Risk of New Glaucoma Diagnosis and Surgery for Patients with Intravitreal Injections in the TriNetX Database

To quantify the long-term risk of incident glaucoma and of undergoing glaucoma surgery associated with intravitreal injection therapy using a large electronic health record network.

Retrospective cohort study.

Patients with no prior glaucoma diagnosis in the TriNetX US Collaboration Network seen between 03/14/2006-03/14/2026 with either exudative age-related macular degeneration (AMD) and intravitreal injection or nonexudative AMD with no history of injection.

Patients with exudative AMD who received intravitreal injections (Current Procedural Terminology 67028) were compared with patients with nonexudative AMD. Patients with retinal vascular occlusions, proliferative diabetic retinopathy, retinal ischemia, pseudoexfoliation syndrome or pigment dispersion syndrome were excluded. Cohorts were propensity score matched 1:1 for age, sex, race, ethnicity, and systemic comorbidities. Time-to-event analyses were performed, and effect estimates included risk ratios (RR), odds ratios (OR), and hazard ratios (HR).

New glaucoma diagnosis (International Classification of Diseases-10 H40) and glaucoma surgical interventions.

After exclusions and matching, each cohort contained 27,967 patients. Incident glaucoma occurred in 15.1% (4,218/27,967) of injection patients versus 12.9% (3,621/27,967) of controls (RR 1.17; OR 1.19; HR 1.08, p<0.001). Any glaucoma surgery occurred in 1.6% (435/27,967) of injection patients compared with 0.8% (236/27,967) of controls (RR 1.84; OR 1.86; HR 1.66, p<0.001). Patients with intravitreal injection were more likely to undergo glaucoma tube implantation (p<0.001), laser trabeculoplasty (p<0.001), cyclodestructive procedures (p=0.001), and trabeculectomy (p=0.03). Incisional angle surgery trended toward significance (p=0.054).

In a large cohort, intravitreal injection therapy for exudative AMD was associated with higher risks of incident glaucoma and glaucoma surgery compared with matched nonexudative AMD controls, corresponding to a number needed to harm of approximately 47 for incident glaucoma.