Oral Ursodeoxycholic Acid Is Associated With Decreased Rate of AMD

Cholelithiasis is associated with decreased risk of age-related macular degeneration (AMD). Ursodeoxycholic acid (UDCA), a bile acid used to dissolve cholesterol gallstones, has been shown to be retina-protective in several mouse models. This study sought to determine if UDCA may protect against AMD.

A retrospective cohort study was conducted using data between January 1, 2000 to June 30, 2022 in Optum's de-identified Clinformatics Data Mart database. All patients had a history of cholelithiasis, cholecystitis, or cholecystectomy. The exposed cohort included patients taking UDCA. Controls did not take UDCA and were matched 1:3 for age (±3 years), sex, race, type of gallbladder disease, and insurance coverage start and end date (±4 months). All included patients were 55 years old or older, had at least two years of data in the dataset, and no prior history of AMD. Inverse probability of treatment weighting (IPTW) was used to balance covariates at baseline. Cox proportional hazard regression modeling with IPTW was used to compare progression to AMD between the cohorts.

A total of 5,863 patients taking UDCA and 17,164 matched controls were analyzed. In both cohorts after IPTW, roughly 56% of patients had cholelithiasis, 16% had cholecystitis, and 28% had cholecystectomy. Age and sex were balanced at baseline between cohorts (UDCA: 70.5 ± 9.54 years old and 58.6% female; controls: 70.3 ± 9.59 years old and 57.4% female). In the UDCA cohort, 384/5,705 (6.74%) were diagnosed with AMD. In the control cohort, 1,559/17,322 (9.00%) were diagnosed with AMD. This corresponded to a significantly decreased hazard of AMD (adjusted hazard ratio = 0.65, 95% CI: 0.58-0.74, P < 0.0001).

UDCA was associated with a 35% reduction in the hazard of AMD in patients with underlying gallbladder disease. Determining the mechanism for this protective effect could improve understanding of AMD pathogenesis. These results also suggest that clinical trials evaluating the use of UDCA for AMD could be valuable.