Background Indirect traumatic optic neuropathy (TON) is an acute injury of the optic nerve associated with severe visual dysfunction, which may be a result of secondary mechanical injury and vascular disorder of the optic nerve due to trauma. We analyzed the natural course of axonal loss and blood flow disturbances in patients with indirect TON to find a possible therapeutic window. Methods A cohort of 54 patients with indirect TON recruited between October 2008 and October 2010 at Beijing Tongren Hospital was retrospectively analyzed. The patients were divided into no light perception group (NLP) and better than NLP (btNLP) group. Specifically, the thickness of the retinal nerve fiber layer (RNFL) measured by spectral domain optical coherence tomography (SD-OCT), and hemodynamic parameters of the ophthalmic artery (OA), central retinal artery (CRA) and posterior ciliary artery (PCA) were determined. Results Two weeks after injury, there was a statistically significant decrease in the thickness of RNFL in the btNLP group as compared with the fellow control eyes (P <0.05). In contrast, in the NLP group, RNFL thickness slightly increased for 2 weeks following injury, then overtly reduced after 4 weeks (P <0.05). Peak systolic velocity (PSV) of CRA was significantly decreased 4 weeks after injury (P <0.05) in both the NLP group and btNLP group (P <0.05). The thickness of RNFL in the NLP group was negatively correlated with PSV of CRA after 1 week of injury (P <0.05, r=-0.962). Conclusions SD-OCT is a useful supplement in detecting the axonal loss in TON. The dynamic change of the thickness of RNFL appears to correlate with the hemodynamic disturbances in the natural course of TON. The first 2 weeks following an injury is critical and should be considered as the therapeutic window for TON patients.