Periodontal disease and glaucoma. A systematic review and Meta-Analysis

Periodontal disease and glaucoma. 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A systematic review and Meta-Analysis Anderson Vilchez-Chavez, Rachid Bouchikh-El Jarroudi, Isabel Silva-Ocas, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7816535/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Topic To assess the association between periodontal disease and glaucoma in adults through systematic review and meta-analysis of observational studies. Clinical relevance This study suggests that periodontal disease may increase the likelihood of developing glaucoma. Recognizing oral health as a potential modifiable risk factor could promote interdisciplinary prevention strategies and earlier detection of glaucoma in at-risk individuals. Methods This review followed PRISMA 2020 guidelines and was registered in PROSPERO (CRD42023428738). A systematic search was performed in PubMed/Medline, Scopus, Web of Science, Embase, Cochrane Library, LILACS, Google Scholar and journals with the highest impact in Ophthalmology, available until August 26th, 2025. Eligible articles were independently screened and quality assessed by three reviewers. All observational clinical studies reporting quantitative effect estimates and 95% confidence interval (95%CI) for the association between periodontal disease and glaucoma were included. Effect estimates for the association with glaucoma were pooled using random effects meta-analysis (Review Manager Version 5.4). Results 946 studies were screened, and 6 studies were included in the systematic review: 3 cohort studies, 1 nested case-control study and 2 cross-sectional studies. The populations evaluated were adults (n = 1,153,308). Different diagnostic methods were used for periodontal disease and glaucoma (clinical, self-reported, and disease classification codes), with variations in the criteria used and the type of glaucoma evaluated. Pooled effect estimates indicated a positive association between periodontal disease and glaucoma (OR: 1.72; 95%CI: 1.13–2.63; p-value: 0.010, I 2 : 99%). Conclusion The findings of this review, based on observational studies involving over one million individuals, suggest an association between periodontal disease and glaucoma. Patients with periodontal disease appear to be more likely to develop glaucoma than patients without it. However, additional long-term studies are needed. Ophthalmology Periodontal Diseases Risk Factors Systematic Review Meta-Analysis Figures Figure 1 Figure 2 Introduction Periodontal disease -PD- (or periodontitis, often referred as the same condition) is a multifactorial chronic inflammatory pathology, caused by a disruption in the balance between the oral microbial biofilm and the host immune response. This imbalance results in chronic inflammation and tissue destruction 1 . The disease is influenced by various factors, including poor oral hygiene, genetic predisposition, and systemic conditions such as diabetes and cardiovascular disease 2 . According to the World Health Organization, the global prevalence of PD ranges from 9.4% to 43.7%, being more common in adults and in high-income countries 3 . Glaucoma, is a group of ocular disorders (primary open-angle glaucoma, primary angle-closure glaucoma, secondary open and angle-closure glaucoma, among others) of multifactorial etiology 4 , characterized by optic neuropathy which, in many cases, is associated with elevated intraocular pressure 5 . It is the second leading cause of irreversible blindness worldwide 6 . The global prevalence of glaucoma in 40–80 years patients is 3.5% and the number of people with glaucoma worldwide is expected to be 111.8 million by 2040 7 . In recent years, increasing attention has been paid to the role of systemic inflammation in the development and progression of glaucoma. PD, a chronic inflammatory condition of the supporting tissues of the teeth, has been proposed as a potential contributing factor to optic nerve damage 8 , 9 . Although the precise mechanisms linking PD and glaucoma remain unclear, several hypotheses have been proposed. For instance, the dysbiotic oral microbiota associated with PD may trigger systemic immune responses that contribute to neurodegeneration in the optic nerve. In animal models, lipopolysaccharide derived from oral bacteria of glaucoma patients have shown to exacerbate optic nerve damage 10 . Additionally, PD may induce subclinical systemic inflammation leading to endothelial dysfunction, which could impair optic nerve perfusion and contribute to optic nerve damage 11 . Growing evidence has highlighted the broader role of human microbiota in health and disease. Beyond its impact on oral health, PD has been linked to a range of systemic diseases 12 – 14 , including cardiovascular disease 15 , diabetes mellitus 16 , metabolic syndrome 17 , rheumatoid arthritis 18 , osteoporosis 19 , and respiratory diseases 20 . This association is thought to occur through bacterial dissemination and a systemic inflammatory response, allowing periodontal pathogens and inflammatory mediators to affect distant organs. Notably, PD has also been implicated in ocular conditions such as diabetic retinopathy and age-related macular degeneration 21 – 23 . It is noteworthy the concept of a “gut-ocular axis”, which suggests that the composition and health of the gut microbiome may influence ocular homeostasis and immune regulation 8 , 24 . Oral, gut and ocular microbiota has been associated with inflammatory and neurodegenerative disorders, including glaucoma 8 , 11 . These findings support the possibility that microbial imbalance may be a common pathway linking PD and ocular diseases. Indeed, a growing number of articles have been published suggesting a connection between periodontal and ocular health 13 , 21 , 23 , 25 , 26 . However, to our knowledge, no systematic review has been conducted regarding this topic. The aim of this systematic review was to assess the association between PD and glaucoma. Methods This systematic review was conducted in compliance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement 27 . The PECO framework was used: Population (adults), Exposure (PD), Comparison (No PD) and Outcome (Glaucoma). The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42023428738). Eligibility criteria The eligibility criteria were the following: (i) observational clinical studies (cohorts, case-control and cross-sectional studies); (ii) conducted in adult population of either sex; (iii) reporting a quantitative estimate of effect and a 95% confidence interval (CI) for association between PD (exposition) and glaucoma (outcome). We included all studies regardless of the diagnostic approach employed for either glaucoma or PD, including clinical assessments, administrative diagnostic code-based, or self-reported data. Only studies in the adult population were included due to the low prevalence of PD in pediatric patients 28 . Studies retracted by the author and/or the journal were not included in the metanalysis. Studies where the study design was not included or was not well specified in their designs were also excluded. Information Sources and Search strategy Two authors (AVC and ISO) conducted a systemic literature search for relevant clinical studies available until August 26th, 2025. The databases included were PubMed/Medline, Scopus, Embase, Web of Science, Cochrane Library, LILACS and Google Scholar. Terms related to “glaucoma” and “periodontal disease” were used to build search strategy and adapted to each database (Supplement 1). Additionally, a manual search was performed in the journals with the highest impact in Ophthalmology, according to the Scimago Journal Rank: Progress in Retinal and Eye Research, Ophthalmology, Annual Review of Vision Science, JAMA Ophthalmology, Ocular Surface, American Journal of Ophthalmology, British Journal of Ophthalmology, Ophthalmology Retina, Survey of Ophthalmology, Ophthalmology and Glaucoma. Data collection process After the search, all identified citations were imported into Rayyan (Qatar Computing Research Institute, Doha, Qatar) for reference management. No automation features were employed. Duplicates were identified and removed to ensure the uniqueness of each reference. Two authors (ISO and RBE) independently did a title and abstract blind screen. Then, full texts of the selected titles were retrieved and reviewed to assess their eligibility. If the article was not available online, the corresponding author was contacted. Any disagreements arising during the selection process were resolved through discussion, with a third reviewer (JGO) acting as an arbitrator when required. Data extraction Three authors (JGO, CBM and RBE) independently assessed each of the selected articles, and the following information was collected: First author, year of publication, country in which the study was conducted, data source, study period, study design, age and sex, study objective(s), main outcome, diagnosis of periodontitis criteria, diagnosis criteria of glaucoma, confounding factors assessed, sample size, and number of participants with PD and without PD. Study risk of bias assessment Three authors (JGO, CBM and RBE) independently assessed the methodological quality of the studies using the Newcastle-Ottawa Scale (NOS) 29 for non-randomized studies. A fourth author (ECC) resolved discrepancies in this process. The methodological quality of the studies was classified into low risk of bias (7–9 points), moderate risk of bias (4–6 points) and high risk of bias (0–3 points) 30 . Effect measures and Synthesis methods Non-relevant heterogeneity was considered to exist if the Higgins value (I 2 ) was less than 40%, according to the Cochrane Manual 31 . For the meta-analysis, Odds Ratio (OR) was used as a measurement of the association effect between PD and glaucoma, with a 95% confidence interval (95% CI), assuming a random effects model and inverse variance method due to the assumption of heterogeneity among the studies found in the exploratory search, because they are samples of studies with different designs, diagnoses and contexts. A subgroup analysis was performed based on the study design (cohort, nested case-control). Subgroup analysis by age and/or sex was not performed. Statistical analysis was performed with Review Manager (RevMan) software version 5.4. Results Study selection The literature search in databases yielded 946 articles, of which 208 were eliminated. Next, 738 articles were selected based on their title and abstract, and 11 articles were chosen for full review; in addition, 2 articles found through a manual search were selected. All 13 articles were read in their entirety, and 3 articles were excluded for wrong type of publication 26 , 32 , 33 and 3 for wrong exposition 34 – 36 (Fig. 1 ). One study 37 was excluded due to overlapping data with another included study 38 , as both used the same database (BigMouth Dental Data Repository) and the earlier sample was fully encompassed within the latter. Finally, 6 articles were included 38 – 43 (Tables 1 and 2 ). Study characteristics The 6 studies 38 – 43 included in the systematic review were observational studies: 3 cohort studies 40 – 42 , 1 nested case-control study 43 , and 2 cross-sectional studies 38 , 39 . A total of 1,153,308 participants were included. The sample sizes of included studies ranged from 147 43 to 528,089 40 participants. In terms of geographical location, 3 studies were conducted in the United States 38 , 40 , 43 , and the other 3 in Asia (Taiwan and South Korea) 39 , 41 , 42 . The two studies conducted in South Korea included are from different databases 39 , 41 . A prospective cohort study (n = 528,089) was conducted solely among male health professionals 40 . Another prospective cohort study (n = 124,904) assessed mostly women (65.3%, 8,1498 out of 124,904) 41 . In this prospective cohort study information about urban or rural population was done, including only urban population 41 . PD and glaucoma Diagnostic criteria Different diagnostic criteria were used for PD and glaucoma. PD was diagnosed using clinical criteria in two studies 39 , 40 (tooth count as oral health indicator in one study 40 and periodontal status using the community periodontal index in the other study 39 ), disease classification codes in two 38 , 42 , and questionnaires (self-report) in two 41 , 43 . Glaucoma was diagnosed using clinical criteria in two studies 39 , 43 : intraocular pressure, visual field, optic nerve assessment and Shaffer grade in one study 43 and intraocular pressure, visual field, optic nerve assessment and Van Herick grade in the other study 39 ; disease classification codes in one 42 , and questionnaires in three 38 , 40 , 41 . Risk of bias in studies The 6 included articles were assessed using the NOS scale. Low risk of bias was observed in the selection, comparability, and outcome dimension in most studies; however, in one prospective cohort study 41 showed high risk of bias in the outcome dimension (Table 3 ). Syntheses of results This result showed high heterogeneity, according to Higgins' value (I 2 : 99%). Figure 2 shows the estimated effects. These were: combined effect. OR: 1.72; 95%CI: 1.13–2.63; p-value: 0.010, I 2 : 99%; cohort studies. OR: 1.51; 95%CI: 1.12–2.03; p-value: 0.007, I 2 : 94%; nested case-control study. OR: 1.10; 95%CI: 0.56–2.16; p-value: 0.790; = I 2 : not applicable; cross-sectional studies. OR: 2.53; 95%CI: 1.66–3.87; p-value: <0.004, I 2 : 88%. Table 1 General characteristics of the included studies. Article Country / Source / Study period Design Aim(s) of study Main result PD diagnosis Glaucoma diagnosis Covariates analysed in the articles Pasquale et al. 2016 (41) U.S. HPFS (Health Professionals Follow-up Study) 1986–2012 Prospective cohort study Evaluate the association between oral health history and risk of primary open-angle glaucoma and its subtypes. Number of natural teeth, periodontal disease, and root canal treatment were not associated with primary open angle glaucoma (periodontitis was not associated with risk of glaucoma) The number of natural teeth and periodontal disease history was registered from 1986, and every 2 years was asked about tooth loss and new diagnoses of periodontal disease with bone loss. Results were validated with the final number of teeth and radiography, respectively. Every two years questionnaires to participants asking about the development of glaucoma; the reported glaucoma cases were confirmed by their eye care providers with the results of the tests (intraocular pression, visual field loss and optic nerve structural information). Glaucoma family history, African ancestry, Asian ancestry, body mass index, pack-years of smoking, hypertension, diabetes, physical activity, alcohol consumption, caffeine intake, updated number of eye exams reported during follow-up, self-reported history of cataract diagnosis or extraction, age-related macular degeneration, hypertension, diabetes, and recent report of physical examination. Byun et al. 2020 (42) Korea KoGES: Korean Genome and Epidemiology Study 2004–2016 Prospective cohort study Evaluate the association between periodontitis and glaucoma. The risk of developing glaucoma was higher in patients with periodontitis. The participants were questioned about their history of periodontitis by trained interviewers: “Have you ever had a diagnosis of periodontitis?”. The participants were questioned about their history of glaucoma by trained interviewers: “Do you have any history of glaucoma?”. Age, sex, income group, body mass index, smoking, alcohol consumption, hypertension, diabetes mellitus, and hyperlipidemia. Sun et al. 2020 (43) Taiwan LHID2000: Longitudinal Health Insurance Database 2000 1995–2013 Retrospective cohort study Clarify the potential association of periodontitis and development of glaucoma and its subtypes, primary open-angle glaucoma and primary close-angle glaucoma. The risk of developing glaucoma was higher in patients with periodontitis. Disease classification codes: ICD-9-CM codes 523.3 and 523.4. Disease classification codes: ICD-9-CM code 365. Age, sex, comorbidities, and corticosteroid use. Polla et al. 2017 (44) U.S. SUNY Downstate Eye clinics* 2010–2013 Nested Case-control study Evaluate possible associations between POAG, dental health, and the oral microbiome. The number of teeth (an oral health indicator) and alterations in the amounts of oral bacteria may be associated with glaucoma pathology (periodontitis was not associated with risk of glaucoma) Subjects were asked to complete a self-administered questionnaire to collect information about their dental health (e.g. number of natural teeth, signs of periodontal or gum disease etc.). Questionnaire responses were reviewed by a trained member of the research team and any missing, incomplete items or discrepancies clarified. Open angles (≥ III Shaffer grade), presence of a characteristic glaucomatous visual field defect and optic nerve head with cup to disc ratio > 0.8 in at least one eye based on clinical examination. In addition, all cases were either using intraocular pression lowering agents or had undergone glaucoma surgery. Sex and age. Chatzopoulos et al. 2024 (39) U.S. BigMouth Dental Data Repository 2011–2021 Cross-sectional Investigate the relationship between periodontitis and systemic conditions. This study showed the relationship between periodontal disease and glaucoma Patients were classified into 2 groups based on the presence of planned or completed Current Dental Terminology codes: periodontitis group when codes for surgical and non-surgical treatment of periodontal disease were used; non-periodontitis group when patients had at least one D1110 code (dental prophylaxis in the absence of periodontal disease) and none of the codes in the periodontitis group. Self-reported systemic diseases based on a questionnaire completed at the initial visit and updated every 6 to 12 months. Age and gender Noh et al. 2025 (40) Korea Korea National Health and Nutrition Examination Survey (KNHANES) 2010–2011 Cross-sectional Investigate the relationship between periodontitis and open-angle glaucoma The risk of developing glaucoma was higher in patients with periodontitis. Periodontal status using the community periodontal index (CPI) developed by the World Health Organization: the CPI ranged from 0–4 and was defined as healthy periodontal status (CPI = 0), bleeding of the gingiva (CPI = 1), dental plaque and bleeding (CPI = 2), periodontal pouch depth ≥ 3.5 mm and < 5.5 mm (CPI = 3), and periodontal pouch depth ≥ 5.5 mm (CPI = 4). Periodontitis was defined as a CPI value of 3 or 4 at least one site of the periodontal pouch. Patients with increased intraocular pression (≥ 22 mmHg), with open angle (peripheral anterior chamber depth > 1/4 of the peripheral corneal thickness), corresponding visual field defects AND: (1) neuroretinal rim loss with a vertical or horizontal cup-to-disc ratio of ≥ 0.7 or an asymmetry of ≥ 0.2; (2) presence of optic disc haemorrhage; OR (3) presence of retinal nerve fibre layer defect. In cases without visual field defects, the diagnostic criteria would be the same except for point (1), which would be neuroretinal rim loss with a vertical cup-to-disc ratio of ≥ 0.9, or a vertical cup-to-disc ratio asymmetry of ≥ 0.3, and excluding point (2). Age, sex, diabetes mellitus, hypertension, smoking rate and drinking rate. *Database not found on the internet Table 2 Sample summary of the included studies. Study Sample characteristics: age (range) / gender (percentage of males) / race With PD Without PD Total sample size Glaucoma Total Glaucoma Total Pasquale et al. 2016 (41) 40–75 years 100% males Majority: Caucasian 226 (0.1%) 229,935 259 (0.09%) 298,154 528,089 Byun et al. 2020 (42) 40 years (minimum) - maximum: no reported (> 65 years: not reported) 34,7% males Race: not reported 187 (2%) 9,572 1,054 (0.9%) 115,332 124,904 Sun et al. 2020 (43) 20 years (minimum) - maximum: no reported (> 65 years: 9.2%) 49% males Race: not reported 4,875 (2,5%) 194,090 3,516 (1,8%) 194,090 388,180 Polla et al. 2017 (44) 40–87 years (age-matched) 44,9% males (majority of women in controls) Majority: African-American 46 (65,7%) 70 49 (63,6%) 77 147 Chatzopoulos et al. 2024 (39) Range age: not reported [mean (SD): 47.4 (17.9) years] 44.8% males Majority: White people 4,644 (11%) 42,377 2,542 (3,9%) 65,930 108,307 Noh et al 2025 (40) 19 years (minimum) - maximum: no reported (> 60 years: 12.68%) 50.79% males Race: not reported 80 (8,2%) 972 117 (4,3%) 2,709 3,681 Table 3 Newcastle-Ottawa scale (NOS) for the risk of bias and quality assessment of non-randomized studies Selection Comparability Outcome Total score Author Year Representativeness of the exposed cohort Selection of the non-exposed cohort Ascertainment of exposure Demonstration that outcome of interest was not present at start of study Comparability of cohorts on the basis of the design or analysis Assessment of outcome Was follow-up long enough for outcomes to occur Adequacy of follow up of cohorts Pascuale et al. (36) 2016 * * ** * * * 7 Byun et al. (39) 2020 * * * ** 5 Sun et al. (38) 2020 * * * * ** * * * 9 Author Year Adequate definition of patient cases Representativeness of patient cases Selection of controls Definition of controls Control for important or additional factors Ascertainment of exposure Same method of ascertainment for participants Nonresponse rate Polla et al. (37) 2017 * * * * ** * 7 Author Year Representativeness of the sample Sample size Non-respondents/missing data Ascertainment of the exposure (risk factor) Comparability of subjects in different outcome groups on the basis of design or analysis. Confounding factors controlled Assessment of outcome Blinding of outcome assessors Statistical test Total score Chatzopoulos et al. (40) 2024 * * * * 4 Noh et al. (40) 2025 * * ** * * * 7 Discussion In recent decades, several hypotheses have been suggested trying to explain the physiopathology underlying the association between PD and glaucoma. Hence, several groups have investigated their potential association 43 , 44 . To the best of our knowledge, this is the first time that a systematic review and meta-analysis has been carried out regarding this topic. PD is characterized by the breakdown of periodontal tissues 45 , 46 . This allows translocation of oral bacteria and inflammatory mediators into systemic circulation 24 , 43 , 45 . The aforementioned process acts as a trigger for the inflammatory cascade, leading to a state of chronic subclinical inflammation 45 , 46 . Such inflammation may contribute to glaucoma through several pathways: (i) cytokines and inflammatory mediators may promote the onset and/or progression of the disease by exerting direct neurotoxic effects on the optic nerve 47 , 48 ; (ii) oxidative stress 49 , resulting in retinal ganglion cell loss via mitochondrial dysfunction 50 , 51 , ultimately contributing to glaucomatous damage 52 ; (iii) endothelial dysfunction 45 , 53 , leading to optic nerve hypoperfusion due to impaired flow-mediated vasodilation 11 ; and (iv) systemic inflammation associated with PD may exacerbate comorbidities such as hypertension and diabetes, the first recognized as significant risk factors for glaucoma 54 – 56 . Our data, based on observational studies involving over one million individuals, provides evidence of a possible positive association between PD and glaucoma. In fact, dysbiotic oral pathogens may influence the development of inflammatory eye diseases through immune dysfunction 57 . Periodontal disease has been linked to several eye diseases and has also been associated with an increased risk of developing cataracts 58 , Age-Macular Degeneration 22 , diabetic retinopathy 21 , uveitis, keratitis and scleritis 59 . In addition, a recent study showed that glaucoma patients often have poor periodontal health 35 . However, data from cohort studies show that the difference in the proportion of patients with and without PD who develop glaucoma is relatively small (0.1% vs 0.09% and 2% vs 0.9% in prospective cohorts 40 , 41 ; 2.5% vs 1.8% in the retrospective cohort 42 ; Table 2 ). In our study, the difference in the proportions is small as well: 2.1% vs 1.1% overall. Although the difference is statistically significant, the percentage difference in glaucoma attributable to PD is only 1%. Nevertheless, evidence suggests that the association between glaucoma and PD is more pronounced in older adults and in patients with hypertension 39 , 41 , being recognized cofactors for glaucoma 56 , 60 , 61 . Taken together, these findings support the hypothesis that PD may contribute as a cofactor in the development of glaucoma rather than representing a direct etiological cause. Certain limitations must be taken into account when interpreting the results. The scarce number of articles included (n = 6) in this systematic review, the different study designs included in the analysis, and the high heterogeneity found is probably the main drawback for generalization of the obtained results on PD and glaucoma association. Five out of 6 analyzed studies gave the same message in favor of the studied association 38 – 42 , our results also show that depending on the type of study design analyzed (Table 2 ), the raw likelihood of observing the association between periodontitis and glaucoma varies. Nested case-control study did not provide evidence on this association 43 , meanwhile cohort 40 – 42 and cross-sectional studies 38 , 39 yes (Table 2 ). In fact, if we want to analyze whether having periodontitis is a risk factor for developing glaucoma, we should only consider cohort studies, as it is the model par excellence for studying the occurrence of events (in this case glaucoma) following exposure to a factor (in this case PD) and the natural progression of a disease. As a strength of this systematic review, the pool of cohort studies also provided evidence statistically significant on this association, despite the fact that the follow-up period was variable among studies -from 1 to 26 years- (Fig. 2 and Table 2 ). This variability among the follow-up in the different studies may influence the results, since the longer the follow-up period, the older the patients are and the more risk factors for glaucoma (age itself, and cardiovascular diseases) are likely to appear Our systematic review only included observational studies. Our review did not include clinical trials. Hence, it was not considered whether information on PD (comorbidity) had been collected at the baseline visit (baseline characteristics) in glaucoma clinical trials; and the same in PD clinical trials (glaucoma as baseline comorbidity). In fact, the analysis of the baseline visits of any clinical trial (prior to receiving any treatment) could be like a cross-sectional study with more inclusion and exclusion criteria, generally (2 cross-sectional studies were included in this systematic revision). This could have contributed to the loss of prospective information on the association between PD and glaucoma. PD and glaucoma diagnostic criteria were not uniform among analyzed studies. There is no guarantee that patients diagnosed with glaucoma were patients with a confirmed diagnosis of glaucoma, and the same is true for patients with PD. Some studies relied partly on self-reported data for diagnosing glaucoma 37 , 38 , 41 and PD 41,43 , despite the fact that self-reporting is not a reliable method for accurately identifying either condition 62 – 66 . Co-variables and confounding variables analyzed in the manuscripts included in this systematic review were not considered in our analysis, mainly due to the lacking of the standardization of this information in the studies. This fact could under- or over-estimated the ORs. A prospective cohort study 41 and a cross-sectional study 39 were conducted in South Korea. Although the two studies used different databases, it cannot be ruled out that the study populations may overlap. Although the small proportion of glaucoma explained by PD, the findings of this meta-analysis help us to a better understanding of glaucoma in relation to the whole body, specifically oral health and neuroprotection. In front of this scenario, patients with a history of PD could have an increased risk of developing glaucoma, the two main clinical implications would be related to preventing the development of glaucoma. The first one would be to promote oral health in patients with glaucoma risk factors 60 , so that correct prevention of PD would reduce the risk of developing glaucoma or disease progression. Interdisciplinary work between dentists and ophthalmologists could be a new standard approach. The second point that could be addressed is glaucoma screening. Although there is no clear consensus among different clinical practice guidelines on which patients should be screened for glaucoma, there’s agreement on screening in patients at risk of developing glaucoma due to the presence of risk factors 67 . Based on our results, patients with PD have 1.72 times the odds of developing glaucoma compared with patients without PD (OR: 1.72), an issue that could be addressed in future clinical practice guidelines as a population to be screened. Nonetheless, cost-effective analysis of the screening would need assessment. Additionally, the results open new horizons in the field of research. Recognizing risk factors (like PD) and detecting the risk of progression 42 could be useful for a better treatment and follow-up individualization. Identification of patient with high risk of progression let a stricter IOP control to achieve earlier (like minimally invasive glaucoma surgery) 68 or more aggressive intervention, achieving a multi-mechanism or multimodal approach for interventional glaucoma 69 . For this reason, prospective randomized studies would be of great interest to assess whether treatment of PD influences glaucoma progression, thus also opening new therapeutic alternatives, so that IOP control would no longer be the only modifiable factor for glaucoma development and progression, but also PD. Conclusion The findings of this review, based on observational studies involving over one million individuals, suggest an association between PD and glaucoma. Patients with PD appear to be more likely to develop glaucoma than patients without it, however, additional long-term studies are needed. Declarations Financial Support: None Conflict of Interest: The authors declare no conflict of interest related with this project. Funding: The authors received no financial support for the research, authorship, and/or publication of this article. Previous Meeting Presentation: A partial report was presented at: Congreso de la Asociación Peruana de Periodoncia y Osteointegracion, 2023 (Lima - Perú). World Glaucoma Congress, 2023 (Rome, Italy) 99º Congreso de la Sociedad Española de Oftalmología (SEO), 2023 (Sevilla, Spain) Author contribution statement AVC : Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Validation, Writing - original draft, Writing - review & editing; RBE : Data curation, Formal analysis, Investigation, Validation, Writing - original draft, Writing - review & editing; ISO : Data curation, Formal analysis, Investigation, Validation, Writing - original draft; KRF : Formal analysis, Investigation, Validation, Writing - original draft; CBM : Data curation, Formal analysis, Investigation, Validation, Writing - original draft; ECC : Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Supervision, Validation; TGO : Formal analysis, Investigation, Validation, Supervision, Validation, Writing - original draft; SV : Formal analysis, Investigation, Methodology, Supervision, Validation, Writing - review & editing; JGO: Data curation, Formal analysis, Investigation, Methodology, Supervision, Validation, Writing - original draft, Writing - review & editing. 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Sci Rep . 2020;10(1):17568. doi:10.1038/s41598-020-74589-6 Polla D, Astafurov K, Hawy E, Hyman L, Hou W, Danias J. A Pilot Study to Evaluate the Oral Microbiome and Dental Health in Primary Open-Angle Glaucoma. J Glaucoma . 2017;26(4):320. doi:10.1097/IJG.0000000000000465 Astafurov K, Elhawy E, Ren L, et al. Oral Microbiome Link to Neurodegeneration in Glaucoma. Barnes S, ed. PLoS ONE . 2014;9(9):e104416. doi:10.1371/journal.pone.0104416 Cardoso EM, Reis C, Manzanares-Céspedes MC. Chronic periodontitis, inflammatory cytokines, and interrelationship with other chronic diseases. Postgrad Med . 2018;130(1):98-104. doi:10.1080/00325481.2018.1396876 Vitkov L, Muñoz LE, Knopf J, et al. Connection between Periodontitis-Induced Low-Grade Endotoxemia and Systemic Diseases: Neutrophils as Protagonists and Targets. Int J Mol Sci . 2021;22(9):4647. doi:10.3390/ijms22094647 Varghese SS, Thomas H, Jayakumar ND, Sankari M, Lakshmanan R. Estimation of salivary tumor necrosis factor-alpha in chronic and aggressive periodontitis patients. Contemp Clin Dent . 2015;6(Suppl 1):S152-S156. doi:10.4103/0976-237X.166816 Nakazawa T, Nakazawa C, Matsubara A, et al. Tumor Necrosis Factor-α Mediates Oligodendrocyte Death and Delayed Retinal Ganglion Cell Loss in a Mouse Model of Glaucoma. J Neurosci . 2006;26(49):12633-12641. doi:10.1523/JNEUROSCI.2801-06.2006 Chen M, Cai W, Zhao S, et al. Oxidative stress-related biomarkers in saliva and gingival crevicular fluid associated with chronic periodontitis: A systematic review and meta-analysis. J Clin Periodontol . 2019;46(6):608-622. doi:10.1111/jcpe.13112 Chrysostomou V, Rezania F, Trounce IA, Crowston JG. Oxidative stress and mitochondrial dysfunction in glaucoma. Curr Opin Pharmacol . 2013;13(1):12-15. doi:10.1016/j.coph.2012.09.008 Jassim AH, Fan Y, Pappenhagen N, Nsiah NY, Inman DM. Oxidative Stress and Hypoxia Modify Mitochondrial Homeostasis During Glaucoma. Antioxid Redox Signal . 2021;35(16):1341-1357. doi:10.1089/ars.2020.8180 Zanon-Moreno V, Marco-Ventura P, Lleo-Perez A, et al. Oxidative Stress in Primary Open-angle Glaucoma. J Glaucoma . 2008;17(4):263. doi:10.1097/IJG.0b013e31815c3a7f Tonetti MS, D’Aiuto F, Nibali L, et al. Treatment of Periodontitis and Endothelial Function. N Engl J Med . 2007;356(9):911-920. doi:10.1056/NEJMoa063186 McMonnies CW. Glaucoma history and risk factors. J Optom . 2017;10(2):71-78. doi:10.1016/j.optom.2016.02.003 Preshaw PM, Alba AL, Herrera D, et al. Periodontitis and diabetes: a two-way relationship. Diabetologia . 2012;55(1):21-31. doi:10.1007/s00125-011-2342-y Muñoz Aguilera E, Suvan J, Buti J, et al. Periodontitis is associated with hypertension: a systematic review and meta-analysis. Cardiovasc Res . 2020;116(1):28-39. doi:10.1093/cvr/cvz201 Arjunan P. Eye on the Enigmatic Link: Dysbiotic Oral Pathogens in Ocular Diseases; The Flip Side. Int Rev Immunol . 2021;40(6):409-432. doi:10.1080/08830185.2020.1845330 Yeh LJ, Shen TC, Sun KT, Lin CL, Hsia NY. Periodontitis and Subsequent Risk of Cataract: Results From Real-World Practice. Front Med . 2022;9:721119. doi:10.3389/fmed.2022.721119 Chau SF, Lee CY, Huang JY, Chou MC, Chen HC, Yang SF. The Existence of Periodontal Disease and Subsequent Ocular Diseases: A Population-Based Cohort Study. Medicina (Mex) . 2020;56(11):621. doi:10.3390/medicina56110621 Gedde SJ, Vinod K, Wright MM, et al. Primary Open-Angle Glaucoma Preferred Practice Pattern®. Ophthalmology . 2021;128(1):P71-P150. doi:10.1016/j.ophtha.2020.10.022 Pazos M, Traverso CE, Viswanathan A. European Glaucoma Society – Terminology and guidelines for glaucoma, 6th Edition. Br J Ophthalmol . 2025;109(Suppl 1):1-212. doi:10.1136/bjophthalmol-2025-egsguidelines Paul ME, Tseng VL, Kitayama K, Yu F, Coleman AL. Evaluating Discrepancies in Self-Reported Glaucoma and Electronic Health Records in the National Institutes of Health All of Us Database. Ophthalmol Glaucoma . 2023;6(5):521-529. doi:10.1016/j.ogla.2023.03.003 Neustaeter A, Vehof J, Snieder H, Jansonius NM. Glaucoma in large-scale population-based epidemiology: a questionnaire-based proxy. Eye . 2021;35(2):508-516. doi:10.1038/s41433-020-0882-4 Bond JC, Casey SM, McDonough R, McLone SG, Velez M, Heaton B. Validity of individual self-report oral health measures in assessing periodontitis for causal research applications. J Periodontol . 2024;95(9):892-906. doi:10.1002/JPER.23-0551 Lertpimonchai A, Tuntrakul S, Rattanasiri S, et al. Validity of Simple Self-Reported Periodontal Status Questions. Int Dent J . 2023;73(1):121-127. doi:10.1016/j.identj.2022.10.006 Jin L, Pelekos G, Tonetti M, Deng K. Diagnostic accuracy of self-reported measures of periodontal disease: A clinical validation study using the 2017 case definitions. J Clin Periodontol . Published online 2021. doi:10.1111/jcpe.13484 Galvez-Olortegui J, Jarroudi RBE, Silva-Ocas I, et al. Systematic review of clinical practice guidelines for the diagnosis and management of open angle glaucoma. Research Square . Preprint posted online January 6, 2025. doi:10.21203/rs.3.rs-4843576/v2 Galvez-Olortegui J, Burgueño-Montañes C, Silva-Ocas I, Bernales-Urbina S, Galvez-Olortegui T. Minimally Invasive Glaucoma Surgery (MIGS) recommendations in Clinical Practice Guidelines for open angle glaucoma and MIGS procedures: A scoping review. Eur J Ophthalmol . 2025;35(2):602-610. doi:10.1177/11206721241276223 Micheletti JM, Shultz M, Singh IP, Samuelson TW. An Emerging Multi-mechanism and Multi-modal Approach in Interventional Glaucoma Therapy. Ophthalmol Ther . 2025;14(1):13-22. doi:10.1007/s40123-024-01073-z Additional Declarations The authors declare no competing interests. Supplementary Files Supplementglaucomaperio.docx Systematic literature search strategy and retrieved records. Cite Share Download PDF Status: Posted Version 1 posted 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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glaucoma.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7816535/v1/0eeb07b148710c3c17d02500.png"},{"id":93342622,"identity":"66b69567-d39c-4862-8756-9801697ee7e8","added_by":"auto","created_at":"2025-10-12 14:43:24","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":329199,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eForest plot.\u003c/strong\u003e Mean differences from individual studies (blue squares) are displayed in rows, with confidence intervals (CI) represented by horizontal lines. The pooled mean difference from all studies is shown as a diamond, extending to the pooled CI. Meta-analysis statistics are summarized at the bottom left. \u003cu\u003ePD\u003c/u\u003e: periodontal disease\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7816535/v1/3f3854f2b03c2f148394eb65.png"},{"id":93343972,"identity":"4b81c50a-ed28-4d34-816d-d0ea17fc5e93","added_by":"auto","created_at":"2025-10-12 14:59:25","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2393666,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7816535/v1/19437adf-8bc5-466c-90c6-e9c7c8c356a5.pdf"},{"id":93342629,"identity":"03302eca-74c5-42bc-b8b8-f26d00826943","added_by":"auto","created_at":"2025-10-12 14:43:24","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":24017,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSystematic literature search strategy and retrieved records.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Supplementglaucomaperio.docx","url":"https://assets-eu.researchsquare.com/files/rs-7816535/v1/5e6f063e9d0a71716adc229c.docx"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003ePeriodontal disease and glaucoma. A systematic review and Meta-Analysis\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePeriodontal disease -PD- (or periodontitis, often referred as the same condition) is a multifactorial chronic inflammatory pathology, caused by a disruption in the balance between the oral microbial biofilm and the host immune response. This imbalance results in chronic inflammation and tissue destruction\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. The disease is influenced by various factors, including poor oral hygiene, genetic predisposition, and systemic conditions such as diabetes and cardiovascular disease\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. According to the World Health Organization, the global prevalence of PD ranges from 9.4% to 43.7%, being more common in adults and in high-income countries\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eGlaucoma, is a group of ocular disorders (primary open-angle glaucoma, primary angle-closure glaucoma, secondary open and angle-closure glaucoma, among others) of multifactorial etiology\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e, characterized by optic neuropathy which, in many cases, is associated with elevated intraocular pressure\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. It is the second leading cause of irreversible blindness worldwide\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. The global prevalence of glaucoma in 40\u0026ndash;80 years patients is 3.5% and the number of people with glaucoma worldwide is expected to be 111.8\u0026nbsp;million by 2040\u003csup\u003e7\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eIn recent years, increasing attention has been paid to the role of systemic inflammation in the development and progression of glaucoma. PD, a chronic inflammatory condition of the supporting tissues of the teeth, has been proposed as a potential contributing factor to optic nerve damage\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Although the precise mechanisms linking PD and glaucoma remain unclear, several hypotheses have been proposed. For instance, the dysbiotic oral microbiota associated with PD may trigger systemic immune responses that contribute to neurodegeneration in the optic nerve. In animal models, lipopolysaccharide derived from oral bacteria of glaucoma patients have shown to exacerbate optic nerve damage\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. Additionally, PD may induce subclinical systemic inflammation leading to endothelial dysfunction, which could impair optic nerve perfusion and contribute to optic nerve damage\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eGrowing evidence has highlighted the broader role of human microbiota in health and disease. Beyond its impact on oral health, PD has been linked to a range of systemic diseases\u003csup\u003e\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e, including cardiovascular disease\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e, diabetes mellitus\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e, metabolic syndrome\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e, rheumatoid arthritis\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e, osteoporosis\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e, and respiratory diseases\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. This association is thought to occur through bacterial dissemination and a systemic inflammatory response, allowing periodontal pathogens and inflammatory mediators to affect distant organs. Notably, PD has also been implicated in ocular conditions such as diabetic retinopathy and age-related macular degeneration\u003csup\u003e\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eIt is noteworthy the concept of a \u0026ldquo;gut-ocular axis\u0026rdquo;, which suggests that the composition and health of the gut microbiome may influence ocular homeostasis and immune regulation\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e. Oral, gut and ocular microbiota has been associated with inflammatory and neurodegenerative disorders, including glaucoma\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. These findings support the possibility that microbial imbalance may be a common pathway linking PD and ocular diseases. Indeed, a growing number of articles have been published suggesting a connection between periodontal and ocular health\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e,\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e,\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e,\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. However, to our knowledge, no systematic review has been conducted regarding this topic. The aim of this systematic review was to assess the association between PD and glaucoma.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis systematic review was conducted in compliance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. The PECO framework was used: Population (adults), Exposure (PD), Comparison (No PD) and Outcome (Glaucoma). The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42023428738).\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eEligibility criteria\u003c/h2\u003e\u003cp\u003eThe eligibility criteria were the following: (i) observational clinical studies (cohorts, case-control and cross-sectional studies); (ii) conducted in adult population of either sex; (iii) reporting a quantitative estimate of effect and a 95% confidence interval (CI) for association between PD (exposition) and glaucoma (outcome). We included all studies regardless of the diagnostic approach employed for either glaucoma or PD, including clinical assessments, administrative diagnostic code-based, or self-reported data. Only studies in the adult population were included due to the low prevalence of PD in pediatric patients\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eStudies retracted by the author and/or the journal were not included in the metanalysis. Studies where the study design was not included or was not well specified in their designs were also excluded.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eInformation Sources and Search strategy\u003c/h3\u003e\n\u003cp\u003eTwo authors (AVC and ISO) conducted a systemic literature search for relevant clinical studies available until August 26th, 2025. The databases included were PubMed/Medline, Scopus, Embase, Web of Science, Cochrane Library, LILACS and Google Scholar. Terms related to \u0026ldquo;glaucoma\u0026rdquo; and \u0026ldquo;periodontal disease\u0026rdquo; were used to build search strategy and adapted to each database (Supplement 1). Additionally, a manual search was performed in the journals with the highest impact in Ophthalmology, according to the Scimago Journal Rank: Progress in Retinal and Eye Research, Ophthalmology, Annual Review of Vision Science, JAMA Ophthalmology, Ocular Surface, American Journal of Ophthalmology, British Journal of Ophthalmology, Ophthalmology Retina, Survey of Ophthalmology, Ophthalmology and Glaucoma.\u003c/p\u003e\n\u003ch3\u003eData collection process\u003c/h3\u003e\n\u003cp\u003eAfter the search, all identified citations were imported into Rayyan (Qatar Computing Research Institute, Doha, Qatar) for reference management. No automation features were employed. Duplicates were identified and removed to ensure the uniqueness of each reference. Two authors (ISO and RBE) independently did a title and abstract blind screen. Then, full texts of the selected titles were retrieved and reviewed to assess their eligibility. If the article was not available online, the corresponding author was contacted. Any disagreements arising during the selection process were resolved through discussion, with a third reviewer (JGO) acting as an arbitrator when required.\u003c/p\u003e\n\u003ch3\u003eData extraction\u003c/h3\u003e\n\u003cp\u003e Three authors (JGO, CBM and RBE) independently assessed each of the selected articles, and the following information was collected: First author, year of publication, country in which the study was conducted, data source, study period, study design, age and sex, study objective(s), main outcome, diagnosis of periodontitis criteria, diagnosis criteria of glaucoma, confounding factors assessed, sample size, and number of participants with PD and without PD.\u003c/p\u003e\n\u003ch3\u003eStudy risk of bias assessment\u003c/h3\u003e\n\u003cp\u003eThree authors (JGO, CBM and RBE) independently assessed the methodological quality of the studies using the Newcastle-Ottawa Scale (NOS)\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e for non-randomized studies. A fourth author (ECC) resolved discrepancies in this process. The methodological quality of the studies was classified into low risk of bias (7\u0026ndash;9 points), moderate risk of bias (4\u0026ndash;6 points) and high risk of bias (0\u0026ndash;3 points)\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eEffect measures and Synthesis methods\u003c/h2\u003e\u003cp\u003eNon-relevant heterogeneity was considered to exist if the Higgins value (I\u003csup\u003e2\u003c/sup\u003e) was less than 40%, according to the Cochrane Manual\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. For the meta-analysis, Odds Ratio (OR) was used as a measurement of the association effect between PD and glaucoma, with a 95% confidence interval (95% CI), assuming a random effects model and inverse variance method due to the assumption of heterogeneity among the studies found in the exploratory search, because they are samples of studies with different designs, diagnoses and contexts. A subgroup analysis was performed based on the study design (cohort, nested case-control). Subgroup analysis by age and/or sex was not performed. Statistical analysis was performed with Review Manager (RevMan) software version 5.4.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003eStudy selection\u003c/h2\u003e\u003cp\u003eThe literature search in databases yielded 946 articles, of which 208 were eliminated. Next, 738 articles were selected based on their title and abstract, and 11 articles were chosen for full review; in addition, 2 articles found through a manual search were selected. All 13 articles were read in their entirety, and 3 articles were excluded for wrong type of publication\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e,\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e,\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e and 3 for wrong exposition\u003csup\u003e\u003cspan additionalcitationids=\"CR35\" citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). One study\u003csup\u003e\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u003c/sup\u003e was excluded due to overlapping data with another included study\u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e, as both used the same database (BigMouth Dental Data Repository) and the earlier sample was fully encompassed within the latter.\u003c/p\u003e\u003cp\u003eFinally, 6 articles were included\u003csup\u003e\u003cspan additionalcitationids=\"CR39 CR40 CR41 CR42\" citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e (Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eStudy characteristics\u003c/h2\u003e\u003cp\u003eThe 6 studies\u003csup\u003e\u003cspan additionalcitationids=\"CR39 CR40 CR41 CR42\" citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e included in the systematic review were observational studies: 3 cohort studies\u003csup\u003e\u003cspan additionalcitationids=\"CR41\" citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e, 1 nested case-control study\u003csup\u003e\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e, and 2 cross-sectional studies\u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e,\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u003c/sup\u003e. A total of 1,153,308 participants were included. The sample sizes of included studies ranged from 147\u003csup\u003e43\u003c/sup\u003e to 528,089\u003csup\u003e40\u003c/sup\u003e participants. In terms of geographical location, 3 studies were conducted in the United States\u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e,\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e,\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e, and the other 3 in Asia (Taiwan and South Korea)\u003csup\u003e\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e,\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e,\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e. The two studies conducted in South Korea included are from different databases\u003csup\u003e\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e,\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e. A prospective cohort study (n\u0026thinsp;=\u0026thinsp;528,089) was conducted solely among male health professionals\u003csup\u003e\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u003c/sup\u003e. Another prospective cohort study (n\u0026thinsp;=\u0026thinsp;124,904) assessed mostly women (65.3%, 8,1498 out of 124,904)\u003csup\u003e\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e. In this prospective cohort study information about urban or rural population was done, including only urban population\u003csup\u003e\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003ePD and glaucoma Diagnostic criteria\u003c/h2\u003e\u003cp\u003eDifferent diagnostic criteria were used for PD and glaucoma. PD was diagnosed using clinical criteria in two studies\u003csup\u003e\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e,\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u003c/sup\u003e (tooth count as oral health indicator in one study\u003csup\u003e\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u003c/sup\u003e and periodontal status using the community periodontal index in the other study\u003csup\u003e\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u003c/sup\u003e), disease classification codes in two\u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e,\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e, and questionnaires (self-report) in two\u003csup\u003e\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e,\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eGlaucoma was diagnosed using clinical criteria in two studies\u003csup\u003e\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e,\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e: intraocular pressure, visual field, optic nerve assessment and Shaffer grade in one study\u003csup\u003e\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e and intraocular pressure, visual field, optic nerve assessment and Van Herick grade in the other study\u003csup\u003e\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u003c/sup\u003e; disease classification codes in one\u003csup\u003e\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e, and questionnaires in three\u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e,\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e,\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eRisk of bias in studies\u003c/h2\u003e\u003cp\u003eThe 6 included articles were assessed using the NOS scale. Low risk of bias was observed in the selection, comparability, and outcome dimension in most studies; however, in one prospective cohort study\u003csup\u003e\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e showed high risk of bias in the outcome dimension (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003eSyntheses of results\u003c/h2\u003e\u003cp\u003eThis result showed high heterogeneity, according to Higgins' value (I\u003csup\u003e2\u003c/sup\u003e: 99%). Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows the estimated effects. These were:\u003c/p\u003e\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003ecombined effect. OR: 1.72; 95%CI: 1.13\u0026ndash;2.63; p-value: 0.010, I\u003csup\u003e2\u003c/sup\u003e: 99%;\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003ecohort studies. OR: 1.51; 95%CI: 1.12\u0026ndash;2.03; p-value: 0.007, I\u003csup\u003e2\u003c/sup\u003e: 94%;\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003enested case-control study. OR: 1.10; 95%CI: 0.56\u0026ndash;2.16; p-value: 0.790; = I\u003csup\u003e2\u003c/sup\u003e: not applicable;\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003ecross-sectional studies. OR: 2.53; 95%CI: 1.66\u0026ndash;3.87; p-value: \u0026lt;0.004, I\u003csup\u003e2\u003c/sup\u003e: 88%.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\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\u003eGeneral characteristics of the included studies.\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=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" 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\u003eArticle\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCountry / Source / Study period\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eDesign\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eAim(s) of study\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eMain result\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003ePD diagnosis\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eGlaucoma diagnosis\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eCovariates analysed in the articles\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePasquale et al.\u003c/p\u003e\u003cp\u003e2016 (41)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eU.S.\u003c/p\u003e\u003cp\u003eHPFS\u003c/p\u003e\u003cp\u003e(Health Professionals Follow-up Study)\u003c/p\u003e\u003cp\u003e1986\u0026ndash;2012\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eProspective cohort study\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eEvaluate the association between oral health history and risk of primary open-angle glaucoma and its subtypes.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNumber of natural teeth, periodontal disease, and root canal treatment were not associated with primary open angle glaucoma (periodontitis was not associated with risk of glaucoma)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eThe number of natural teeth and periodontal disease history was registered from 1986, and every 2 years was asked about tooth loss and new diagnoses of periodontal disease with bone loss. Results were validated with the final number of teeth and radiography, respectively.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eEvery two years questionnaires to participants asking about the development of glaucoma; the reported glaucoma cases were confirmed by their eye care providers with the results of the tests (intraocular pression, visual field loss and optic nerve structural information).\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eGlaucoma family history, African ancestry, Asian ancestry, body mass index, pack-years of smoking, hypertension, diabetes, physical activity, alcohol consumption, caffeine intake, updated number of eye exams reported during follow-up, self-reported history of cataract diagnosis or extraction, age-related macular degeneration, hypertension, diabetes, and recent report of physical examination.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eByun et al.\u003c/p\u003e\u003cp\u003e2020 (42)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eKorea\u003c/p\u003e\u003cp\u003eKoGES: Korean Genome and Epidemiology Study\u003c/p\u003e\u003cp\u003e2004\u0026ndash;2016\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eProspective cohort study\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eEvaluate the association between periodontitis and glaucoma.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eThe risk of developing glaucoma was higher in patients with periodontitis.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eThe participants were questioned about their history of periodontitis by trained interviewers: \u0026ldquo;Have you ever had a diagnosis of periodontitis?\u0026rdquo;.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eThe participants were questioned about their history of glaucoma by trained interviewers: \u0026ldquo;Do you have any history of glaucoma?\u0026rdquo;.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eAge,\u003c/p\u003e\u003cp\u003esex, income group, body mass index, smoking, alcohol consumption, hypertension, diabetes mellitus, and hyperlipidemia.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSun et al.\u003c/p\u003e\u003cp\u003e2020 (43)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTaiwan\u003c/p\u003e\u003cp\u003eLHID2000: Longitudinal Health Insurance Database 2000\u003c/p\u003e\u003cp\u003e1995\u0026ndash;2013\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRetrospective cohort study\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eClarify the potential association of periodontitis and development of glaucoma and its subtypes, primary open-angle glaucoma and primary close-angle glaucoma.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eThe risk of developing glaucoma was higher in patients with periodontitis.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eDisease classification codes:\u003c/p\u003e\u003cp\u003eICD-9-CM codes 523.3 and 523.4.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eDisease classification codes:\u003c/p\u003e\u003cp\u003eICD-9-CM code 365.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eAge, sex, comorbidities, and corticosteroid use.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePolla et al.\u003c/p\u003e\u003cp\u003e2017 (44)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eU.S.\u003c/p\u003e\u003cp\u003eSUNY Downstate Eye clinics*\u003c/p\u003e\u003cp\u003e2010\u0026ndash;2013\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNested Case-control study\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eEvaluate possible associations between POAG, dental health, and the oral microbiome.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eThe number of teeth (an oral health indicator) and alterations in the amounts of oral bacteria may be associated with glaucoma pathology (periodontitis was not associated with risk of glaucoma)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eSubjects were asked to complete a self-administered questionnaire to collect information about their dental health (e.g. number of natural teeth, signs of periodontal or gum disease etc.). Questionnaire responses were reviewed by a trained member of the research team and any missing, incomplete items or discrepancies clarified.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eOpen angles (\u0026ge;\u0026thinsp;III Shaffer grade), presence of a characteristic glaucomatous visual field defect and optic nerve head with cup to disc ratio\u0026thinsp;\u0026gt;\u0026thinsp;0.8 in at least one eye based on clinical examination. In addition, all cases were either using intraocular pression lowering agents or had undergone glaucoma surgery.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eSex and age.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChatzopoulos et al. 2024 (39)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eU.S.\u003c/p\u003e\u003cp\u003eBigMouth Dental Data Repository\u003c/p\u003e\u003cp\u003e2011\u0026ndash;2021\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCross-sectional\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eInvestigate the relationship between periodontitis and systemic conditions.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eThis study showed the relationship between periodontal disease and glaucoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003ePatients were classified into 2 groups based on the presence of planned or completed Current Dental Terminology codes: periodontitis group when codes for surgical and non-surgical treatment of periodontal disease were used; non-periodontitis group when patients had at least one D1110 code (dental prophylaxis in the absence of periodontal disease) and none of the codes in the periodontitis group.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eSelf-reported systemic diseases based on a questionnaire completed at the initial visit and updated every 6 to 12 months.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eAge and gender\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNoh et al. 2025 (40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eKorea\u003c/p\u003e\u003cp\u003eKorea National Health and Nutrition Examination Survey (KNHANES)\u003c/p\u003e\u003cp\u003e2010\u0026ndash;2011\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCross-sectional\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eInvestigate the relationship between periodontitis and open-angle glaucoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eThe risk of developing glaucoma was higher in patients with periodontitis.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003ePeriodontal status using the community periodontal index (CPI) developed by the World Health Organization: the CPI ranged from 0\u0026ndash;4 and was defined as healthy periodontal status (CPI\u0026thinsp;=\u0026thinsp;0), bleeding of the gingiva (CPI\u0026thinsp;=\u0026thinsp;1), dental plaque and bleeding (CPI\u0026thinsp;=\u0026thinsp;2), periodontal pouch depth\u0026thinsp;\u0026ge;\u0026thinsp;3.5 mm and \u0026lt;\u0026thinsp;5.5 mm (CPI\u0026thinsp;=\u0026thinsp;3), and periodontal pouch depth\u0026thinsp;\u0026ge;\u0026thinsp;5.5 mm (CPI\u0026thinsp;=\u0026thinsp;4).\u003c/p\u003e\u003cp\u003ePeriodontitis was defined as a CPI value of 3 or 4 at least one site of the periodontal pouch.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003ePatients with increased intraocular pression (\u0026ge;\u0026thinsp;22 mmHg), with open angle (peripheral anterior chamber depth\u0026thinsp;\u0026gt;\u0026thinsp;1/4 of the peripheral corneal thickness), corresponding visual field defects AND: (1) neuroretinal rim loss with a vertical or horizontal cup-to-disc ratio of \u0026ge;\u0026thinsp;0.7 or an asymmetry of \u0026ge;\u0026thinsp;0.2; (2) presence of optic disc haemorrhage; OR (3) presence of retinal nerve fibre layer defect. In cases without visual field defects, the diagnostic criteria would be the same except for point (1), which would be neuroretinal rim loss with a vertical cup-to-disc ratio of \u0026ge;\u0026thinsp;0.9, or a vertical cup-to-disc ratio asymmetry of \u0026ge;\u0026thinsp;0.3, and excluding point (2).\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eAge, sex, diabetes mellitus, hypertension, smoking rate and drinking rate.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"8\"\u003e*Database not found on the internet\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSample summary of the included studies.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" 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=\"left\" 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\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eStudy\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eSample characteristics: age (range) / gender (percentage of males) / race\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003eWith PD\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u003cp\u003eWithout PD\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eTotal sample size\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eGlaucoma\u003c/b\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003eGlaucoma\u003c/b\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePasquale et al.\u003c/p\u003e\u003cp\u003e2016 (41)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e40\u0026ndash;75 years\u003c/p\u003e\u003cp\u003e100% males\u003c/p\u003e\u003cp\u003eMajority: Caucasian\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e226 (0.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e229,935\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e259 (0.09%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e298,154\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e528,089\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eByun et al.\u003c/p\u003e\u003cp\u003e2020 (42)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e40 years (minimum) - maximum: no reported\u003c/p\u003e\u003cp\u003e(\u0026gt;\u0026thinsp;65 years: not reported)\u003c/p\u003e\u003cp\u003e34,7% males\u003c/p\u003e\u003cp\u003eRace: not reported\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e187 (2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9,572\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1,054 (0.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e115,332\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e124,904\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSun et al.\u003c/p\u003e\u003cp\u003e2020 (43)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20 years (minimum) - maximum: no reported\u003c/p\u003e\u003cp\u003e(\u0026gt;\u0026thinsp;65 years: 9.2%)\u003c/p\u003e\u003cp\u003e49% males\u003c/p\u003e\u003cp\u003eRace: not reported\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4,875 (2,5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e194,090\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3,516 (1,8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e194,090\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e388,180\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePolla et al.\u003c/p\u003e\u003cp\u003e2017 (44)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e40\u0026ndash;87 years (age-matched)\u003c/p\u003e\u003cp\u003e44,9% males (majority of women in controls)\u003c/p\u003e\u003cp\u003eMajority: African-American\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e46 (65,7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e49 (63,6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e77\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e147\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChatzopoulos et al. 2024 (39)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRange age: not reported\u003c/p\u003e\u003cp\u003e[mean (SD): 47.4 (17.9) years]\u003c/p\u003e\u003cp\u003e44.8% males\u003c/p\u003e\u003cp\u003eMajority: White people\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4,644 (11%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e42,377\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2,542 (3,9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e65,930\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e108,307\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNoh et al 2025 (40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19 years (minimum) - maximum: no reported\u003c/p\u003e\u003cp\u003e(\u0026gt;\u0026thinsp;60 years: 12.68%)\u003c/p\u003e\u003cp\u003e50.79% males\u003c/p\u003e\u003cp\u003eRace: not reported\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e80 (8,2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e972\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e117 (4,3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e2,709\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e3,681\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eNewcastle-Ottawa scale (NOS) for the risk of bias and quality assessment of non-randomized studies\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"11\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"4\" nameend=\"c6\" namest=\"c3\"\u003e\u003cp\u003eSelection\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eComparability\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c10\" namest=\"c8\"\u003e\u003cp\u003eOutcome\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u003cp\u003eTotal score\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAuthor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eYear\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eRepresentativeness of the exposed cohort\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eSelection of the non-exposed cohort\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003eAscertainment of exposure\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003eDemonstration that outcome of interest was not present at start of study\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003eComparability of cohorts on the basis of the design or analysis\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003eAssessment of outcome\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003eWas follow-up long enough for outcomes to occur\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eAdequacy of follow up of cohorts\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePascuale et al. (36)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2016\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e**\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eByun et al. (39)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2020\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e**\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSun et al. (38)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2020\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e**\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAuthor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eYear\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eAdequate definition of patient cases\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eRepresentativeness of patient cases\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003eSelection of controls\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003eDefinition of controls\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003eControl for important or additional factors\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003eAscertainment of exposure\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003eSame method of ascertainment for participants\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eNonresponse rate\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePolla et al. (37)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2017\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e**\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAuthor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eYear\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eRepresentativeness of the sample\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eSample size\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003eNon-respondents/missing data\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003eAscertainment of the exposure (risk factor)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003eComparability of subjects in different outcome groups on the basis of design or analysis. Confounding factors controlled\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u003cb\u003eAssessment of outcome\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e\u003cb\u003eBlinding of outcome assessors\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u003cb\u003eStatistical test\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e\u003cb\u003eTotal score\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChatzopoulos et al. (40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2024\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNoh et al. (40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2025\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e**\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn recent decades, several hypotheses have been suggested trying to explain the physiopathology underlying the association between PD and glaucoma. Hence, several groups have investigated their potential association \u003csup\u003e\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e,\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u003c/sup\u003e. To the best of our knowledge, this is the first time that a systematic review and meta-analysis has been carried out regarding this topic.\u003c/p\u003e\u003cp\u003ePD is characterized by the breakdown of periodontal tissues\u003csup\u003e\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e,\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u003c/sup\u003e. This allows translocation of oral bacteria and inflammatory mediators into systemic circulation\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e,\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e,\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u003c/sup\u003e. The aforementioned process acts as a trigger for the inflammatory cascade, leading to a state of chronic subclinical inflammation\u003csup\u003e\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e,\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u003c/sup\u003e. Such inflammation may contribute to glaucoma through several pathways: (i) cytokines and inflammatory mediators may promote the onset and/or progression of the disease by exerting direct neurotoxic effects on the optic nerve\u003csup\u003e\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e,\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e\u003c/sup\u003e; (ii) oxidative stress\u003csup\u003e\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e\u003c/sup\u003e, resulting in retinal ganglion cell loss via mitochondrial dysfunction\u003csup\u003e\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e,\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e\u003c/sup\u003e, ultimately contributing to glaucomatous damage\u003csup\u003e\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e\u003c/sup\u003e; (iii) endothelial dysfunction\u003csup\u003e\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e,\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e\u003c/sup\u003e, leading to optic nerve hypoperfusion due to impaired flow-mediated vasodilation\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e; and (iv) systemic inflammation associated with PD may exacerbate comorbidities such as hypertension and diabetes, the first recognized as significant risk factors for glaucoma\u003csup\u003e\u003cspan additionalcitationids=\"CR55\" citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eOur data, based on observational studies involving over one million individuals, provides evidence of a possible positive association between PD and glaucoma. In fact, dysbiotic oral pathogens may influence the development of inflammatory eye diseases through immune dysfunction\u003csup\u003e\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e\u003c/sup\u003e. Periodontal disease has been linked to several eye diseases and has also been associated with an increased risk of developing cataracts\u003csup\u003e\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e\u003c/sup\u003e, Age-Macular Degeneration\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e, diabetic retinopathy\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e, uveitis, keratitis and scleritis\u003csup\u003e\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e\u003c/sup\u003e. In addition, a recent study showed that glaucoma patients often have poor periodontal health\u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eHowever, data from cohort studies show that the difference in the proportion of patients with and without PD who develop glaucoma is relatively small (0.1% vs 0.09% and 2% vs 0.9% in prospective cohorts\u003csup\u003e\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e,\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e; 2.5% vs 1.8% in the retrospective cohort\u003csup\u003e\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). In our study, the difference in the proportions is small as well: 2.1% vs 1.1% overall. Although the difference is statistically significant, the percentage difference in glaucoma attributable to PD is only 1%.\u003c/p\u003e\u003cp\u003eNevertheless, evidence suggests that the association between glaucoma and PD is more pronounced in older adults and in patients with hypertension\u003csup\u003e\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e,\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e, being recognized cofactors for glaucoma\u003csup\u003e\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e,\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e,\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e\u003c/sup\u003e. Taken together, these findings support the hypothesis that PD may contribute as a cofactor in the development of glaucoma rather than representing a direct etiological cause.\u003c/p\u003e\u003cp\u003eCertain limitations must be taken into account when interpreting the results.\u003c/p\u003e\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eThe scarce number of articles included (n\u0026thinsp;=\u0026thinsp;6) in this systematic review, the different study designs included in the analysis, and the high heterogeneity found is probably the main drawback for generalization of the obtained results on PD and glaucoma association.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eFive out of 6 analyzed studies gave the same message in favor of the studied association\u003csup\u003e\u003cspan additionalcitationids=\"CR39 CR40 CR41\" citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e, our results also show that depending on the type of study design analyzed (Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), the raw likelihood of observing the association between periodontitis and glaucoma varies. Nested case-control study did not provide evidence on this association\u003csup\u003e\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e, meanwhile cohort\u003csup\u003e\u003cspan additionalcitationids=\"CR41\" citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e and cross-sectional studies\u003csup\u003e\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e,\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u003c/sup\u003e yes (Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). In fact, if we want to analyze whether having periodontitis is a risk factor for developing glaucoma, we should only consider cohort studies, as it is the model par excellence for studying the occurrence of events (in this case glaucoma) following exposure to a factor (in this case PD) and the natural progression of a disease. As a strength of this systematic review, the pool of cohort studies also provided evidence statistically significant on this association, despite the fact that the follow-up period was variable among studies -from 1 to 26 years- (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). This variability among the follow-up in the different studies may influence the results, since the longer the follow-up period, the older the patients are and the more risk factors for glaucoma (age itself, and cardiovascular diseases) are likely to appear\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e Our systematic review only included observational studies. Our review did not include clinical trials. Hence, it was not considered whether information on PD (comorbidity) had been collected at the baseline visit (baseline characteristics) in glaucoma clinical trials; and the same in PD clinical trials (glaucoma as baseline comorbidity). In fact, the analysis of the baseline visits of any clinical trial (prior to receiving any treatment) could be like a cross-sectional study with more inclusion and exclusion criteria, generally (2 cross-sectional studies were included in this systematic revision). This could have contributed to the loss of prospective information on the association between PD and glaucoma.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003ePD and glaucoma diagnostic criteria were not uniform among analyzed studies. There is no guarantee that patients diagnosed with glaucoma were patients with a confirmed diagnosis of glaucoma, and the same is true for patients with PD. Some studies relied partly on self-reported data for diagnosing glaucoma\u003csup\u003e\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e,\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e,\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e and PD\u003csup\u003e41,43\u003c/sup\u003e, despite the fact that self-reporting is not a reliable method for accurately identifying either condition\u003csup\u003e\u003cspan additionalcitationids=\"CR63 CR64 CR65\" citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e66\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eCo-variables and confounding variables analyzed in the manuscripts included in this systematic review were not considered in our analysis, mainly due to the lacking of the standardization of this information in the studies. This fact could under- or over-estimated the ORs.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eA prospective cohort study\u003csup\u003e\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e and a cross-sectional study\u003csup\u003e\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u003c/sup\u003e were conducted in South Korea. Although the two studies used different databases, it cannot be ruled out that the study populations may overlap.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e\u003cp\u003eAlthough the small proportion of glaucoma explained by PD, the findings of this meta-analysis help us to a better understanding of glaucoma in relation to the whole body, specifically oral health and neuroprotection. In front of this scenario, patients with a history of PD could have an increased risk of developing glaucoma, the two main clinical implications would be related to preventing the development of glaucoma. The first one would be to promote oral health in patients with glaucoma risk factors\u003csup\u003e\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e\u003c/sup\u003e, so that correct prevention of PD would reduce the risk of developing glaucoma or disease progression. Interdisciplinary work between dentists and ophthalmologists could be a new standard approach.\u003c/p\u003e\u003cp\u003eThe second point that could be addressed is glaucoma screening. Although there is no clear consensus among different clinical practice guidelines on which patients should be screened for glaucoma, there\u0026rsquo;s agreement on screening in patients at risk of developing glaucoma due to the presence of risk factors\u003csup\u003e\u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e\u003c/sup\u003e. Based on our results, patients with PD have 1.72 times the odds of developing glaucoma compared with patients without PD (OR: 1.72), an issue that could be addressed in future clinical practice guidelines as a population to be screened. Nonetheless, cost-effective analysis of the screening would need assessment.\u003c/p\u003e\u003cp\u003eAdditionally, the results open new horizons in the field of research. Recognizing risk factors (like PD) and detecting the risk of progression\u003csup\u003e\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e could be useful for a better treatment and follow-up individualization. Identification of patient with high risk of progression let a stricter IOP control to achieve earlier (like minimally invasive glaucoma surgery)\u003csup\u003e\u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e\u003c/sup\u003e or more aggressive intervention, achieving a multi-mechanism or multimodal approach for interventional glaucoma\u003csup\u003e\u003cspan citationid=\"CR69\" class=\"CitationRef\"\u003e69\u003c/span\u003e\u003c/sup\u003e. For this reason, prospective randomized studies would be of great interest to assess whether treatment of PD influences glaucoma progression, thus also opening new therapeutic alternatives, so that IOP control would no longer be the only modifiable factor for glaucoma development and progression, but also PD.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe findings of this review, based on observational studies involving over one million individuals, suggest an association between PD and glaucoma. Patients with PD appear to be more likely to develop glaucoma than patients without it, however, additional long-term studies are needed.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFinancial Support:\u0026nbsp;\u003c/strong\u003eNone\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest:\u003c/strong\u003e The authors declare no conflict of interest related with this project.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThe authors received no financial support for the research, authorship, and/or publication of this article.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003ePrevious Meeting Presentation:\u0026nbsp;\u003c/strong\u003eA partial report was presented at:\u0026nbsp;\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eCongreso de la Asociaci\u0026oacute;n Peruana de Periodoncia y Osteointegracion, 2023 (Lima - Per\u0026uacute;).\u003c/li\u003e\n \u003cli\u003eWorld Glaucoma Congress, 2023 (Rome, Italy)\u003c/li\u003e\n \u003cli\u003e99\u0026ordm; Congreso de la Sociedad Espa\u0026ntilde;ola de Oftalmolog\u0026iacute;a (SEO), 2023 (Sevilla, Spain)\u003c/li\u003e\u003cp\u003e\u003cstrong\u003eAuthor contribution statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAVC\u003c/u\u003e: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Validation, Writing - original draft, Writing - review \u0026amp; editing; \u003cu\u003eRBE\u003c/u\u003e: Data curation, Formal analysis, Investigation, Validation, Writing - original draft, Writing - review \u0026amp; editing; \u003cu\u003eISO\u003c/u\u003e: Data curation, Formal analysis, Investigation, Validation, Writing - original draft; \u003cu\u003eKRF\u003c/u\u003e: Formal analysis, Investigation, Validation, Writing - original draft; \u003cu\u003eCBM\u003c/u\u003e: Data curation, Formal analysis, Investigation, Validation, Writing - original draft; \u003cu\u003eECC\u003c/u\u003e: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Supervision, Validation; \u003cu\u003eTGO\u003c/u\u003e: Formal analysis, Investigation, Validation, Supervision, Validation, Writing - original draft; \u003cu\u003eSV\u003c/u\u003e: Formal analysis, Investigation, Methodology, Supervision, Validation, Writing - review \u0026amp; editing; JGO: Data curation, Formal analysis, Investigation, Methodology, Supervision, Validation, Writing - original draft, Writing - review \u0026amp; editing.\u003c/p\u003e\n\u003c/ul\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKinane DF, Stathopoulou PG, Papapanou PN. 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Validity of Simple Self-Reported Periodontal Status Questions. \u003cem\u003eInt Dent J\u003c/em\u003e. 2023;73(1):121-127. doi:10.1016/j.identj.2022.10.006\u003c/li\u003e\n\u003cli\u003eJin L, Pelekos G, Tonetti M, Deng K. Diagnostic accuracy of self-reported measures of periodontal disease: A clinical validation study using the 2017 case definitions. \u003cem\u003eJ Clin Periodontol\u003c/em\u003e. Published online 2021. doi:10.1111/jcpe.13484\u003c/li\u003e\n\u003cli\u003eGalvez-Olortegui J, Jarroudi RBE, Silva-Ocas I, et al. Systematic review of clinical practice guidelines for the diagnosis and management of open angle glaucoma. \u003cem\u003eResearch Square\u003c/em\u003e. Preprint posted online January 6, 2025. doi:10.21203/rs.3.rs-4843576/v2\u003c/li\u003e\n\u003cli\u003eGalvez-Olortegui J, Burgue\u0026ntilde;o-Monta\u0026ntilde;es C, Silva-Ocas I, Bernales-Urbina S, Galvez-Olortegui T. Minimally Invasive Glaucoma Surgery (MIGS) recommendations in Clinical Practice Guidelines for open angle glaucoma and MIGS procedures: A scoping review. \u003cem\u003eEur J Ophthalmol\u003c/em\u003e. 2025;35(2):602-610. doi:10.1177/11206721241276223\u003c/li\u003e\n\u003cli\u003eMicheletti JM, Shultz M, Singh IP, Samuelson TW. An Emerging Multi-mechanism and Multi-modal Approach in Interventional Glaucoma Therapy. \u003cem\u003eOphthalmol Ther\u003c/em\u003e. 2025;14(1):13-22. doi:10.1007/s40123-024-01073-z\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Scientia Clinical and Epidemiological Research Institute","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Periodontal Diseases, Risk Factors, Systematic Review, Meta-Analysis","lastPublishedDoi":"10.21203/rs.3.rs-7816535/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7816535/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eTopic\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo assess the association between periodontal disease and glaucoma in adults through systematic review and meta-analysis of observational studies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical relevance\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;This study suggests that periodontal disease may increase the likelihood of developing glaucoma. Recognizing oral health as a potential modifiable risk factor could promote interdisciplinary prevention strategies and earlier detection of glaucoma in at-risk individuals.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis review followed PRISMA 2020 guidelines and was registered in PROSPERO (CRD42023428738). A systematic search was performed in PubMed/Medline, Scopus, Web of Science, Embase, Cochrane Library, LILACS, Google Scholar and journals with the highest impact in Ophthalmology, available until August 26th, 2025. Eligible articles were independently screened and quality assessed by three reviewers. All observational clinical studies reporting quantitative effect estimates and 95% confidence interval (95%CI) for the association between periodontal disease and glaucoma were included. Effect estimates for the association with glaucoma were pooled using random effects meta-analysis (Review Manager Version 5.4).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e946 studies were screened, and 6 studies were included in the systematic review: 3 cohort studies, 1 nested case-control study and 2 cross-sectional studies. The populations evaluated were adults (n = 1,153,308). Different diagnostic methods were used for periodontal disease and glaucoma (clinical, self-reported, and disease classification codes), with variations in the criteria used and the type of glaucoma evaluated. Pooled effect estimates indicated a positive association between periodontal disease and glaucoma (OR: 1.72; 95%CI: 1.13–2.63; p-value: 0.010, I\u003csup\u003e2\u003c/sup\u003e: 99%).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe findings of this review, based on observational studies involving over one million individuals, suggest an association between periodontal disease and glaucoma. Patients with periodontal disease appear to be more likely to develop glaucoma than patients without it. However, additional long-term studies are needed.\u003c/p\u003e","manuscriptTitle":"Periodontal disease and glaucoma. 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