In glaucoma, we currently have one target: intraocular pressure (IOP). Lowering IOP slows or stops the progression or development of glaucoma.1 Generally speaking, a treatment that protects the optic nerve without going through the primary mechanism of lowering IOP would be considered a neuroprotective agent.
Neuroprotective trials are tough to perform, however. One needs a good number of patients taking many visual field tests for many years in order to show any benefit of an adjunctive neuroprotective therapy. Of course, in a neuroprotective study, we would have to treat both the neuroprotection arm and the control arm with IOP-lowering medications, as is the standard of care. So perhaps a more feasible way to find a medicine that might slow glaucoma would be to look out into our world, perhaps by using big data, to see if ordinary people treated with certain medications have a slower rate of glaucoma progression.
Joshua Stein, MD, MS, has been doing just this (for many topics), and has elucidated a promising potential neuroprotective agent: the HMG coA reductase inhibitor, or statin. These medications, indicated for hypercholesterolemia, have been associated with a reduced incidence of glaucoma in a number of observational studies. Using a Medicare claims database with more than 500,000 individuals with hyperlipidemia, Dr. Stein found that for every three months of statin consumption, one’s risk of developing open angle glaucoma (according to Medicare) decreased by about 1%2. For individuals who continuously took statins for two years, the risk of glaucoma was 8% lower. Additionally, for every month of statin exposure the likelihood of requiring medical treatment decreased by 0.4%.
In a second study,3 looking at which statins and which doses were effective in this manner, Dr. Stein found that there was no additional protective effect from using the highest dose as compared to lower doses, and that it didn’t seem to matter whether a generic or branded statin were used. This work provides a strong rationale for a prospective randomized trial comparing statin use versus standard of care for neuroprotection in open angle glaucoma.
Heijl A, Leske MC, Hyman L, Yang Z, Bengtsson B; EMGT Group. Intraocular pressure reduction with a fixed treatment protocol in the Early Manifest Glaucoma Trial. Acta Ophthalmol. 2011;89(8):749-754.
Stein JD, Newman-Casey PA, Talwar N, Nan B, Richards JE, Musch DC. The relationship between statin use and open-angle glaucoma. Ophthalmology. 2012;119(10):2074-2081.
Talwar N, Musch DC, Stein JD. Association of Daily Dosage and Type of Statin Agent With Risk of Open-Angle Glaucoma. JAMA Ophthalmol. 2017 Jan 19. [Epub ahead of print]
Dr. Nathan M. Radcliffe is the director of the glaucoma service and a clinical assistant professor at New York Univeristy Langone Ophthalmology Associates and is a cataract and glaucoma surgeon at the New York Eye Surgery Center.