Skip to main content
NCBI home page
NIHPA Author Manuscripts logoLink to NIHPA Author Manuscripts
. Author manuscript; available in PMC: 2024 Jan 1.
Published in final edited form as: Ophthalmic Plast Reconstr Surg. 2022 Nov 17;39(4):336–340. doi: 10.1097/IOP.0000000000002310

Associations Between Thyroid Eye Disease and Glaucoma Among Those Enrolled in the National Institutes of Health All of Us Research Program

Arash Delavar 1,2,3, Bharanidharan Radha Saseendrakumar 1,2, Tonya C Lee 1,2,3, Nicole J Topilow 3, Michelle A Ting 3, Catherine Y Liu 3, Bobby S Korn 3, Robert N Weinreb 2,4, Don O Kikkawa 3, Sally L Baxter 1,2,5
PMCID: PMC10188653  NIHMSID: NIHMS1838396  PMID: 36394556

Abstract

Purpose:

To assess the association between thyroid eye disease (TED) and glaucoma.

Methods:

Patients aged 18 and over enrolled in the NIH All of Us Research Program, a nationwide cohort, were extracted. Those with conditions relating to TED were identified and compared with 2020 US Census matched controls without a diagnosis of TED in a 1:4 ratio. We used Pearson’s chi-square tests to study demographics by TED status, and logistic regression to generate odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the association between TED and glaucoma (any type, including glaucoma suspect), using those without TED as the reference group. Multivariable models were adjusted for age, gender, race/ethnicity, eye doctor visits, and smoking status.

Results:

A total of 393 cases of TED were identified, as well as 1572 US Census-matched controls. The median age of the cohort was 63 years (interquartile range: 48–73 years). Age, gender, and race/ethnicity varied by TED status (p<0.001). Overall, 114 (29.0%) of TED cases had a diagnosis of glaucoma, compared to 94 (6.0%) of non-TED controls. On bivariate logistic regression models, those diagnosed with TED were significantly more likely to be diagnosed with glaucoma compared to controls (OR: 6.42; 95% CI: 4.76–8.70; p<0.001). This trend persisted on multivariable logistic regression controlling for confounding factors (OR: 3.37; 95% CI: 1.85–6.20 p<0.001).

Conclusion:

Individuals with TED were significantly more likely to be diagnosed with glaucoma. Clinicians caring for patients with TED should be aware of this elevated risk and arrange glaucoma evaluation, accordingly. \

Précis:

In this nationwide study, we found that those diagnosed with thyroid eye disease were significantly more likely than controls to be diagnosed with glaucoma, even after adjusting for potential confounders.

INTRODUCTION

Thyroid eye disease (TED) is group of ophthalmic manifestations often associated with autoimmune disorders of the thyroid gland.1 TED is most commonly associated with Graves’ disease, but may also include other thyroid disorders including Hashimoto’s thyroiditis and may occur in euthyroid patients.1,2 It results from autoantigens shared between the thyroid and tissues in the orbit.1,3 Several biologic factors result in the expansion of orbital contents and proptosis.1,4,5. These include lymphocytic infiltration of orbital tissues, cytokine secretion and associated inflammation and edema, excess glycosaminoglycan secretion by fibroblasts, and enhanced fibroblast differentiation into either myofibroblasts or adipocytes.1,3–5

TED has been postulated to cause higher intraocular pressure and glaucoma since at least the early 1900s.6 There are several proposed mechanisms in the literature that attempt explain this connection. First, direct pressure on the globe from expansion of tissues in the orbit may increase intraocular pressure.6 Second, outflow of aqueous humor in some patients may be impeded by increased episcleral venous pressure resulting from external pressure on the globe.6–8 In other patients, there may be mucopolysaccharide deposition in the trabecular meshwork with increased outflow resistance.9–11 Third, TED is associated with chronic surface and anterior chamber inflammation and formation of peripheral anterior synechiae, which may cause outflow resistance and secondary angle closure.6,12–14 Lastly, since many patients are treated with ocular and systemic steroids in the acute phase of TED, steroid-induced intraocular pressure spikes may occur.6,15 Though many mechanisms have been proposed, the extent of the clinical relationship between TED and glaucoma still remains to be elucidated.

Betzler et al. published a systematic review of studies looking at the association between TED and glaucoma from 1991 to 2021.6 Overall, they reported the prevalence of glaucoma among those with a diagnosis of TED ranged from 0.4%–13.5%,6 and concluded that those with TED are at higher risk for glaucoma.6,16–18 Notably, all studies were performed at a single center. However, one Danish study with a broader definition for the exposure variable (Graves’ disease and toxic nodular goiter without orbitopathy) and not included in this systematic review on TED patients did utilize EHR data from multiple centers, and found no association with glaucoma.19 Further, there has been only one study18 that has compared glaucoma prevalence rates with a control group, while the others subjectively compared rates with those found in prior publications.

In this study, we assess the relationship between TED and glaucoma among individuals enrolled in the NIH All of Us Research Program, a multicenter nationwide dataset, in order to compare prevalence of glaucoma among TED patients with a control group. Understanding the extent of any association can help inform future practice guidelines aiming to promote appropriate care for this population.

METHODS

Study Population

We obtained data from the National Institutes of Health (NIH) All of Us Research Program, a nationwide database with an emphasis on diversity.20 Participants provided written informed consent at enrollment in the study, which was approved by the NIH All of Us IRB. All of Us collects a wide range of data from participants, including electronic health record (EHR) data.20 All of Us data undergo de-identification processes prior to becoming available to researchers, and according to data sharing policies results with less than 20 respondents are suppressed in this study.20 Secondary analyses of de-identified data, such as those evaluated for our study, are considered non-human subjects research, which was verified by the University of California San Diego IRB. The study adhered to the Health Insurance Portability and Accountability Act (HIPAA) and the tenets of the Declaration of Helsinki.

Our case group consisted of US-based adults aged 18 and over with a diagnosis of TED. We defined TED as those with a relevant thyroid disease and diagnosis of proptosis or lid retraction on International Classification of Diseases (ICD) codes. Glaucoma status was defined as any type of glaucoma on ICD codes, including glaucoma suspect. Open-angle glaucoma status included both primary and secondary definitions. Names for diagnoses used to create our study cohort can be found in Supplemental Digital Content 1. At the time of our analysis, 372 380 participants had enrolled in the All of Us Research Program, and a total of 393 individuals were identified with a diagnosis of TED. These patients were derived from at least 14 states – with state information not available for some patients due to privacy.

Our control group consisted of US-based adults aged 18 and over without a diagnosis of TED using the definition described above. We selected a sample from the non-TED cohort that matched gender and racial/ethnic demographics from the 2020 US Census. We then randomly selected 1572 of these individuals, representing a control cohort four times the size of our case cohort. Prior studies have shown that control-to-case ratios exceeding 4:1 do not confer any additional statistical benefit.21

Variables

Demographic information was extracted from participants’ survey responses in the All of Us Basics survey.22 Gender was categorized as male, female, and other/skipped. Age in years was categorized as <40, 40–64, 65–74, 75–84, ≥85. Racial and ethnic categories were coded as non-Hispanic (NH) White, NH African American, NH Asian, and Hispanic (any race) individuals. To characterize smoking status, we studied the following question in the All of Us Lifestyle survey:22 “Have you smoked at least 100 cigarettes in your entire life?” Further, to understand engagement with eye care clinicians, we studied the following question in the All of Us Healthcare Access and Utilization survey:22 “During the past 12 months, have you seen or talked to an optometrist, ophthalmologist, or eye doctor (someone who prescribes eyeglasses)?” Prior glaucoma surgery was defined using specific procedures listed in Supplemental Digital Content 1.

Data Analysis

Demographic information and survey responses were stratified by TED status and analyzed using Pearson’s chi-squared tests to generate unadjusted p-values, using the Holm-Bonferroni adjustment for multiple comparisons. We used bivariate and multivariable logistic regression to generate odds ratios (ORs) and 95% confidence intervals (CIs) to characterize the association between TED and glaucoma. Potential covariates were identified using a directed acyclic graph23 of known and suspected confounders for the association between TED and glaucoma (Supplemental Digital Content 2). Age, gender, race/ethnicity, education, income, insurance status, pregnancy, smoking, cardiovascular disease, diabetes, and eye doctor visits were considered. Paths between the exposure and outcome were identified using the back-door criterion.23 We found that adjusting for age, gender, race/ethnicity, smoking status, and eye doctor visits in the prior year provided the minimal sufficient adjustment for estimating the relationship between TED and glaucoma (Supplemental Digital Content 2). Statistical tests were two-sided, and p-values were considered statistically significant at the α = 0.05 level. Analyses were conducted on the NIH All of Us Researcher Workbench using R software version 4.1.0 on cloud based Jupyter notebooks.

RESULTS

A total of 393 cases of thyroid eye disease were identified, as well 1572 controls. The median age of the entire cohort was 63 (interquartile range: 48–73). Female gender accounted for 78.1% of cases and 50.8% of controls, which significantly differed on unadjusted chi-square tests (p<0.001). Cases were also more likely to be NH African American (28.0% vs 10.9%) and less likely to be NH Asian (1.8% vs. 4.8%) than controls (p<0.001). Further, cases were more likely to have a diagnosis of glaucoma (29.0% vs 6.0%, p<0.001), have a history of open-angle glaucoma (7.9% vs 2.4%, p<0.001), have a history of glaucoma surgery (2.5% vs 0.4%, p<0.001), and to have seen an eye doctor in the previous 12 months (29.5% vs 17.8%, p<0.001). No difference was found for smoking status between cases and controls (44.0% vs. 42.6%, p=0.42) (Table 1).

Table 1.

Select characteristics among those with and without thyroid eye disease enrolled in the NIH All of Us Research Program.

Characteristicsa TED diagnosis No TED diagnosis P-valueb
Total, No. (%) 393 (20.0) 1572 (80.0)
Median age (IQR) 66 (56–74) 62 (46–73)
Age category, No. (%) <0.001
 <40 21 (5.3) 280 (17.8)
 40–64 160 (40.7) 601 (38.2)
 65–74 116 (29.5) 355 (22.6)
 75–84 81 (20.6) 261 (16.6)
 ≥85 <20 75 (4.8)
Gender, No. (%) <0.001
 Female 307 (78.1) 798 (50.8)
 Male 79 (20.1) 774 (49.2)
 Other/Skipped <20 <20
Race/Ethnicity <0.001
 NH White 200 (50.9) 978 (62.2)
 NH African American 110 (28.0) 172 (10.9)
 NH Asian <20 75 (4.8)
 Hispanic (any race) 59 (15.0) 282 (17.9)
 Other/Skipped <20 65 (4.1)
Smoked ≥100 cigarettes in life, No. (%) 0.42
 Yes 173 (44.0) 670 (42.6)
 No 211 (53.7) 740 (47.1)
 NA <20 162 (10.3)
Seen eye doctor in prior 12 months, No. (%) <0.001
 Yes 116 (29.5) 280 (17.8)
 No 25 (6.4) 141 (9.0)
 NA 252 (64.1) 1151 (73.2)
Glaucoma diagnosis, No. (%) <0.001
 Yes 114 (29.0) 94 (6.0)
 No 279 (71.0) 1478 (94.0)
Open-angle glaucoma diagnosis, No. (%) <0.001
 Yes 31 (7.9) 37 (2.4)
 No 362 (92.1) 1535 (97.6)
Glaucoma surgery, No. (%) <0.001
 Yes <20 <20
 No 383 (97.5) 1566 (99.6)
Open in a new tab

Abbreviations: TED, thyroid eye disease; No., number; IQR, interquartile range; NH, non-Hispanic.

a

Per the All of Us Research Program data sharing policies, cells with less than 20 respondents are suppressed.

b

P-values were generated from Pearson’s chi-squared tests using the Holm-Bonferroni adjustment for multiple comparisons.

Overall, 114 (29.0%) of TED cases had a diagnosis of glaucoma, compared to 94 (6.0%) of non-TED controls. On bivariate logistic regression models, those with a diagnosis of TED were significantly more likely to have a diagnosis of glaucoma (OR: 6.42; 95% CI: 4.76–8.70; p<0.001). This trend persisted even after controlling for age, gender, race/ethnicity (OR: 5.72; 95% CI: 4.08–8.04; p<0.001) and smoking status (OR: 5.39; 95% CI: 3.82–7.64; p<0.001) in our models. Trends were attenuated but were significant on our DAG-informed models which included eye doctor visits as a variable (OR: 3.37; 95% CI: 1.85–6.20; p<0.001) (Figure 1).

Figure 1.

Figure 1.

Open in a new tab

Forest plot illustrating odds ratios (OR) and 95% confidence intervals (CI) calculated from bivariate and multivariable logistic regression models for the association between thyroid eye disease (TED) and glaucoma, with those without TED as the reference group. Final models were adjusted for age category, gender, race/ethnicity, smoking status, and eye doctor visits in the prior year.

DISCUSSION

In this multicenter nationwide study assessing the association between TED and glaucoma, we found that those with TED were more likely to be diagnosed with glaucoma of any type. These results are in line with several prior studies demonstrating similar associations.16,17 However, other studies have reported24–26 that glaucoma rates did not differ from those found in the general population. Further, a Danish study of Graves’ disease and toxic nodular goiter without orbitopathy found no association with glaucoma,19 which may be due to the lack of orbital changes in these patients.19

We found that our prevalence rate of glaucoma among TED patients (29.0%) is considerably higher than the highest prevalence previously reported (13.5%),17 which studied open-angle glaucoma. This discrepancy may be due to differences in definition of glaucoma. In the current study, glaucoma was defined broadly to include all types of glaucoma based on diagnostic ICD-9 and ICD-10 codes. In contrast, other studies defined glaucoma based on history or examination findings, including intraocular pressure (measured using a variety of techniques), prescribed glaucoma medications, and glaucomatous visual field defects, among others.6,16,24,27

Betzler et al. described how understanding the epidemiological connection between TED and glaucoma is challenging, as anterior segment disease among TED patients can make imaging and diagnosis of visual field defects difficult.6 Moreover, the comorbidity of dysthyroid optic neuropathy, which can affect 3%–7% of TED patients,28 can be mistaken for glaucomatous visual field defects and obfuscates the diagnosis.6 These potential biases may be partially mitigated by studying TED patients who are treated at a variety of institutions, as was done in this study. However, as this is the first US-based study to use multicenter EHR data, it is difficult to draw direct comparisons with prior literature. More evidence is needed to understand the true magnitude of the clinical relationship between TED and glaucoma, which may be possible with the NIH All of Us Research Program as enrollment increases or with other large population-based datasets. Further, more research is needed to understand potential effect modification of this association by glaucoma type. Though we had access to glaucoma type in our dataset, including open-angle glaucoma, we were unable to perform regression modeling due to a small sample size.

Nevertheless, those who provide care for patients with TED should be aware of its association with all types of glaucoma in order to facilitate early detection and treatment, and reduce the possibility of permanent vision loss. Current clinical practice guidelines from the European Group on Graves’ Orbitopathy (EUGOGO) do not specifically recommend glaucoma evaluations for TED patients.29 Presentation to an eye doctor for management of TED provides an opportunity to examine a potentially high-risk group for glaucoma. As the exact glaucoma risk associated with a TED diagnosis is being delineated, clinicians should assess their patients’ optic nerves and refer them for further management, as necessary.

Other than associations between TED and glaucoma, we found significantly greater representation of females in our TED group compared to the control group. Female gender is a well-established risk factor for the development of TED, which is thought to be related to females having higher risk of autoimmune disease generally and Graves’ disease specifically.30 However, among Graves’ disease patients, males are thought to be at higher risk for more severe TED, which is likely related to differences in smoking prevalence by gender.30,31 However, it should be noted that we did not observe any significant difference in smoking prevalence by TED status, though this finding is unadjusted for confounding factors such as gender.

We also found significant differences in the prevalence of TED by race and ethnicity, which has been reported in the literature.30 In particular, NH Africans Americans in our study had nearly a threefold greater representation in the TED group than the control group, while NH Asians had nearly a threefold reduced representation. Of note, we sampled the control group to be consistent with US demographics based on US Census statistics. This is consistent with prior studies showing that those of African descent have the highest risk of TED, followed by Caucasians, and Asians having the lowest risk.32,33 Further research is needed to understand genetic risk factors associated with race and ethnicity among those with TED.

We also observed significantly greater engagement with eye specialists in the prior year among TED patients compared with controls. This is an expected finding as those with a diagnosed eye disorder are naturally more likely to utilize more eye care related services. This makes visits to an eye specialist an important confounding variable in our analysis, as greater engagement with eye specialists increases surveillance bias and the likelihood that someone with glaucoma will be diagnosed. Though we controlled for this variable in our analysis, it is possible that residual confounding may have occurred, as is true for any observational research study.

Our study must be understood in the context of a few additional limitations. First, the eye specialist visits in the prior year survey question may be influenced by social desirability bias. This may have led to an overestimation among TED patients in particular compared to controls, which may have biased our models towards the null. Second, as we used ICD codes and clinical notes were not available in this database, we were thus unable to determine TED or glaucoma severity with optic nerve health or visual field examinations. This is particularly relevant for glaucoma suspect cases. However, glaucoma suspects comprised <20 of our cases, and sub-analyses of logistic regression models with suspect cases removed were largely unchanged (results not shown). Further, as ICD codes were determined by a variety of different clinicians from different institutions, there is potential for interobserver variability and misclassification of diagnoses.

Third, there may have been some selection bias, as most of the All of Us participants who elected to participate in the NIH All of Us Research Program, like other longitudinal research cohorts that require participation on part of enrollees, are of higher socioeconomic status than the general US population. We do not expect this bias to affect our case and control groups differently. Still, it is possible that generalizability may be affected, though to a lesser degree than other study cohorts that do not emphasize diverse enrollment like the NIH All of Us Research Program. Finally, because ophthalmic examination data such as intraocular pressure is currently limited in All of Us, we have limited ability to understand the pathophysiological underpinnings mediating the association between TED and glaucoma.

In conclusion, we found that those with TED were significantly more likely to have been diagnosed with glaucoma. In light of this study’s findings in the context of previous literature, clinicians should be suspicious of glaucoma development among TED patients, which requires further evaluation with baseline structural and function testing, as well as close follow-up. Future studies should take advantage of emerging EHR-based data to help quantify this relationship for this relatively rare disease. As vision loss from glaucoma is irreversible, understanding the extent of this relationship is essential for clinicians who care for TED patients.

Supplementary Material

Supplemental Digital Content 1
Supplemental Digital Content 2

Supplemental Digital Content 2. Directed acyclic graph of known and suspected confounders for the association between TED and glaucoma. Age, gender, race/ethnicity, education, income, insurance status, pregnancy, smoking, cardiovascular disease, diabetes, and eye doctor visits were considered. Age, gender, race/ethnicity, smoking status, and eye doctor visits in the prior year provided the minimal sufficient adjustment for estimating this relationship.

Financial Support:

Author Arash Delavar is a recipient of the Research to Prevent Blindness (New York, NY) Medical Student Eye Research Fellowship. This study was supported by the National Institutes of Health Grants DP5OD029610 and P30EY022589 (Bethesda, MD, USA) and an unrestricted departmental grant from Research to Prevent Blindness. The All of Us Research Program is supported (or funded) by grants through the National Institutes of Health, Office of the Director: Regional Medical Centers: 1 OT2 OD026549; 1 OT2 OD026554; 1 OT2 OD026557; 1 OT2 OD026556; 1 OT2 OD026550; 1 OT2 OD 026552; 1 OT2 OD026553; 1 OT2 OD026548; 1 OT2 OD026551; 1 OT2 OD026555; IAA #: AOD 16037; Federally Qualified Health Centers: HHSN 263201600085U; Data and Research Center: 5 U2C OD023196; Biobank: 1 U24 OD023121; The Participant Center: U24 OD023176; Participant Technology Systems Center: 1 U24 OD023163; Communications and Engagement: 3 OT2 OD023205; 3 OT2 OD023206; and Community Partners: 1 OT2 OD025277; 3 OT2 OD025315; 1 OT2 OD025337; 1 OT2 OD025276. In addition to the funded partners, the All of Us Research Program would not be possible without the contributions made by its participants.

Footnotes

Propriety Interest Statement: Author Catherine Y. Liu, MD, PhD is a Site Investigator for the ongoing phase IV Tepezza clinical trial (ID: NCT04583735) sponsored by Horizon Therapeutics Inc. to evaluate efficacy of teprotumumab as a treatment option for chronic inactive thyroid eye disease (TED).

References

  • 1.Perros P, Neoh C, Dickinson J. Thyroid eye disease. BMJ. 2009;338:b560. [DOI] [PubMed] [Google Scholar]
  • 2.Salvi M, Zhang ZG, Haegert D, et al. Patients with endocrine ophthalmopathy not associated with overt thyroid disease have multiple thyroid immunological abnormalities. J Clin Endocrinol Metab. 1990;70(1):89–94. [DOI] [PubMed] [Google Scholar]
  • 3.Khoo TK, Bahn RS. Pathogenesis of Graves’ ophthalmopathy: the role of autoantibodies. Thyroid. 2007;17(10):1013–1018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Gianoukakis AG, Khadavi N, Smith TJ. Cytokines, Graves’ disease, and thyroid-associated ophthalmopathy. Thyroid. 2008;18(9):953–958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Shan SJ, Douglas RS. The pathophysiology of thyroid eye disease. J Neuroophthalmol. 2014;34(2):177–185. [DOI] [PubMed] [Google Scholar]
  • 6.Betzler BK, Young SM, Sundar G. Intraocular Pressure and Glaucoma in Thyroid Eye Disease. Ophthalmic Plast Reconstr Surg. 2022;38(3):219–225. [DOI] [PubMed] [Google Scholar]
  • 7.Abraham C, Kim HH, Lissner GS, Ebroon DA, Tanna AP. Episcleral Venous Pressure in Normal Eyes and in Eyes with Thyroid Ophthalmopathy. Investigative Ophthalmology & Visual Science; 2003. [Google Scholar]
  • 8.Potemkin VV, Goltsman EV, Kovaleva MS. Episcleral venous pressure level in patients with thyroid associated orbitopathy. Ophthalmology journal. 2018;11(3):21–25. [Google Scholar]
  • 9.Tripathy D, Rao A, Banerjee A, Padhy D. Aqueous misdirection in thyroid eye disease. BMJ Case Rep. 2014;2014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Knepper PA, Covici S, Fadel JR, Mayanil CS, Ritch R. Surface-tension properties of hyaluronic Acid. J Glaucoma. 1995;4(3):194–199. [PubMed] [Google Scholar]
  • 11.Duncan KG, Jumper MD, Ribeiro RC, et al. Human trabecular meshwork cells as a thyroid hormone target tissue: presence of functional thyroid hormone receptors. Graefes Arch Clin Exp Ophthalmol. 1999;237(3):231–240. [DOI] [PubMed] [Google Scholar]
  • 12.Parekh AS, Mansouri K, Weinreb RN, Tafreshi A, Korn BS, Kikkawa DO. Twenty-four-hour intraocular pressure patterns in patients with thyroid eye disease. Clin Exp Ophthalmol. 2015;43(2):108–114. [DOI] [PubMed] [Google Scholar]
  • 13.Xu N, Huang D, Yang H, Lai Z, Luo Q. Ocular surface characteristics and impression cytology in patients with active versus inactive Thyroid Eye Disease. Eye Sci. 2012;27(2):64–68. [DOI] [PubMed] [Google Scholar]
  • 14.Bodh SA, Kumar V, Raina UK, Ghosh B, Thakar M. Inflammatory glaucoma. Oman J Ophthalmol. 2011;4(1):3–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Roberti G, Oddone F, Agnifili L, et al. Steroid-induced glaucoma: Epidemiology, pathophysiology, and clinical management. Surv Ophthalmol. 2020;65(4):458–472. [DOI] [PubMed] [Google Scholar]
  • 16.Cockerham KP, Pal C, Jani B, Wolter A, Kennerdell JS. The prevalence and implications of ocular hypertension and glaucoma in thyroid-associated orbitopathy. Ophthalmology. 1997;104(6):914–917. [DOI] [PubMed] [Google Scholar]
  • 17.Ohtsuka K, Nakamura Y. Open-angle glaucoma associated with Graves disease. Am J Ophthalmol. 2000;129(5):613–617. [DOI] [PubMed] [Google Scholar]
  • 18.Behrouzi Z, Rabei HM, Azizi F, et al. Prevalence of open-angle glaucoma, glaucoma suspect, and ocular hypertension in thyroid-related immune orbitopathy. J Glaucoma. 2007;16(4):358–362. [DOI] [PubMed] [Google Scholar]
  • 19.Brandt F, Thvilum M, Hegedus L, Brix TH. Hyperthyroid patients without Graves’ orbitopathy are not at increased risk of developing glaucoma: a nationwide Danish register-based case-control study. Endocrine. 2018;59(1):137–142. [DOI] [PubMed] [Google Scholar]
  • 20.All of Us Research Program I, Denny JC, Rutter JL, et al. The “All of Us” Research Program. N Engl J Med. 2019;381(7):668–676. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Grimes DA, Schulz KF. Compared to what? Finding controls for case-control studies. Lancet. 2005;365(9468):1429–1433. [DOI] [PubMed] [Google Scholar]
  • 22.NIH All of Us Research Program Investigators. Survey Explorer. https://databrowser.researchallofus.org/. Accessed 28 June, 2022.
  • 23.Textor J, van der Zander B, Gilthorpe MS, Liskiewicz M, Ellison GT. Robust causal inference using directed acyclic graphs: the R package ‘dagitty’. Int J Epidemiol. 2016;45(6):1887–1894. [DOI] [PubMed] [Google Scholar]
  • 24.Kalmann R, Mourits MP. Prevalence and management of elevated intraocular pressure in patients with Graves’ orbitopathy. Br J Ophthalmol. 1998;82(7):754–757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.da Silva FL, de Lourdes Veronese Rodrigues M, Akaishi PM, Cruz AA. Graves’ orbitopathy: frequency of ocular hypertension and glaucoma. Eye (Lond). 2009;23(4):957–959. [DOI] [PubMed] [Google Scholar]
  • 26.Kim JW, Ko J, Woo YJ, Bae HW, Yoon JS. Prevalence of Ocular Hypertension and Glaucoma as Well as Associated Factors in Graves’ Orbitopathy. J Glaucoma. 2018;27(5):464–469. [DOI] [PubMed] [Google Scholar]
  • 27.Eslami F, Borzouei S, Khanlarzadeh E, Seif S. Prevalence of increased intraocular pressure in patients with Graves’ ophthalmopathy and association with ophthalmic signs and symptoms in the north-west of Iran. Clin Ophthalmol. 2019;13:1353–1359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Blandford AD, Zhang D, Chundury RV, Perry JD. Dysthyroid optic neuropathy: update on pathogenesis, diagnosis, and management. Expert Rev Ophthalmol. 2017;12(2):111–121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Bartalena L, Kahaly GJ, Baldeschi L, et al. The 2021 European Group on Graves’ orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves’ orbitopathy. Eur J Endocrinol. 2021;185(4):G43–G67. [DOI] [PubMed] [Google Scholar]
  • 30.Stan MN, Bahn RS. Risk factors for development or deterioration of Graves’ ophthalmopathy. Thyroid. 2010;20(7):777–783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Wiersinga WM, Bartalena L. Epidemiology and prevention of Graves’ ophthalmopathy. Thyroid. 2002;12(10):855–860. [DOI] [PubMed] [Google Scholar]
  • 32.Aguwa UT, Srikumaran D, Brown N, Woreta F. Improving Racial Diversity in the Ophthalmology Workforce: A Call to Action for Leaders in Ophthalmology. Am J Ophthalmol. 2021;223:306–307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Tsai CC, Kau HC, Kao SC, Hsu WM. Exophthalmos of patients with Graves’ disease in Chinese of Taiwan. Eye (Lond). 2006;20(5):569–573. [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplemental Digital Content 1
NIHMS1838396-supplement-Supplemental_Digital_Content_1.docx (26.6KB, docx)
Supplemental Digital Content 2

Supplemental Digital Content 2. Directed acyclic graph of known and suspected confounders for the association between TED and glaucoma. Age, gender, race/ethnicity, education, income, insurance status, pregnancy, smoking, cardiovascular disease, diabetes, and eye doctor visits were considered. Age, gender, race/ethnicity, smoking status, and eye doctor visits in the prior year provided the minimal sufficient adjustment for estimating this relationship.

NIHMS1838396-supplement-Supplemental_Digital_Content_2.tiff (30.6MB, tiff)

RESOURCES