10], and only one study reported artifacts and error analysis [11]. No studies have reported any potential complications.

Risk of bias assessment

Table 1 presents the quality of the included RCTs and non-RCTs based on the Jadad scale scores.

Table 1 Quality of the included studies according to the Jadad scale scores
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All data from the articles were carefully reviewed for potential bias. Each of the fifteen studies underwent a risk of bias analysis, which revealed a low risk of bias. However, studies three and five showed a moderate risk of bias in domain 3 (D3) due to missing information about the intended classification of the intervention and a low to moderate risk of bias in domain 5 (D5) owing to missing data. The overall bias data are presented in a risk of bias plot, which shows that all included studies had low to moderate risk of bias, depicted in green and yellow, respectively. However, the overall bias was considered to be low. Figures 2 and 3 outline the variables included in the risk-of-bias assessment plot and summary.

Fig. 2
figure 2

Graphical representation of the risk of bias analysis of individual studies. A low risk of bias was shown in 13 studies, and a moderate risk of bias was demonstrated in two studies

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Fig. 3
figure 3

Schematic representation of the summary of the risk of bias analysis. Plot showing an overall low risk of bias

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Meta-analysis

Only six studies were included in the meta-analysis, which focused on success rates and imaging assessments. Eight studies were excluded because they did not report success or complication rates. The analysis included 3040 patients from studies reporting success and failure rates. Figure 4 shows a forest plot representing the success rates of the imaging assessments. In this meta-analysis of six studies involving 3,040 patients, we investigated the correlation between myopia and glaucoma, emphasizing structural and functional implications such as the formation of abnormal clusters, tissue microstructures, and aqueous outflow, in addition to risk factors and assessment modalities, mainly OCT, in high-myopia populations (OR = 12.0, 95% CI 10.1–4.7, P < 0.00001). These findings are consistent with those of the sensitivity analysis. The forest plot visually represents the odds ratios and corresponding CIs across the included studies. Each horizontal line, or “branch,” represents individual research, with the point estimate (dot) indicating the odds ratio. The horizontal line through the square conveys the CI, and the dot size reflects the weight of each study in the meta-analysis.

Fig. 4
figure 4

A forest plot representing the success rates of the imaging assessments revealed the relationship between myopia and glaucoma, focusing on structural and functional implications. The forest plot represents the odds ratios and corresponding CIs. Each horizontal line represents individual research, and the point estimate (dot) indicates the odds ratio

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In Study 1, conducted by Ehongo et al. [2], the observed odds ratio of 0.274, along with a narrow confidence interval, strongly suggested a protective effect against the development of glaucoma in individuals with myopia. This finding implies that people with myopia may have a lower likelihood of experiencing glaucomatous changes than those without myopia. In Study 7 by Zemborain et al. [24], the reported odds ratio of 1.703 indicated a moderate increase in the likelihood of glaucoma among myopic patients. Although the effect was not as pronounced as in other studies, it still signifies a notable increase in the risk of myopia-associated glaucoma.

In Study 10 by Lim et al. [14], a substantial odds ratio of 20.792 was reported, highlighting a strong and statistically significant association between myopia and the occurrence of glaucoma. This high odds ratio suggests a significantly heightened risk of glaucomatous changes in individuals with myopia, emphasizing the importance of considering myopia as a potential risk factor. Studies 12 and 11, which were conducted by Hung et al. and Nakano et al. [7, 22] further contributed to the evidence by demonstrating odds ratios of 17.100 and 17.000, respectively. These findings reinforce a significant link between myopia and glaucomatous changes, such as elongation and thinning of the lamina cribrosa, resulting in intralaminar changes and steepening of the translaminar cribrosa pressure gradient. The consistent odds ratios in these studies underscore the robustness of the observed association, strengthening the argument that myopia is a noteworthy factor in the context of glaucoma risk.

Finally, Study 15, conducted by Awadalla et al. [11], significantly strengthens the existing evidence by revealing an odds ratio of 15.540. These findings add further weight to the body of knowledge, indicating a significant link between myopia and the development of glaucoma. The consistent odds ratios reported in these studies collectively enhance our understanding of the association and underscore the importance of considering myopia as a potential risk factor for glaucomatous changes.

The results collectively underscore the consistency and robustness of the observed associations, as depicted in the forest plot. The dispersion of individual study results visually demonstrates the heterogeneity across the study estimates around the overall summary estimate. The forest plot is a powerful tool for revealing the nuanced findings of a meta-analysis, facilitating the interpretation of the collective evidence concerning myopia and its relationship with glaucoma.

The quantitative outcomes of the meta-analysis (OR = 12.0, 95% CI 10.1–4.7, P < 0.00001) revealed a substantial and statistically significant association between high myopia and glaucoma risk, further bolstering the hypothesis that high myopia is a notable risk factor for the development of glaucomatous changes. These comprehensive meta-analyses deepen our understanding of the association between high myopia and glaucoma and provide valuable insights into the scientific literature. Supplementary Tables 2 and 3 present the structural findings, such as refractive error, axial length, visual acuity, visual field index, and IOP, along with all corresponding extraction data.

Discussion

A clinical study involving 519 eyes with an average axial length of 29.5 ± 2.2 mm revealed that glaucomatous optic neuropathy increased gradually from 12.2 to 42.1% across different axial length groups [2, 3]. This prevalence was linked to a larger parapapillary delta zone and a larger optic disc after adjusting for age and axial length, which aligned with the histological findings. In highly myopic eyes, it is crucial to differentiate between myopic maculopathy and high myopia-associated glaucomatous optic neuropathy, especially in patients with a secondarily enlarged optic disc or a large delta zone. These factors are associated with a greater risk of glaucomatous optic neuropathy in highly myopic eyes and should be rigorously evaluated [26].

A recent study confirmed a link between the severity of myopia and the risk of open-angle glaucoma. This was based on a dose–response meta-analysis that analyzed 24 studies involving 514,265 individuals from 11 countries [6, 9, 19]. The findings revealed a progressively greater risk of open-angle glaucoma with increasing myopia severity. Specifically, the risk increased by approximately 20% per diopter of myopia, with a more pronounced increase in individuals with higher degrees of myopia, indicating a significant nonlinear relationship [27, 28]. Haarman et al. [27] meta-analysis revealed a substantial association between myopia and posterior subcapsular and nuclear cataracts. In contrast, a clear association between myopia and cortical cataracts has not been reported [19].

Understanding the interplay between myopia and glaucoma

The intersection between myopia and glaucoma is a critical area of investigation. The consistent increase in the POAG rate with increasing myopia highlights the need for comprehensive assessment strategies [18]. Few studies have established a strong link between high myopia and glaucoma, suggesting a correlation between myopia severity and vulnerability to optic nerve damage [20, 29, 30]. It is well documented that myopic eyes are at an increased risk of developing glaucoma, and this risk appears to be more pronounced with higher degrees of myopia. Structural changes associated with high myopia, such as elongation of the globe and thinning of the pRNFL, can exacerbate the vulnerability of the optic nerve to glaucomatous damage. Longitudinal studies have shown that the progression of glaucomatous changes in myopic eyes can vary, with some studies reporting a greater rate of progression owing to the combined effects of myopia and glaucoma. For example, longitudinal evaluations have indicated that myopic eyes with glaucoma exhibit a steeper decline in RNFL thickness than nonmyopic glaucomatous eyes, suggesting that myopia may be an additive risk factor for more rapid disease progression [31].

In addition, the prevalence of glaucoma in myopic individuals seeking corneal refractive surgery is notably high, underscoring the importance of vigilant screening in this population. A study conducted by Biswas et al. [15] in Hong Kong, China, revealed that 5.1% of myopic individuals seeking corneal refractive surgery had undiagnosed or undetected glaucoma. Many  patients showed significant pRNFL thinning, and measurements of the neuroretinal rim were obtained using SD-OCT. Additionally, narrowed neuroretinal rim and optic disc excavation were observed in color optic disc stereo photographs. These findings highlight the need for increased awareness and early intervention strategies for managing patients with myopia who are at risk of glaucoma.

Advanced imaging modalities and risk factors in highly myopia-associated glaucoma patients

OCT has emerged as an indispensable tool for assessing and monitoring glaucoma, particularly in highly myopic populations, where its ability to measure the pRNFL and GCC thickness allows for the early detection of structural changes that often precede functional loss. The versatility of OCT is further exemplified by its application in various imaging techniques, including EDI-OCT and OCT angiography, which have proven crucial for the detailed assessment of glaucomatous damage in myopic eyes [31, 32]. These imaging modalities are particularly valuable given the complex structural changes associated with high myopia, such as globe elongation and pRNFL thinning, exacerbating the risk of glaucomatous damage. Our study consolidates the existing evidence on the risk factors associated with glaucoma in highly myopic patients, emphasizing the importance of understanding patient demographics, axial length, and refractive error. Notably, the predominance of female participants in certain studies correlates with known sex-related predispositions to glaucoma, particularly angle-closure glaucoma. However, conflicting evidence regarding the influence of sex on open-angle glaucoma underscores the need for further research to clarify this association [33, 34]. A thorough review of diagnostic imaging modalities, mainly OCT, is essential to optimize the detection and management of glaucoma in highly myopic individuals. Although OCT remains the cornerstone of imaging in this context, integrating additional modalities, such as color fundus imaging, reflects the evolving landscape of diagnostic technologies. Incorporating these advanced imaging tools is crucial for enhancing the specificity and sensitivity of glaucoma detection, thereby improving treatment outcomes in this high-risk population. Future research should refine these imaging techniques and develop specialized normative databases for highly myopic populations to address this subgroup’s unique challenges and enhance diagnostic accuracy and clinical management [35, 36].

Limitations and quality assessment

One notable limitation of this study is the potential for false-positive diagnoses when OCT is used for highly myopic eyes. Myopia-related structural changes, such as pRNFL thinning, may mimic glaucomatous damage, leading to diagnostic inaccuracies. Although the use of myopic normative database can mitigate this issue, variability in OCT interpretation across different studies remains a concern. Future research should prioritize the development and validation of specialized normative databases for myopic populations to increase the specificity and accuracy of glaucoma diagnoses in these patients. Furthermore, an assessment of the quality of the included studies using the Jadad scale revealed predominantly high-quality research, emphasizing the reliability of the synthesized evidence. However, because no problems have been reported, obtaining a complete picture of the risks that might arise with imaging methods and what they mean for people with high myopic glaucoma is difficult.

Future directions and clinical implications

These findings underscore the importance of longitudinal studies that focus on the progression of myopia and its correlation with glaucoma development. In addition, investigating the impact of interventions aimed at controlling myopia and reducing the risk of subsequent glaucomatous damage remains a promising avenue for future research. Integrating multimodal imaging approaches and leveraging artificial intelligence for artifact and error analysis in imaging techniques could increase diagnostic precision and minimize discrepancies.

Conclusion

Our study provides evidence for a relationship between myopia and glaucoma, emphasizing the importance of OCT and other imaging modalities for early detection and monitoring. Understanding the complex relationships among myopia severity, structural changes, and functional changes is essential for improving the treatment of glaucoma in highly myopic individuals.