
==== Front
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Sci Rep
Scientific Reports
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Nature Publishing Group UK London

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10.1038/s41598-024-71524-x
Article
Association of rheumatoid arthritis with age-related macular degeneration in nationwide longitudinal cohort study
Yoon Je Moon 1
Eun Yeonghee 2
Han Kyungdo 3
Kim Bong Sung 3
Jung Wonyoung 4
Kim Hyungjin 56
Shin Dong Wook dwshin.md@gmail.com

478
Lim Dong Hui ldhlse@gmail.com

19
1 grid.264381.a 0000 0001 2181 989X Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
2 grid.264381.a 0000 0001 2181 989X Division of Rheumatology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
3 https://ror.org/017xnm587 grid.263765.3 0000 0004 0533 3568 Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea
4 grid.264381.a 0000 0001 2181 989X Department of Family Medicine and Supportive Care Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
5 grid.264381.a 0000 0001 2181 989X Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
6 grid.264381.a 0000 0001 2181 989X Department of Medical Humanities, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
7 https://ror.org/04q78tk20 grid.264381.a 0000 0001 2181 989X Department of Digital Health, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea
8 https://ror.org/04q78tk20 grid.264381.a 0000 0001 2181 989X Department of Clinical Study Design and Evaluation, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, 81 Irwon-Ro, Gangnam-gu, Seoul, 06351 Republic of Korea
9 https://ror.org/04q78tk20 grid.264381.a 0000 0001 2181 989X Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-gu, Seoul, 06351 Republic of Korea
9 9 2024
9 9 2024
2024
14 2099713 3 2024
28 8 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Previous studies on the association between age-related macular degeneration (AMD) and rheumatoid arthritis (RA) have shown conflicting results. We sought to assess the association between AMD with/without visual disability (VD) and the risk of RA using National Health Insurance data in South Korea. In total, 3,537,293 individuals who underwent health checkups in 2009 were included and followed until 2019. Participants with VD were defined as those with loss of vision or a visual field defect as certified by the Ministry of Health and Welfare of Korea. Using multivariable adjusted Cox regression analysis, RA hazard ratios were estimated for control and AMD with/without VD groups. In total, 43,772 participants (1.24%) were diagnosed with RA. Individuals with AMD were at higher risk of RA compared to controls, regardless of the presence of VD (aHR 1.11; 95% CI 1.02–1.21). Among individuals with AMD, different risk levels of RA were observed between those without VD (aHR 1.13; 95% CI 1.03–1.21) and those with VD (aHR 0.90; 95% CI 0.64–1.27). AMD was associated with a higher risk of RA, which remained significant as a trend even after adjusting for lifestyle factors and comorbidities.

Keywords

Nationwide cohort
Rheumatoid arthritis
Age-related macular degeneration
Visual disability
Subject terms

Macular degeneration
Rheumatoid arthritis
http://dx.doi.org/10.13039/501100003725 National Research Foundation of Korea NRF-2021R1C1C1007795 Lim Dong Hui http://dx.doi.org/10.13039/501100003710 Korea Health Industry Development Institute HI20C1073 Lim Dong Hui issue-copyright-statement© Springer Nature Limited 2024
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pmcIntroduction

Age-related macular degeneration (AMD) is a disease that affects the retinal macular area and is an important cause of visual impairment1. The prevalence of AMD varies according to ethnicity, but by 2040, 300 million people globally are predicted to have the disease2. AMD impairs the quality of life and causes functional disability in older adults3,4.

There are various risk factors for AMD, such as age, genetics, diet, and smoking, and inflammation plays a crucial role in AMD development5,6. A recent study revealed associations between AMD and other diseases like Alzheimer's disease and Parkinson's disease and proposed that inflammation and oxidative stress are potential mechanisms to explain these connections7.

Rheumatoid arthritis (RA) is a systemic autoimmune disorder, of which inflammation of the synovial joints is a hallmark8. Inflammation is a cardinal feature of RA, and oxidative stress is linked to the disease process of RA9. Therefore, there is biological plausibility that AMD is linked to RA.

Previous cohort studies have indicated an increased risk of AMD in RA patients. A cohort study using the U.S. MarketScan database, which included > 37,000 RA patients, reported that RA patients had a two-fold greater risk for AMD compared to controls10. Similarly, an English cohort study including 260,000 RA patients reported a modestly increased risk of subsequent AMD admission in the RA cohort compared to the reference cohort11. In contrast, a cross-sectional study of 4,813 participants of the U.S. National Health and Nutrition Examination Survey did not identify any association between AMD status and RA12. In addition, a cohort study in England found no increase in the risk of RA in patients with AMD. RA patients also appeared to be relatively spared from AMD in a prospective cohort study of 993 RA patients from Canada when compared to published data from racially similar general populations13. Therefore, the relationship between AMD and RA is still unclear, and data on the risk of RA in AMD patients from Asia remain inadequate (Supplementary Table 1).

In response to this gap, we attempted to compare the risk of incident RA between AMD patients and non-AMD controls in a large nationwide South Korean population-based cohort.

Methods

Data source

The data used in this study were obtained from the National Health Information Database (NHID). All individuals in South Korea are included in the National Health Insurance Service (NHIS) system. The NHIS produces and maintains the NHID, which is a public database containing information on healthcare utilization, health screening, sociodemographic factors, and mortality of all Koreans14. The database on healthcare utilization contains information on diagnosis and treatment performed in hospitals. The NHIS uses the Korean Classification of Diseases, which is a classification scheme considered equivalent to the International Classification of Diseases15,16.

Health screening data are obtained from the national health screening program, which is provided to all Koreans over the age of 40 and all employees regardless of age every two years. This includes information on health behaviors obtained from doctor’s counseling and questionnaires filled out by subjects, as well as the results of anthropometric measurements, blood pressure, visual acuity, hearing, and blood and urine tests. Blood pressure was measured after resting for 5 min in a sitting position on the day of the health screening. Blood test items included glucose, total cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol, triglycerides, and creatinine, and tests were performed after 8 h of fasting. The NHIS certifies and regularly conducts quality control evaluation of the hospitals that carry out health screening. The cohort profile was explained in detail in previous review articles15–17. In 2009, 66% of people participated in the health screening program18.

Study population

Individuals under the age of 50 who participated in a health screening program in 2009 were included in this study. Among all individuals, 250,392 were excluded due to missing data. A total of 683,044 individuals diagnosed with RA before the health screening examination were also excluded. Finally, 3,537,293 individuals were included in the analysis. Figure 1 shows the eligibility criteria and a flow chart of patient enrollment.Fig. 1 Flow diagram for identifying the study population for incident fractures.

Definition of AMD and visual disability (VD)

Individuals with AMD were identified with a diagnostic code for AMD (International Classification of Diseases 10th revision [ICD-10] code H353) registered by an ophthalmologist in the 1 year prior to the health screening. The definition of AMD as involving a claim with the ICD-10 code for AMD (H353) has also been used in previous epidemiological research on AMD7.

The national disability registration system established by Korean government in 1988 determines welfare benefits according to the type and severity of a disability19. In order to be registered as an individual with a VD, a person must submit documents about their disability diagnosis performed by an ophthalmologist according to detailed criteria (Supplementary Table 2). Individuals with VD were defined as those with a VD certification from the Ministry of Health and Welfare of Korea.

Study outcome and follow-up

The primary outcome was newly diagnosed RA during the study period. Newly diagnosed RA was identified based on the diagnostic code for seropositive RA (ICD-10 code M05) or seronegative RA (ICD-10 code M06) with a prescription of any of the synthetic or biologic disease-modifying anti-rheumatic drugs. A previous study showed that RA was defined by a high positive predictive value and accuracy regarding the ICD-10 code and the prescription of disease-modifying anti-rheumatic drugs in the Korean claims database20. Study individuals were followed from the date of health screening (during 2009) to the date of RA occurrence, death, or December 31, 2019—whichever came first.

Covariates

A number of studies addressing risk factors for RA were reviewed21–23. Among the health screening variables, variables that were likely related to RA were included in the multivariable regression model. The selected variables were age, sex, hypertension, diabetes, dyslipidemia, income status, smoking, drinking habits, physical activity, and Charlson comorbidity index (CCI).

Individuals taking anti-hypertensive medications or with systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg were considered to have hypertension. Individuals taking anti-diabetic medications or with fasting glucose ≥ 126 mg/dL were considered to have diabetes mellitus. Individuals taking lipid-lowering medications or with total cholesterol ≥ 240 mg/dL were considered to have dyslipidemia.

Individuals with an income level less than the bottom 20th percentile based on health insurance premiums were defined as low-income residents.

Smoking status was divided into three categories: non-smokers, current smokers, and ex-smokers. Alcohol consumption status was divided into three categories according to average daily alcohol intake: non-drinkers, those with an average intake < 30 g/day, and those with an average intake ≥ 30 g/day. Regular exercise was defined as moderate physical activity carried out for ≥ 30 min ≥ 5 times a week or strenuous physical activity carried out for ≥ 20 min ≥ 3 times a week. Body mass index was calculated as weight in kilograms divided by the square of height in meters (kg/m2).

CCI a well-known and widely used indicator of comorbidity, was calculated as a weighted summed count for 19 diseases. The weights (points) assigned to each condition were as follows: 1 = myocardial infarction, congestive heart failure, peripheral vascular disease, cerebrovascular disease, dementia, chronic pulmonary disease, connective tissue disease, ulcer disease, mild liver disease, or diabetes; 2 = hemiplegia, moderate or severe renal disease, diabetes with end-organ damage, any tumor without metastasis, leukemia, or lymphoma; 3 = moderate or severe liver disease; or 6 = metastatic solid tumor, or acquired immunodeficiency syndrome. These weights were assigned depending on the mortality risk associated with each condition24. CCI score was determined using ICD-10 codes25.

Study protocol approvals

This study adhered to the Declaration of Helsinki, and the study protocol was reviewed and approved by the institutional review board (IRB) of Samsung Medical Center (SMC IRB no. 2022-03-060). The Deliberative Committee of the NHIS approved the conditional use of the database for this study. Informed consent from participants was waived by the IRB of Samsung Medical Center because of the retrospective nature of the study and the analysis used anonymous and public data.

Statistical analysis

Data are described as mean ± standard deviation (SD) and numerical (%) values. Differences between groups (non-AMD vs. AMD or AMD without VD vs. AMD with VD) were investigated using an independent t test for continuous data and the chi-squared test for categorical data.

We analyzed the cumulative incidence of RA in the study population using the Kaplan–Meier curve. Cox regression analysis was conducted to estimate the hazard ratio (HR) and 95% confidence interval (CI) values for the risk of RA development associated with AMD and VD. Variables included in the multivariable adjusted Cox regression model are as follows: model 1 = age and sex; model 2 = model 1 plus income, place, body mass index, smoking habits, alcohol consumption habits, and regular exercise; model 3 = model 2 plus diabetes, hypertension, dyslipidemia, and CCI.

Additional stratified analyses were performed to evaluate the interaction effect of AMD and VD in RA with other variables. Individuals were stratified by age, sex, and the presence of any comorbidity (diabetes, hypertension, or dyslipidemia).

Sensitivity analyses defining RA using only ICD-10 codes were performed.

All statistical analyses were performed using SAS version 9.4 (SAS Institute, Inc., Cary, NC, USA). P < 0.05 was considered to be statistically significant.

Results

Baseline characteristics

Of 3,537,293 individuals, a total 41,412 individuals (1.17%) had AMD at the time of their health screening. Compared to individuals without AMD, those with AMD were more likely to be female, older, non-smokers, and non-drinkers; have a higher income; be a rural inhabitant; and be diagnosed with hypertension, diabetes, or dyslipidemia (all P < 0.001).

Of the 41,412 individuals with AMD, 3,014 (7.28%) had VD at the time of their health screening. Compared to AMD individuals without VD, those with VD were more likely to be male, older, current smokers, and heavy drinkers; have a lower income; be a rural inhabitant; and be diagnosed with diabetes. Detailed characteristics are shown in Table 1 and Supplementary Table 3.Table 1 Baseline characteristics of individuals with/without AMD.

	AMD	
Absent (n = 3,495,881)	Present (n = 41,412)	P Value	
Sex (male)	1,830,670 (52.4)	19,579 (47.3)	< 0.0001	
Age (years)	60.3 ± 8.2	67.1 ± 8.5	< 0.0001	
Hypertension	1,581,146 (45.2)	24,620 (59.5)	< 0.0001	
Diabetes	527,803 (15.1)	9,572 (23.1)	< 0.0001	
Dyslipidemia	952,198 (27.2)	13,957 (33.7)	< 0.0001	
Regular exercise*	752,494 (21.5)	8,923 (21.6)	0.9148	
Smoking	 < 0.0001	
Non-smoker	2,236,065 (64.0)	29,213 (70.5)		
Ex-smoker	593,459 (17.0)	7,254 (17.5)		
Current smoker	666,357 (19.1)	4,945 (11.9)		
Alcohol consumption	 < 0.0001	
None	2,194,227 (62.8)	30,482 (73.6)		
 < 30 g/day	1,059,557 (30.3)	9,164 (22.1)		
 > 30 g/day	242,097 (6.9)	1,766 (4.3)		
Income, lowa	757,889 (21.7)	7,549 (18.2)	< 0.0001	
Place (urban)	1,607,381 (46.0)	17,453 (42.1)	< 0.0001	
Body mass index (kg/m2)	24.1 ± 3.0	24.0 ± 3.0	< 0.0001	
Waist circumference (cm)	82.3 ± 8.3	82.8 ± 8.3	< 0.0001	
Fasting glucose (mg/dL)	102.3 ± 27.7	104.6 ± 30.1	< 0.0001	
Systolic blood pressure (mmHg)	126.6 ± 15.8	128.3 ± 16.0	< 0.0001	
Diastolic blood pressure (mmHg)	78.1 ± 10.2	77.6 ± 10.1	< 0.0001	
High-density lipoprotein cholesterol (mg/dL)	55.4 ± 31.0	54.9 ± 33.2	0.0006	
Low-density lipoprotein cholesterol (mg/dL)	118.8 ± 39.4	117.8 ± 40.1	< 0.0001	
Triglycerides residentsb(mg/dL)	121.5 (121.5–121.6)	120.7 (120.1–121.3)	0.0322	
Glomerular filtration rate (mL/min/1.73 m2)	82.9 ± 33.7	79.9 ± 35.5	< 0.0001	
Charlson comorbidity index	1.13 ± 1.27	1.72 ± 1.51	< 0.0001	
Numeric continuous parameters are described using mean ± standard deviation values and categorical parameters are described by numeric (%) values.

*Regular exercise was defined as strenuous physical activity performed for ≥ 30 min ≥ 5 times a week.

aIndividuals with an income of less than the lower 20th percentile were defined as low-income residents.

bTriglycerides are expressed as a geometric mean value (95% confidence interval).

AMD, age-related macular degeneration.

Incidence of RA by AMD and the presence of VD

Overall, 43,772 individuals (1.24%) were diagnosed with RA during the mean follow-up period of 9.9 years. Figure 2 shows the cumulative incidence of RA according to AMD with/without VD. Individuals with AMD displayed a significantly higher incidence of RA compared to those without AMD (Fig. 2A). AMD individuals without VD showed a significantly higher incidence of RA compared to controls or those with VD (Fig. 2B).Fig. 2 Cumulative incidence probability of rheumatoid arthritis (RA) according to presence of age-related macular degeneration (AMD). (A) Graph of cumulative incidence probability of RA grouped by the presence of AMD. (B) Graph of cumulative incidence probability of RA grouped by the presence of AMD with/without VD.

After adjusting for age, sex, and other covariates (model 3), the HR of RA was 1.11 (95% CI 1.02–1.21) in the AMD group compared to the control group, while the HRs of RA in AMD individuals without and with VD were 1.13 (95% CI 1.03–1.23) and 0.90 (95% CI 0.64–1.27), respectively. The detailed data are shown in Table 2.Table 2 Cox regression analysis of RA development by AMD.

	Total N	Number of RA patients	Duration (PYs)	Incidence rate (/1,000 PYs)	HR (95% CI)	
Crude	Model 1*	Model 2a	Model 3b	
Control	3,495,881	43,205	34,649,814	1.25	1 (ref.)	1 (ref.)	1 (ref.)	1 (ref.)	
AMD	41,412	567	395,237	1.43	1.15 (1.06–1.27)	1.17 (1.08–1.27)	1.17 (1.08–1.27)	1.11 (1.02–1.21)	
P Value	0.0009	0.0002	0.0003	0.0142	
Control	3,495,881	43,205	34,649,814	1.25	1 (ref.)	1 (ref.)	1 (ref.)	1 (ref.)	
AMD without VD	38,398	535	367,158	1.46	1.17 (1.07–1.27)	1.19 (1.09–1.29)	1.18 (1.09–1.29)	1.13 (1.03–1.23)	
AMD with VD	3,014	32	28,079	1.14	0.91 (0.65–1.29)	0.96 (0.68–1.36)	0.96 (0.68–1.36)	0.90 (0.64–1.27)	
P for trendc	0.004	0.001	0.0011	0.0371	
Hazard ratio (95% confidence interval) values were calculated using a Cox proportional hazards model.

*Adjusted for age and sex.

aAdjusted for age, sex, smoking habits, alcohol consumption habits, regular exercise, income, place, and body mass index.

bAdjusted for age, sex, smoking habits, alcohol consumption habits, regular exercise, income, place, body mass index, diabetes, hypertension, dyslipidemia, and Charlson comorbidity index.

cP for trend was calculated by the (adjusted) hazard ratios among control, AMD without VD, and AMD with VD groups.

RA, rheumatoid arthritis; AMD, age-related macular degeneration; N, number; PYs, person-years; HR, hazard ratio; CI confidence interval; ref., reference; VD, visual disability.

Stratified analyses

Age, sex, and the presence of a comorbidity (hypertension, diabetes, or dyslipidemia) showed no significant interactive effect with AMD on RA development (P for interaction > 0.05). Further, age, sex, and the presence of a comorbidity (hypertension, diabetes, or dyslipidemia) did not display a significant interactive effect with AMD with or without VD on RA (P for interaction > 0.05).

Sensitivity analyses

In the sensitivity analysis defining RA using only ICD-10 codes, the HR of RA in the AMD group (1.14; 95% CI 1.11–1.18) was similar to the results from the original definition using both of ICD-10 codes and prescriptions. Detailed results of the sensitivity analysis are shown in Supplementary Table 4.

Discussion

In our study, AMD was associated with an increased risk of RA compared to in the control group without AMD. Compared to controls, patients with AMD without VD exhibited an increased RA risk, while those with AMD with VD did not demonstrate an increase in RA risk. The association between AMD and RA was maintained regardless of age, sex, and comorbidities (hypertension, diabetes, and dyslipidemia).

Contrary to the results of our study reporting an increased risk of RA in AMD patients, a previous study using linked hospital episode statistics in England reported that the risk of RA after AMD was not increased (standardized rate ratio, 0.98; 95% CI 0.94–1.02)11. However, since the study used data based on hospital admissions and day care specialist care, it did not include outpatient diagnoses, so the risk of RA may have been underestimated. Our study has the advantage of including patients diagnosed in the outpatient clinic using a claims database that covers both outpatient and inpatient patients. Another study using data from the U.S. National Health and Nutrition Examination Survey also did not show an association between AMD and RA (odds ratio, 0.70; 95% CI 0.35–1.37). Since the study was conducted with a cross-sectional design and RA cases included those that were self-reported, differences in study design and outcome definition may have caused the difference in outcome between studies.

Previous studies have described an increased risk of AMD in RA patients. One study in England found that RA was associated with a modest increase in hospital episodes of subsequent AMD compared to in the reference cohort (standardized rate ratio, 1.15; 95% CI 1.12–1.19)11. The U.S. study also showed that the risk of non-exudative AMD was increased two-fold in RA patients compared to in matched controls (odds ratio, 2.08; 95% CI 1.98–2.18)10. Considering the results of our study, which increased the risk of RA in AMD patients, the association between RA and AMD is considered to be bidirectional rather than unidirectional.

AMD was associated with an increased risk of RA even after adjusting for several confounding factors. As an explanation for the association between AMD and RA, the possible pathogenetic link between the two diseases can be considered. A previous study reported that the levels of circulating CD56+ T-cells were increased in the peripheral blood of patients with AMD26. In addition, CD56+ T-cells were identified in biopsy samples from patients with interstitial pneumonitis associated with RA; CD56 ligation on T cells is known to induce the production of inflammatory cytokines such as IL-2, TNF-α, and MIP-1β, and CD56 + T cells are believed to be more pathogenic than their CD56- counterparts27. There is evidence suggesting that inflammation plays a significant role in the pathogenesis of AMD. AMD patients have elevated levels of pro-inflammatory cytokines such as interleukin-1β28, and interleukin-6 and C-reactive protein contribute to the development and progression of AMD29,30. Although the precise mechanisms by which infiltrating CD56 + T cells contribute to perpetuating chronic inflammation, given the shared inflammatory pathways implicated in both RA and AMD, CD56 + T cells may represent a critical pathogenic factor in these conditions.

In addition, tumor necrosis factor α is involved in choroidal neovascularization31,32. These pro-inflammatory cytokines also play a critical role in the pathogenesis of RA33. Hypoxia-inducible factors are associated with choroidal neovascularization in AMD and aggravate synovial hypertrophy by stimulating angiogenesis and promoting pannus formation in RA34.

In our study, there was no increased risk of incident RA in AMD patients with VD. The cause of the relatively small number of diagnoses of RA in patients with VD is unclear, but several factors can be considered. A recent cohort study demonstrated that people with VD had less non-ophthalmic medical care use than those without VD35. In addition, visually impaired people experience a deteriorated socioeconomic status after the onset of impairment, which in turn affects health care utilization in patients with VD25. Also, low socioeconomic status is associated with a delay in RA diagnosis36. Therefore, in order to interpret our findings showing that the risk of incident RA did not increase in AMD patients with VD, it is necessary to consider the possibility that RA may be underdiagnosed in this population.

Our study has several limitations. First, a population-based cohort was constructed using a claims database, but selection bias may exist because only individuals who participated in the health examination were included. Second, since RA and AMD were defined only with the diagnostic code and drug prescription registered in a claim, there may be patients who were not captured in the study. However, in the case of AMD, the operational definition adapted in other previous studies was used7,37, and, in RA, the operational definition validated in the previous study was used to increase the reliability of the study20. Third, since only the variables included in the health checkup were integrated in the analysis, inflammatory markers such as C-reactive protein, which were not included in the health check-up, were not included in the variables. Fourth, since our study was conducted only in Koreans, generalization to other races is limited. Finally, due to the limitations of this study design, we could determine the association between AMD and RA, but not causality. Further studies using methods like Mendelian randomization are necessary to confirm this. Despite these limitations, our study is meaningful in that it identified the RA risk in AMD patients in a large population-based cohort, and it is the first study to show that there is a difference in the diagnosis of RA according to VD.

Conclusions

AMD is associated with a higher RA risk, which remained significant even after adjusting for lifestyle factors and comorbidities. While our findings suggest a link between AMD and a higher risk of RA, further research is necessary to confirm these results and understand the underlying mechanisms.

Supplementary Information

Supplementary Tables.

Supplementary Information

The online version contains supplementary material available at 10.1038/s41598-024-71524-x.

Author contributions

D.W.S. and D.H.L. had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Conception and design: J.M.Y., Y.E., K.H., D.W.S. and D.H.L. Acquisition of data: K.H. and B.S.K. Analysis and interpretation of the data: J.M.Y., Y.E., K.H., B.S.K., H.K., D.W.S. and D.H.L. Statistical expertise: K.H. and B.S.K. Drafting of the article: J.M.Y., Y.E., D.W.S. and D.H.L. Final approval of the manuscript: all authors.

Funding

This research was supported by a National Research Foundation of Korea grant provided by the Korean Ministry of Education (NRF-2021R1C1C1007795; Seoul, Korea), which was received by D.H.L. This research was also partially supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant no. HI20C1073). The funding organizations had no role in the design or conduct of the study.

Data availability

The data that support the findings of this study are available from NHIS. Restrictions apply to the availability of these data, which were used under license for this study. Data are available at https://nhiss.nhis.or.kr with the permission of NIHS. For inquiries regarding data access, please contact Je Moon Yoon.

Competing interests

The authors declare no competing interests.

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

These authors contributed equally: Je Moon Yoon and Yeonghee Eun.
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