Memantine of no benefit in glaucoma treatment
Long-term treatment with memantine is well tolerated but does not effectively prevent glaucomatous progression in patients with open-angle glaucoma (OAG), according to the results of two phase III trials.
The overall population comprised 2,298 bilateral OAG patients with glaucomatous optic disc damage and visual field loss in one eye, intraocular pressure (IOP) ≤21 mm Hg, and high-risk of progression. The two trials followed the same protocol, wherein patients were randomized to receive memantine 20 mg (n=974) or 10 mg (n=664) or placebo (n=660) tablets daily for 48 months.
The predefined primary efficacy measure was glaucomatous visual field progression, as assessed using full-threshold standard automated perimetry (SAP). Other efficacy measures were glaucomatous progression of visual field (measured using frequency doubling technology [FDT]) and optic nerve damage (evaluated using stereoscopic optic disc photographs). Safety evaluations included adverse events (AEs), best-corrected visual acuity (BVCA), biomicroscopy, IOP and ophthalmoscopy.
Compared with placebo, use of memantine for 48 months did not delay glaucomatous progression significantly in the individual studies and pooled analyses. The pooled risk reduction ratio for SAP-assessed progression was −0.13 (95 percent CI, −0.40 to 0.09) with the 10-mg dose and −0.17 (−0.46 to 0.07) with the 20-mg dose. Similar results were obtained per FDT and stereoscopic optic disc photographs.
Memantine was well tolerated, and dizziness was the most frequently reported AE. Changes in biomicroscopy and ophthalmoscopy findings with ≥1 severity grade increase, BVCA, mean IOP, and average central corneal thickness were comparable among the three treatment groups.
An uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, memantine is currently approved in several countries for the treatment of moderate to severe Alzheimer’s and Parkinson’s diseases. The drug can inhibit overstimulation of the NMDA receptor and potentially provide neuroprotection by preventing excessive calcium influx, the investigators said.
However, pooled results of visual field and optic disc analyses from the two trials revealed no consistent or beneficial effects of memantine in OAG based on ophthalmic assessments from the two trials, they added.