Comprehensive Assessment of Glaucoma in Patients with High Myopia: A Systematic Review and Meta-analysis with a Discussion on Structural and Functional Imaging Modalities

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Quiroz-Reyes, Erick A. Quiroz-Gonzalez, Miguel A. Quiroz-Gonzalez, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4355898/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 11 Oct, 2024 Read the published version in International Ophthalmology → Version 1 posted 7 You are reading this latest preprint version Abstract Purpose: The interplay between myopia and glaucoma has gained attention, with escalating myopia demonstrating a significant association with increased POAG rates, particularly in patients with severe myopia. This systematic review aimed to comprehensively analyze the relationship between myopia and glaucoma, focusing on the structural and functional implications, risk factors, and assessment modalities, particularly optical coherence tomography (OCT), in highly myopic populations. Methods: According to the PRISMA guidelines, a meticulous search strategy was employed across multiple databases from 2012 to 2024. The inclusion criteria included individuals aged 18 years or older with myopia exceeding 6 diopters or an axial length > 26 mm who were diagnosed with chronic glaucoma. Various study designs, including randomized controlled trials (RCTs), prospective cohort studies, and observational studies, were incorporated. Quality assessment was performed using the Jadad Scale, and statistical analyses were performed to summarize the study characteristics and outcomes. Results: Of the 350 initial articles, 15 met the inclusion criteria. OCT assessments revealed structural changes such as thinning of the retinal nerve fiber layer preceding functional losses. Meta-analyses demonstrated a heightened risk of POAG with increasing myopia severity, showing a significant nonlinear relationship. In this meta-analysis of six studies involving 3,040 patients, we demonstrated a relationship between myopia and glaucoma (OR = 12.0, 95% CI: 10.1–4.7, P <0.00001). Conclusion: This comprehensive analysis consolidates the evidence of the relationship between myopia and glaucoma, emphasizing the pivotal role of OCT and other imaging modalities in early detection and monitoring. glaucoma high myopia optical coherence tomography optical coherent tomography imaging retinal nerve fiber layer ganglion cell complex Figures Figure 1 Figure 2 Figure 3 Figure 4 Plain language summary Glaucoma is a major cause of permanent blindness around the world. It causes damage to the visual nerve that gets worse over time. The main way to treat open-angle glaucoma and its many causes is to lower eye pressure. More research is being done on the relationship between nearsightedness and glaucoma. It has been found that increasing nearsightedness is significantly linked to higher rates of glaucoma, especially in people with serious nearsightedness. The point of this review was to look at the link between myopia and glaucoma in a more in-depth way, focusing on the structural and functional effects, risk factors, and assessment methods, especially optical coherence tomography, in people who are very nearsighted. A thorough search approach was used across several databases from 2012 to 2024. People ages 18 or older with myopia greater than 6 diopters or an axial length greater than 26 mm and a diagnosis of chronic glaucoma were eligible. Randomized controlled trials, prospective cohort studies, and observational studies were some of the study methods that were used. Quality of the work, and statistical methods were used to make a summary of the study's features and results. Out of the 350 original published articles, only 15 met the requirements to be included. These studies mostly used different optical tomography tests to show structural changes, like the ocular nerve fiber layer damage before functional loss. According to meta-analyses, the chance of chronic glaucoma went up as myopia got worse, showing a strong nonlinear relationship. The fact that myopia and glaucoma are linked shows how important it is to use thorough evaluation methods. Severe myopia is strongly linked to damage to the visual nerve. Over the past few years, optical tomography has become an important imaging tool that helps find damage in the optic nerve early on. On the other hand, glaucoma patients' sex-related tendencies need more research. This thorough study brings together data that shows a link between nearsightedness and glaucoma, highlighting how important optical tomography and other imaging techniques are for early detection and ongoing monitoring. To better handle glaucoma in people who are highly myopic, we need to understand how the severity of myopia, changes in structure, and changes in function all affect each other. 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 impede its progression is to lower intraocular pressure (IOP), which can be achieved using medicinal, laser, or surgical procedures (2). The primary risk factors for POAG include older age, heightened intraocular pressure, sub-Saharan African ancestry, familial history, and significant myopia. Moreover, advanced age, hyperopia, and East Asian descent are the 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 its definition. While some studies have indicated a greater risk for angle-closure glaucoma in women, there is no clear sex inclination for 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, there has been a growing global occurrence of myopia. The link between myopia and POAG is widely acknowledged. Extensive studies involving large populations have consistently shown an increase in POAG rates with increasing myopia. Moreover, this connection appears notably stronger in patients with severe myopia (7). Individuals with myopia commonly exhibit reduced retinal nerve fiber layer initially (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 pose a risk of permanent vision loss in the later stages of life (9,10). In patients with mild-to-moderate myopia, in which the axial length is less than 26.5 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 ganglion cell body layer (11,12). These structural changes, such as thinning of the retinal nerve fiber layer, often precede functional losses that are detectable by standard visual field tests (1). . The current study aimed to analyze the interrelationship and association between myopia and glaucoma, along with identifying the associated risk factors and structural and functional findings that could assist in effectively monitoring these conditions. We mainly focused on the ganglion cell complex (GCC) and retinal nerve fiber layer (RNFL) and their roles in detecting glaucoma in patients with myopia. The examination of the GCC layer is more sensitive than that of the circumpapillary RNFL (pRNFL). The pRNFL is the most commonly used parameter for evaluating glaucoma. In ganglion cells, the primary segment affected is the inner plexiform layer, followed by the macular retinal nerve fiber layer (mRNFL) and ganglion cell layers. We also discuss the association between IOP and axial length. Materials and Methods Study Design This study was meticulously designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and employed a PICOS framework to explore the relationship between chronic glaucoma and high myopia. The population (P) for examination included individuals with highly myopic conditions and those assessed using various assessment modalities, particularly optical coherence tomography (OCT). Intervention (I) examined the use of OCT imaging. Comparison (C) involving the evaluation of alternative imaging diagnostic modalities used in chronic glaucoma assessment within the highly myopic population. Outcomes (O) of interest spanned diverse domains: examining documented evidence of visual field abnormalities; identifying OCT abnormalities consistent with retinal nerve fiber layer and ganglion cell complex longitudinal abnormalities; discerning high-risk factors; scrutinizing structural and functional findings; identifying the most effective longitudinal evaluation methods for glaucoma in individuals with high myopia, and exploring the relationship between IOP and axial length. This comprehensive evaluation aimed to deepen the understanding of glaucoma in this demographic population, optimize diagnostic accuracy, and enhance monitoring strategies by determining the optimal parameters for detection and follow-up. Setting (S) for this thorough review encompassed studies conducted in hospital and private settings with a publication timeframe spanning from 2012 to 2024. To gather relevant literature, databases such as Web of Science, MEDLINE, Embase, PubMed, and other pertinent sources were systematically searched. Incorporating various study designs, our study included randomized controlled trials (RCTs), prospective cohort studies, and observational studies to simultaneously compare three or more interventions. This approach ensured a comprehensive examination of diverse research methodologies to synthesize evidence and draw robust conclusions regarding the complex interplay between chronic glaucoma and high myopia. Inclusion and Exclusion Criteria The inclusion criteria were meticulously defined to include patients aged 18 years or older with myopia exceeding 6 diopters or an axial length > 26 mm, including phakic or pseudophakic individuals diagnosed with chronic glaucoma, spanning pigmentary glaucoma, primary open-angle glaucoma, and myopic glaucoma, among others. The study scope covered articles published between January 2012 and October 2024, exclusively focusing on RCTs, prospective cohort studies, and network meta-analyses while prioritizing original research articles published in English. We excluded articles that met any of the following criteria: (1) studies published before 2012, (2) studies not published in English, (3) studies involving optic injuries but did not report any type of glaucoma, (4) studies involving various kinds of imaging assessment tools that were not related to glaucoma diagnosis; (5) were case reports, (6) were systematic reviews, or (7) were review articles. Literature Selection Process The literature selection process employed a refined search strategy (Appendix 1 in the Supplementary file) amalgamating Medical Subject Headings (MeSH) and text words, strategically utilizing Boolean operators (e.g., "AND," "OR," and "NOT") to construct search strings. These strings, initially inclusive of terms such as "myopia," "glaucoma, “imaging assessment tools," and "optical coherence tomography," underwent adaptive modifications tailored to specific databases and platforms, ensuring exhaustive retrieval of the relevant literature. Search string used The search strings "(high myopia) AND (pigmentary glaucoma OR primary open-angle glaucoma OR myopic glaucoma OR glaucoma) AND (imaging assessment) AND (optical coherence tomography)" and ""(high myopia OR pigmentary glaucoma OR primary open-angle glaucoma OR myopic glaucoma OR glaucoma) AND (imaging assessment tool OR optical coherence tomography)" were used for the analysis. Quality of Literature Selection 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 respective study design, methodology, and risk of bias, with a particular focus on synthesizing evidence concerning the efficacy and safety of imaging diagnostic modalities compared with OCT in individuals with glaucoma and high myopia. The Jadad scale was used to analyze the quality of the studies (a score of 0 indicated poor quality and a score of 5 indicated high quality). The risk of bias in the included studies was assessed using the Robivis tool (ROBINS-I). Meta-Analysis The meta-analysis included descriptive methodologies to summarize the characteristics of the selected studies, including patient demographics, myopia features, glaucoma typology, imaging tools employed, observed outcomes, associated complications, and inherent limitations. Depending on the availability of data, we performed a meta-analysis to compare interventions and outcomes across studies. Statistical analysis was conducted using IBM SPSS Statistics for Windows, version 26.0 (IBM Corp., Armonk, NY, USA). These procedures offer a comprehensive assessment of the study outcomes incorporated within this analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, and forest plots were constructed based on the available data. 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. After excluding 56 articles that did not align with the study's focus—either lacking information on the imaging assessment used (n = 41) or incomplete data (n = 15)—15 studies were included in this study. These studies were published between 2012 and 2024. A PRISMA chart delineating the comprehensive process of literature collection and screening is shown in Fig. 1. Among these studies, 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 studies. Study Characteristics Patient Demographics A total of 3078 patients were included in these 15 studies, 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 sex distribution. The age of the patients in the included studies ranged from 20 to 84 years, with most being > 50 years. All the patients had highly myopic eyes with an axial length ≥ 26 mm and refractive error >-6 diopters. Imaging technology used Twelve of the 14 included studies used different types of OCT assessments, including enhanced depth imaging OCT, optical nerve head OCT, OCT angiography, stratus OCT, and swept-source OCT. However, one study (14) Click or tap here to enter text. used color fundus images. Risk factors, structural findings, and functional findings Outcomes of the study Among the included studies, four studies discussed different diagnostic assessment tools (4, 5, 14,15), four studies mainly discussed glaucomatous damage (16,17,18,19,20), six studies reported the use of OCT assessments (5,8,19,21,22,23), three studies discussed associations with myopia (2,4,5), and three reported visual field progression and microstructure, such as the distribution of lamina cribrosa defects (LCDs) in the optic disc and the proportion of abnormal clusters. The presence of segment errors has 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 shows the quality of the included RCT and non-RCT studies based on the Jadad scale scores. Fourteen of the 15 studies were of high quality, whereas the remaining studies were of moderate quality. Figures 2 and 3 show the variables included in the risk-of-bias assessment plot and summary, respectively. Table 1 – Quality of the included studies according to the Jadad scale scores Name of the Study Selection bias Performance bias Reporting bias Attribution bias Other bias Results Quality of the study Ehongo et al. 1 1 1 1 0 4 High Yu-Fan et al. 1 1 1 1 0 4 High Miki et al. 1 1 0 1 1 4 High Fan et al. 1 1 1 1 0 4 High Chang et al. 1 1 0 1 0 3 Moderate Mohammad Noureldine et al. 1 1 1 1 0 4 High Zemborain et al. 1 1 1 1 0 4 High Lee et al. 1 1 1 1 0 4 High Rezapour et al. 1 1 1 1 1 5 High Lim et al. 1 1 1 1 1 5 High Nakano et al. 1 1 1 1 0 4 High Hung et al. 1 1 1 1 1 5 High Park et al. 1 1 1 1 1 5 High Yamada et al. 1 1 1 1 0 4 High Awadalla et al. 1 1 1 1 0 4 High Selection bias: Has the study included comparison between groups or existing data? Performance bias : Has the study reported the estimated effects clearly? Reporting bias: Was the study free from problems with measurements or classification of outcomes? Attribution bias: Has the study reported complete outcome data? Other Bias: Was the study free from limitations? Jadad Scale Score: “0 to 2” à Low quality; “3” à Moderate quality; “4 to 5” à High quality Meta-analysis Only six studies were included in the meta-analysis, which included an analysis of success rates and imaging assessments. Eight studies were excluded because no details on the success or complication rates were reported. The studies that reported success and failure rates included 3040 patients. Figure 4 shows a forest plot constructed to represent the success rates of the imaging assessments. In this meta-analysis of six studies involving 3,040 patients, we demonstrated the relationship between myopia and glaucoma, focusing on structural and functional implications, such as the formation of abnormal clusters, tissue microstructures and aqueous outflow, risk factors, and assessment modalities, particularly OCT, within high-myopia populations (OR = 12.0, 95% CI: 10.1–4.7, P < 0.00001). These findings were consistent with those of the sensitivity analysis. The forest plot provides a visual representation of the odds ratios and corresponding CIs across the included studies. Each horizontal line, or "branch," represents an individual study and the point estimate (dot) indicates the odds ratio. The horizontal line through the square represents the CI, and the size of the dot reflects the weight of each study in the meta-analysis. In Study 1 (24), the observed odds ratio of 0.274, coupled with a narrow CI, suggests a compelling indication of a protective effect against the development of glaucoma in individuals with myopia. This finding implies that myopic individuals may exhibit a reduced likelihood of experiencing glaucomatous changes compared with their nonmyopic counterparts. In study 7 (12), the reported odds ratio of 1.703 points indicated a moderate increase in the likelihood of glaucoma among myopic patients. Although the effect was not as pronounced as in some other studies, it still signifies a notable elevation in the risk of glaucoma associated with myopia in this particular investigation. Study 10 (19) showed a substantial odds ratio of 20.792, underscoring a robust and statistically significant association between myopia and the occurrence of glaucoma. The high odds ratio in this study suggested a markedly heightened risk of glaucomatous changes in individuals with myopia, emphasizing the importance of considering myopia as a potential risk factor. Both studies 11 and 12 (16,25) contribute to the growing body of evidence by demonstrating odds ratios of 17.100 and 17.000, respectively. These findings collectively reinforce a significant link between myopia and glaucomatous changes such as elongation and thinning of the lamina cribrosa resulting in intralaminar changes and a steepening of the translaminar cribrosa pressure gradient. The consistent odds ratios in these studies underscore the robustness of the observed association, strengthening the argument for myopia as a noteworthy factor in the context of glaucoma risk. Finally, Study 15 (26) adds weight to the overall evidence by presenting an odds ratio of 15.540. This finding further supports the existing body of knowledge indicating a substantial connection between myopia and glaucoma development. The consistent odds ratios across these studies collectively contribute to a comprehensive understanding of the association, emphasizing the importance of myopia as a potential risk factor for glaucomatous changes. These results collectively emphasize the consistency and strength of the observed associations, as supported by the forest plot. Heterogeneity across studies was visually represented by the spread of the individual study estimates around the overall summary estimate. The forest plot serves as a powerful tool for revealing the nuanced findings of the meta-analysis, aiding in the interpretation of the collective evidence on myopia and its connection to 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 myopia and glaucoma risk, further supporting the hypothesis that myopia is a notable risk factor for the development of glaucomatous changes. These detailed meta-analysis results enhance our understanding of the relationship between myopia and glaucoma and contribute valuable insights to the scientific literature. A detailed description of the structural findings, such as refractive error, axial length, visual acuity, visual field index and intraocular pressure, and all the corresponding extraction data are presented respectively in the Appendix 2, and the Appendix 3 in the Supplementary file. Discussion A clinical study involving 519 eyes with an average axial length of 29.5 ± 2.2 mm revealed a gradual increase in glaucomatous optic neuropathy incidence from 12.2–42.1% across different axial length groups (2,3). The prevalence was correlated with a larger parapapillary delta zone and/or a larger optic disc after adjusting for age and axial length, which was consistent with the histological findings. In highly myopic eyes, distinguishing between myopic maculopathy and high myopia-associated glaucomatous optic neuropathy is crucial, especially in patients with a secondarily enlarged optic disc or a large delta zone. These factors are associated with a greater likelihood of glaucomatous optic neuropathy in highly myopic eyes and should be carefully assessed (27) . One study confirmed the link between myopia severity and open-angle glaucoma risk through a dose‒response meta-analysis, which included an analysis of 24 studies involving 514,265 individuals from 11 countries (9,18,6). 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 (28,29). A meta-analysis performed by Haarman et al. (28) revealed a significant link between myopia and posterior subcapsular and nuclear cataracts. However, a clear association between myopia and cortical cataracts has not been reported (18). Understanding the Interplay between Myopia and Glaucoma The intersection between myopia and glaucoma is a critical area of investigation. The consistent increase in POAG rates with increasing myopia underlines the need for comprehensive assessment strategies (17). Few studies have established a strong link between severe myopia and glaucoma, suggesting a correlation between myopia severity and vulnerability to optic nerve damage (20,24,30) . Structural and Functional Imaging Modalities in Glaucoma Monitoring OCT is a pivotal tool for glaucoma assessment in highly myopic populations. Its ability to measure the nerve fiber layer and ganglion cell complex in the retina helps to identify early structural changes that occur before function is lost. The use of different OCT tests in different studies demonstrates its flexibility. These tests include enhanced depth imaging OCT and OCT angiography, which emphasize the importance of determining glaucomatous damage. Role of Risk Factors and Associations Our study consolidates the evidence on the risk factors associated with glaucoma in patients with high myopia, confirming the importance of understanding patient demographics, axial length, and refractive error. The predominance of female participants in certain studies aligns with the sex-related predispositions observed in glaucoma, especially angle-closure glaucoma. However, conflicting findings regarding the influence of sex on open-angle glaucoma warrant further investigation. Diagnostic Assessment and Future Directions A thorough review of diagnostic imaging methods and comparisons with OCT helps to determine the best methods for detecting and treating glaucoma in people who are nearsighted. While most studies have focused on OCT assessments, the incorporation of alternative imaging tools such as color fundus images highlights the evolving landscape of diagnostic technologies. Limitations and Quality Assessment Assessing 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, it is difficult to obtain a full picture of the risks that might arise with imaging methods and what they mean for people with high myopic glaucoma. 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. Additionally, 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 enhance diagnostic precision and minimize discrepancies. Conclusion Our study provides evidence for a relationship between myopia and glaucoma, emphasizing the significance of OCT and other imaging modalities for early detection and monitoring. Understanding the complex relationships among myopia severity, structural changes, and functional changes is important for improving the treatment of glaucoma in highly myopic individuals. Abbreviations AL, axial length GCC, ganglion cell complex CI, confidence interval IOP, intraocular pressure mRNFL, macular retinal nerve fiber layer MeSH, Medical Subject Headings OCT, optical coherence tomography ORs, odds ratios POAG, primary open angle glaucoma PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-analyses PICO, participant, intervention, comparator, outcomes dot, point estimate RCT, randomized controlled trials RNFL, retinal nerve fiber layer pRNFL, peripapillary retinal nerve fiber layer ROBINS-I, Risk Of Bias In Non-randomized Studies - of Interventions Declarations Acknowledgments We express our deep appreciation to the technical staff of the Retina Department of Oftalmologia Integral ABC (a Medical and Surgical Nonprofit Organization), Mexico City, Mexico, which is affiliated with The Postgraduate Division Studies at the National Autonomous University of Mexico. Funding details No funding or grant support was received for this study. Disclosure statement The authors declare no conflicts of interest. Data availability statement The datasets used in this study have been included in the main text. Photographs and figures from this study may be released via a written application to the Photographic Laboratory and Clinical Archives Retina Department at the Oftalmologia Integral ABC Medical and Surgical Assistance Institution (Nonprofit Organization), Av. Paseo de las Palmas 735 suite 303, Lomas de Chapultepec, Mexico City 11000, Mexico and the corresponding author upon request. Ethics approval and consent to participate This study adhered to the tenets of the Declaration of Helsinki and received full approval. from the appropriate research ethics committee, institutional review committee, and institutional teaching department (the institution did not provide reference numbers for the systematic review and network meta-analysis studies). Author contributions All the authors made a significant contribution to the work reported, whether 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; agreed on the journal to which the article has been submitted; and agreed to be accountable for all aspects of the work. Institutional review board statement This study was conducted at the Retina Department of the Oftalmología Integral ABC. Institution in Mexico City, Mexico. The Institutional Review Board approved the study. institutional guidelines. No reference numbers have been provided for this systematic review. or meta-analysis. 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J., Johnson, C. A., Keltner, J. L., Philip Miller, J., Parrish, R. K., Roy Wilson, M., & Kass, M. A. (2002). The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. Archives of Ophthalmology (Chicago, Ill. : 1960) , 120 (6), 714–720. https://doi.org/10.1001/ARCHOPHT.120.6.714 Ha, A., Kim, C. Y., Shim, S. R., Chang, I. B., & Kim, Y. K. (2022). Degree of Myopia and Glaucoma Risk: A Dose-Response Meta-analysis. American Journal of Ophthalmology , 236 , 107–119. https://doi.org/10.1016/J.AJO.2021.10.007 Jonas, J. B., Aung, T., Bourne, R. R., Bron, A. M., Ritch, R., & Panda-Jonas, S. (2017). Glaucoma. Lancet (London, England) , 390 (10108), 2183–2193. https://doi.org/10.1016/S0140-6736(17)31469-1 Miki, A., Ikuno, Y., Weinreb, R. N., Asai, T., Usui, S., & Nishida, K. (2019). En Face Optical Coherence Tomography Imaging of Beta and Gamma Parapapillary Atrophy in High Myopia. Ophthalmology. Glaucoma , 2 (1), 55–62. https://doi.org/10.1016/J.OGLA.2018.11.008 Perera, S. A., Wong, T. Y., Tay, W. T., Foster, P. J., Saw, S. M., & Aung, T. (2010). Refractive error, axial dimensions, and primary open-angle glaucoma: the Singapore Malay Eye Study. Archives of Ophthalmology (Chicago, Ill. : 1960) , 128 (7), 900–905. https://doi.org/10.1001/ARCHOPHTHALMOL.2010.125 Nakano, N., Hangai, M., Noma, H., Nukada, M., Mori, S., Morooka, S., Takayama, K., Kimura, Y., Ikeda, H. O., Akagi, T., & Yoshimura, N. (2013). Macular imaging in highly myopic eyes with and without glaucoma. American Journal of Ophthalmology , 156 (3). https://doi.org/10.1016/J.AJO.2013.04.028 Park, S. C., De Moraes, C. G. V., Teng, C. C., Tello, C., Liebmann, J. M., & Ritch, R. (2012). Enhanced depth imaging optical coherence tomography of deep optic nerve complex structures in glaucoma. Ophthalmology , 119 (1), 3–9. Zemborain, Z. Z., Jarukasetphon, R., Tsamis, E., De Moraes, C. G., Ritch, R., & Hood, D. C. (2020). Optical Coherence Tomography Can Be Used to Assess Glaucomatous Optic Nerve Damage in Most Eyes With High Myopia. Journal of Glaucoma , 29 (10), 833–845. https://doi.org/10.1097/IJG.0000000000001631 Sun, M. T., Tran, M., Singh, K., Chang, R., Wang, H., & Sun, Y. (2023). Glaucoma and Myopia: Diagnostic Challenges. Biomolecules , 13 (3). https://doi.org/10.3390/BIOM13030562 Rezapour, J., Proudfoot, J. A., Bowd, C., Dohleman, J., Christopher, M., Belghith, A., Vega, S. M., Dirkes, K., Suh, M. H., Jonas, J. B., Hyman, L., Fazio, M. A., Sella, R., Afshari, N. A., Weinreb, R. N., & Zangwill, L. M. (2022). Bruch Membrane Opening Detection Accuracy in Healthy Eyes and Eyes With Glaucoma With and Without Axial High Myopia in an American and Korean Cohort. American Journal of Ophthalmology , 237 , 221–234. https://doi.org/10.1016/J.AJO.2021.11.030 Alasil, T., Wang, K., Yu, F., Field, M. G., Lee, H., Baniasadi, N., De Boer, J. F., Coleman, A. L., & Chen, T. C. (2014). Correlation of retinal nerve fiber layer thickness and visual fields in glaucoma: a broken stick model. American Journal of Ophthalmology , 157 (5). Miglior s; Pfeiffer N, Torri V et al.(2007). Predictive factors for open-angle glaucoma among patients with ocular hypertension in the European Glaucoma Prevention Study. Ophthalmology , 114 (1), 3–9. https://doi.org/10.1016/J.OPHTHA.2006.05.075 Haarman, A. E. G., Enthoven, C. A., Willem Tideman, J. L., Tedja, M. S., Verhoeven, V. J. M., & Klaver, C. C. W. (2020). The Complications of Myopia: A Review and Meta-Analysis. Investigative Ophthalmology & Visual Science , 61 (4). https://doi.org/10.1167/IOVS.61.4.49 Jonas, J. B., Weber, P., Nagaoka, N., & Ohno-Matsui, K. (2017). Glaucoma in high myopia and parapapillary delta zone. PloS One , 12 (4). https://doi.org/10.1371/JOURNAL.PONE.0175120 Mwanza, J. C., Sayyad, F. E., Aref, A. A., & Budenz, D. L. (2012). Rates of abnormal retinal nerve fiber layer and ganglion cell layer OCT scans in healthy myopic eyes: Cirrus versus RTVue. Ophthalmic Surgery, Lasers & Imaging : The Official Journal of the International Society for Imaging in the Eye , 43 (6 Suppl). https://doi.org/10.3928/15428877-20121003-01 Additional Declarations No competing interests reported. Supplementary Files CopiadeAppendix1SearchStrategySupplementaryMaterials3.docx CopiadeAppendix2.Supplementaryfile.docx CopiadeAppendix3Supplementaryfile.docx CopiadePRISMA2020checklist1.docx Cite Share Download PDF Status: Published Journal Publication published 11 Oct, 2024 Read the published version in International Ophthalmology → Version 1 posted Editorial decision: Revision requested 18 Aug, 2024 Reviews received at journal 05 Jul, 2024 Reviewers agreed at journal 03 Jul, 2024 Reviewers invited by journal 13 May, 2024 Editor assigned by journal 07 May, 2024 Submission checks completed at journal 07 May, 2024 First submitted to journal 06 May, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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18:27:48","extension":"docx","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":17657,"visible":true,"origin":"","legend":"","description":"","filename":"CopiadeAppendix1SearchStrategySupplementaryMaterials3.docx","url":"https://assets-eu.researchsquare.com/files/rs-4355898/v1/9eaa471d39bab497ba200648.docx"},{"id":56682985,"identity":"96cc4de5-3a9d-46eb-ab28-fbf232e0ca8b","added_by":"auto","created_at":"2024-05-17 18:27:47","extension":"docx","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":15271,"visible":true,"origin":"","legend":"","description":"","filename":"CopiadeAppendix2.Supplementaryfile.docx","url":"https://assets-eu.researchsquare.com/files/rs-4355898/v1/26b7f9233e96d62be2313e4c.docx"},{"id":56682989,"identity":"d2330785-8d5b-47aa-9d56-ecb78bfd1475","added_by":"auto","created_at":"2024-05-17 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Modalities","fulltext":[{"header":"Plain language summary","content":"\u003cp\u003eGlaucoma is a major cause of permanent blindness around the world. It causes damage to the visual nerve that gets worse over time. The main way to treat open-angle glaucoma and its many causes is to lower eye pressure. More research is being done on the relationship between nearsightedness and glaucoma. It has been found that increasing nearsightedness is significantly linked to higher rates of glaucoma, especially in people with serious nearsightedness. The point of this review was to look at the link between myopia and glaucoma in a more in-depth way, focusing on the structural and functional effects, risk factors, and assessment methods, especially optical coherence tomography, in people who are very nearsighted. A thorough search approach was used across several databases from 2012 to 2024. People ages 18 or older with myopia greater than 6 diopters or an axial length greater than 26 mm and a diagnosis of chronic glaucoma were eligible. Randomized controlled trials, prospective cohort studies, and observational studies were some of the study methods that were used. Quality of the work, and statistical methods were used to make a summary of the study\u0026apos;s features and results. Out of the 350 original published articles, only 15 met the requirements to be included. These studies mostly used different optical tomography tests to show structural changes, like the ocular nerve fiber layer damage before functional loss. According to meta-analyses, the chance of chronic glaucoma went up as myopia got worse, showing a strong nonlinear relationship. The fact that myopia and glaucoma are linked shows how important it is to use thorough evaluation methods. Severe myopia is strongly linked to damage to the visual nerve. Over the past few years, optical tomography has become an important imaging tool that helps find damage in the optic nerve early on. On the other hand, glaucoma patients\u0026apos; sex-related tendencies need more research. This thorough study brings together data that shows a link between nearsightedness and glaucoma, highlighting how important optical tomography and other imaging techniques are for early detection and ongoing monitoring. To better handle glaucoma in people who are highly myopic, we need to understand how the severity of myopia, changes in structure, and changes in function all affect each other.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eGlaucoma 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 impede its progression is to lower intraocular pressure (IOP), which can be achieved using medicinal, laser, or surgical procedures (2). The primary risk factors for POAG include older age, heightened intraocular pressure, sub-Saharan African ancestry, familial history, and significant myopia. Moreover, advanced age, hyperopia, and East Asian descent are the primary risk factors associated with primary angle-closure glaucoma (PACG)(3).\u003c/p\u003e \u003cp\u003eThe 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 its definition. While some studies have indicated a greater risk for angle-closure glaucoma in women, there is no clear sex inclination for patients with open-angle glaucoma. Notably, women's longer life expectancy increases their susceptibility to glaucoma and eventually, glaucoma-related vision loss (6).\u003c/p\u003e \u003cp\u003eIn recent years, there has been a growing global occurrence of myopia. The link between myopia and POAG is widely acknowledged. Extensive studies involving large populations have consistently shown an increase in POAG rates with increasing myopia. Moreover, this connection appears notably stronger in patients with severe myopia (7). Individuals with myopia commonly exhibit reduced retinal nerve fiber layer initially (8).\u003c/p\u003e \u003cp\u003eOptical 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 pose a risk of permanent vision loss in the later stages of life (9,10). In patients with mild-to-moderate myopia, in which the axial length is less than 26.5 mm, the size of the optic disc remains comparable to that in nonmyopic eyes (6).\u003c/p\u003e \u003cp\u003ePhotographs 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 ganglion cell body layer (11,12). These structural changes, such as thinning of the retinal nerve fiber layer, often precede functional losses that are detectable by standard visual field tests (1).\u003c/p\u003e \u003cp\u003e.\u003c/p\u003e \u003cp\u003eThe current study aimed to analyze the interrelationship and association between myopia and glaucoma, along with identifying the associated risk factors and structural and functional findings that could assist in effectively monitoring these conditions. We mainly focused on the ganglion cell complex (GCC) and retinal nerve fiber layer (RNFL) and their roles in detecting glaucoma in patients with myopia. The examination of the GCC layer is more sensitive than that of the circumpapillary RNFL (pRNFL). The pRNFL is the most commonly used parameter for evaluating glaucoma. In ganglion cells, the primary segment affected is the inner plexiform layer, followed by the macular retinal nerve fiber layer (mRNFL) and ganglion cell layers. We also discuss the association between IOP and axial length.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003e This study was meticulously designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and employed a PICOS framework to explore the relationship between chronic glaucoma and high myopia. The population (P) for examination included individuals with highly myopic conditions and those assessed using various assessment modalities, particularly optical coherence tomography (OCT). Intervention (I) examined the use of OCT imaging. Comparison (C) involving the evaluation of alternative imaging diagnostic modalities used in chronic glaucoma assessment within the highly myopic population. Outcomes (O) of interest spanned diverse domains: examining documented evidence of visual field abnormalities; identifying OCT abnormalities consistent with retinal nerve fiber layer and ganglion cell complex longitudinal abnormalities; discerning high-risk factors; scrutinizing structural and functional findings; identifying the most effective longitudinal evaluation methods for glaucoma in individuals with high myopia, and exploring the relationship between IOP and axial length. This comprehensive evaluation aimed to deepen the understanding of glaucoma in this demographic population, optimize diagnostic accuracy, and enhance monitoring strategies by determining the optimal parameters for detection and follow-up. Setting (S) for this thorough review encompassed studies conducted in hospital and private settings with a publication timeframe spanning from 2012 to 2024. To gather relevant literature, databases such as Web of Science, MEDLINE, Embase, PubMed, and other pertinent sources were systematically searched.\u003c/p\u003e \u003cp\u003eIncorporating various study designs, our study included randomized controlled trials (RCTs), prospective cohort studies, and observational studies to simultaneously compare three or more interventions. This approach ensured a comprehensive examination of diverse research methodologies to synthesize evidence and draw robust conclusions regarding the complex interplay between chronic glaucoma and high myopia.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eInclusion and Exclusion Criteria\u003c/h2\u003e \u003cp\u003eThe inclusion criteria were meticulously defined to include patients aged 18 years or older with myopia exceeding 6 diopters or an axial length\u0026thinsp;\u0026gt;\u0026thinsp;26 mm, including phakic or pseudophakic individuals diagnosed with chronic glaucoma, spanning pigmentary glaucoma, primary open-angle glaucoma, and myopic glaucoma, among others. The study scope covered articles published between January 2012 and October 2024, exclusively focusing on RCTs, prospective cohort studies, and network meta-analyses while prioritizing original research articles published in English. We excluded articles that met any of the following criteria: (1) studies published before 2012, (2) studies not published in English, (3) studies involving optic injuries but did not report any type of glaucoma, (4) studies involving various kinds of imaging assessment tools that were not related to glaucoma diagnosis; (5) were case reports, (6) were systematic reviews, or (7) were review articles.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eLiterature Selection Process\u003c/h2\u003e \u003cp\u003eThe literature selection process employed a refined search strategy (Appendix \u003cb\u003e1\u003c/b\u003e in the Supplementary file) amalgamating Medical Subject Headings (MeSH) and text words, strategically utilizing Boolean operators (e.g., \"AND,\" \"OR,\" and \"NOT\") to construct search strings. These strings, initially inclusive of terms such as \"myopia,\" \"glaucoma, \u0026ldquo;imaging assessment tools,\" and \"optical coherence tomography,\" underwent adaptive modifications tailored to specific databases and platforms, ensuring exhaustive retrieval of the relevant literature.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section3\"\u003e \u003ch2\u003eSearch string used\u003c/h2\u003e \u003cp\u003eThe search strings \"(high myopia) AND (pigmentary glaucoma OR primary open-angle glaucoma OR myopic glaucoma OR glaucoma) AND (imaging assessment) AND (optical coherence tomography)\" and \"\"(high myopia OR pigmentary glaucoma OR primary open-angle glaucoma OR myopic glaucoma OR glaucoma) AND (imaging assessment tool OR optical coherence tomography)\" were used for the analysis.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eQuality of Literature Selection\u003c/h2\u003e \u003cp\u003eRobust 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 respective study design, methodology, and risk of bias, with a particular focus on synthesizing evidence concerning the efficacy and safety of imaging diagnostic modalities compared with OCT in individuals with glaucoma and high myopia. The Jadad scale was used to analyze the quality of the studies (a score of 0 indicated poor quality and a score of 5 indicated high quality). The risk of bias in the included studies was assessed using the Robivis tool (ROBINS-I).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eMeta-Analysis\u003c/h2\u003e \u003cp\u003eThe meta-analysis included descriptive methodologies to summarize the characteristics of the selected studies, including patient demographics, myopia features, glaucoma typology, imaging tools employed, observed outcomes, associated complications, and inherent limitations. Depending on the availability of data, we performed a meta-analysis to compare interventions and outcomes across studies. Statistical analysis was conducted using IBM SPSS Statistics for Windows, version 26.0 (IBM Corp., Armonk, NY, USA). These procedures offer a comprehensive assessment of the study outcomes incorporated within this analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, and forest plots were constructed based on the available data.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eLiterature Selection\u003c/h2\u003e \u003cp\u003eAfter 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. After excluding 56 articles that did not align with the study's focus\u0026mdash;either lacking information on the imaging assessment used (n\u0026thinsp;=\u0026thinsp;41) or incomplete data (n\u0026thinsp;=\u0026thinsp;15)\u0026mdash;15 studies were included in this study. These studies were published between 2012 and 2024. A PRISMA chart delineating the comprehensive process of literature collection and screening is shown in Fig.\u0026nbsp;1. Among these studies, 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 studies.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eStudy Characteristics\u003c/h2\u003e \u003cdiv id=\"Sec12\" class=\"Section3\"\u003e \u003ch2\u003ePatient Demographics\u003c/h2\u003e \u003cp\u003eA total of 3078 patients were included in these 15 studies, and the number of females (n\u0026thinsp;=\u0026thinsp;1557) was slightly greater than the number of males (n\u0026thinsp;=\u0026thinsp;1521), excluding one study \u003cb\u003e(13)\u003c/b\u003e that did not disclose sex distribution. The age of the patients in the included studies ranged from 20 to 84 years, with most being \u0026gt;\u0026thinsp;50 years. All the patients had highly myopic eyes with an axial length\u0026thinsp;\u0026ge;\u0026thinsp;26 mm and refractive error \u0026gt;-6 diopters.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eImaging technology used\u003c/h2\u003e \u003cp\u003eTwelve of the 14 included studies used different types of OCT assessments, including enhanced depth imaging OCT, optical nerve head OCT, OCT angiography, stratus OCT, and swept-source OCT. However, one study \u003cb\u003e(14)\u003c/b\u003e Click or tap here to enter text. used color fundus images.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eRisk factors, structural findings, and functional findings\u003c/h2\u003e \u003cdiv id=\"Sec15\" class=\"Section3\"\u003e \u003ch2\u003eOutcomes of the study\u003c/h2\u003e \u003cp\u003eAmong the included studies, four studies discussed different diagnostic assessment tools (4, 5, 14,15), four studies mainly discussed glaucomatous damage (16,17,18,19,20), six studies reported the use of OCT assessments (5,8,19,21,22,23), three studies discussed associations with myopia (2,4,5), and three reported visual field progression and microstructure, such as the distribution of lamina cribrosa defects (LCDs) in the optic disc and the proportion of abnormal clusters. The presence of segment errors has been reported (2,8,10), and only one study reported artifacts and error analysis (11). No studies have reported any potential complications.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eRisk of bias assessment\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the quality of the included RCT and non-RCT studies based on the Jadad scale scores. Fourteen of the 15 studies were of high quality, whereas the remaining studies were of moderate quality. Figures\u0026nbsp;2 and 3 show the variables included in the risk-of-bias assessment plot and summary, respectively.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u0026ndash; Quality of the included studies according to the Jadad scale scores\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eName of the Study\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSelection bias\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePerformance bias\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReporting bias\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAttribution bias\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eOther bias\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eResults\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eQuality of the study\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEhongo et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHigh\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYu-Fan et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHigh\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMiki et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHigh\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFan et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHigh\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChang et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eModerate\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMohammad Noureldine et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHigh\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZemborain et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHigh\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLee et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHigh\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRezapour et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHigh\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLim et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHigh\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNakano et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHigh\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHung et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHigh\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePark et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHigh\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYamada et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHigh\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAwadalla et al.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHigh\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cp\u003e\u003cstrong\u003eSelection bias:\u003c/strong\u003e Has the study included comparison between groups or existing data?\u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePerformance bias\u003c/strong\u003e: Has the study reported the estimated effects clearly?\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eReporting bias:\u003c/strong\u003e Was the study free from problems with measurements or classification of outcomes?\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAttribution bias:\u003c/strong\u003e Has the study reported complete outcome data?\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOther Bias:\u003c/strong\u003e Was the study free from limitations?\u003c/p\u003e\n\u003cp\u003eJadad Scale Score: \u0026ldquo;0 to 2\u0026rdquo; \u0026agrave; Low quality; \u0026ldquo;3\u0026rdquo; \u0026agrave; Moderate quality; \u0026ldquo;4 to 5\u0026rdquo; \u0026agrave; High quality\u003c/p\u003e\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eMeta-analysis\u003c/h2\u003e \u003cp\u003eOnly six studies were included in the meta-analysis, which included an analysis of success rates and imaging assessments. Eight studies were excluded because no details on the success or complication rates were reported. The studies that reported success and failure rates included 3040 patients. Figure\u0026nbsp;4 shows a forest plot constructed to represent the success rates of the imaging assessments. In this meta-analysis of six studies involving 3,040 patients, we demonstrated \u003cb\u003ethe relationship between myopia and glaucoma, focusing on structural and functional implications, such as the formation of abnormal clusters, tissue microstructures and aqueous outflow, risk factors, and assessment modalities, particularly OCT, within high-myopia populations (OR\u0026thinsp;=\u0026thinsp;12.0, 95% CI: 10.1\u0026ndash;4.7, P\u0026thinsp;\u0026lt;\u0026thinsp;0.00001). These findings were consistent with those of the sensitivity analysis. The forest plot provides a visual representation of the odds ratios and corresponding CIs across the included studies. Each horizontal line, or \"branch,\" represents an individual study and the point estimate (dot) indicates the odds ratio. The horizontal line through the square represents the CI, and the size of the dot reflects the weight of each study in the meta-analysis.\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003cb\u003eIn Study 1 (24), the observed odds ratio of 0.274, coupled with a narrow CI, suggests a compelling indication of a protective effect against the development of glaucoma in individuals with myopia. This finding implies that myopic individuals may exhibit a reduced likelihood of experiencing glaucomatous changes compared with their nonmyopic counterparts. In study 7\u003c/b\u003e (12), \u003cb\u003ethe reported odds ratio of 1.703 points indicated a moderate increase in the likelihood of glaucoma among myopic patients. Although the effect was not as pronounced as in some other studies, it still signifies a notable elevation in the risk of glaucoma associated with myopia in this particular investigation.\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003cb\u003eStudy 10 (19) showed a substantial odds ratio of 20.792, underscoring a robust and statistically significant association between myopia and the occurrence of glaucoma. The high odds ratio in this study suggested a markedly heightened risk of glaucomatous changes in individuals with myopia, emphasizing the importance of considering myopia as a potential risk factor. Both studies 11 and 12 (16,25) contribute to the growing body of evidence by demonstrating odds ratios of 17.100 and 17.000, respectively. These findings collectively reinforce a significant link between myopia and glaucomatous changes such as\u003c/b\u003e elongation and thinning of the lamina cribrosa resulting in intralaminar changes and a steepening of the translaminar cribrosa pressure gradient. \u003cb\u003eThe consistent odds ratios in these studies underscore the robustness of the observed association, strengthening the argument for myopia as a noteworthy factor in the context of glaucoma risk.\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003cb\u003eFinally, Study 15 (26) adds weight to the overall evidence by presenting an odds ratio of 15.540. This finding further supports the existing body of knowledge indicating a substantial connection between myopia and glaucoma development. The consistent odds ratios across these studies collectively contribute to a comprehensive understanding of the association, emphasizing the importance of myopia as a potential risk factor for glaucomatous changes.\u003c/b\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eThese results collectively emphasize the consistency and strength of the observed associations, as supported by the forest plot. Heterogeneity across studies was visually represented by the spread of the individual study estimates around the overall summary estimate. The forest plot serves as a powerful tool for revealing the nuanced findings of the meta-analysis, aiding in the interpretation of the collective evidence on myopia and its connection to glaucoma.\u003c/b\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eThe quantitative outcomes of the meta-analysis (OR\u0026thinsp;=\u0026thinsp;12.0, 95% CI: 10.1\u0026ndash;4.7, P\u0026thinsp;\u0026lt;\u0026thinsp;0.00001) revealed a substantial and statistically significant association between myopia and glaucoma risk, further supporting the hypothesis that myopia is a notable risk factor for the development of glaucomatous changes. These detailed meta-analysis results enhance our understanding of the relationship between myopia and glaucoma and contribute valuable insights to the scientific literature. A detailed description of the structural findings, such as refractive error, axial length, visual acuity, visual field index and intraocular pressure, and all the corresponding extraction data are presented respectively in the Appendix 2, and the Appendix 3 in the Supplementary file.\u003c/b\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eA clinical study involving 519 eyes with an average axial length of 29.5 \u0026plusmn; 2.2 mm revealed a gradual increase in glaucomatous optic neuropathy incidence from 12.2\u0026ndash;42.1% across different axial length groups (2,3). The prevalence was correlated with a larger parapapillary delta zone and/or a larger optic disc after adjusting for age and axial length, which was consistent with the histological findings. In highly myopic eyes, distinguishing between myopic maculopathy and high myopia-associated glaucomatous optic neuropathy is crucial, especially in patients with a secondarily enlarged optic disc or a large delta zone. These factors are associated with a greater likelihood of glaucomatous optic neuropathy in highly myopic eyes and should be carefully assessed (27) .\u003c/p\u003e \u003cp\u003eOne study confirmed the link between myopia severity and open-angle glaucoma risk through a dose‒response meta-analysis, which included an analysis of 24 studies involving 514,265 individuals from 11 countries (9,18,6). 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 (28,29).\u003c/p\u003e \u003cp\u003eA meta-analysis performed by Haarman et al. (28) revealed a significant link between myopia and posterior subcapsular and nuclear cataracts. However, a clear association between myopia and cortical cataracts has not been reported (18).\u003c/p\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eUnderstanding the Interplay between Myopia and Glaucoma\u003c/h2\u003e \u003cp\u003eThe intersection between myopia and glaucoma is a critical area of investigation. The consistent increase in POAG rates with increasing myopia underlines the need for comprehensive assessment strategies (17). Few studies have established a strong link between severe myopia and glaucoma, suggesting a correlation between myopia severity and vulnerability to optic nerve damage (20,24,30) .\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003eStructural and Functional Imaging Modalities in Glaucoma Monitoring\u003c/h2\u003e \u003cp\u003eOCT is a pivotal tool for glaucoma assessment in highly myopic populations. Its ability to measure the nerve fiber layer and ganglion cell complex in the retina helps to identify early structural changes that occur before function is lost. The use of different OCT tests in different studies demonstrates its flexibility. These tests include enhanced depth imaging OCT and OCT angiography, which emphasize the importance of determining glaucomatous damage.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003eRole of Risk Factors and Associations\u003c/h2\u003e \u003cp\u003eOur study consolidates the evidence on the risk factors associated with glaucoma in patients with high myopia, confirming the importance of understanding patient demographics, axial length, and refractive error. The predominance of female participants in certain studies aligns with the sex-related predispositions observed in glaucoma, especially angle-closure glaucoma. However, conflicting findings regarding the influence of sex on open-angle glaucoma warrant further investigation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003eDiagnostic Assessment and Future Directions\u003c/h2\u003e \u003cp\u003eA thorough review of diagnostic imaging methods and comparisons with OCT helps to determine the best methods for detecting and treating glaucoma in people who are nearsighted. While most studies have focused on OCT assessments, the incorporation of alternative imaging tools such as color fundus images highlights the evolving landscape of diagnostic technologies.\u003c/p\u003e \u003cdiv id=\"Sec23\" class=\"Section3\"\u003e \u003ch2\u003eLimitations and Quality Assessment\u003c/h2\u003e \u003cp\u003eAssessing 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, it is difficult to obtain a full picture of the risks that might arise with imaging methods and what they mean for people with high myopic glaucoma.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec24\" class=\"Section2\"\u003e \u003ch2\u003eFuture Directions and Clinical Implications\u003c/h2\u003e \u003cp\u003eThese findings underscore the importance of longitudinal studies that focus on the progression of myopia and its correlation with glaucoma development. Additionally, 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 enhance diagnostic precision and minimize discrepancies.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur study provides evidence for a relationship between myopia and glaucoma, emphasizing the significance of OCT and other imaging modalities for early detection and monitoring. Understanding the complex relationships among myopia severity, structural changes, and functional changes is important for improving the treatment of glaucoma in highly myopic individuals.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAL, axial length\u003c/p\u003e\n\u003cp\u003eGCC, ganglion cell complex\u003c/p\u003e\n\u003cp\u003eCI, confidence interval\u003c/p\u003e\n\u003cp\u003eIOP, intraocular pressure\u003c/p\u003e\n\u003cp\u003emRNFL, macular retinal nerve fiber layer\u003c/p\u003e\n\u003cp\u003eMeSH, Medical Subject Headings\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOCT, optical coherence tomography\u003c/p\u003e\n\u003cp\u003eORs, odds ratios\u003c/p\u003e\n\u003cp\u003ePOAG, primary open angle glaucoma\u003c/p\u003e\n\u003cp\u003ePRISMA, Preferred Reporting Items for Systematic Reviews and Meta-analyses\u003c/p\u003e\n\u003cp\u003ePICO, participant, intervention, comparator, outcomes\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003edot, point estimate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRCT, randomized controlled trials\u003c/p\u003e\n\u003cp\u003eRNFL, retinal nerve fiber layer\u003c/p\u003e\n\u003cp\u003epRNFL, peripapillary retinal nerve fiber layer\u003c/p\u003e\n\u003cp\u003eROBINS-I, Risk Of Bias In Non-randomized Studies - of Interventions\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe express our deep appreciation to the technical staff of the Retina Department of Oftalmologia Integral ABC (a Medical and Surgical Nonprofit Organization), Mexico City, Mexico,\u0026nbsp;which is affiliated with The Postgraduate Division Studies at the National Autonomous University of Mexico.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding or grant support was received for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosure statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used in this study have been included in the main text.\u0026nbsp;Photographs and figures from this study may be released via a written application to the Photographic Laboratory and Clinical Archives Retina Department\u0026nbsp;at the Oftalmologia Integral ABC Medical and Surgical Assistance Institution (Nonprofit Organization), Av. Paseo de las Palmas 735 suite 303, Lomas de Chapultepec, Mexico City 11000, Mexico and the corresponding author upon request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study adhered to the tenets of the Declaration of Helsinki and received full approval. from the appropriate research ethics committee, institutional review committee, and institutional teaching department (the institution did not provide reference numbers for the systematic review and network meta-analysis studies).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the authors made a significant contribution to the work reported, whether 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; agreed on the journal to which the article has been submitted; and agreed to be accountable for all aspects of the work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInstitutional review board statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted at the Retina Department of the Oftalmolog\u0026iacute;a Integral ABC. Institution in Mexico City, Mexico. The Institutional Review Board approved the study. institutional guidelines. No reference numbers have been provided for this systematic review. or meta-analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Retina Department of the Oftalmologia Integral ABC (Medical and Surgical Nonprofit Organization) is affiliated with the Postgraduate Studies Division of the National Autonomous University of Mexico, Av. Paseo de las Palmas 735 Suite 303, Lomas de Chapultepec, Mexico City 11000, Mexico\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eFlaxman, S. R., Bourne, R. R. A., Resnikoff, S., Ackland, P., Braithwaite, T., Cicinelli, M. V., Das, A., Jonas, J. B., Keeffe, J., Kempen, J., Leasher, J., Limburg, H., Naidoo, K., Pesudovs, K., Silvester, A., Stevens, G. A., Tahhan, N., Wong, T., Taylor, H., \u0026hellip; Zheng, Y. (2017). 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Degree of Myopia and Glaucoma Risk: A Dose-Response Meta-analysis. \u003cem\u003eAmerican Journal of Ophthalmology\u003c/em\u003e, \u003cem\u003e236\u003c/em\u003e, 107\u0026ndash;119. https://doi.org/10.1016/J.AJO.2021.10.007\u003c/li\u003e\n\u003cli\u003eJonas, J. B., Aung, T., Bourne, R. R., Bron, A. M., Ritch, R., \u0026amp; Panda-Jonas, S. (2017). Glaucoma. \u003cem\u003eLancet (London, England)\u003c/em\u003e, \u003cem\u003e390\u003c/em\u003e(10108), 2183\u0026ndash;2193. https://doi.org/10.1016/S0140-6736(17)31469-1\u003c/li\u003e\n\u003cli\u003eMiki, A., Ikuno, Y., Weinreb, R. N., Asai, T., Usui, S., \u0026amp; Nishida, K. (2019). En Face Optical Coherence Tomography Imaging of Beta and Gamma Parapapillary Atrophy in High Myopia. \u003cem\u003eOphthalmology. Glaucoma\u003c/em\u003e, \u003cem\u003e2\u003c/em\u003e(1), 55\u0026ndash;62. https://doi.org/10.1016/J.OGLA.2018.11.008\u003c/li\u003e\n\u003cli\u003ePerera, S. A., Wong, T. Y., Tay, W. T., Foster, P. J., Saw, S. M., \u0026amp; Aung, T. (2010). Refractive error, axial dimensions, and primary open-angle glaucoma: the Singapore Malay Eye Study. \u003cem\u003eArchives of Ophthalmology (Chicago, Ill. : 1960)\u003c/em\u003e, \u003cem\u003e128\u003c/em\u003e(7), 900\u0026ndash;905. https://doi.org/10.1001/ARCHOPHTHALMOL.2010.125\u003c/li\u003e\n\u003cli\u003eNakano, N., Hangai, M., Noma, H., Nukada, M., Mori, S., Morooka, S., Takayama, K., Kimura, Y., Ikeda, H. O., Akagi, T., \u0026amp; Yoshimura, N. (2013). Macular imaging in highly myopic eyes with and without glaucoma. \u003cem\u003eAmerican Journal of Ophthalmology\u003c/em\u003e, \u003cem\u003e156\u003c/em\u003e(3). https://doi.org/10.1016/J.AJO.2013.04.028\u003c/li\u003e\n\u003cli\u003ePark, S. C., De Moraes, C. G. V., Teng, C. C., Tello, C., Liebmann, J. M., \u0026amp; Ritch, R. (2012). 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A., \u0026amp; Budenz, D. L. (2012). Rates of abnormal retinal nerve fiber layer and ganglion cell layer OCT scans in healthy myopic eyes: Cirrus versus RTVue. \u003cem\u003eOphthalmic Surgery, Lasers \u0026amp; Imaging : The Official Journal of the International Society for Imaging in the Eye\u003c/em\u003e, \u003cem\u003e43\u003c/em\u003e(6 Suppl). https://doi.org/10.3928/15428877-20121003-01\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"international-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"inte","sideBox":"Learn more about [International Ophthalmology](https://www.springer.com/journal/10792)","snPcode":"10792","submissionUrl":"https://submission.nature.com/new-submission/10792/3","title":"International Ophthalmology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"glaucoma, high myopia, optical coherence tomography, optical coherent tomography imaging, retinal nerve fiber layer, ganglion cell complex","lastPublishedDoi":"10.21203/rs.3.rs-4355898/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4355898/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose: \u003c/strong\u003eThe interplay between myopia and glaucoma has gained attention, with escalating myopia demonstrating a significant association with increased POAG rates, particularly in patients with severe myopia. This systematic review aimed to comprehensively analyze the relationship between myopia and glaucoma, focusing on the structural and functional implications, risk factors, and assessment modalities, particularly optical coherence tomography (OCT), in highly myopic populations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e According to the PRISMA guidelines, a meticulous search strategy was employed across multiple databases from 2012 to 2024. The inclusion criteria included individuals aged 18 years or older with myopia exceeding 6 diopters or an axial length \u0026gt; 26 mm who were diagnosed with chronic glaucoma. Various study designs, including randomized controlled trials (RCTs), prospective cohort studies, and observational studies, were incorporated. Quality assessment was performed using the Jadad Scale, and statistical analyses were performed to summarize the study characteristics and outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Of the 350 initial articles, 15 met the inclusion criteria. OCT assessments revealed structural changes such as thinning of the retinal nerve fiber layer preceding functional losses. Meta-analyses demonstrated a heightened risk of POAG with increasing myopia severity, showing a significant nonlinear relationship. In this meta-analysis of six studies involving 3,040 patients, we demonstrated a relationship between myopia and glaucoma (OR = 12.0, 95% CI: 10.1–4.7, P \u0026lt;0.00001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e This comprehensive analysis consolidates the evidence of the relationship between myopia and glaucoma, emphasizing the pivotal role of OCT and other imaging modalities in early detection and monitoring.\u003c/p\u003e","manuscriptTitle":"Comprehensive Assessment of Glaucoma in Patients with High Myopia: A Systematic Review and Meta-analysis with a Discussion on Structural and Functional Imaging Modalities","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-17 18:27:41","doi":"10.21203/rs.3.rs-4355898/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-08-19T02:43:43+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-06T03:44:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"176392582917675024192631902661374145529","date":"2024-07-03T04:35:13+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-05-14T01:42:51+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-05-07T06:37:39+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-05-07T05:27:52+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Ophthalmology","date":"2024-05-07T00:10:03+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"international-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"inte","sideBox":"Learn more about [International Ophthalmology](https://www.springer.com/journal/10792)","snPcode":"10792","submissionUrl":"https://submission.nature.com/new-submission/10792/3","title":"International Ophthalmology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"62e1252c-3ba6-493e-aba9-4c076fff2a45","owner":[],"postedDate":"May 17th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-10-14T16:00:04+00:00","versionOfRecord":{"articleIdentity":"rs-4355898","link":"https://doi.org/10.1007/s10792-024-03321-4","journal":{"identity":"international-ophthalmology","isVorOnly":false,"title":"International Ophthalmology"},"publishedOn":"2024-10-11 15:57:13","publishedOnDateReadable":"October 11th, 2024"},"versionCreatedAt":"2024-05-17 18:27:41","video":"","vorDoi":"10.1007/s10792-024-03321-4","vorDoiUrl":"https://doi.org/10.1007/s10792-024-03321-4","workflowStages":[]},"version":"v1","identity":"rs-4355898","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4355898","identity":"rs-4355898","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}