Abstract
ObjectiveTumor Necrosis Factor (TNF) mediates retinal ganglion cell death in glaucoma. Anti-TNF drugs are neuroprotective in an animal model of glaucoma. It is unclear whether medications with anti-TNF properties such as bupropion have an impact on the risk of developing open-angle glaucoma (OAG) in humans. The purpose of this study is to determine whether bupropion use alters the risk of developing OAG.MethodsClaims data for beneficiaries age ≥35 years with no pre-existing OAG enrolled in a large nationwide U.S. managed care network continuously for ≥4 years between 2001-2011 was analyzed to identify patients who had been newly-diagnosed with OAG. The amount of bupropion use as captured from outpatient pharmacy claims over a four-year period was also quantified for each beneficiary. Multivariable Cox regression modeling assessed the impact of bupropion and other antidepressant medications on the risk of developing OAG with adjustment for sociodemographic characteristics of the enrollees along with medical and ocular comorbidities.ResultsOf 638,481 eligible enrollees, 15,292 (2.4%) developed OAG. After adjustment for confounding factors including use of other antidepressant medication classes, each additional month of bupropion use was associated with a 0.6% reduced risk of OAG (HR = 0.994, (95% CI: 0.989-0.998), p = 0.007). Compared to nonusers, those with 24-48 months of bupropion use had a 21% reduced hazard (HR=0.79, (CI: 0.65-0.94), p = 0.0099) of OAG. This association did not differ among persons taking bupropion for depression or for other reasons (p-interaction = 0.82). There was no significant association between use of tricyclic antidepressants (HR = 1.000, (CI: 0.997-1.004), p = 0.95) or selective serotonin reuptake inhibitors (HR = 0.999, (CI: 0.997-1.001), p = 0.39) and development of OAG.ConclusionThese findings suggest bupropion use may be beneficial in reducing the risk of OAG. If prospective studies confirm the findings of this analysis, this may identify a novel therapeutic target for OAG.
Highlights
Randomized clinical trials (RCT) suggest that intraocular pressure (IOP)-lowering medications, laser trabeculoplasty, or glaucoma filtration surgery slow disease progression for patients with open-angle glaucoma (OAG) but these measures are not curative.[1,2,3] Importantly, some patients with OAG appear to demonstrate disease progression despite achieving low IOPs, suggesting that non-IOP related factors might contribute to or perpetuate optic nerve damage
After adjustment for confounding factors including use of other antidepressant medication classes, each additional month of bupropion use was associated with a 0.6% reduced risk of OAG (HR = 0.994, p = 0.007)
These immune cells produce cytokines such as tumor necrosis factor (TNF) that bind to TNF receptor 1, which is upregulated in the human glaucomatous optic nerve.[6,8,9]
Summary
Randomized clinical trials (RCT) suggest that intraocular pressure (IOP)-lowering medications, laser trabeculoplasty, or glaucoma filtration surgery slow disease progression for patients with open-angle glaucoma (OAG) but these measures are not curative.[1,2,3] Importantly, some patients with OAG appear to demonstrate disease progression despite achieving low IOPs, suggesting that non-IOP related factors might contribute to or perpetuate optic nerve damage. The discovery, characterization, and identification of effective treatments of risk factors for OAG besides lowering IOP can reduce the burden of vision loss from this disease. In animal models [4,5] and in humans,[6,7,8] elevated IOP serves as a stressor to incite neuro-inflammation with activation of immune cells resident to the retina and optic nerve These immune cells produce cytokines such as tumor necrosis factor (TNF) that bind to TNF receptor 1, which is upregulated in the human glaucomatous optic nerve.[6,8,9] Intravitreal TNF injection mimics glaucomatous damage in normal mice; TNF binding to a related receptor, TNF receptor 2, mediates retinal ganglion cell death in a murine angle closure glaucoma model.[10] Intraperitoneal injection of enteracept, a medication which blocks TNF activity, has been found to be neuroprotective in a rodent model of glaucoma.[11] Ocular x-ray radiation prevents monocyte entry into the optic nerve and attenuates optic nerve damage in a murine model of glaucoma.[12] These latter data further support the notion that blocking neuro-inflammation may protect the optic nerve from glaucomatous damage
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