Interventional Vitamin Mix Glaucoma Study (IVMGS): study protocol for a prospective, randomized, two-arm,...

Glaucoma is a leading cause of irreversible blindness, characterized by progressive degeneration of retinal ganglion cells. Current treatments primarily lower intraocular pressure but do not directly provide neuroprotection. Preclinical studies from our group have identified dysfunction in one-carbon metabolism as a contributor to glaucomatous neurodegeneration in rodent models. The Interventional Vitamin Mix Glaucoma Study will evaluate whether 12 months of supplementation with key one-carbon metabolism cofactors and precursors (vitamins B₆, B₉, B₁₂, and choline) can improve inner retinal function and provide neuroprotection compared with standard care alone.

The Interventional Vitamin Mix Glaucoma Study is a Phase 2a, open-label, randomized, two-arm clinical trial. Participants will be assigned in a one-to-one ratio to receive either daily one-carbon metabolism supplementation plus standard care or standard care alone. The study will enroll 80 patients with primary open-angle glaucoma, normal tension glaucoma, or pseudoexfoliation glaucoma, each with mild-to-moderate visual field loss in at least one eye. Recruitment will take place from March 2025 to March 2026 at St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden. The primary outcome is change in the photopic negative response measured by full-field electroretinography. Secondary outcomes include changes in visual field parameters, retinal nerve fiber layer thickness, and ganglion cell-inner plexiform layer thickness. Exploratory outcomes will include changes in blood-based metabolomic and DNA methylation profiles.

One-carbon metabolism-based supplementation has been shown to reduce retinal ganglion cell loss in rodent models of glaucoma. This trial will investigate whether such supplementation improves retinal function and confers neuroprotection in patients with glaucoma. The use of full-field electroretinography as the primary outcome aims to detect early functional improvements in the retina. If successful, this approach could support a low-cost, widely available neuroprotective strategy to be used alongside existing intraocular pressure-lowering therapies.

This trial is registered at ClinicalTrials.gov (NCT06885827), first posted on 20 March 2025.