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Study Protocol

Association between impaired lung function and glaucoma: A systematic review and meta-analysis

[version 1; peer review: awaiting peer review]
Daniela De Paula
https://orcid.org/0009-0001-9166-232X
1, Peter Doran1, Cormac McCarthy1,2, Deborah Wallace
https://orcid.org/0000-0003-2363-106X
1
Daniela De Paula
https://orcid.org/0009-0001-9166-232X
1, Peter Doran1, Cormac McCarthy1,2, Deborah Wallace
https://orcid.org/0000-0003-2363-106X
1
PUBLISHED 13 May 2026
Author details Author details
OPEN PEER REVIEW
REVIEWER STATUS AWAITING PEER REVIEW

Abstract

Background

Glaucoma is a leading cause of irreversible blindness worldwide. It is a chronic, progressive, age-related fibrotic disease, frequently asymptomatic at early stages which progresses gradually, resulting in significant vision loss if undetected.

Observational evidence suggests that impaired lung function is potentially associated with higher risk of glaucoma. If confirmed, this association could have implications for clinical practice. However, no systematic reviews or meta-analyses have evaluated these data. This systematic review and meta-analysis aims to evaluate the association between impaired lung function and glaucoma and to identify the outcome measures commonly used in studies assessing lung function in relation to glaucoma risk.

Methods

The review will include searches in four electronic databases (PubMed, Embase, Scopus and Web of Science). Observational studies (e.g.: cross-sectional studies, cohort studies) will be eligible for inclusion. Secondary research sources, as well as grey literature will be excluded. Articles entirely not in English will be excluded as the team do not have the resources to facilitate translation.

Screening of titles and abstracts, and full text screening of included articles will be carried out independently by two researchers. A narrative synthesis approach will be taken to analyse the extracted data. If a group of studies with a sufficiently comparable data is identified, a meta-analysis will be performed. Quality of included studies will be assessed using risk of bias tools.

Conclusions

The findings of this systematic review and meta-analysis will advance our understanding of the “lung–eye axis”, through exploring the association of impaired lung function and glaucoma. Findings may potentially support biomarker discovery, highlight current gaps in research and contribute to patients’ stratification for targeted glaucoma screening in high-risk groups.

Keywords

Glaucoma; (Impaired) Lung Function; Fibrosis; Systematic Review; Meta-analysis

Corresponding author: Daniela De Paula
Competing interests: No competing interests were disclosed.
Grant information: This research is funded by the UCD Clinical Research Centre. The corresponding author, Daniela De Paula, received funding as part of a PhD programme in Clinical Trials.
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Copyright:  © 2026 De Paula D et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
How to cite: De Paula D, Doran P, McCarthy C and Wallace D. Association between impaired lung function and glaucoma: A systematic review and meta-analysis [version 1; peer review: awaiting peer review]. HRB Open Res 2026, 9:50 (https://doi.org/10.12688/hrbopenres.14443.1) First published: 13 May 2026, 9:50 (https://doi.org/10.12688/hrbopenres.14443.1) Latest published: 13 May 2026, 9:50 (https://doi.org/10.12688/hrbopenres.14443.1)

Introduction

Glaucoma is an optic neuropathy and a leading cause of irreversible blindness worldwide.1,2 It is a chronic, progressive, age-related fibrotic disease involving extracellular matrix (ECM) remodelling and accumulation. Glaucoma is frequently asymptomatic at early stages and progresses gradually, resulting in significant vision loss if undetected. This poses a substantial public health issue with socioeconomic burdens.3 The “vascular theory” of glaucoma suggests that insufficient blood supply to the optic nerve head (ONH) may impair optic nerve perfusion and oxygenation, resulting in a loss of the Retinal Ganglion Cells (RGCs).4 Available therapeutic approaches cannot restore RGCs and vision loss, making the identification of other potentially modifiable risk factors and screening high-risk population for early detection of glaucoma essential for appropriate treatment and prevention of sight loss.

Impaired lung function has been described as a predictor of morbidity and mortality and may predispose the development of multiple disease processes.5 Studies have reported that the retina and optic nerve may be affected by chronic obstructive pulmonary disease (COPD)-related hypoxemia, similar to the vascular theory of glaucoma.6–8 Furthermore, COPD has been found to induce the development of hemodynamic disturbances and oxidative stress, which are implicated in the pathogenesis of glaucoma.9,10

Another condition known to cause lung function impairment is Idiopathic pulmonary fibrosis (IPF), a rare progressive interstitial lung disease with poor prognosis, characterized by irreversible decline in lung function.11–13 Although they might not seem obviously connected, glaucoma and fibrotic lung disease such as IPF share several mechanisms that drive ECM remodelling and accumulation and ultimately organ dysfunction. The pathophysiological connection between glaucoma and lung fibrosis involves shared molecular pathways such as transforming growth factor-beta (TGF- β), Lysyl Oxidase-Like 1 (LOXL1) and Endothelin-1 signalling.14–16 Similarly to glaucoma and other fibrotic diseases, IPF also lacks early detection biomarkers and meaningful clinical trials outcomes.17–20 Furthermore, it has been reported that impaired lung function or respiratory insufficiency can cause systemic hypoxia and oxidative stress and impact the ocular health,16 the so-called “lung-eye axis”. Supporting this connection, recent study by Yu et al.,21 demonstrated that impaired lung function is a potential biomarker for glaucoma risk. Although there were some methodological limitations, this study strengthens the evidence for this potential association.

The available observational evidence demonstrating that impaired lung function is potentially associated with higher risk of glaucoma might have value in clinical practice and is worth further evaluation.21,22 This systematic review will investigate the existing evidence on the association between impaired lung function and glaucoma, where impaired lung function will include objectively measured pulmonary function abnormalities (e.g. reduced FEV1, FVC, DLCO, FEV1/FVC ratio below study-defined thresholds), regardless of whether the measurements are associated with diagnosed respiratory disease. These findings may contribute to better biomarkers and clinically meaningful outcomes17 such as patients’ stratification for targeted glaucoma screening in high-risk groups.

Aims and objectives

The primary objective of this systematic review and meta-analysis is to assess whether there is an association between impaired lung function and glaucoma.

The secondary objective is to identify and describe the outcome measures most commonly used in studies assessing lung function in relation to glaucoma risk.

Methods

This systematic review and meta-analysis will follow the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) checklist23 to help with identify the research question, conduct study screening, select, appraise and synthesise results and reporting. The present protocol has been registered with PROSPERO (Registration number: CRD420261337091), and any significant amendments will be updated on the website.

Research question

For this study, the PICO (Population/Problem, Intervention/Issue, Comparison and Outcome) framework proposed by Richardson et al.24 will be used to facilitate searching for a precise answer for a clinical question. The framework utilisation for this review is further developed below:

P: Adults (Males and females ≥18 years of age)

I: Impaired lung function will include objectively measured pulmonary function abnormalities (e.g. reduced FEV1, FVC, DLCO, FEV1/FVC ratio below study-defined thresholds), whether or not associated with diagnosed respiratory disease.

C: n/a

O: Glaucoma, Elevated Intraocular Pressure (IOP)

Eligibility criteria

The inclusion and exclusion criteria that will be applied for study selection in this systematic review and meta-analysis are summarised in Table 1.

Table 1. Inclusion and exclusion criteria.

Inclusion criteriaExclusion criteria
Population Humans (Males and females)Animal studies
Age ≥18 years of age<18 years of age
Study design Observational studies (cross-sectional, case-control, and cohort studies) will be eligible. Interventional studies will only be included if baseline lung function and glaucoma outcomes are reported.Secondary research sources (i.e. reviews; systematic, scoping etc.)
Language English languageArticles that are written entirely not in English
Publication date Publications with no restricted date range-

Search method

The search strategy for this review was informed by a specialist librarian and members of our research team in University College Dublin (UCD) and was designed to maximise sensitivity. The following online databases are suggested for initial inclusion: PubMed/MEDLINE, Embase, Scopus, and Web of science. Controlled vocabulary (e.g. MeSH and Emtree terms) and free-text keywords will be used, and no methodological filters will be applied.

The authors are interested in locating literature that discusses impaired lung function as a biomarker or indicator of glaucoma risk. As such, terms related to both populations and individuals who had a pulmonary function test including spirometry taken and vocabulary related to risk and prevalence of glaucoma will be selected to build the search.

Search terms that will compose the Systematic Review will be first identified by conducting preliminary searches for these terms and identifying similar phrases, key words or other iterations of relevance. Terms unique to databases, such as MeSH and Subject Headings, will also be identified and included. The search will not be limited to publication dates. Only English language papers will be included as the research team do not have the resources for translation.

All the reference lists will be reviewed from the studies to be included will be reviewed to identify additional eligible studies. Forward citation tracking (identifying articles that cite the included studies) and backward citation searching (screening the reference lists of included studies) approach will be undertaken where appropriate. If required, authors of relevant included studies may be contacted to obtain missing data or further clarification.

Search strategy

A sample search strategy for the PubMed database is provided below. The search string, including search terms, Boolean operators, and fields of reference (e.g. Title/Abstract), is provided in Table 2.

  • 1. Respiratory or pulmonary function: Impaired lung function, reduced pulmonary function, pulmonary impairment, respiratory dysfunction, pulmonary dysfunction, decreased lung function, reduced respiratory capacity, respiratory insufficiency, compromised pulmonary function, compromised respiratory capacity, lung function decline, respiratory Function Tests, Pulmonary Diffusing Capacity, Vital Capacity, Forced Expiratory Volume, Spirometry, PFTs, LFTs, spirometry, vital capacity, FVC, DLCO, diffusing capacity, forced expiratory volume, FEV1, FEV1/FVC ratio, FEV1 FVC, FEV1 FVC ratio.

  • 2. Glaucoma and Intraocular Pressure: Glaucoma, Intraocular Pressure, IOP, pseudoexfoliation glaucoma (PXFG), primary open-angle glaucoma (POAG), exfoliation syndrome (XFS).

  • 3. (1) AND (2).

Table 2. Pubmed search query.

((“Respiratory Function Tests”[MeSH Terms] OR “Pulmonary Diffusing Capacity”[Mesh] OR “Vital Capacity”[MeSH Terms] OR “Forced Expiratory Volume”[MeSH Terms] OR “pulmonary function”[Title/Abstract] OR “lung function decline”[Title/Abstract] OR “decreased lung function”[Title/Abstract] OR “impaired lung function”[Title/Abstract] OR “Reduced pulmonary function”[Title/Abstract] OR “Compromised pulmonary function”[Title/Abstract] OR “Pulmonary impairment”[Title/Abstract] OR “Respiratory dysfunction”[Title/Abstract] OR “Pulmonary dysfunction”[Title/Abstract] OR “reduced respiratory capacity”[Title/Abstract] OR “Respiratory insufficiency”[Title/Abstract] OR “Lung function deterioration”[Title/Abstract] OR “Compromised respiratory capacity”[Title/Abstract] OR “Respiratory function test*”[Title/Abstract] OR “pulmonary function test*”[Title/Abstract] OR PFTS [Title/Abstract] OR LFTs [Title/Abstract] OR “Spirometry”[Title/Abstract] OR “vital capacity”[Title/Abstract] OR FVC [Title/Abstract] OR “Pulmonary diffusing capacity”[Title/Abstract] OR “lung diffusion test*”[Title/Abstract] OR “dlco”[Title/Abstract] OR “Diffusing capacity”[Title/Abstract] OR “forced expiratory volume”[Title/Abstract] OR “forced expiratory volume in 1 second”[Title/Abstract] OR FEV1[Title/Abstract] OR “FEV1/FVC ratio”[Title/Abstract] OR “fev1 fvc”[Title/Abstract] OR “fev1 fvc ratio”[Title/Abstract] OR “lung function test*”[Title/Abstract] OR “lung diffusion capacity”[Title/Abstract] OR “lung insufficiency”[Title/Abstract] OR “forced vital capacity”[Title/Abstract] OR “diffusing capacity for carbon monoxide”[Title/Abstract]) AND (“Glaucoma”[MeSH Terms] OR “Exfoliation Syndrome”[Mesh] OR “Intraocular Pressure”[Mesh] OR “Intraocular Pressure”[Title/Abstract] OR IOP [Title/Abstract] OR “Glaucoma”[Title/Abstract] OR “Exfoliation Syndrome”[Title/Abstract] OR “pseudoexfoliation glaucoma”[Title/Abstract] OR PXFG [Title/Abstract] OR “primary open-angle glaucoma”[Title/Abstract] OR POAG [Title/Abstract] OR XFS [Title/Abstract]))

Screening

The references retrieved from the search results from each database will be imported to Covidence, a systematic review tool which the licence was obtained through the UCD Library. Duplicates will be removed prior to screening. The articles’ titles and abstracts will be screened by two reviewers, the first (DP) and second (DW) reviewers, as per the eligibility criteria. The reviewers will complete a form containing the potential articles eligible to be included.

Full text screening will be conducted in duplicate by two reviewers DP and DW. Authors of the papers may be contacted for further information, if necessary. A third reviewer (CMC) will be available to resolve any conflicts in inclusion or exclusion decisions. The authors will provide the reasons for exclusion of articles previously included for full text screening. The search strategy as well as studies selection process will be outlined in accordance with the PRISMA statement.23 The studies selection process will be summarised in a PRISMA flow diagram.

Data extraction

A data extraction form will be generated using Covidence. The first reviewer (DP) will extract relevant data from this form from the included studies. The second reviewer (DW) will perform a random sample verification (10%) and any conflicts that arise during the extraction process will be documented and discussed. If resolutions cannot be decided, a third reviewer (CMC) will assist.

A sample of the data and associated fields for extraction are outlined in Table 3. A pilot data extraction form will be used to extract the data, with any revisions made after consultation with the research team. If the reviewers’ extractions differ, discussion and further review of the studies will be conducted until consensus is reached.

Table 3. Data extraction table.

Field Characteristics
General information

  • • First author name and publication year

  • • Type of study/study design

  • • Country of origin etc.

Data Collection

  • • Data collection period

  • • Sampling method

  • • Sample size (total, female, male)

  • • Age of participants (range, mean [SD])

Outcomes

  • • Primary Outcome

  • • Secondary Outcome

  • • Assessment method (registry, self-report, etc.)

Risk of bias assessment

Risk of bias tools will be selected according to study design, with Newcastle–Ottawa Scale (NOS)25 for cohort/case-control studies and Joanna Briggs Institute’s (JBI)26 tool for cross-sectional studies. Studies will be assessed by one person (DP) and checked by another person (DW). GRADE system of rating quality of evidence will be used by the team for rating the certainty of evidence.27

Data synthesis

A narrative synthesis approach will be provided in the text and tables to summarise the study characteristics and results of the extracted data. If a group of studies with a sufficiently comparable intervention/issue and outcome and similar population characteristics is identified, we will perform a meta-analysis examining the association between lung function and glaucoma.

For quantitative synthesis, eligible effect measures will include odds ratios (ORs), risk ratios (RRs), and hazard ratios (HRs), with 95% confidence intervals (CIs). Where appropriate, studies reporting categorical lung function outcomes will be synthesised using ORs and RRs. Mean differences (MDs) or standardised mean differences (SMDs) will be used to synthesise studies reporting continuous lung function outcomes, with 95% CIs.

Meta-analysis will be conducted using a random-effects model, considering the expected heterogeneity between the studies. We will try to minimise the heterogeneity by grouping them by study type, and similar lung function measurements, and outcomes. Different effect measures will not be combined in the same meta-analyses if conversion into a common metric is not appropriate. Where this is not possible, results will be synthesised separately and presented narratively. Remaining heterogeneity will also be discussed using visual inspection of the results of the forest plot along with the χ2 test (with statistical significance set at p < 0.05), and the I2 statistic results.

Both crude and adjusted estimates will be extracted. However, adjusted estimates will be prioritised for meta-analysis. Where only crude estimates are available, these will be synthesised separately or examined in sensitivity analyses.

Analysis of subgroups or subsets

Where sufficient data is available and meta-analysis is feasible, a subgroup analysis will be conducted to explore heterogeneity further based on the following, but not limited to: (a) sex, (b) age, (c) glaucoma subtype, (d) lung function metric used, (e) smoking status, (f ) study design. A sensitivity analysis will be carried out according to overall study quality where studies will be categorised according to their risk of bias using the appropriate assessment tool (NOS or JBI). Comparisons will be made using both using random and fixed-effect models and by excluding possible outlying studies, if the visual inspection of the forest plot shows poorly overlapping CIs.

Dissemination

This review will be published in an open access peer reviewed journal, as well as results being shared at relevant academic conferences and meetings. The findings from this review will be integrated into the results of a larger study investigating Biomarkers of Fibrotic diseases for Clinical Trials.

Protocol registration

This protocol has been registered on PROSPERO (PROSPERO), an accessible open-source software repository for researchers that aids in open collaboration. The protocol can be located at the following link: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261337091. Association between impaired lung function and glaucoma: A systematic review and meta-analysis.

Study status

This review is ongoing, with preliminary searches underway.

Discussion

Glaucoma and impaired lung function, which is often associated with respiratory disease diagnosis such as lung fibrosis, represent a significant global health burden. The management of these conditions is particularly challenging due to the lack of reliable biomarkers for early detection. Glaucoma is progressive, irreversible and typically diagnosed at advanced stages, when the visual field loss is already noticeable.

The existing evidence suggesting an association between impaired lung function and glaucoma is promising and could help with patients’ stratification for targeted glaucoma screening in high-risk groups. However, to date, no systematic reviews or meta-analyses have pooled and synthesized these data.

This systematic review and meta-analysis intend to investigate whether impaired lung function is associated with glaucoma. We will also identify the outcome measures most commonly used in studies exploring the relationship between lung function and glaucoma. The findings will advance our understanding of the “lung–eye axis”, support biomarker discovery, and highlight current gaps in research, with potential implications for clinical practice where patients with impaired lung function could be referred for glaucoma screening. We will use rigorous methodology, and results will be reported as stated by PRISMA statement. However, the quality of this systematic review will be limited by the number of studies available in the literature as well as the quality of the individual studies.

Ethics and consent

Ethical approval and consent were not required.

Protocol amendments

Amendments to this protocol will be agreed upon by the authors prior to implementation. Any amendments will be documented and reported in the PROSPERO register and publication of the study.

Data availability statement

Underlying data

No data are associated with this article.

Reporting guidelines

The PRISMA-P checklist is publicly accessible via the Open Science Framework (OSF) repository under the project “Association between impaired lung function and glaucoma: A systematic review and meta-analysis ”.

Checklist title: The file PRISMA-P-checklist_Impaired lung function_Glaucoma.doc.

DOI: https://doi.org/10.17605/OSF.IO/AHR74.28

Licence: Data are available under the terms of the CC0 1.0 Universal.

Acknowledgments

We acknowledge the contribution of UCD Librarian Mr Diarmuid Stokes for his assistance in developing the search strategy.

References

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De Paula D, Doran P, McCarthy C and Wallace D. Association between impaired lung function and glaucoma: A systematic review and meta-analysis [version 1; peer review: awaiting peer review]. HRB Open Res 2026, 9:50 (https://doi.org/10.12688/hrbopenres.14443.1)
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