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Glaucoma: The Newest Autoimmune Disease?

— Researchers argue for a "paradigm shift"

MedpageToday
An ophthalmologist measures the intraocular pressure of a patient’s eye using a tonometer.

Another study points to the likelihood that primary open-angle glaucoma (POAG) is an autoimmune phenomenon, with Korean researchers reporting that people with rheumatoid arthritis (RA) are also at significantly greater risk for developing the eye disorder.

Glaucoma was diagnosed at a rate of 981.1 cases per 100,000 person-years in cohort of 2,049 RA patients, compared with 679.5 cases per 100,000 person-years among 8,196 matched non-RA controls, according to Suk-Yong Jang, MD, JD, PhD, of Yonsei University in Seoul, and colleagues.

That worked out to a hazard ratio of 1.44 (95% CI 1.13-1.84) for the RA patients, the researchers reported in . "It is possible that POAG may have an autoimmune component such as RA," they concluded.

This is hardly the first study to suggest that glaucoma has autoimmune roots. Discussion of the possibility goes back more than 20 years. Since 2018, a burst of reviews made the case for the link. Some of the evidence comes from animal models, such as a study showing that tumor necrosis factor inhibitor etanercept (Enbrel) counters the chief pathology seen in glaucoma induced in rats. Others have identified excess T-cell activity in human glaucoma patients.

One , was titled: "Is glaucoma an autoimmune disease?"; took away the question mark and declared: "Glaucoma is an autoimmune disease." Just last year, a study supporting the link took the opposite approach from the new Korean study: it examined the prevalence of autoimmune disease among a cohort of POAG patients, indeed finding a significantly increased rate.

But as the first of those reviews cautioned, it's too early to say that all POAG cases are autoimmune. For starters, whether drugs for treating other autoimmune diseases (such as RA) are also effective against spontaneous human glaucoma hasn't been established. And, perhaps unfortunately, this wasn't examined in the Korean study.

What the new research does do is solidify the link on epidemiological grounds, with nationwide data on thousands of patients.

Jang and colleagues pulled records for all patients in Korea's universal healthcare system 60 and older with RA diagnoses, from 2002 to 2013, yielding the 2,049-patient case group. Controls, identified to outnumber cases by 4:1, were matched by sex, age, income, place of residence, frequency of healthcare contacts, comorbidity index, and certain specific types of comorbidities and medications. Overall, the goal was to identify non-RA patients with similar propensity to develop glaucoma.

Recent onset of RA and age 75 and up were both associated with relatively higher risk of POAG than in the overall results:

  • RA diagnosis within 2 years: HR 1.83, 95% CI 1.28-2.61
  • Age 75 or older: HR 2.12, 95% CI 1.34-3.35

The researchers said that a direct causative relationship -- i.e., that RA itself triggers glaucoma -- "is not likely," given this increased risk within the first months after RA diagnosis. Rather, they suggested, both conditions may be epiphenomena of an underlying autoimmune process.

"Considering that POAG has an insidious onset over decades, our results suggest that the immune complex involved in RA has the potential to simultaneously cause damage to tissues that are associated with the development of POAG including the retina or optic nerve," the group wrote, adding that antibodies against heat shock proteins as well as abnormal T-cell activity (both seen in lab studies of glaucoma) are possible vehicles.

Overall, Jang and colleagues argued, "a paradigm shift" may be due for glaucoma.

  • author['full_name']

    John Gever was Managing Editor from 2014 to 2021; he is now a regular contributor.

Disclosures

The study was funded from internal institutional sources. Authors declared they had no relevant financial interests.

Primary Source

JAMA Network Open

Kim SH, et al "Development of open-angle glaucoma in adults with seropositive rheumatoid arthritis in Korea" JAMA Netw Open 2022; DOI: 10.1001/jamanetworkopen.2022.3345.