PMID- 30082073 OWN - NLM STAT- MEDLINE DCOM- 20190916 LR - 20190916 IS - 1549-4713 (Electronic) IS - 0161-6420 (Linking) VI - 125 IP - 12 DP - 2018 Dec TI - Oral Memantine for the Treatment of Glaucoma: Design and Results of 2 Randomized, Placebo-Controlled, Phase 3 Studies. PG - 1874-1885 LID - S0161-6420(18)30029-0 [pii] LID - 10.1016/j.ophtha.2018.06.017 [doi] AB - PURPOSE: To evaluate the effectiveness and safety of oral memantine as a potential neuroprotective agent in open-angle glaucoma (OAG) at risk for progression. DESIGN: Two randomized, double-masked, placebo-controlled, parallel-group, multicenter, 48-month studies identically designed, initiated 1 year apart, and completed in 2006. Protocol amendments included a 1-year extension (first study) and change in primary endpoint and analysis (second study). PARTICIPANTS: Patients (2298 total) with bilateral OAG; glaucomatous optic disc damage and visual field loss in 1 eye; glaucomatous optic disc damage and/or visual field loss in the contralateral eye (at screening), topically treated or untreated intraocular pressure (IOP) of 21 mmHg or less (at baseline); and at risk of glaucomatous progression (per prespecified criteria). METHODS: Patients were randomized 3:2:2 to receive memantine 20 mg, memantine 10 mg, or placebo tablets daily. Glaucomatous progression was assessed in the intent-to-treat population by full-threshold standard automated perimetry (SAP), frequency doubling technology (FDT), and stereoscopic optic disc photographs, standardized by quality control assessment at centralized reading centers. Safety evaluations included adverse events (AEs), best-corrected visual acuity, biomicroscopy, IOP, and ophthalmoscopy. Efficacy data from each study were analyzed per protocol. Pooled analyses of efficacy and safety data were also performed. MAIN OUTCOME MEASURES: The predefined primary efficacy measure was glaucomatous visual field progression, as measured by SAP. Additional efficacy measures included glaucomatous progression of visual field (FDT) and optic nerve damage (stereoscopic optic disc photographs). RESULTS: The proportion of patients who completed the studies was similar among groups (80%-83%). Compared with placebo, daily treatment with memantine 10 mg or 20 mg for 48 months did not delay glaucomatous progression significantly in the individual studies and pooled analyses. The pooled risk reduction ratio (95% confidence interval) assessed by SAP was -0.13 (-0.40, 0.09) and -0.17 (-0.46, 0.07) for memantine 10 mg and 20 mg, respectively. Results were similar per FDT and stereoscopic optic disc photographs. The most common AEs leading to treatment discontinuations were dizziness, headache, fatigue, and nausea. CONCLUSIONS: With technologies available when the studies were conducted, daily treatment with memantine over 48 months was not shown to prevent glaucomatous progression in this patient population. CI - Copyright (c) 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved. FAU - Weinreb, Robert N AU - Weinreb RN AD - Hamilton Glaucoma Center, Shiley Eye Institute and Department of Ophthalmology, University of California San Diego, La Jolla, California. Electronic address: rweinreb@ucsd.edu. FAU - Liebmann, Jeffrey M AU - Liebmann JM AD - Edward S. Harkness Eye Institute, Columbia University Medical Center, New York, New York. FAU - Cioffi, George A AU - Cioffi GA AD - Edward S. Harkness Eye Institute, Columbia University Medical Center, New York, New York. FAU - Goldberg, Ivan AU - Goldberg I AD - Discipline of Ophthalmology, University of Sydney and Sydney Eye Hospital, Sydney, Australia. FAU - Brandt, James D AU - Brandt JD AD - UC Davis Eye Center, University of California, Davis, Sacramento, California. FAU - Johnson, Chris A AU - Johnson CA AD - Department of Ophthalmology, University of Iowa, Iowa City, Iowa. FAU - Zangwill, Linda M AU - Zangwill LM AD - Hamilton Glaucoma Center, Shiley Eye Institute and Department of Ophthalmology, University of California San Diego, La Jolla, California. FAU - Schneider, Susan AU - Schneider S AD - Allergan plc, Irvine, California. FAU - Badger, Hanh AU - Badger H AD - Allergan plc, Irvine, California. FAU - Bejanian, Marina AU - Bejanian M AD - Allergan plc, Irvine, California. LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20180803 PL - United States TA - Ophthalmology JT - Ophthalmology JID - 7802443 RN - 0 (Excitatory Amino Acid Antagonists) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - W8O17SJF3T (Memantine) SB - IM MH - Administration, Oral MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Disease Progression MH - Double-Blind Method MH - Excitatory Amino Acid Antagonists/*therapeutic use MH - Female MH - Glaucoma, Open-Angle/diagnosis/*drug therapy MH - Humans MH - Intraocular Pressure/*drug effects MH - Male MH - Memantine/*therapeutic use MH - Middle Aged MH - Ophthalmoscopy MH - Optic Nerve Diseases/diagnosis/drug therapy MH - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors MH - Research Design MH - Slit Lamp Microscopy MH - Treatment Outcome MH - Visual Acuity/physiology MH - Visual Fields/physiology MH - Young Adult EDAT- 2018/08/08 06:00 MHDA- 2019/09/17 06:00 CRDT- 2018/08/08 06:00 PHST- 2018/01/05 00:00 [received] PHST- 2018/05/16 00:00 [revised] PHST- 2018/06/12 00:00 [accepted] PHST- 2018/08/08 06:00 [pubmed] PHST- 2019/09/17 06:00 [medline] PHST- 2018/08/08 06:00 [entrez] AID - S0161-6420(18)30029-0 [pii] AID - 10.1016/j.ophtha.2018.06.017 [doi] PST - ppublish SO - Ophthalmology. 2018 Dec;125(12):1874-1885. doi: 10.1016/j.ophtha.2018.06.017. Epub 2018 Aug 3.