Increased Nonexudative Age-Related Macular Degeneration Diagnosis Among Medicare Beneficiaries With Rheumatoid Arthritis

Abstract

Purpose AMD is the leading cause of blindness in the United States. The role of secondary inflammatory disease on AMD progression is largely unknown. Here we investigate the association between AMD and rheumatoid arthritis (RA), using MarketScan data for patients aged ≥65 years on Medicare. Methods Baseline data were extracted for subjects with at least two International Classification, Ninth Revision (ICD-9) diagnosis codes of RA and control subjects (no RA) and were matched at baseline by propensity score. Matched cohort data were extracted post-baseline time and examined up to 4.5 years of follow-up for ICD-9 diagnosis code AMD records. Multivariable regression models compared risk of an AMD diagnosis post-baseline for RA subjects and matched controls. Days until first AMD diagnosis between RA patients and controls was examined using survival analysis. Results Risk of new AMD diagnosis was elevated in RA patients (odds ratio [OR] 2.08; 95% confidence interval [CI] 1.98–2.18), with an increase in nonexudative AMD patients ( P < 0.0001). Risk was elevated in female ( n = 27,548) (OR 1.11; 95% CI 1.05–1.17) compared with male ( n = 9704; P < 0.001) patients. The time to first AMD diagnosis was shorter for RA subjects than controls ( P < 0.0001). Conclusions Our analysis provides support of association between RA diagnosis and increased nonexudative AMD diagnosis.

Systemic Inflammation by Collagen-Induced Arthritis Affects the Progression of Age-Related Macular Degeneration Differently in Two Mouse Models of the Disease

“… 56 In addition to genetics and a healthy lifestyle, individuals who live longer lives are found to have increased levels of anti-inflammatory markers, while increased proinflammatory markers are associated with increased disease (as reviewed by Franceschi 57 ). Our patient database analysis, 23 as well as studies performed by others, observed increased number of AMD cases in the presence of systemic disease, suggesting a role for inflammaging in AMD risk and pathogenesis.…”

“…In addition, we identified an increased risk of dry AMD diagnosis among patients with rheumatoid arthritis (RA), along with an earlier time of diagnosis, through retrospective analysis of a Medicare patient database. 23 This study also identified an increased risk of AMD among female patients with RA compared to males. While reports linking an increased incidence of AMD among females in the general population are conflicting, a higher prevalence of females (65%) to males (35%) is diagnosed with AMD according to the 2010 National Eye Institute consensus.…”

“…These combined results in the CNV and retinal degeneration models correlate with our Marketscan analysis of Medicare patients, which identified an increased risk of dry AMD, and not wet AMD, in the presence of RA. 23 Together, these results suggest that systemic inflammation and the corresponding immune response in CIA or RA affect pathology in dry and wet AMD differentially. While systemic inflammation in CIA or RA was partially protective and resulted in reduced choroidal neovascularization or no increased risk for wet AMD, respectively, CIA was found to augment RPE damage and loss of retinal thickness, and RA increased the risk for dry AMD.…”

“…As we previously identified an increased risk and earlier time of diagnosis of dry AMD among patients with RA, 23 we sought to investigate how systemic inflammation may affect disease severity in animal models of AMD. Using the CIA model for RA, the CNV laser-induced model to assess angiogenesis associated with wet AMD, and the NaIO 3 -induced retinal degeneration model to model RPE and photoreceptor degeneration in dry AMD, we found that systemic inflammation affected AMD pathology differentially.…”

Systemic levels of interleukin‐6 in patients with age‐related macular degeneration: a systematic review and meta‐analysis

“…These circumstances have led to a general interest in markers of chronic low‐grade inflammation in relation to diseases with a complex pathogenesis and where ageing is an important risk factor, such as neurodegenerative disease, inflammatory diseases, cancer and AMD. Indeed, several studies find an epidemiological association between these diseases (Tsai et al 2015; Bak et al 2017; Lin et al 2017; Singh & Cleveland 2018; Hamedani et al 2019; Schnabolk et al 2019). Perhaps the most well‐studied cytokine in the context of chronic low‐grade inflammation is interleukin‐6 (IL‐6) (Bruunsgaard 2006).…”