Because tumor necrosis factor plays a role in most neurodegenerative diseases of the eye, and because etanercept has shown promise in improving recovery of injured facial nerves, authors of a recent study sought to determine whether etanercept can be used to protect retinal ganglion cells and improve visual outcomes after injury.
Blunt force trauma can result in traumatic optic neuropathy (TON), a cause of permanent vision loss. Direct injury to the optic nerve may result from a foreign body or a bone fragment coming into contact with the optic nerve, or indirect injury may result from forces as concussive shock waves or compression of the optic nerve by the bones in the optic canal. Currently, no evidence-based therapy is available to effectively treat patients with TON.
Because tumor necrosis factor (TNF) plays a role in most neurodegenerative diseases of the eye, and because the anti-TNF agent etanercept has shown promise in improving recovery of injured facial nerves, authors of a recent study, published in Investigative Ophthalmology and Visual Science, sought to determine whether etanercept can be used to protect retinal ganglion cells (RGC) and improve visual outcomes after injury.
In the study of mouse optic nerves, which were subjected to optic nerve crush or sonication-induced TON, 5 mice with each injury type were treated with either injections of etanercept at a dose of 10 mg/kg of body weight or injections of saline. Injections took place daily for 7 days. In both injury groups, TNF was upregulated at the gene and protein level within hours of the injury (6 hours in the crush group and 24 hours in the TON group).
In both injury groups, in etanercept-treated mice, the injured eyes showed greater survival of RGC compared to the saline-treated mice. At 2 weeks after injury, the percentage-based increase in RGC counts for the etanercept-treated mice (versus the saline-treated mice) was 24.23% in the crush group and 20.42% in the TON group.
Additionally, in both injury groups, etanercept-treated mice had significant and maintained improvement (versus the saline-treated group) in visual function at weeks 1 and 2 post-injury as measured by pattern electroretinogram. “Functionality is the ultimate outcome measure for evaluating a treatment's effectiveness,” wrote the authors, adding that “our findings indicate that eyes treated with etanercept had significantly higher a-wave amplitudes than untreated injured controls.”
The authors note that their study was limited by the rapid administration of etanercept post-injury; in a clinical setting, anti-TNF agents are unlikely to be given immediately after an injury occurs. However, they say, their findings support and approach to using anti-TNF agents such as etanercept in the acute phase after injury. The research team has begun further studies to help determine how long after injury etanercept can be administered in order to provide neuroprotection and yield acceptable visual outcomes for patients.
Tse BC, Dvoriantchikova G, Tao W, et al. Tumor necrosis factor inhibition in the acute management of traumatic optic neuropathy. Invest Ophthalmol Vis Sci. 2018;59(7): 2905-2912. doi: 10.1167/iovs.18-24431.