Traumatic Optic Neuropathy Treatment Trial (TONTT)
Condition: Traumatic Optic Neuropathy
MeSH terms: Peripheral Nervous System Diseases; Optic Nerve Diseases; Optic Nerve Injuries
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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.
    


Intervention name(s): Recombinant human erythropoietin (EPO); Observation; Methyl prednisolone
Intervention type(s): Drug; Other; Drug
Intervention description(s): 4000 units per vial; Just observation; 250 mg every 6 hours for 3 days.
Other intervention name(s): EPO (Pooyesh darou Co., Tehran); Depo-Medrol
Intervention MeSH terms: Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Epoetin Alfa; Prednisolone hemisuccinate; Prednisolone phosphate
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: Single (Care Provider)
Primary purpose: Treatment
Keywords: Erythropoietin; Traumatic Optic Neuropathy; Visual function