Recorded ocular diagnoses in adults with homocystinuria: A propensity score-matched cohort study

To compare ocular diagnoses in adults with and without homocystinuria (HCU), including vitreous degeneration in a large, real-world cohort.

Retrospective propensity score-matched cohort study.

658 adults with HCU and 658 propensity score-matched controls without HCU.

Using the U.S. TriNetX Research Network, patients with HCU were matched to controls by demographic characteristics and systemic comorbidities associated with ocular disease. Outcomes included cataract, glaucoma, dry eye disease, vitreous degeneration, myopia, and age-related macular degeneration. Patients with the corresponding diagnosis before the ophthalmic index encounter were excluded from primary time-to-event analyses. Cox models estimated hazard ratios (HRs); log-rank P values were Holm-adjusted across six outcomes. A secondary analysis included diagnoses recorded before or after index.

Vitreous degeneration was recorded after index in 45/581 patients with HCU (7.75%) and 29/607 controls (4.78%). HCU was associated with a higher risk of first recorded vitreous degeneration (HR, 1.77; 95% CI, 1.11-2.82; nominal P = 0.016), but not after Holm correction (adjusted P = 0.094). HCU was not significantly associated with other common eye diseases including cataract, glaucoma, AMD, myopia, and DED. Ectopia lentis could not be meaningfully evaluated because the number of recorded cases was below the TriNetX minimum reportable sample size. In the secondary analysis, vitreous degeneration was recorded in 74/658 patients with HCU (11.25%) and 50/658 controls (7.60%; prevalence ratio, 1.48; 95% CI, 1.05-2.08; nominal P = 0.024).

HCU was associated with a higher risk of vitreous degeneration, but the primary association did not remain significant after multiplicity correction. Prospective studies using standardized ophthalmic assessments are needed to determine whether this signal represents a reproducible HCU-related vitreous phenotype.