Traumatic optic neuropathy treatment trial (TONTT): open label, phase 3, multicenter, semi-experimental trial

Kashkouli, Mohsen Bahmani; Yousefi, Sahar; Nojomi, Marzieh; Sanjari, Mostafa Soltan; Pakdel, Farzad; Entezari, Morteza; Razavi, Mohammad Etezad; Razeghinejad, Mohammad Reza; Esmaeli, Manuchehr; Shafiee, Masoud; Bagheri, Mansoureh

doi:10.1007/s00417-017-3816-5

Cited by 42 publications

(38 citation statements)

References 27 publications

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“… 5 , 8 , 9 Current treatment options for TON include observation, high-dose corticosteroid use, or surgical decompression of the optic canal. 9 – 13 In a prospective, comparative, nonrandomized interventional study of TON visual outcomes, the International Optic Nerve Trauma Study found that, after adjusting for baseline visual acuity, no clear benefit of either corticosteroid therapy or optic canal decompression surgery was observed. 14 , 15 Hence, effective therapy for visual recovery in TON remains elusive.…”

mentioning

confidence: 99%

Tumor Necrosis Factor Inhibition in the Acute Management of Traumatic Optic Neuropathy

Tse¹,

Dvoriantchikova²,

Tao³

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PurposeTo determine the effectiveness of etanercept, a tumor necrosis factor (TNF) inhibitor, in conferring neuroprotection to retinal ganglion cells (RGCs) and improving visual outcomes after optic nerve trauma with either optic nerve crush (ONC) or sonication-induced traumatic optic neuropathy (SI-TON) in mice.MethodsMouse optic nerves were unilaterally subjected to ONC (n = 20) or SI-TON (n = 20). TNF expression was evaluated by using immunohistochemistry and quantitative RT-PCR (qRT-PCR) in optic nerves harvested 6 and 24 hours post ONC (n = 10) and SI-TON (n = 10). Mice in each injury group received daily subcutaneous injections of either etanercept (10 mg/kg of body weight; five mice) or vehicle (five mice) for 7 days. Pattern electroretinograms were performed on all mice at 1 and 2 weeks after injury. ONC mice were killed at 2 weeks after injury, while SI-TON mice were euthanized at 4 weeks after injury. Whole retina flat-mounts were used for RGC quantification.ResultsImmunohistochemistry and qRT-PCR showed upregulation of TNF protein and gene expression within 24 hours after injury. In both models, etanercept use immediately following optic nerve injury led to higher RGC survival when compared to controls, which was comparable between the two models (24.23% in ONC versus 20.42% in SI-TON). In both models, 1 and 2 weeks post injury, mice treated with etanercept had significantly higher a-wave amplitudes than untreated injured controls.ConclusionsTreatment with etanercept significantly reduced retinal damage and improved visual function in both animal models of TON. These findings suggest that reducing TNF activity in injured optic nerves constitutes an effective therapeutic approach in an acute setting.

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mentioning

confidence: 99%

Tumor Necrosis Factor Inhibition in the Acute Management of Traumatic Optic Neuropathy

Tse¹,

Dvoriantchikova²,

Tao³

et al. 2018

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

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“… 13) The same study group recently showed the effect of intravenous EPO for TON in an open-label, phase 3, multicenter, semi-experimental trial. 14) All three groups (EPO, 69; steroid, 15; observation, 16) showed significant improvement of BCVA in patients with TON. Interestingly, color vision was significantly improved in the EPO group.…”

Section: Treatment Of Indirect Tonmentioning

confidence: 87%

“…A new treatment option for TON is the cytokine hormone erythropoietin (EPO). 13 14) EPO has been reported to be effective for reducing neural apoptosis and protecting brain ischemic injury. 9) A pilot study of intravenous EPO for TON showed a promising result, in that patients in the EPO-treated group showed a significantly better visual outcome than the observation group.…”

Section: Treatment Of Indirect Tonmentioning

confidence: 99%

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