RHEUMATOID DISEASES AND GLAUCOMA RISK

Glaucoma is characterized by retinal ganglion cell (RGC) neurodegeneration. Elevated intraocular pressure (IOP) is a major risk factor for the development of glaucomatous optic neuropathy and RGC loss. However, pressure-independent mechanisms also play a role in RGC damage. 

Both antibodies and CD4 T–cells as well as microbiota take part in the pathogenesis of both glaucoma and rheumatoid arthritis (RA).

Heat shock proteins (HSPs) which originate in bacteria cross-react with RGC epitopes and were detected in a rat model of retinal injury. Enhanced expression of HSPs in the retina was associated with glaucoma-like neuropathology and previous studies have also suggested a pathogenic role for HSPs in RA. 

Since autoimmunity and inflammation, the main characteristics of rheumatic diseases, are related to glaucoma, it was suggested that glaucoma should be included in the spectrum of autoimmune disorders.

A few studies related to the association of rheumatoid diseases and glaucoma are presented here:

1. A Mendelian randomization (MR) analysis was performed by Meng et al, to investigate the causal effects of six common rheumatic diseases on glaucoma. MR is an established approach for making causal inferences in epidemiology.

Six rheumatic diseases were included: ankylosing spondylitis (AS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sicca syndrome/Sjögren’s sydrome (SS), dermatomyositis (DM), and gout.

Using two-sample MR, the authors found that AS is associated with a higher risk of both POAG and PACG.

Considering the high incidence of AS in the general population (0.1%–0.5%), it is necessary to further explore the relationship between AS and glaucoma in future studies.

Two-sample MR suggests that AS is related to a higher risk of both POAG [odds ratio (OR): 1.28, 95% confidence interval (CI) 1.13–1.44; p = 1.1 × 10−4] and PACG (OR: 1.55, 95% CI: 1.09–2.09, p = 1.4 × 10−2). 

Multivariable MR shows a similar trend of the effect of AS on POAG (OR: 1.52, 95% CI: 1.22–1.90, p = 1.9 × 10−4) and PACG (OR: 2.05, 95% CI: 1.06–3.95, p = 3.2 × 10−2). 

However, no significant association was observed between the other five rheumatic diseases and glaucoma.

Therefore, AS is related to an increased risk of POAG and PACG, and the importance of glaucoma screening in these patients cannot be stressed enough.

Meng Y, Tan Z, Su Y, Li L, Chen C. Causal association between common rheumatic diseases and glaucoma: a Mendelian randomization study. Front Immunol. 2023 Sep 19;14:1227138. doi: 10.3389/fimmu.2023.1227138. PMID: 37799717; PMCID: PMC10550209.

2. However, Kim et al, conducted a cohort study of 10245 older Korean adults risk-set matched using propensity score, and reported patients with RA were more likely than matched controls to subsequently develop POAG, with hazard ratios ranging from 1.44 to 2.12.

These findings suggest that RA is associated with subsequent development of glaucoma. The role of an immune-mediated common pathophysiological pathway warrants further investigation.

Kim SH, Jeong SH, Kim H, Park E, Jang S. Development of Open-Angle Glaucoma in Adults With Seropositive Rheumatoid Arthritis in Korea. JAMA Netw Open. 2022;5(3):e223345. doi:10.1001/jamanetworkopen.2022.3345.

3. Teng used a two-sample Mendelian MR analysis to investigate the causal associations between RA, cataract and glaucoma in European and East Asian populations. Results revealed that RA had an increased risk of cataract (OR = 1.041, 95% CI = 1.019–1.064; P = 2.08×10−4) and glaucoma (OR = 1.029, 95% CI = 1.003–1.057; P = 2.94×10−2).

The authors concluded that oxidative stress and local inflammation are responsible for these causal associations.

Teng M, Wang J, Su X, Tian Y, Wang J, Zhang Y (2024) Causal associations between rheumatoid arthritis, cataract and glaucoma in European and East Asian populations: A bidirectional two-sample mendelian randomization study. PLoS ONE 19(3): e0299192. doi:10.1371/journal.pone.0299192.