Comparison of Ecacy Between Steroid Therapy and Observation Therapy in the Treatment of Traumatic Optic Neuropathy-a Meta-analysis

Background: Until now, the exact pathophysiology of traumatic optic neuropathy(TON) is still unclear, its management has remained controversial. The effect of steroid in TON remains unclear. The purpose of this study is to compare the effect of steroid therapy with observation therapy in the treatment of traumatic optic neuropathy(TON). Methods: A systematic literature search was performed in data sources including CENTRAL, PubMed, EMBASE, Web of Science, Cochrane Library, MEDLINE, Chinese databases including Wanfang and China National Knowledge Infrastructure for to nd relevant studies. The statistical analysis was performed by RevMan 5.3 software. Results: Eight studies including 263 eyes were enrolled in this study. The rate of improvement of VA in the steroid group was not better than that of the observation group (OR=2.17, 95%, CI=1.23-3.83, P=0.007), with no heterogeneity (I 2 =0,P=0.43). Conclusions: Patients with TON receiving steroid treatment may not have a better visual recovery than observation therapy. Steroid therapy is not recommend in patients with TON. Further larger randomized clinical trials are needed to evaluate the effect of steroid therapy for TON in the future.


Background
Traumatic optic neuropathy (TON) describes an injury to the optic nerve following either blunt or penetrating trauma. [1] Until now, the exact pathophysiology of TON is still unclear, its management has remained controversial. Treatment options include observation alone, corticosteroid administration, and/or surgical decompression. [2] Since the early 1980s, steroid have been used in an attempt to reduce the abnormal swelling that follows an injury to the optic nerve and improve visual recovery. [3]In a study by Anderson et al [3], it was found that some patients who were administered corticosteroids shortly after injury recovered some vision within 6 hours of treatment initiation. [4]However, others found no clear bene t of corticosteroid therapy. [5] The effect of steroid in TON remains unclear.
The purpose of this systematic review was to examine the effect of steroid and to make recommendations for best practice in the treatment of TON.

Search strategy
We searched the following databases: CENTRAL, PubMed, EMBASE, Web of Science, Cochrane Library, MEDLINE, Chinese databases including Wanfang and China National Knowledge Infrastructure from database inception through until July 20, 2020. There were no language restrictions. The following search terms were used: " (

Eligibility Criteria
We planned to include all the studies of TON in which any steroid regime was compared to observation group. Animal studies, conference proceedings, editorials, abstracts and studies with incomplete data were excluded.

Data collection and analysis
Page 3/8 Two review authors independently screened and reviewed the titles and abstracts resulting from all retrieved records. We obtained full-text articles of studies that appeared to meet the inclusion criteria. Both authors then assessed the articles to ensure that they met our inclusion criteria. Any disagreement was resolved by discussion and a consensus opinion was reached. The reports that did not completely ful ll the inclusion criteria were excluded.
We used Review Manager software (version 5.3, Cochrane Collaboration, Oxford, UK) for all the statistical analyses.
Before carrying out a meta-analysis we assessed heterogeneity by examining the characteristics of the study, the forest plot of results in the studies, and the results of the Chi 2 statistic and I 2 value for statistical heterogeneity.

Selection of Studies And Characteristics of the Included Studies
The original searches identi ed 315 reports of studies. We read the titles and abstracts of these studies for potential inclusion in the review. The full-text articles of studies that appeared to meet the inclusion criteria were obtained. In addition, references from these articles were reviewed to ensure that no potentially relevant studies were missed. Finally, eight studies [4,5,[7][8][9][10][11][12] including 263 eyes were enrolled in this analysis. Characteristics of included studies are presented in Table 1. Of these studies, three were performed in China, two in USA, one in Iran, Malaysia and Singapore respectively (Table 1). Outcomes of the Meta-analysis

Discussion
Traumatic optic neuropathy (TON) was rst described by Hippocrates in 500 BC. [13] It mainly affects young, economically active males and is an rare cause of visual loss following blunt or penetrating head trauma with a reported incidence of 0.7-2.5% in previous studies. [14][15][16] The pathophysiology of TON is likely to be multifactorial, and the concept of primary and secondary injury has been proposed[16-18]: Following trauma, there is an immediate shearing of a proportion of retinal ganglion cell axons, an irreversible process that results in neuronal loss. There is then a degree of optic nerve swelling within the tight con nes of the optic canal secondary to direct mechanical trauma and vascular ischemia. The ensuing compartment syndrome further impairs the already compromised blood supply to surviving retinal ganglion cells, setting up a downward spiral toward apoptotic cell death. This two-stage model of TON forms the basis for optic nerve decompression by medical or surgical means, in order to break this vicious cycle and to preserve the remaining retinal ganglion cells that survived the initial insult. It is caused by the transmission of forces to the optic nerve from a distant site, without any overt damage to the surrounding tissue structures. TON could result in partial to complete loss of vision. The loss of visual acuity is usually instantaneous and, without treatment, permanent. [19] The treatment of TON is still controversial because it is a challenge to perform large, randomized controlled trials in the relatively small patient population of TON.
Steroid treatment was used from the ndings from the Second National Acute Spinal Cord Injury Study (NASCIS-II). [20] It is supposed that large doses of steroid may slow the cell degenerative process, increase the blood supply to the injured area, and decrease cell damage secondary to ischemia and hypoxemia. [21] The use of steroid to treat TON injuries was rst reported by Anderson et al in 1982. [3] One study by Cook et al [22] concluded that treatment with corticosteroids was signi cantly better than no treatment. However, other literatures have not shown any signi cantly better visual outcome in the steroid than observation. [23,24] The results of steroid interventions have still shown to be uncertain. [5,8] In the studies included in this meta-analysis, only the results of Lee et al [4] and Levin et al [5] favored experimental group who receiving intravenous steroid had a better visual recovery as compared with observation group. The others [7][8][9][10][11][12] all favored observation group. When we took all the studies into meta-analysis, the result didn't showed a better visual recovery in patients receiving steroid treatment compared with observation therapy.
There are a few limitations in the present study. Parts of studies including into this meta-analysis failed to be RCT, the application method for steroid and de nition of visual improvement in different studies were not consistent.

Conclusions
In conclusion, to the best of our knowledge, this is the rst meta-analysis to compare the effect of steroid therapy to observation therapy in the treatment of TON. Availability of data and materials Not applicable.

Competing interests
The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Funding
None.

Authors' contributions
Peipei Zhang, Chao Xue reviewed the literature and contributed to manuscript drafting; Ying Chen reviewed the literature reviewed the literature and designed the methods; Xuening Su were responsible for the revision of the manuscript for important intellectual content; all authors issued nal approval for the version to be submitted. Figure 1 Forest plots comparing the results of the steroid group with observation group