Malabsorption Syndromes and Risk of Age-Related Macular Degeneration

Despite mechanistic links connecting malnutrition and gut microbiome with retinal health, clinical research exploring the relationship between malabsorption syndromes and age-related macular degeneration (AMD) remains limited. This study compared the risks of AMD diagnosis in patients with and without various malabsorption syndrome diagnoses.

Retrospective cohort study of aggregated, deidentified patient data from multiple health care organizations across the United States using the TriNetX US Collaborative Research Network in November 2025.

Adults with a cataract-related International Classification of Diseases (ICD) encounter diagnosis codes and no baseline AMD ICD encounter diagnosis codes were divided into groups based on the presence of ICD encounter diagnosis codes for celiac disease, ulcerative colitis (UC), Crohn's disease (CrD), chronic pancreatitis (CP), and short bowel syndrome (SBS). Within the CP cohort, patients with pancreatic enzyme replacement therapy (PERT) prescription orders were subanalyzed. For each cohort, a corresponding control cohort of patients without the respective ICD encounter diagnosis codes was created.

The study and control cohorts were propensity-matched 1:1 on demographic factors, comorbidities, and disease-related conditions and prescription orders. The matched cohorts were compared on the risk of having AMD ICD encounter diagnoses.

Risk ratios (RRs) and 95% confidence intervals (CIs) of having an AMD ICD encounter diagnosis code with an accompanying retinal OCT Common Procedural Terminology code. Significance was defined as CI ≤0.9 or ≥1.1.

Compared with controls without inflammatory bowel diseases, the CrD cohort (n = 9537, RR = 1.42, CI = 1.15-1.74), but not the UC cohort (n = 15 039, RR = 1.28, CI = 1.09-1.51), had a higher risk of having early/intermediate AMD. Chronic pancreatitis was associated with an increased risk of AMD (n = 12 856, RR = 1.82, CI = 1.53-2.16), even in the PERT subset (n = 3812, RR = 1.83, CI = 1.35-2.48). Short bowel syndrome (n = 3747) was associated with an increased risk of advanced/exudative AMD (RR = 1.98, CI = 1.31-2.98), but not early/intermediate AMD (RR = 1.28, CI = 0.96-1.71). Celiac disease was not associated with increased AMD risk (n = 9315, RR = 1.09, CI = 0.88-1.35).

Chronic noninfectious causes of malabsorption syndromes-CrD, CP, and SBS-may represent underrecognized risk factors of AMD. This explorative study adds clinical evidence for a potential role of the gut-retina axis in the pathogenesis of AMD.

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.