Researchers at Massachusetts Eye and Ear (MEE) in Boston have found clinical evidence to support earlier laboratory findings of a link between primary open-angle glaucoma (POAG) and autoimmune diseases.1
In a group of patients undergoing cataract and/or glaucoma surgery, those with POAG were significantly more likely to have an underlying autoimmune condition such as rheumatoid arthritis (RA), psoriasis, Graves disease, and/or Raynaud syndrome.
Sources of inspiration. The glaucoma patients of Lucy Q. Shen, MD, at MEE, provided the original impetus for this study. In 2018, several of them flagged an earlier study on an autoimmune mechanism underlying neuronal loss in glaucoma2—and asked about alternative therapy for their glaucoma.
Next, she said, “Dr. Maltish Lorenzo, a medical student at the time, was motivated to start a study on immunologic biomarkers in patients undergoing glaucoma surgery. To prevent potential interference with other autoimmune conditions in our study population, we excluded those patients with inflammatory and autoimmune diseases.” But after a few months of screening and recruiting, Dr. Lorenzo told Dr. Shen that this would necessitate ruling out a significant number of glaucoma patients, as many had autoimmune diseases. “Based on his observation, we decided to examine the prevalence of autoimmune diseases in patients with POAG.”
Study specifics. The researchers evaluated 172 patients with POAG and 179 controls. Results showed that 17.4% of patients with POAG and 10.1% of controls (p = .044) had an autoimmune disease, with RA and psoriasis the most common in both groups. In addition, 6.4% of POAG patients and 3.4% of controls had more than one autoimmune condition.
Clues and surprises. The team’s investigation provided three important clues about the link between POAG and autoimmunity, Dr. Shen said:
1. Agreement. While the researchers naturally hoped that their clinical findings would line up with those from the earlier laboratory study, “it still surprised us, in a good way, that they agreed,” Dr. Shen said. In particular, the finding that T-cell–mediated autoimmune diseases were more prevalent in POAG patients than controls is consistent with the earlier results, which showed a key role of T-cells in mediating glaucomatous neurodegeneration.2
2. Role of steroids. A subgroup analysis of POAG patients with and without autoimmune disease did not show a difference in glaucoma severity. When the researchers analyzed this finding, they found that the POAG patients with autoimmune diseases were more likely to use steroids. This may have modulated disease severity, they hypothesized.
3. A role for CD4? An unexpected clue came from a separate study on HIV patients and retinal nerve fiber layer (RNFL) thickness: In this investigation, patients with HIV and low CD4 counts had a thicker RNFL.3 “This is consistent with our theory that autoimmunity, in particular T-cell–mediated mechanism, is involved in glaucomatous optic nerve damage,” Dr. Shen said. “Low CD4 counts may have protected these HIV patients from losing RNFL.”
Looking ahead. The MEE team has an ongoing prospective study to assess various immunologic biomarkers in glaucoma, Dr. Shen said, in hopes of further validating the link between autoimmunity and glaucoma. “One day, I do hope that I will be able to tell my patients—especially those who have inspired me on this journey—that we have new treatment options for their glaucoma.”
1 Lorenzo MM et al. Ophthalmol Glau. Published online Aug. 18, 2021.
2 Chen H et al. Nat Commun. 2018;9(1):3209.
3 Van Tassel SH et al. Int J Ophthalmol. 2019;12(5):789-794.
Relevant financial disclosures: Dr. Shen—American Glaucoma Society: S; Topcon: S.
For full disclosures and the disclosure key, see below.
Full Financial Disclosures
Dr. Ambati iVeena: O; NEI: S; Research to Prevent Blindness: S.
Dr. Bursztyn None.
Dr. Hunter Lippincott Williams & Wilkins: P; Luminopia: C,O; Rebion: C,O,P; Slack: P.
Dr. Shen American Glaucoma Society: S; Topcon: S.
||Consultant fee, paid advisory boards, or fees for attending a meeting.
||Employed by a commercial company.
||Lecture fees or honoraria, travel fees or reimbursements when speaking at the invitation of a commercial company.
||Equity ownership/stock options in publicly or privately traded firms, excluding mutual funds.
||Patents and/or royalties for intellectual property.
||Grant support or other financial support to the investigator from all sources, including research support from government agencies (e.g., NIH), foundations, device manufacturers, and/or pharmaceutical companies.
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