The pathophysiology of Traumatic Optic Neuropathy (TON) is thought to be multifactorial, and
some researchers have also postulated a primary and secondary mechanism of injury.TON is
categorized as direct or indirect.In indirect TON cases, the injury to the axons is thought
to be induced by shearing forces that are transmitted to the fibers or to the vascular supply
of the nerve. Studies have shown that forces applied to the frontal bone and malar eminences
are transferred and concentrated in the area near the optic canal. The tight adherence of the
optic nerve's dural sheath to the periosteum within the optic canal is also thought to
contribute to this segment of the nerve being extremely susceptible to the deformative
stresses of the skull bones. Such injury leads to ischemic injury to the axons of the retinal
ganglion cells within the optic canal. At present, no studies validate a particular approach
to the management of TON. There are three management lines for these patients that include
1)observation only;2)medical treatment with high or megadoses of methylprednisolone; and
3)surgical intervention. Generally no line precedes the others and additionally, medical or
surgical interventions may result in serious side effects or complications. In 2005, the
results of the Corticosteroid Randomization after Significant Head Injury (CRASH) trial
raised concerns regarding the use of mega dose steroids in traumatic brain injury. This study
was the largest randomized study that evaluated steroids in patients with traumatic brain
injury and was stopped early due to the significantly increased risk of death in patients
that received mega dose steroids at their 6-month follow-up when compared with the placebo
group (25.7% vs 22.3%; Relative Risk 1.15 Confidence Interval 1.07 to 1.24; p=0.0001).
Although the etiology of the increased risk of death was not determined, the findings of this
study should be taken into consideration when managing cases of TON with concurrent traumatic
brain injury. Very recently it has been shown the cytokine hormone erythropoietin (EPO) that
had been long known and used as a valuable agent to promote hematopoiesis has been protective
in experimental models of mechanical trauma, neuroinflammation, cerebral and retinal
ischemia, and even in a human stroke trial, and most notably in optic nerve transection. A
double blind placebo-controlled multicenter trial on EPO add-on treatment in chronic
schizophrenic men was performed. Treatment over 12 weeks with high-dose weekly (40,000 IU
intravenously) EPO led to significant improvement of cognitive performance compared to
placebo controls. Different studies have been performed on the effect of EPO on neuropathy in
different studies. The investigators recently published our results on treating patients with
TON with EPO and found it safe and effective. Patients were compared with a historical
control group of patients who received no treatment for TON. A better visual recovery was
found. The aim of this study is to determine the effectiveness of EPO on TON in a Multi-
center clinical trial using a semi-experimental design.
Phase:
Phase 1/Phase 2
Details
Lead Sponsor:
Tehran University of Medical Sciences
Collaborators:
Iran University of Medical Sciences Mashhad University of Medical Sciences Shahid Beheshti University of Medical Sciences