GLP-1 Drug Linked to Cases of Rare Vision-Altering Condition

Two patients taking the GLP-1 receptor agonist dulaglutide (Trulicity) developed choroidal lymphoid hyperplasia (CLH), a rare, benign condition of the uveal tract, that resolved after the patients stopped the drug.

In both cases, the patients developed vision loss in one eye after 2 to 3 months of treatment with the GLP-1 drug, leading to CLH diagnosis. The dulaglutide dose was 1.5 mg weekly in one case and 3 mg weekly in the other. Visual acuity returned to normal 1 month after stopping dulaglutide for one patient and after 10 days for the second patient. Both patients remained free of ocular and systemic disease at last follow-up.

Although the circumstances suggest an association between the GLP-1 agonist and lymphoid hyperplasia, the mechanisms remain unclear, reported Jasmine H. Francis, MD, of Memorial Sloan Kettering Cancer Center in New York City, and colleagues in a correspondence to the New England Journal of Medicine.

“We have seen no additional patients and have no new thoughts about the etiology or mechanism to explain why the drug would cause this,” Francis told MedPage Today. “The take-home message is that this is exceedingly rare, but if it’s recognized, it can be reversible.”

The cases are the latest links between GLP-1 receptor agonists and eye disorders. Multiple reports have suggested an association with nonarteritic anterior ischemic optic neuropathy (NAION). A review by the European Medicines Agency specifically implicated semaglutide (Ozempic, Wegovy, Rybelsus), prompting a recommendation to update product information. Other studies have found no association between the drugs and NAION.

Studies of diabetic retinopathy have yielded mixed results. GLP-1 drugs seem to have a protective effect in age-related macular degeneration. Another recent study suggested that better treatment for diabetes, including GLP-1 agonists, has reduced the risk of progressive diabetic retinal disease but not the prevalence.

CLH is a subcategory of ophthalmic lymphoid hyperplasia, a proliferation of non-malignant lymphocytes in the uveal tract, conjunctiva, eyelid, or orbit. Occasionally the condition evolves into low-grade lymphoid neoplasm. The condition might be triggered by an antigenic response.

The first patient in the series was a 47-year-old man who developed blurry vision in one eye 2 months after starting dulaglutide. Fundoscopy revealed a creamy-orange macular and juxtapapillary choroidal infiltrate with orange pigment. Additional imaging studies showed choroidal and retinal abnormalities. PET/CT imaging showed multisystem lymphadenopathy. Findings of a lymph node biopsy were consistent with lymphoid hyperplasia.

The patient initiated treatment with an oral glucocorticoid and antibiotic, but the condition had not improved after 2 weeks. Subtenon glucocorticoid injection produced temporary regression, but CLH returned 10 months later.

A month after stopping the GLP-1 drug because of gastrointestinal symptoms, the CLH had markedly improved, including 20/20 visual acuity. The response persisted for 43 months, during which time the patient used semaglutide and tirzepatide (Mounjaro, Zepbound) without incident.

The second patient was a 70-year-old woman who had 20/150 vision 3 months after starting dulaglutide. She, too, had creamy-orange macular and juxtapapillary choroidal infiltrate with orange pigment, associated with choroidal and retinal abnormalities. PET/CT imaging showed systemic lymphadenopathy. On the basis of experience with the first case, the patient stopped dulaglutide, and 10 days later she had marked improvement in ophthalmic findings, including improvement in visual acuity to 20/25. Follow-up imaging showed resolution of multisystem lymphadenopathy.

“The systemic involvement, timing of disease onset after drug initiation, and prompt resolution on cessation of the drug therapy increase concern for a potential association between lymphoid hyperplasia and dulaglutide in these two patients,” Francis and co-authors wrote. “The mechanism of this potential drug effect is unclear. We speculate that activation of the GLP-1 receptor in choroidal endothelial cells may explain local choroidal hyperplasia but would not explain the systemic lymphadenopathy.”

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