In our study, both pRNFL thickness and GCIPL thickness were decreased in eyes with TON compared to controls. This finding is consistent with many previous studies on TON [16, 21–26]. Medierios et al. [21] and López-de-Eguileta et al. [22] have reported cases of gradual RNFL loss, ganglion cell complex loss, and Bruch’s membrane opening-minimum rim width loss measured with OCT in TON patients. Cunha et al. [23] have reported progressive thinning of RNFL and macular thickness in three TON patients. Sung et al. [24] and Lee et al. [25] have studied OCT measurements of TON patients showing both reductions in RNFL and GCIPL thicknesses. Chan et al. [26] reported thinning of RNFL and ganglion cell complex, and also subfoveal choroidal thinning in TON patients with chronic mild traumatic brain injury.
In this study, there was a significant reduction of the average vessel density in the RPC segment in TON patients compared to controls. In addition, the vessel density of the RPC segment in TON patients was also significantly lower than that in healthy controls in all four quadrants when compared by sectors. The average superficial parafoveal vessel density in patients with TON was also lower than in controls, however, the difference did not reach statistical significance. In a recent study, Ma et al. have analyzed retinal microvascular alterations in affected eyes compared to unaffected fellow eyes in 73 indirect TON patients following craniofacial trauma by OCT-A [16] and found that vessel densities in macular and peripapillary areas are significantly lower in TON eyes than in fellow eyes [16]. Our study results also revealed that the intraretinal vessel density in the was significantly affected by TON, support previous findings reported by Ma et al [16]. Chan et al. previously have analyzed OCT findings in chronic subclinical indirect TON patients and demonstrated that subfoveal choroidal thinning is significantly worse in eyes of TON patients than in eyes of controls [26]. Yan et al. have studied angiographic changes in the optic disc, choroid, and retinal arterial circulation after optic nerve contusion with fundus fluorescein angiography and indocyanine green angiography in 30 patients, and found seriously damaged choroidal and retinal arterial circulation [27]. Blood supply of the optic nerve head and choroid circulation are closely correlated as both the choroid and the anterior part of the optic nerve head are supplied by short posterior capillary arteries [15, 28]. Furthermore, Shi et al. have reported decreased perfusion of the central retinal artery in TON eyes [14]. Ustymowicz et al. have also revealed a significant blood flow decrease in the central retinal artery of TON patients which correlates with functional nerve impairment [13]. Results of the present study are in line with previous studies showing a significant reduction of intraocular blood flow in TON.
In this study, there were significant associations between microvascular density and the degree of visual field defect and low visual acuity in TON patients. Lower vessel density of the inferior RPC segment and temporal DRCP showed significant associations with worse visual field results. The lower inferior sector vessel density of the RPC segment was also significantly associated with a low visual acuity less than 20/200. Previous studies on other structural parameters such as pRNFL [14, 17, 25] and GCIPL [17, 25] in TON patients have also reported significant correlations between OCT parameters and visual functional parameters such as visual acuity [14, 17, 25], color vision [25], visual evoked potential (VEP) results [17, 25], and the degree of visual field defect [25]. Regarding OCT-A parameters, Ma et al. have reported that the prognostic association between time-dependent retinal vasculature alteration measured with OCT-A and patients’ post-injury eyesight is weak [16]. They reported that a preserved vision was not associated with time-dependent alteration in retinal thickness or vascular attenuation [16]. However, Gao et al. have compared retinal vessel density measured with OCT-A and visual functional parameters of 77 TON patients who have undergone a surgery with 18 TON patients who have received conservative treatments [17] and found that TON patients who have undergone a surgery have thicker RNFL, thicker ganglion cell complex, higher RPC vessel density, and higher macular vessel density with better visual acuity and VEP results [17]. Based on our study results, we may consider vessel densities of RPC and DRCP in OCT-A as well as parameters in OCT as useful biomarkers related to the severity of visual functional deficits in TON patients.
To the best of our knowledge, studies on associations between OCT parameters and OCT-A parameters in TON patients have not been reported yet. However, in patients with other types of optic neuropathies such as ischemic optic neuropathy [8, 29, 30], optic disc drusen [31, 32], glaucoma [10], and neuromyelitis optica spectrum disorders [12], significant associations between OCT and OCT-A parameters have been reported. In the present study, the vessel density of RPC was significantly associated with pRNFL thickness, suggesting that OCT-A could also reflect the degree of neuroaxonal damage in the retinal layer.
This study has several limitations. First, the sample size was small due to the rarity of this disease. In addition, this was not a longitudinal study. Thus, we could not analyze the correlation of factors considering time passage. Second, vessel density was measured using OCT-A in which the angiographic signal was based on movement. However, many other factors such as blood flow velocity, morphology, and alterations in the vascular endothelial barrier could compromise the measurement of perfusion. Third, this study was conducted in a single center with a population of Asian ethnicity.
Despite these limitations of this study, this is one of the few limited reports using OCT-A to observe intraretinal microvascular alterations in TON. This study confirms that indirect TON can induce significant microvascular changes. It shows significant associations of OCTA parameters with functional and structural parameters, suggesting that OCTA is a potentially useful biomarker to assess both functional status and the degree of structural damage in TON.