Abstract
Globally, 2.2 billion people live with some form of vision impairment and/or eye disease. To date, most systematic reviews examining associations have focused on a single eye disease and there is no systematic evaluation of the relationships between eye diseases and diverse physical and mental health outcomes. Moreover, the strength and reliability of the literature is unclear. We performed an umbrella review of observational studies with meta analyses for any physical and/or mental comorbidities associated with eye disease. For each association, random-effects summary effect size, heterogeneity, small-study effect, excess significance bias and 95% prediction intervals were calculated, and used to grade significant evidence from convincing to weak. 34 studies were included covering 58 outcomes. No outcomes yielded convincing evidence, six outcomes yielded highly suggestive results (cataract positively associated with type 2 diabetes, open-angled glaucoma positively associated with myopia and diabetes, diabetic retinopathy positively associated with cardiovascular disease and cardiovascular mortality, and retinopathy of prematurity positively associated with chorioamnionitis), eight outcomes yielded suggestive results (diabetic retinopathy positively associated with all-cause mortality and depression, diabetic macular oedema positively associated with dyslipidaemia, cataract positively associated with gout, nuclear sclerosis positively associated with all-cause mortality, open angled glaucoma positively associated with migraine and hypertension, and age-related macular degeneration positively associated with diabetes), and 18 outcomes yielded weak evidence. Results show highly suggestive or suggestive evidence for associations between several types of eye diseases with several comorbid outcomes. Practitioners and public health policies should note these findings when developing healthcare policies.
摘要
全球22亿人患有视力障碍和/或各种眼疾。到目前为止, 大多数系统综述都是针对眼病而进行的, 没有系统地评价眼病与各种生理和心理健康结果之间的关系。此外, 文献的影响力和可靠性尚不清楚。我们对与眼病相关的任何全身和/或精神共患疾病的meta分析的观察性研究进行了伞形评价。对于每项研究, 我们都计算了随机效应的总效应量、异质性、小型研究效应、显著性偏差和95%的可信区间, 并将显著性证据等级从信服到较弱进行了划分。共纳入34项研究, 包括58项结果。其中没有一项结果的证据等级达到信服, 6个结果的证据等级达到高度有意义 (白内障与2型糖尿病正相关, 开角型青光眼与近视和糖尿病正相关, 糖尿病视网膜病变与心血管疾病和心血管死亡率正相关, 早产儿视网膜病变与绒毛膜羊膜炎呈正相关, 8项结果的证据等级为有意义 (糖尿病视网膜病变与全因死亡率和抑郁呈正相关, 糖尿病黄斑水肿与血脂异常呈正相关, 白内障与痛风呈正相关, 核硬化与全因死亡率呈正相关, 开角型青光眼与偏头痛和高血压呈正相关, 年龄相关性黄斑变性与糖尿病呈正相关, 18项结果的证据不足。结果显示多种眼病与多种共患疾病之间的相关性为高度有意义或有意义等级的证据。相关人员在制定公共卫生保健政策时应注意这些发现。
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
World Health Organization. Blindness and vision impairment: The key facts. 2019. https://www.who.int/en/news-room/fact-sheets/detail/blindness-and-visual-impairment. Accessed May 6, 2020.
Bourne RR, Flaxman SR, Braithwaite T, Cicinelli MV, Das A, Jonas JB, et al. Magnitude, temporal trends, and projections of the global prevalence of blindness and distance and near vision impairment: a systematic review and meta-analysis. Lancet Glob Health. 2017;5:e888–e897.
Fricke TR, Tahhan N, Resnikoff S, Papas E, Burnett A, Ho SM, et al. Global prevalence of presbyopia and vision impairment from uncorrected presbyopia: systematic review, meta-analysis, and modelling. Ophthalmology. 2018;125:1492–9.
Swenor BK, Simonsick EM, Ferrucci L, Newman AB, Rubin S, Wilson V, et al. Visual impairment and incident mobility limitations: the health, aging and body composition study. J Am Geriatr Soc. 2015;63:46–54.
Chen Y-J, Yeung L, Sun C-C, Huang C-C, Chen K-S, Lu Y-H. Age-related macular degeneration in chronic kidney disease: a meta-analysis of observational studies. Am J Nephrol. 2018;48:278–91.
Luo C, Chen X, Jin H, Yao K. The association between gout and cataract risk: a meta-analysis. PloS One. 2017;12:e0180188.
Shi Y, Liu P, Guan J, Lu Y, Su K. Association between glaucoma and obstructive sleep apnea syndrome: a meta-analysis and systematic review. PloS One. 2015;10:e0115625–e0115625.
Choi HG, Lee MJ, Lee S-M. Visual impairment and risk of depression: a longitudinal follow-up study using a national sample cohort. Sci Rep. 2018;8:2083.
Hong T, Mitchell P, Burlutsky G, Liew G, Wang JJ. Visual impairment, hearing loss and cognitive function in an older population: longitudinal findings from the Blue Mountains Eye Study. PLoS One. 2016;11:e0147646.
Meyer-Rochow VB, Hakko H, Ojamo M, Uusitalo H, Timonen M. Suicides in visually impaired persons: a nation-wide register-linked study from finland based on thirty years of data. PloS One. 2015;10:e0141583–e0141583.
Rajala U, Pajunpää H, Koskela P, Keinänen-Kiukaanniemi S. High cardiovascular disease mortality in subjects with visual impairment caused by diabetic retinopathy. Diabetes Care. 2000;23:957.
McCarty CA, Nanjan MB, Taylor HR. Vision impairment predicts 5 year mortality. Br J Ophthalmol. 2001;85:322–6.
Ioannidis JP. Integration of evidence from multiple meta-analyses: a primer on umbrella reviews, treatment networks and multiple treatments meta-analyses. CMAJ. 2009;181:488–93.
Ioannidis J. Next-generation systematic reviews: prospective meta-analysis, individual-level data, networks and umbrella reviews. Br J Sports Med. 2017;51:1456–8.
Aromataris E, Fernandez R, Godfrey CM, Holly C, Khalil H, Tungpunkom P. Summarizing systematic reviews: methodological development, conduct and reporting of an umbrella review approach. Int J Evid Based Health. 2015;13:132–40.
Radua J, Ramella‐Cravaro V, Ioannidis JP, Reichenberg A, Phiphopthatsanee N, Amir T, et al. What causes psychosis? An umbrella review of risk and protective factors. World Psychiatry. 2018;17:49–66.
Raglan O, Kalliala I, Markozannes G, Cividini S, Gunter MJ, Nautiyal J, et al. Risk factors for endometrial cancer: an umbrella review of the literature. Int J Cancer. 2019;145:1719–30.
Theodoratou E, Tzoulaki I, Zgaga L, Ioannidis JP. Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ. 2014;348:g2035.
Shea BJ, Reeves BC, Wells G, Thuku M, Hamel C, Moran J, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ. 2017;358:j4008.
Veronese N, Solmi M, Caruso MG, Giannelli G, Osella AR, Evangelou E, et al. Dietary fiber and health outcomes: an umbrella review of systematic reviews and meta-analyses. Am J Clin Nutr. 2018;107:436–44.
Veronese N, Demurtas J, Pesolillo G, Celotto S, Barnini T, Calusi G, et al. Magnesium and health outcomes: an umbrella review of systematic reviews and meta-analyses of observational and intervention studies. Eur J Nutr. 2020;59:263–72.
Machado MO, Veronese N, Sanches M, Stubbs B, Koyanagi A, Thompson T, et al. The association of depression and all-cause and cause-specific mortality: an umbrella review of systematic reviews and meta-analyses. BMC Med. 2018;16:1–13.
DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.
Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.
Riley RD, Higgins JP, Deeks JJ. Interpretation of random effects meta-analyses. BMJ. 2011;342:d549.
Bortolato B, Köhler CA, Evangelou E, León‐Caballero J, Solmi M, Stubbs B, et al. Systematic assessment of environmental risk factors for bipolar disorder: an umbrella review of systematic reviews and meta‐analyses. Bipolar Disord. 2017;19:84–96.
Dragioti E, Evangelou E, Larsson B, Gerdle B. Effectiveness of multidisciplinary programmes for clinical pain conditions: an umbrella review. J Rehabil Med. 2018;50:779–91.
Ioannidis JP, Trikalinos TA. An exploratory test for an excess of significant findings. Clin Trials. 2007;4:245–53.
Ioannidis JP. Clarifications on the application and interpretation of the test for excess significance and its extensions. J Math Psychol. 2013;57:184–7.
Dragioti E, Karathanos V, Gerdle B, Evangelou E. Does psychotherapy work? An umbrella review of meta‐analyses of randomized controlled trials. Acta Psychiatr Scand. 2017;136:236–46.
Li X, Meng X, Timofeeva M, Tzoulaki I, Tsilidis KK, Ioannidis JP. et al. Serum uric acid levels and multiple health outcomes: umbrella review of evidence from observational studies, randomised controlled trials, and Mendelian randomisation studies. BMJ. 2017;357:j2376
Akbari M, Akbari S, Pasquale LR. The association of primary open-angle glaucoma with mortality: a meta-analysis of observational studies. Arch Ophthalmol. 2009;127:204–10.
Marcus MW, de Vries MM, Junoy Montolio FG, Jansonius NM. Myopia as a risk factor for open-angle glaucoma: a systematic review and meta-analysis. Ophthalmology. 2011;118:1989–94.e2.
Li L, Wan X, Zhao G. Meta-analysis of the risk of cataract in type 2 diabetes. BMC Ophthalmol. 2014;14:94.
Chen X, Jhanji V, Chen C, Chen H. Serological association of Chlamydia pneumoniae infection with age-related macular degeneration: a systematic review and meta-analysis. PloS One. 2014;9:e103466.
Zhou M, Wang W, Huang W, Zhang X. Diabetes mellitus as a risk factor for open-angle glaucoma: a systematic review and meta-analysis. PloS One. 2014;9:e102972.
Bae HW, Lee N, Lee HS, Hong S, Seong GJ, Kim CY. Systemic hypertension as a risk factor for open-angle glaucoma: a meta-analysis of population-based studies. PloS One. 2014;9:e108226.
Zhao D, Cho J, Kim MH, Friedman DS, Guallar E. Diabetes, fasting glucose, and the risk of glaucoma: a meta-analysis. Ophthalmology. 2015;122:72–78.
Song E, Sun H, Xu Y, Ma Y, Zhu H, Pan C-W. Age-related cataract, cataract surgery and subsequent mortality: a systematic review and meta-analysis. PloS One. 2014;9:e112054.
Au SCL, Tang S-M, Rong S-S, Chen L-J, Yam JCS. Association between hyperglycemia and retinopathy of prematurity: a systemic review and meta-analysis. Sci Rep. 2015;5:9091.
Das R, Kerr R, Chakravarthy U, Hogg RE. Dyslipidemia and diabetic macular edema: a systematic review and meta-analysis. Ophthalmology. 2015;122:1820–7.
Fernandez AB, Panza GA, Cramer B, Chatterjee S, Jayaraman R, Wu W-C. Age-related macular degeneration and incident stroke: a systematic review and meta-analysis. PloS One. 2015;10:e0142968.
Zhou L-X, Sun C-L, Wei L-J, Gu Z-M, Lv L, Dang Y. Lower cognitive function in patients with age-related macular degeneration: a meta-analysis. Clin Interv Aging 2016;11:215–23.
Chan PYL, Tang S-M, Au SCL, Rong S-S, Lau HHW, Ko STC, et al. Association of gestational hypertensive disorders with retinopathy of prematurity: a systematic review and meta-analysis. Sci Rep. 2016;6:30732.
Wang J, Xue Y, Thapa S, Wang L, Tang J, Ji K. Relation between age-related macular degeneration and cardiovascular events and mortality: a systematic review and meta-analysis. BioMed Res Int. 2016;2016:8212063.
Zhu X-R, Zhang Y-P, Bai L, Zhang X-L, Zhou J-B, Yang J-K. Prediction of risk of diabetic retinopathy for all-cause mortality, stroke and heart failure: Evidence from epidemiological observational studies. Medicine. 2017;96:e5894.
McGuinness MB, Karahalios A, Finger RP, Guymer RH, Simpson JA. Age-related macular degeneration and mortality: a systematic review and meta-analysis. Ophthalmic Epidemiol. 2017;24:141–52.
Zhou Y, Zhang Y, Shi K, Wang C. Body mass index and risk of diabetic retinopathy: a meta-analysis and systematic review. Medicine. 2017;96:e6754.
Xu C, Li J, Li Z, Mao X. Migraine as a risk factor for primary open angle glaucoma: a systematic review and meta-analysis. Medicine. 2018;97:e11377.
Zhou Y, Wang C, Shi K, Yin X. Relationship between dyslipidemia and diabetic retinopathy: a systematic review and meta-analysis. Medicine. 2018;97:e12283.
Zhou Y, Wang C, Shi K, Yin X. Relation of metabolic syndrome and its components with risk of diabetic retinopathy: a meta-analysis of observational studies. Medicine. 2018;97:e12433.
Villamor-Martinez E, Cavallaro G, Raffaeli G, Mohammed Rahim OMM, Gulden S, Ghazi AMT, et al. Chorioamnionitis as a risk factor for retinopathy of prematurity: An updated systematic review and meta-analysis. PloS One. 2018;13:e0205838.
Huang J, Tang Y, Zhu T, Li Y, Chun H, Qu Y, et al. Cumulative evidence for association of sepsis and retinopathy of prematurity. Medicine. 2019;98:e17512.
Huon L-K, Liu SY-C, Camacho M, Guilleminault C. The association between ophthalmologic diseases and obstructive sleep apnea: a systematic review and meta-analysis. Sleep Breath. 2016;20:1145–54.
Druet-Cabanac M, Boussinesq M, Dongmo L, Farnarier G, Bouteille B, Preux PM. Review of epidemiological studies searching for a relationship between onchocerciasis and epilepsy. Neuroepidemiology. 2004;23:144–9.
Wu C, You Z. Meta-analysis of the relationship between depression and diabetic retinopathy. Biomed Res. 2018;29:0970–938X.
Xin X, Sun Y, Li S, Xu H, Zhang D. Age-related macular degeneration and the risk of all-cause and cardiovascular mortality: a meta-analysis of cohort studies. Retina. 2018; 38. https://journals.lww.com/retinajournal/Fulltext/2018/03000/AGE_RELATED_MACULAR_DEGENERATION_AND_THE_RISK_OF.7.aspx.
Wang X, Tang L, Gao L, Yang Y, Cao D, Li Y. Myopia and diabetic retinopathy: a systematic review and meta-analysis. Diabetes Res Clin Pr. 2016;111:1–9.
Guo VY, Cao B, Wu X, Lee JJW, Zee BC. Prospective association between diabetic retinopathy and cardiovascular disease—a systematic review and meta-analysis of cohort studies. J Stroke Cerebrovasc Dis. 2016;25:1688–95.
Chatziralli IP, Sergentanis TN. Risk factors for intraoperative floppy iris syndrome: a meta-analysis. Ophthalmology. 2011;118:730–5.
Song D, Li C, Wang Z, Zhao Y, Shen B, Zhao W. Association of non‐alcoholic fatty liver disease with diabetic retinopathy in type 2 diabetic patients: a meta‐analysis of observational studies. J Diabetes Investig. 2020.
Xu X-H, Sun B, Zhong S, Wei D-D, Hong Z, Dong A-Q. Diabetic retinopathy predicts cardiovascular mortality in diabetes: a meta-analysis. BMC Cardiovasc Disord. 2020;20:1–8.
Kim SJ, Port AD, Swan R, Campbell JP, Chan RVP, Chiang MF. Retinopathy of prematurity: a review of risk factors and their clinical significance. Surv Ophthalmol. 2018;63:618–37.
Oh J-W, Park C-W, Moon KC, Park JS, Jun JK. The relationship among the progression of inflammation in umbilical cord, fetal inflammatory response, early-onset neonatal sepsis, and chorioamnionitis. PloS One. 2019;14:e0225328–e0225328.
Bolinger MT, Antonetti DA. Moving past anti-VEGF: novel therapies for treating diabetic retinopathy. Int. J. Mol. Sci. 2016;17:1498.
Tsai T, Kuehn S, Tsiampalis N, Vu M-K, Kakkassery V, Stute G, et al. Anti-inflammatory cytokine and angiogenic factors levels in vitreous samples of diabetic retinopathy patients. PloS One. 2018;13:e0194603–e0194603.
Domingueti CP, Dusse LMS, das Graças Carvalho M, de Sousa LP, Gomes KB, Fernandes AP. Diabetes mellitus: the linkage between oxidative stress, inflammation, hypercoagulability and vascular complications. J Diabetes Complicat. 2016;30:738–45.
Donnelly R, Emslie-Smith AM, Gardner ID, Morris AD. Vascular complications of diabetes. BMJ. 2000;320:1062–6.
Kern TS, Barber AJ. Retinal ganglion cells in diabetes. J Physiol. 2008;586:4401–8.
Ioannidis JPA. The mass production of redundant, misleading, and conflicted systematic reviews and meta-analyses. Milbank Q. 2016;94:485–514.
Author information
Authors and Affiliations
Contributions
MT: conceptualisation, data collection, writing manuscript. LS: conceptualisation, supervision, critical appraisal of manuscript and revision writing; NV: conceptualisation, data analysis, writing manuscript, revision of manuscript; DP: conceptualisation, data analysis, writing manuscript, revision of manuscript; YB: conceptualisation, writing manuscript, critical appraisal; TG: conceptualisation, writing manuscript, critical appraisal; SP: conceptualisation, supervision, critical appraisal of manuscript and revision writing.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Rights and permissions
About this article
Cite this article
Trott, M., Smith, L., Veronese, N. et al. Eye disease and mortality, cognition, disease, and modifiable risk factors: an umbrella review of meta-analyses of observational studies. Eye 36, 369–378 (2022). https://doi.org/10.1038/s41433-021-01684-x
Received:
Revised:
Accepted:
Published:
Version of record:
Issue date:
DOI: https://doi.org/10.1038/s41433-021-01684-x
This article is cited by
-
Community-based interventions to detect visual impairment in community-dwelling older adults aged ≥ 75 years: a systematic review
BMC Public Health (2025)
-
Mortality and ocular parameters and diseases
Eye (2025)
-
An eyecare foundation model for clinical assistance: a randomized controlled trial
Nature Medicine (2025)
-
Susceptibility to eye diseases in relation to age and kidney failure among Taiwanese adults
BMC Geriatrics (2024)
-
Association of diabetic retinopathy on all-cause and cause-specific mortality in older adults with diabetes: National Health and Nutrition Examination Survey, 2005–2008
Scientific Reports (2024)
