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    Two Lipids Linked to Glaucoma Risk


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    Analyzing data from thousands of study participants, researchers from Harvard and Icahn School of Medicine at Mount Sinai found that higher levels of two lipids, diglycerides and triglycerides, were associated with an increased risk of glaucoma. Specifically, they report that lipid metabolism is associated with primary open-angle glaucoma (POAG)—and the association was greater in cases of paracentral visual loss.1 Whether or not statins could help treat glaucoma remains unclear, said study author Louis M. Pasquale, MD, at Mount Sinai Health System.

    “POAG, particularly in the subset [of people] with early paracentral loss, has a metabolic signature focused on lipid and mitochondrial metabolism,” said Dr. Pasquale, who hopes the findings shine a light on POAG pathogenesis and inform strategies that could help prevent glaucoma.

    A patient in a medical mask undergoes an eye exam with a slit lamp.

    DIGLYCERIDES AND TRIGLYCERIDES. Certain lipids may play an important role in glaucoma pathogenesis.

    Methodology. In this nested case-control study to identify metabolites associated with POAG, the investigators analyzed blood sample data from more than 80,000 U.S. health profes­sionals participating in the long-term Nurses’ Health Studies and Health Profes­sionals’ Follow-Up Study. They identified individuals who went on to develop POAG during the course of the studies. In all, 599 cases of POAG were documented and compared to 599 matched controls who did not develop glaucoma.1 Then, researchers examined data based on the metabolo­mic profiling of blood samples from all participants. The profiling used liquid chromatography tandem mass spec­trometry to identify 369 metabolites associated with glaucoma. By compar­ing the metabolite profiles of indi­viduals with POAG to those without the condition, the researchers aimed to identify potential biomarkers for glaucoma.

    After adjusting for risk factors, they found that five individual lipids of the 369 metabolites demonstrated a nom­inal adverse association with POAG. Specifically, higher levels of diglycerides and triglycerides were associated with an increased risk of POAG (whereas higher levels of carnitines were associ­ated with a reduced risk of POAG).

    For comparison, they turned to data from the UK Biobank, in which 168 metabolites were measured using nu­clear magnetic resonance spectroscopy in plasma samples from 2,238 prevalent glaucoma cases (a random subset of more than 100,000 participants) and 44,723 controls.

    In all cohorts, “higher levels of diglycerides and triglycerides are adversely associated with glaucoma, suggesting that they play an important role in glaucoma pathogenesis,” the authors wrote.

    “Achieving replication for our find­ings in the UK Biobank sets our work apart from other studies,” Dr. Pasquale said.

    Surprising finding. Researchers went one step further by stratifying POAG into cases with peripheral vision loss and those with paracentral vision loss. The metabolomic signature of dysregu­lated lipid metabolism and mitochon­drial function was more profound in patients with early paracentral visual loss compared to those with peripheral vision loss.

    “This was surprising because the sample size for this subset of POAG patients was small, and the number of retinal ganglion cells affected in early paracentral loss is considerably smaller compared to the overall number of retinal ganglion cells in the retina,” Dr. Pasquale said.

    Treatment. When asked about the possibility of using dyslipidemia-target­ing treatments, such as statins, to lower the risk of glaucoma, Dr. Pasquale said, “The dyslipidemia we uncovered in this study is complex and is not necessarily corrected by statins, which are designed to lower LDL cholesterol.”

    He also said that which lipopro­teins are carrying the lipids adversely associated with POAG remain to be determined.

    Study limitations. The study popu­lation had a high percentage of White participants, so the findings may not be generalizable to other populations with different race and ethnicity composi­tions, the authors wrote.

    Looking ahead. “Our findings can help shed light on POAG pathogenesis and inform preventive strategies,” said Dr. Pasquale. But, he said, many poten­tially unidentified metabolite associa­tions with POAG are unexplored.

    —Christos Evangelou, PhD


    1 Zeleznik OA et al. Nat Commun. 2023;14(1):2860.


    Relevant financial disclosures: Dr. Pasquale—Na­tional Eye Institute: S; Research to Prevent Blind­ness (NYC): S; The Glaucoma Foundation: S.

    For full disclosures and the disclosure key, see below.

    Full Financial Disclosures

    Dr. Dentel None.

    Dr. Shriver None.

    Dr. Subramanian None.

    Dr. Pasquale National Eye Institute: S; Research to Prevent Blindness (NYC): S; The Glaucoma Foundation: S; Twenty Twenty: C; Character Biosciences: C.

    Dr. Yeh None.

    Disclosure Category



    Consultant/Advisor C Consultant fee, paid advisory boards, or fees for attending a meeting.
    Employee E Hired to work for compensation or received a W2 from a company.
    Employee, executive role EE Hired to work in an executive role for compensation or received a W2 from a company.
    Owner of company EO Ownership or controlling interest in a company, other than stock.
    Independent contractor I Contracted work, including contracted research.
    Lecture fees/Speakers bureau L Lecture fees or honoraria, travel fees or reimbursements when speaking at the invitation of a commercial company.
    Patents/Royalty P Beneficiary of patents and/or royalties for intellectual property.
    Equity/Stock/Stock options holder, private corporation PS Equity ownership, stock and/or stock options in privately owned firms, excluding mutual funds.
    Grant support S Grant support or other financial support from all sources, including research support from government agencies (e.g., NIH), foundations, device manufacturers, and\or pharmaceutical companies. Research funding should be disclosed by the principal or named investigator even if your institution receives the grant and manages the funds.
    Stock options, public or private corporation SO Stock options in a public or private company.
    Equity/Stock holder, public corporation US Equity ownership or stock in publicly traded firms, excluding mutual funds (listed on the stock exchange).


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