Most Autoimmune Diseases Show No Association with AMD Development

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A case-control analysis shows the majority of autoimmune diseases demonstrate no effect on the development of new-onset age-related macular degeneration.

A new case-control analysis explored the association between the development of age-related macular degeneration (AMD) and the diagnosis of most autoimmune diseases.1

Results from the analysis revealed no association between the majority of autoimmune diseases and the likelihood of new-onset AMD development – however, common autoimmune disorders, including systemic lupus erythematosus (SLE) and Crohn’s disease, showed moderately increased odds of AMD.

“This is a reassuring finding and suggests that increased surveillance for AMD beyond what is recommended by age-based guidelines is likely unwarranted for the majority of autoimmune diseases,” wrote the investigative team, led by Dimitra Skondra, MD, of the department of ophthalmology and visual science at the University of Chicago.

Evidence has suggested AMD pathogenesis implicates the dysregulation of immune response pathways.2 Further data has shown the pathogenic elements of AMD to resemble autoimmune diseases, but the association between its development and most autoimmune diseases has not been well-established.

To elucidate these associations, Skondra and colleagues performed a case-control analysis using data obtained from the Merative MarketScan Commercial and Medicare Databases between January 2005 and December 2019.2 In the database, the team identified patients aged ≥55 years with new-onset International Classification of Diseases (ICD) coding of dry, wet, or unspecified AMD.

Each AMD case was matched with propensity scores, estimated by age, region, Charlson Comorbidity Index group, and hypertension, to control in the same year. Exposures for the analysis were autoimmune diseases, defined by an outpatient or inpatient claim with a relevant ICD code in the 12 months before the index visit. Autoimmune diseases were classified into seven disease classes: connective tissue, systemic, rheumatic, or multi-organ; vasculitides; gastrointestinal; neurological; endocrine; dermatological; and other autoimmune diseases.

Skondra and colleagues obtained 415,027 cases with new-onset ICD coding of AMD and identified 414,853 controls with propensity scores. Of the AMD cases, 68.5% had dry AMD, 9% had wet AMD, and 22.5% had unspecified AMD. Overall, the team identified 16.1% of cases and 15.9% of controls as having any autoimmune disease.

Multivariable regression analysis revealed the diagnosis of any autoimmune disease did not affect the likelihood of new-onset ICD coding for AMD (odds ratio [OR], 1.01; 95% CI, 0.999 - 1.02). According to the autoimmune disease classes, connective tissue, systemic, rheumatic, or multiorgan and gastrointestinal diseases increased the odds of new-onset ICD coding for AMD (connective tissue, systemic, rheumatic or multiorgan: OR, 1.03 [95% CI, 1.01 - 1.05]; P = .0074; gastrointestinal: OR, 1.04 [95% CI, 1.02 - 1.07]; P = .0009), while the other 5 disease classes showed no effect.

According to the autoimmune diseases, discoid lupus erythematosus (OR, 1.29; 95% CI, 1.12 - 1.48), SLE (OR, 1.21; 95% CI, 1.15 - 1.27), giant cell arteritis (OR, 1.19; 95% CI, 1.09 - 1.30), Sjogren’s syndrome (OR, 1.17; 95% CI, 1.09 - 1.26), and Crohn’s disease (OR, 1.13; 95% CI, 1.06 - 1.22) increased the odds of new-onset ICD coding for AMD in multivariable regression analysis. The remaining autoimmune diseases showed no impact on the likelihood of AMD.

In their conclusion, Skondra and colleagues noted a growing number of individuals in the general population face an increased likelihood of developing AMD. The team suggested the need for follow-up studies to determine whether the degree of the associations between autoimmune diseases and AMD development are clinically meaningful.

“It is unclear whether these statistically significant results also carry clinical significance given that the odds ratios in this study are modest,” investigators wrote. “However, the prevalence of autoimmune diseases is rising and affects as many as 10% of individuals as of 2000 to 2019.”


  1. Moir J, Hyman MJ, Wang J, et al. Associations Between Autoimmune Disease and the Development of Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci. 2023;64(15):45. doi:10.1167/iovs.64.15.45
  2. Ambati J, Atkinson JP, Gelfand BD. Immunology of age-related macular degeneration. Nat Rev Immunol. 2013;13(6):438-451. doi:10.1038/nri3459