Intraretinal microvascular alterations in indirect traumatic optic neuropathy

Intraretinal microvascular alterations in indirect traumatic optic neuropathy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Intraretinal microvascular alterations in indirect traumatic optic neuropathy Kyung-Ah Park, Sei Yeul Oh, Min Chae Kang, Jiyeon HAN, Ga-In Lee This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2376086/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 30 Nov, 2023 Read the published version in Eye → Version 1 posted 7 You are reading this latest preprint version Abstract PURPOSE To quantitatively evaluate macular and peripapillary microvascular alterations in patients with indirect traumatic optic neuropathy (TON) compared to normal controls using optical coherence tomography angiography (OCT-A [Topcon DRI OCT; Triton]) and determine their associations with other ocular parameters. METHODS We enrolled 33 eyes of 33 patients with TON and 34 eyes of 34 healthy controls. OCT-A was used to generate microvascular structure images of the superficial retinal capillary plexus (SRCP), deep retinal capillary plexus (DRCP), and radial peripapillary capillary (RPC) segment in the macula and peripapillary area. Age, gender, and spherical equivalent refractive errors were statistically adjusted for the analysis. RESULTS OCT-A revealed a significant reduction of the average vessel density in the RPC segment in TON patients compared to controls (48.5% ± 6.28 vs. 57.88% ± 3.06%, P < 0.0001, corrected P < 0.0001). 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 inferior sector vessel density of the RPC segment was significantly associated with visual field defects ( P = 0.0253) and visual acuity ( P = 0.0369). The temporal sector vessel density of DRCP was also associated with visual field defects ( P = 0.0377). The RPC segment in the temporal, superior, and inferior sector vessel density had a significant association with the average pRNFL thickness ( P = 0.0092, 0.0171, and < 0.0001, respectively). CONCLUSIONS Patients with indirect TON show significant microvascular alterations compared to controls. This study confirms that TON can induce intraretinal microvascular changes and suggests that OCTA can be a useful biomarker for visual functional and structural changes. Biological sciences/Neuroscience/Visual system Health sciences/Biomarkers optical coherence tomography angiography vessel density traumatic optic neuropathy superficial retinal capillary plexus deep retinal capillary plexus radial peripapillary capillary segment Figures Figure 1 Figure 2 Introduction Traumatic optic neuropathy (TON) is a condition of severe vision loss caused by acute injury to the optic nerve secondary to head or facial trauma. TON is known to occur in about 0.5–5% of patients with closed head injuries and in 2.5% of those with midfacial fractures [ 1 – 5 ]. TON is classified as direct or indirect optic neuropathy. Direct TON occurs when the optic nerve is injured directly by the object that penetrates the orbit which leads to optic nerve avulsion, transaction, nerve sheath or orbital hemorrhage, and orbital emphysema [ 1 ]. Indirect TON occurs when the nerve injury results from compression forces transmitted to the optic nerve via the orbital apex and optic canal [ 1 , 6 ]. Compression forces transmitted to the orbital apex can result in damage to microcirculation, causing ischemia and swelling of the optic nerve [ 1 , 7 ]. Optical coherence tomography angiography (OCT-A) is a promising imaging method for assessing three-dimensional vascular structures in a fast and non-invasive way. As it can show different capillary networks of the retina, choroid, and optic nerve head with high resolution [ 8 ], microvascular changes in various disorders such as glaucoma, optic neuropathies including nonarteritic anterior ischemic optic neuropathy, neuromyelitis optica spectrum disorders, and pathologic myopia have been studied recently using OCT-A [ 8 – 12 ]. These microvascular changes measured using OCT-A are significantly correlated with visual functional parameters in previous studies [ 8 – 12 ]. Several previous studies have investigated microvascular changes in TON using color-coded duplex sonography in arteries [ 13 , 14 ], OCT [ 14 , 15 ], and OCT-A [ 16 , 17 ]. Previous studies have revealed that vasospasm and vascular ischemia can induce swelling of the optic nerve within the optic canal, which causes decreased blood supply to retinal ganglion cells (RGCs) and results in cell death [ 18 ]. Blood flow of the central retinal artery (CRA) is known to be decreased in patients with TON following injury [ 13 , 14 ]. It is also known that eyes affected by TON show thicker choroids possibly due to impaired blood circulation and vascular remodeling [ 15 ]. Recently, Ma et al. have reported significant alterations of intraretinal vessel densities in TON eyes compared to unaffected fellow eyes using OCT-A [ 16 ]. Ma et al. have found that the prognostic association between OCTA parameters and visual prognosis is weak [ 16 ]. Gao et al. have also compared retinal vasculature measured with OCT-A between TON patients who have received surgery and conservative treatments [ 17 ] and found that vision recovery after an effective therapy for indirect TON is associated with increased oxygen saturation of retinal vessels and better availability of oxygen in the retina with thicker retinas and better vessel density, indicating that effective theraphy can mitigate retinal atrophy of severe TON [ 17 ]. So far, research on microvascular alterations in TON measured by OCTA and its clinical implications is very limited. Studies on the association between OCT-A findings and other structural parameters have not been reported yet. Thus, this study aimed to evaluate intraretinal microvascular alterations in macular and peripapillary areas in patients with TON using OCT-A. Associations of OCT-A parameters with functional and structural parameters were also investigated. Methods This cross-sectional study was approved by the Institutional Review Board of Samsung Medical Center (Seoul, Republic of Korea). This study included patients with TON who visited the Department of Neuro-ophthalmology of Samsung Medical Center from October 1st, 2017 to January 31st, 2022. The diagnosis of TON was made based on a history of acute visual loss after a closed blunt injury of the face or head and ocular examination results, including an acute decrease of visual acuity, a relative afferent pupillary defect of the affected eye in unilateral cases, and the development of optic disc pallor during follow-up. Only one eye (the one with worse visual acuity in bilateral cases) of each patient was selected for analysis. Disease-free subjects were recruited as controls from staff and healthy volunteers who had undergone routine eye examinations. None of these controls had a history of ocular or neurologic disease or cranial/facial trauma. Healthy controls were required to have normal optic discs, normal thicknesses of intraretinal layers, and intraocular pressure (IOP) < 21 mmHg. Some of these healthy controls participated in other studies in the same department. Patients and healthy controls with other ophthalmic diseases (glaucoma, a refractive error greater than 6.0 diopters of spherical equivalent (SE) as high myopia and hyperopia or 3.0 diopters of astigmatism in either eye, amblyopia, epiretinal membrane, age-related macular degeneration, diabetic retinopathy, retinal artery/vein occlusion, optic neuropathy other than TON, and so on) and previous retinal surgery that might affect vessel density and those with known systematic/inflammatory diseases (cancer, multiple sclerosis, etc.) were excluded. Visual field perimetry was performed with a Humphrey Field Analyzer using the 24 − 2 SITA-standard protocol (Humphrey 740 Visual Field Analyzer, Carl Zeiss Meditec Inc. Dublin, CA, USA) in patients with TON. Only reliable visual fields (≤ 33% false positives, false negatives, fixation losses < 20%) were selected for the analysis in this study. Mean deviation was used for analysis. Fundus photography and Cirrus HD-OCT (Carl Zeiss Meditec AG, Jena, Germany) were performed for all patients. Detailed protocol of Cirrus HD-OCT measurements was described in a previous study on craniopharyngioma [ 19 ]. (Fig. 1 ) The pRNFL thickness was obtained using an optic disc cube 200 x 200 protocol with Cirrus software. This protocol generated a cube of data through a 6-mm-square grid. A 3.46-mm-diameter circle was automatically centered on the optic disc. The Cirrus HD-OCT software also calculated the average and sectoral macular ganglion cell-inner plexiform layer (GCIPL) thickness. To be included, all scans had to have a signal strength ≥ 6 without motion artifacts. Retinal and peripapillary microvasculatures were analyzed using a Topcon OCT instrument (DRI OCT Triton Plus, Topcon Corporation, Tokyo, Japan) for all patients and healthy controls. (Fig. 1 ) The detailed protocol of measurements was also described in authors’ previous study [ 19 ]. In brief, the Triton swept-source OCT was used to scan each patient using a wavelength of 1,050 nm with a scan speed of 100,000 A-scans per second with two imaging procedures consisting of a 4.5 × 4.5 mm-diameter peripapillary scan centered on the optic disc and a 3.0 × 3.0 mm-diameter perifoveal scan centered on the macula. The superficial retinal capillary plexus (SRCP) extending from 3 µm below the internal limiting membrane (ILM) to 15 µm below the IPL and the deep retinal capillary plexus (DRCP) extending from 15 to 70 µm below the IPL were separated automatically by the OCT instrument software (IMAGEnet 6 V.1.14.8538). The radial peripapillary capillary (RPC) segment extended from the ILM to the posterior boundary of the RNFL. Vessel density was defined as the percentage of area occupied by vessels in a localized region. The software automatically fitted a 3 mm macular circle at the foveal center. Another 3 mm circle was manually fitted at the disc center. To assess scan quality, scan images were included based on the quality assessment criteria suggested by Fenner et al. [ 20 ] All participants underwent both OCT-A and Cirrus HD-OCT imaging on the same day at least 28 days after the accident. Data are presented as mean ± standard deviation (SD). Best-corrected visual acuity was converted to a logarithmic scale (logMAR). Student's t-test was used to compare age. Wilcoxon rank-sum test was used to compare age and SE refractive errors between TON patients and controls. Chi-squared test was used to compare gender between groups. The pRNFL thickness and GCIPL thickness of patients were compared with those of healthy controls using a Wilcoxon rank-sum test and a Student's t-test, respectively. Bonferroni’s correction for multiple comparisons was applied to P- values by multiplying uncorrected P- values by 8. Linear regression analysis was conducted after adjusting for age, gender, and spherical equivalent (SE) to compare vessel density between the patient group and the healthy control group. Bonferroni’s correction for multiple comparisons was applied to P- values by multiplying the uncorrected P- values by 12. Spearman’s correlation coefficients were calculated to analyze associations of microvascular density with visual field defects, intraretinal layer thickness, and best-corrected visual acuity (BCVA). A P- value less than 0.05 was considered statistically significant. All statistical analyses were performed with SAS version 9.4 (SAS Institute Inc, Cary, NC, USA). Results A total of 33 eyes of 33 patients with TON and 34 eyes of 34 healthy controls were included in this study. The mean duration from the accident to the OCTA examination was 23.56 ± 14.43 weeks (range, 4–52 weeks). There was no statistically significant difference in age or SE refractive errors between TON and control groups (Table 1 ). Male patients accounted for 84.85% in the TON group and 73.13% in the healthy control group ( P = 0.0331). Age and gender along with SE refractive errors were adjusted for all analyses regarding OCT and OCTA parameters. Both pRNFL thickness and GCIPL thickness were significantly thinner in the TON group than in the healthy control group in average values (pRNFL, 72.26 ± 15.9㎛ in TON patients vs. 94.47 ± 8.05 ㎛ in controls, P < 0.0001; GCIPL, 58.61 ± 13.38 ㎛ vs. 81.59 ± 5.15 ㎛, P < 0.0001). Table 1 Baseline characteristics of patients with traumatic optic neuropathy and healthy controls (significant values are indicated in bold. N, numbers; M, male; F, female; SER, spherical equivalent refractive error; BCVA, best-corrected visual acuity; VF, visual field; MD, mean deviation. * , P- value by Student’s t-test; † , P- value by Chi-squared test; ‡ , P- value by Wilcoxon rank sum test). Patients (N = 33) Control (N = 34) P- value Age (years) 39.24 ± 17.79 41.29 ± 16.45 0.6545 * Gender (M/F) 28/5 21/13 0.0331 † SER -1.47 ± 2.02 -1.89 ± 2.49 0.5637 ‡ BCVA (logMAR) 2.1 ± 1.82 0 ± 0.01 < 0.0001 ‡ VF MD -20.91 ± 11.63 -0.85 ± 11.63 < 0.0001 ‡ Microvascular density in the macular area There was no significant difference in the average vessel density of SRCP (47.12 ± 3.51% in TON patients, 48.13 ± 2.30% in controls) or DRCP (49.67 ± 4.00% in TON patients, 48.44 ± 1.88% in controls) in the macular area between TON patients and controls after adjusting for age, gender, and SE refractive errors by linear regression analysis. In addition, when macular microvascular density was compared by sectors between patients with TON and controls, there was no statistically significant difference (Table 2 ). Table 2 Comparison of peripapillary and parafoveal vessels in patients with traumatic optic neuropathy and healthy controls (significant values are indicated in bold. N, numbers; RPC, radial peripapillary capillary; SRCP, superficial retinal capillary plexus; DRCP, deep retinal capillary plexus; * , P- value by linear regression with adjustment for age and spherical equivalent. Bonferroni’s correction for multiple comparisons was applied to P- values by multiplying uncorrected P -values by 12). Patients ( N = 33) Control ( N = 34) Corrected P- value RPC (%) Superior 55.77 ± 7.36 64.15 ± 5.73 < 0.0001 * Inferior 57.24 ± 10.19 66.17 ± 6.35 0.0024 * Temporal 39.1 ± 7.16 50.45 ± 5.95 < 0.0001 * Nasal 41.89 ± 7.8 50.72 ± 7.62 0.0011 * SRCP (%) Superior 48.09 ± 5.38 49.59 ± 6.27 0.7992 * Inferior 48.09 ± 5.93 48.88 ± 3.71 0.4956 * Temporal 45.95 ± 4.05 47.45 ± 2.49 0.9168 * Nasal 46.35 ± 3.53 45.95 ± 4.05 1.0000 * DRCP (%) Superior 51.7 ± 4.87 49.69 ± 2.83 0.6912 * Inferior 50.18 ± 8.65 49.74 ± 3.39 1.0000 * Temporal 48.23 ± 4.4 47.77 ± 2.49 1.0000 * Nasal 48.56 ± 3.67 46.57 ± 3.21 0.2940 * Microvascular density in the peripapillary area When peripapillary microvascular density was compared, the average vessel density of the RPC segment in TON patients was significantly lower than that in healthy controls (48.5% ± 6.28 vs. 57.88% ± 3.06%, P < 0.0001, corrected P < 0.0001). 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 (Table 2 ). Associations of vessel density with pRNFL thickness, GCC thickness, BCVA, and visual field defects Relationships between intraretinal vessel densities in each sector and functional parameters including BCVA and mean deviation of visual field test results were analyzed in TON patients (Table 3 ). Worse mean deviation score of the visual field and lower peripapillary vessel density in the inferior quadrant showed a statistically significant association (Estimate: 0.6012, t = 2.68, P = 0.0253 ). (Fig. 2 A) Also, worse mean deviation score of the visual field had a significant association with lower vessel density of DRCP in the temporal area (Estimate: 2.2260, t = 2.43, P = 0.0377). (Fig. 2 B) Lower BCVA, defined as logMAR > 1 showed a significant assocation with lower peripapillary vessel density in the inferior quadrant (Estimate: -0.1103, OR 0.9 (0.81, 0.99), P = 0.0369). Table 3 Association analysis between intraretinal vessel densities and functional parameters (significant values are indicated in bold. RPC, radial peripapillary capillary; BCVA, best-corrected visual acuity; VF, visual field; MD, mean deviation; SRCP, superficial retinal capillary plexus; DRCP, deep retinal capillary plexus. * , P- value by Spearman’s correlation analysis). Estimate t-value P- value * RPC vessel density Superior BCVA -0.0561 -1.21 0.2372 MD of VF 0.5765 1.49 0.1713 Inferior BCVA -0.0482 -1.49 0.1485 MD of VF 0.6012 2.68 0.0253 Temporal BCVA -0.0739 -1.64 0.1127 MD of VF 0.7072 2.23 0.0526 Nasal BCVA -0.0503 -1.02 0.3185 MD of VF -0.2298 -0.53 0.6101 SRCP vessel density Superior BCVA 0.0746 1.23 0.2311 MD of VF 0.0728 0.08 0.9367 Inferior BCVA -0.0480 -0.79 0.4372 MD of VF 1.0556 1.01 0.3406 Temporal BCVA 0.0895 1.10 0.2840 MD of VF 1.4851 1.39 0.1994 Nasal BCVA 0.0886 0.86 0.4010 MD of VF 1.0190 1.04 0.3252 DRCP vessel density Superior BCVA 0.0504 0.7 0.4878 MD of VF 0.5444 0.61 0.5593 Inferior BCVA -0.0364 -0.88 0.3866 MD of VF 0.9848 1.31 0.2224 Temporal BCVA 0.0241 0.32 0.7541 MD of VF 2.2260 2.43 0.0377 Nasal BCVA -0.0149 -0.13 0.8942 MD of VF 1.2096 1.36 0.2073 Relationships between intraretinal vessel densities in each sector and other structural parameters including pRNFL thickness and GCIPL thickness were also analyzed in TON patients (Table 4 ). The pRNFL thickness had a significant association with vessel density of the RPC segment in the temporal sector (Estimate: 1.0929, t = 2.92, P = 0.0092) (Fig. 2 E), in the superior sector (Estimate: 1.1371, t = 2.63, P = 0.0171) (Fig. 2 C), in the inferior sector (Estimate: 1.0125, t = 5.04, P < 0.0001) (Fig. 2 D) respectively. Table 4 Association analysis between intraretinal vessel densities and structural parameters including average peripapillary retinal nerve fiber layer thickness and average ganglion cell-inner plexiform layer thickness (significant values are indicated in bold. RPC, radial peripapillary capillary; pRNFL, peripapillary retinal nerve fiber layer; GCIPL, ganglion cell-inner plexiform layer; SRCP, superficial retinal capillary plexus; DRCP, deep retinal capillary plexus. * , P -value by Spearman’s correlation analysis). Estimate t value P- value * RPC vessel density Superior pRNFL thickness 1.1371 2.63 0.0171 GCIPL thickness 0.1488 0.39 0.6976 Inferior pRNFL thickness 1.0125 5.04 < 0.0001 GCIPL thickness 0.1338 0.58 0.5677 Temporal pRNFL thickness 1.0929 2.92 0.0092 GCIPL thickness 0.2632 0.79 0.4388 Nasal pRNFL thickness 0.1716 0.33 0.7485 GCIPL thickness -0.1852 -0.47 0.6410 SRCP vessel density Superior pRNFL thickness 0.9877 1.58 0.1372 GCIPL thickness 0.6815 1.57 0.1380 Inferior pRNFL thickness 1.0853 1.39 0.1864 GCIPL thickness 0.5228 0.94 0.3654 Temporal pRNFL thickness 0.9723 1.14 0.2750 GCIPL thickness 0.5087 0.84 0.4132 Nasal pRNFL thickness 1.2619 1.12 0.2804 GCIPL thickness 0.7905 1.01 0.3300 DRCP vessel density Superior pRNFL thickness 1.0658 1.49 0.1575 GCIPL thickness 0.7232 1.46 0.1659 Inferior pRNFL thickness 0.9780 1.04 0.3177 GCIPL thickness 0.6211 0.95 0.3601 Temporal pRNFL thickness 0.8389 1.00 0.3350 GCIPL thickness 0.2455 0.41 0.6874 Nasal pRNFL thickness 1.1356 0.83 0.4197 GCIPL thickness 0.6146 0.64 0.5296 Discussion 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. Declarations Competing Interests The authors declare no competing interests. Funding The authors declare no funding or sponsorship. Author Contribution S.Y.O and K.A.P designed and conducted the study. G.I.L, M.C.K and J.H collected the data, managed the study, and and interpreted the data. K.A.P contributed to the review of the manuscript. M.C.K and J.H drafted and revised the manuscript. 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Peripapillary and Macular Flow Changes in Nonarteritic Anterior Ischemic Optic Neuropathy (NAION) by Optical Coherence Tomography Angiography (OCT-A). J Ophthalmol. 2020;2020:3010631. Wright Mayes E, Cole ED, Dang S, Novais EA, Vuong L, Mendoza-Santiesteban C, et al. Optical Coherence Tomography Angiography in Nonarteritic Anterior Ischemic Optic Neuropathy. J Neuroophthalmol. 2017;37:358-64. Engelke H, Shajari M, Riedel J, Mohr N, Priglinger SG, Mackert MJ. OCT angiography in optic disc drusen: comparison with structural and functional parameters. Br J Ophthalmol. 2020;104:1109-13. Leal-González M, Pessanha F, Azevedo González-Oliva M, Pérez-Fernández E, Gili P. Study of peripapillary vascular flow using optical coherence tomography angiography in optic nerve head drusen. Clin Exp Ophthalmol. 2020;48:775-82. Additional Declarations (Not answered) Cite Share Download PDF Status: Published Journal Publication published 30 Nov, 2023 Read the published version in Eye → Version 1 posted Editorial decision: revise 20 Feb, 2023 Review # 1 received at journal 07 Feb, 2023 Reviewer # 1 agreed at journal 07 Feb, 2023 Reviewers invited by journal 19 Jan, 2023 Editor assigned by journal 10 Jan, 2023 Submission checks completed at journal 15 Dec, 2022 First submitted to journal 13 Dec, 2022 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2376086","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":166538960,"identity":"d5658abf-059b-45bb-befc-41b07e2412ea","order_by":0,"name":"Kyung-Ah Park","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyUlEQVRIiWNgGAWjYBACCSBmbGBgSOBnYGNmgHKI1CLZQLIWgwPEapGc3fzs44yKO3nG548lG/Mw2MhuOEBAi7TMMeOZG848Kza7kXY4mYchzZigFjmJBGPGh22HE7fdYG8+zMNwOJEILemfwVo29x8HaflPWIu0RI4x40aglg0MYIcdIKxFcs6ZYsYZZ54lzriRlmw4xyDZeCYhLRK32zcz9lTcSezvP2Ys8abCTraPkBZwxDAwwJQZEFKOqWUUjIJRMApGARYAAK29SXhN5i0SAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0001-7907-5635","institution":"Samsung medical center","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Kyung-Ah","middleName":"","lastName":"Park","suffix":""},{"id":166538961,"identity":"21df8c26-050f-4db9-a01b-55c7c9c5a734","order_by":1,"name":"Sei Yeul Oh","email":"","orcid":"","institution":"Samsung Medical Center, Sungkyunkwan University School of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sei","middleName":"Yeul","lastName":"Oh","suffix":""},{"id":166538962,"identity":"6757d0a7-3517-4364-9a14-7be640a1d047","order_by":2,"name":"Min Chae Kang","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Min","middleName":"Chae","lastName":"Kang","suffix":""},{"id":166538963,"identity":"99767d17-7236-42d2-bf29-c9c34883aa0a","order_by":3,"name":"Jiyeon HAN","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jiyeon","middleName":"","lastName":"HAN","suffix":""},{"id":166538964,"identity":"ff3ae0e0-3571-4d5c-94f1-b4a55f89f8f6","order_by":4,"name":"Ga-In Lee","email":"","orcid":"","institution":"Samsung Medical Center, Sungkyunkwan University School of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ga-In","middleName":"","lastName":"Lee","suffix":""}],"badges":[],"createdAt":"2022-12-14 03:45:45","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2376086/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2376086/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41433-023-02839-8","type":"published","date":"2023-11-30T05:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":31950091,"identity":"dd8964ad-629b-4d54-a28d-90aee715eedc","added_by":"auto","created_at":"2023-01-23 15:13:44","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":3659169,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRepresentative test results of (A) traumatic optic neuropathy patients and (B) healthy controls.\u003c/strong\u003eOptical coherence tomography angiography color-coded density map of the superficial retinal capillary plexus (SRCP), deep retinal capillary plexus (DRCP), and radial peripapillary capillary (RPC) segments showing automated measurement of vessel density with percentage via auto-segmentation. The visual field test of traumatic optic neuropathy patients showed significant visual field defects compared to normal results of healthy controls. The peripapillary retinal nerve fiber layer (pRNFL) and the ganglion cell-inner plexiform layer (GCIPL) thickness of traumatic optic neuropathy patients and healthy controls are presented.\u003c/p\u003e","description":"","filename":"Figure1legend.png","url":"https://assets-eu.researchsquare.com/files/rs-2376086/v1/d85c9ceb6e41aec511f95083.png"},{"id":31950090,"identity":"7b023172-ebf0-45e2-bda7-09ae31ea9b55","added_by":"auto","created_at":"2023-01-23 15:13:44","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":454164,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eScatterplots showing significant associations of intraretinal vessel densities with functional parameters and structural parameters including average peripapillary retinal nerve fiber layer thickness and average ganlion cell-inner plexiform layer thickness in traumatic optic neuropathy patients.\u003c/strong\u003e (\u003cstrong\u003eA\u003c/strong\u003e) Significant association between worse mean deviation score of the visual field and lower peripapillary vessel density in the inferior quadrant (Estimate: 0.6012, t = 2.68, \u003cem\u003eP\u003c/em\u003e = 0.0253); (\u003cstrong\u003eB\u003c/strong\u003e) Significant association between worse mean deviation score of the visual field and lower vessel density of DRCP in the temporal area (Estimate: 2.2260, t = 2.43, \u003cem\u003eP\u003c/em\u003e = 0.0377); \u003cstrong\u003e(C)\u003c/strong\u003e Significant association between pRNFL thickness and vessel density of the RPC segment in the superior sector (Estimate: 1.1371, t = 2.63, \u003cem\u003eP\u003c/em\u003e = 0.0171); (\u003cstrong\u003eD\u003c/strong\u003e) Significant association between pRNFL thickness and vessel density of the RPC in the inferior sector (Estimate: 1.0125, t = 5.04, \u003cem\u003eP\u003c/em\u003e ≤ 0.0001); (\u003cstrong\u003eE\u003c/strong\u003e) Significant association between pRNFL thickness and vessel density of the RPC in the temporal sector (Estimate: 1.0929, t = 2.92, \u003cem\u003eP\u003c/em\u003e = 0.0092).\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-2376086/v1/eeeea2234b0ad06096651ed9.png"},{"id":47424625,"identity":"a6b0956b-13fe-4adf-a918-25b8bb547b46","added_by":"auto","created_at":"2023-12-01 08:41:09","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2087978,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2376086/v1/e91b4c14-1a11-4297-b45a-e0576345ccb3.pdf"}],"financialInterests":"(Not answered)","formattedTitle":"Intraretinal microvascular alterations in indirect traumatic optic neuropathy","fulltext":[{"header":"Introduction","content":"\u003cp\u003eTraumatic optic neuropathy (TON) is a condition of severe vision loss caused by acute injury to the optic nerve secondary to head or facial trauma. TON is known to occur in about 0.5\u0026ndash;5% of patients with closed head injuries and in 2.5% of those with midfacial fractures [\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. TON is classified as direct or indirect optic neuropathy. Direct TON occurs when the optic nerve is injured directly by the object that penetrates the orbit which leads to optic nerve avulsion, transaction, nerve sheath or orbital hemorrhage, and orbital emphysema [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Indirect TON occurs when the nerve injury results from compression forces transmitted to the optic nerve via the orbital apex and optic canal [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Compression forces transmitted to the orbital apex can result in damage to microcirculation, causing ischemia and swelling of the optic nerve [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOptical coherence tomography angiography (OCT-A) is a promising imaging method for assessing three-dimensional vascular structures in a fast and non-invasive way. As it can show different capillary networks of the retina, choroid, and optic nerve head with high resolution [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], microvascular changes in various disorders such as glaucoma, optic neuropathies including nonarteritic anterior ischemic optic neuropathy, neuromyelitis optica spectrum disorders, and pathologic myopia have been studied recently using OCT-A [\u003cspan additionalcitationids=\"CR9 CR10 CR11\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. These microvascular changes measured using OCT-A are significantly correlated with visual functional parameters in previous studies [\u003cspan additionalcitationids=\"CR9 CR10 CR11\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSeveral previous studies have investigated microvascular changes in TON using color-coded duplex sonography in arteries [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], OCT [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], and OCT-A [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Previous studies have revealed that vasospasm and vascular ischemia can induce swelling of the optic nerve within the optic canal, which causes decreased blood supply to retinal ganglion cells (RGCs) and results in cell death [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Blood flow of the central retinal artery (CRA) is known to be decreased in patients with TON following injury [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. It is also known that eyes affected by TON show thicker choroids possibly due to impaired blood circulation and vascular remodeling [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Recently, Ma et al. have reported significant alterations of intraretinal vessel densities in TON eyes compared to unaffected fellow eyes using OCT-A [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Ma et al. have found that the prognostic association between OCTA parameters and visual prognosis is weak [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Gao et al. have also compared retinal vasculature measured with OCT-A between TON patients who have received surgery and conservative treatments [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] and found that vision recovery after an effective therapy for indirect TON is associated with increased oxygen saturation of retinal vessels and better availability of oxygen in the retina with thicker retinas and better vessel density, indicating that effective theraphy can mitigate retinal atrophy of severe TON [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. So far, research on microvascular alterations in TON measured by OCTA and its clinical implications is very limited. Studies on the association between OCT-A findings and other structural parameters have not been reported yet. Thus, this study aimed to evaluate intraretinal microvascular alterations in macular and peripapillary areas in patients with TON using OCT-A. Associations of OCT-A parameters with functional and structural parameters were also investigated.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e This cross-sectional study was approved by the Institutional Review Board of Samsung Medical Center (Seoul, Republic of Korea). This study included patients with TON who visited the Department of Neuro-ophthalmology of Samsung Medical Center from October 1st, 2017 to January 31st, 2022. The diagnosis of TON was made based on a history of acute visual loss after a closed blunt injury of the face or head and ocular examination results, including an acute decrease of visual acuity, a relative afferent pupillary defect of the affected eye in unilateral cases, and the development of optic disc pallor during follow-up. Only one eye (the one with worse visual acuity in bilateral cases) of each patient was selected for analysis. Disease-free subjects were recruited as controls from staff and healthy volunteers who had undergone routine eye examinations. None of these controls had a history of ocular or neurologic disease or cranial/facial trauma. Healthy controls were required to have normal optic discs, normal thicknesses of intraretinal layers, and intraocular pressure (IOP)\u0026thinsp;\u0026lt;\u0026thinsp;21 mmHg. Some of these healthy controls participated in other studies in the same department. Patients and healthy controls with other ophthalmic diseases (glaucoma, a refractive error greater than 6.0 diopters of spherical equivalent (SE) as high myopia and hyperopia or 3.0 diopters of astigmatism in either eye, amblyopia, epiretinal membrane, age-related macular degeneration, diabetic retinopathy, retinal artery/vein occlusion, optic neuropathy other than TON, and so on) and previous retinal surgery that might affect vessel density and those with known systematic/inflammatory diseases (cancer, multiple sclerosis, etc.) were excluded. Visual field perimetry was performed with a Humphrey Field Analyzer using the 24\u0026thinsp;\u0026minus;\u0026thinsp;2 SITA-standard protocol (Humphrey 740 Visual Field Analyzer, Carl Zeiss Meditec Inc. Dublin, CA, USA) in patients with TON. Only reliable visual fields (\u0026le;\u0026thinsp;33% false positives, false negatives, fixation losses\u0026thinsp;\u0026lt;\u0026thinsp;20%) were selected for the analysis in this study. Mean deviation was used for analysis. Fundus photography and Cirrus HD-OCT (Carl Zeiss Meditec AG, Jena, Germany) were performed for all patients. Detailed protocol of Cirrus HD-OCT measurements was described in a previous study on craniopharyngioma [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) The pRNFL thickness was obtained using an optic disc cube 200 x 200 protocol with Cirrus software. This protocol generated a cube of data through a 6-mm-square grid. A 3.46-mm-diameter circle was automatically centered on the optic disc. The Cirrus HD-OCT software also calculated the average and sectoral macular ganglion cell-inner plexiform layer (GCIPL) thickness. To be included, all scans had to have a signal strength\u0026thinsp;\u0026ge;\u0026thinsp;6 without motion artifacts. Retinal and peripapillary microvasculatures were analyzed using a Topcon OCT instrument (DRI OCT Triton Plus, Topcon Corporation, Tokyo, Japan) for all patients and healthy controls. (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) The detailed protocol of measurements was also described in authors\u0026rsquo; previous study [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. In brief, the Triton swept-source OCT was used to scan each patient using a wavelength of 1,050 nm with a scan speed of 100,000 A-scans per second with two imaging procedures consisting of a 4.5 \u0026times; 4.5 mm-diameter peripapillary scan centered on the optic disc and a 3.0 \u0026times; 3.0 mm-diameter perifoveal scan centered on the macula. The superficial retinal capillary plexus (SRCP) extending from 3 \u0026micro;m below the internal limiting membrane (ILM) to 15 \u0026micro;m below the IPL and the deep retinal capillary plexus (DRCP) extending from 15 to 70 \u0026micro;m below the IPL were separated automatically by the OCT instrument software (IMAGEnet 6 V.1.14.8538). The radial peripapillary capillary (RPC) segment extended from the ILM to the posterior boundary of the RNFL. Vessel density was defined as the percentage of area occupied by vessels in a localized region. The software automatically fitted a 3 mm macular circle at the foveal center. Another 3 mm circle was manually fitted at the disc center. To assess scan quality, scan images were included based on the quality assessment criteria suggested by Fenner et al. [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] All participants underwent both OCT-A and Cirrus HD-OCT imaging on the same day at least 28 days after the accident.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eData are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD). Best-corrected visual acuity was converted to a logarithmic scale (logMAR). Student's t-test was used to compare age. Wilcoxon rank-sum test was used to compare age and SE refractive errors between TON patients and controls. Chi-squared test was used to compare gender between groups. The pRNFL thickness and GCIPL thickness of patients were compared with those of healthy controls using a Wilcoxon rank-sum test and a Student's t-test, respectively. Bonferroni\u0026rsquo;s correction for multiple comparisons was applied to \u003cem\u003eP-\u003c/em\u003evalues by multiplying uncorrected \u003cem\u003eP-\u003c/em\u003evalues by 8. Linear regression analysis was conducted after adjusting for age, gender, and spherical equivalent (SE) to compare vessel density between the patient group and the healthy control group. Bonferroni\u0026rsquo;s correction for multiple comparisons was applied to \u003cem\u003eP-\u003c/em\u003evalues by multiplying the uncorrected \u003cem\u003eP-\u003c/em\u003evalues by 12. Spearman\u0026rsquo;s correlation coefficients were calculated to analyze associations of microvascular density with visual field defects, intraretinal layer thickness, and best-corrected visual acuity (BCVA). A \u003cem\u003eP-\u003c/em\u003evalue less than 0.05 was considered statistically significant. All statistical analyses were performed with SAS version 9.4 (SAS Institute Inc, Cary, NC, USA).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 33 eyes of 33 patients with TON and 34 eyes of 34 healthy controls were included in this study. The mean duration from the accident to the OCTA examination was 23.56\u0026thinsp;\u0026plusmn;\u0026thinsp;14.43 weeks (range, 4\u0026ndash;52 weeks). There was no statistically significant difference in age or SE refractive errors between TON and control groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Male patients accounted for 84.85% in the TON group and 73.13% in the healthy control group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0331). Age and gender along with SE refractive errors were adjusted for all analyses regarding OCT and OCTA parameters. Both pRNFL thickness and GCIPL thickness were significantly thinner in the TON group than in the healthy control group in average values (pRNFL, 72.26\u0026thinsp;\u0026plusmn;\u0026thinsp;15.9㎛ in TON patients vs. 94.47\u0026thinsp;\u0026plusmn;\u0026thinsp;8.05 ㎛ in controls, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001; GCIPL, 58.61\u0026thinsp;\u0026plusmn;\u0026thinsp;13.38 ㎛ vs. 81.59\u0026thinsp;\u0026plusmn;\u0026thinsp;5.15 ㎛, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics of patients with traumatic optic neuropathy and healthy controls (significant values are indicated in bold. N, numbers; M, male; F, female; SER, spherical equivalent refractive error; BCVA, best-corrected visual acuity; VF, visual field; MD, mean deviation. \u003csup\u003e*\u003c/sup\u003e, \u003cem\u003eP-\u003c/em\u003evalue by Student\u0026rsquo;s t-test; \u003csup\u003e\u0026dagger;\u003c/sup\u003e, \u003cem\u003eP-\u003c/em\u003evalue by Chi-squared test; \u003csup\u003e\u0026Dagger;\u003c/sup\u003e, \u003cem\u003eP-\u003c/em\u003evalue by Wilcoxon rank sum test).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatients (N\u0026thinsp;=\u0026thinsp;33)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl (N\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP-\u003c/em\u003evalue\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39.24\u0026thinsp;\u0026plusmn;\u0026thinsp;17.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41.29\u0026thinsp;\u0026plusmn;\u0026thinsp;16.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.6545\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender (M/F)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28/5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21/13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.0331\u003c/b\u003e\u003csup\u003e\u003cb\u003e\u0026dagger;\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSER\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-1.47\u0026thinsp;\u0026plusmn;\u0026thinsp;2.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-1.89\u0026thinsp;\u0026plusmn;\u0026thinsp;2.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.5637\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBCVA (logMAR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVF MD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-20.91\u0026thinsp;\u0026plusmn;\u0026thinsp;11.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.85\u0026thinsp;\u0026plusmn;\u0026thinsp;11.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eMicrovascular density in the macular area\u003c/h2\u003e \u003cp\u003eThere was no significant difference in the average vessel density of SRCP (47.12\u0026thinsp;\u0026plusmn;\u0026thinsp;3.51% in TON patients, 48.13\u0026thinsp;\u0026plusmn;\u0026thinsp;2.30% in controls) or DRCP (49.67\u0026thinsp;\u0026plusmn;\u0026thinsp;4.00% in TON patients, 48.44\u0026thinsp;\u0026plusmn;\u0026thinsp;1.88% in controls) in the macular area between TON patients and controls after adjusting for age, gender, and SE refractive errors by linear regression analysis. In addition, when macular microvascular density was compared by sectors between patients with TON and controls, there was no statistically significant difference (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of peripapillary and parafoveal vessels in patients with traumatic optic neuropathy and healthy controls (significant values are indicated in bold. N, numbers; RPC, radial peripapillary capillary; SRCP, superficial retinal capillary plexus; DRCP, deep retinal capillary plexus; \u003csup\u003e*\u003c/sup\u003e, \u003cem\u003eP-\u003c/em\u003evalue by linear regression with adjustment for age and spherical equivalent. Bonferroni\u0026rsquo;s correction for multiple comparisons was applied to \u003cem\u003eP-\u003c/em\u003evalues by multiplying uncorrected \u003cem\u003eP\u003c/em\u003e-values by 12).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatients (\u003cem\u003eN\u003c/em\u003e\u0026thinsp;=\u0026thinsp;33)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl (\u003cem\u003eN\u003c/em\u003e\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCorrected \u003cem\u003eP-\u003c/em\u003evalue\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eRPC (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSuperior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55.77\u0026thinsp;\u0026plusmn;\u0026thinsp;7.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64.15\u0026thinsp;\u0026plusmn;\u0026thinsp;5.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInferior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57.24\u0026thinsp;\u0026plusmn;\u0026thinsp;10.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66.17\u0026thinsp;\u0026plusmn;\u0026thinsp;6.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.0024\u003c/b\u003e\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTemporal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39.1\u0026thinsp;\u0026plusmn;\u0026thinsp;7.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50.45\u0026thinsp;\u0026plusmn;\u0026thinsp;5.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNasal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41.89\u0026thinsp;\u0026plusmn;\u0026thinsp;7.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50.72\u0026thinsp;\u0026plusmn;\u0026thinsp;7.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.0011\u003c/b\u003e\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSRCP (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSuperior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48.09\u0026thinsp;\u0026plusmn;\u0026thinsp;5.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49.59\u0026thinsp;\u0026plusmn;\u0026thinsp;6.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.7992\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInferior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48.09\u0026thinsp;\u0026plusmn;\u0026thinsp;5.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48.88\u0026thinsp;\u0026plusmn;\u0026thinsp;3.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.4956\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTemporal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45.95\u0026thinsp;\u0026plusmn;\u0026thinsp;4.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47.45\u0026thinsp;\u0026plusmn;\u0026thinsp;2.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9168\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNasal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46.35\u0026thinsp;\u0026plusmn;\u0026thinsp;3.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45.95\u0026thinsp;\u0026plusmn;\u0026thinsp;4.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0000\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDRCP (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSuperior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49.69\u0026thinsp;\u0026plusmn;\u0026thinsp;2.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.6912\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInferior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50.18\u0026thinsp;\u0026plusmn;\u0026thinsp;8.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49.74\u0026thinsp;\u0026plusmn;\u0026thinsp;3.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0000\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTemporal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48.23\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47.77\u0026thinsp;\u0026plusmn;\u0026thinsp;2.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0000\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNasal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48.56\u0026thinsp;\u0026plusmn;\u0026thinsp;3.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46.57\u0026thinsp;\u0026plusmn;\u0026thinsp;3.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.2940\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eMicrovascular density in the peripapillary area\u003c/h2\u003e \u003cp\u003eWhen peripapillary microvascular density was compared, the average vessel density of the RPC segment in TON patients was significantly lower than that in healthy controls (48.5% \u0026plusmn; 6.28 vs. 57.88% \u0026plusmn; 3.06%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001, corrected \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). 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 (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eAssociations of vessel density with pRNFL thickness, GCC thickness, BCVA, and visual field defects\u003c/h2\u003e \u003cp\u003eRelationships between intraretinal vessel densities in each sector and functional parameters including BCVA and mean deviation of visual field test results were analyzed in TON patients (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Worse mean deviation score of the visual field and lower peripapillary vessel density in the inferior quadrant showed a statistically significant association (Estimate: 0.6012, t\u0026thinsp;=\u0026thinsp;2.68, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0253 ). (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA) Also, worse mean deviation score of the visual field had a significant association with lower vessel density of DRCP in the temporal area (Estimate: 2.2260, t\u0026thinsp;=\u0026thinsp;2.43, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0377). (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB) Lower BCVA, defined as logMAR\u0026thinsp;\u0026gt;\u0026thinsp;1 showed a significant assocation with lower peripapillary vessel density in the inferior quadrant (Estimate: -0.1103, OR 0.9 (0.81, 0.99), \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0369).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssociation analysis between intraretinal vessel densities and functional parameters (significant values are indicated in bold. RPC, radial peripapillary capillary; BCVA, best-corrected visual acuity; VF, visual field; MD, mean deviation; SRCP, superficial retinal capillary plexus; DRCP, deep retinal capillary plexus. \u003csup\u003e*\u003c/sup\u003e, \u003cem\u003eP-\u003c/em\u003evalue by Spearman\u0026rsquo;s correlation analysis).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEstimate\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003et-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP-\u003c/em\u003evalue\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eRPC vessel density\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSuperior\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBCVA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.0561\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.2372\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMD of VF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5765\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.1713\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eInferior\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBCVA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.0482\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.1485\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMD of VF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.6012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0253\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTemporal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBCVA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.0739\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.1127\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMD of VF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.7072\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0526\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNasal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBCVA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.0503\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.3185\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMD of VF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.2298\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.6101\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSRCP vessel density\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSuperior\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBCVA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0746\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.2311\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMD of VF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0728\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.9367\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eInferior\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBCVA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.0480\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.4372\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMD of VF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.0556\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.3406\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTemporal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBCVA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0895\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.2840\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMD of VF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.4851\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.1994\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNasal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBCVA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0886\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.4010\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMD of VF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.0190\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.3252\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDRCP vessel density\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSuperior\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBCVA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0504\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.4878\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMD of VF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5444\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.5593\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eInferior\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBCVA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.0364\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.3866\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMD of VF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.9848\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.2224\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTemporal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBCVA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0241\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.7541\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMD of VF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.2260\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.0377\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNasal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBCVA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.0149\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.8942\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMD of VF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.2096\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.2073\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eRelationships between intraretinal vessel densities in each sector and other structural parameters including pRNFL thickness and GCIPL thickness were also analyzed in TON patients (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The pRNFL thickness had a significant association with vessel density of the RPC segment in the temporal sector (Estimate: 1.0929, t\u0026thinsp;=\u0026thinsp;2.92, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0092) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eE), in the superior sector (Estimate: 1.1371, t\u0026thinsp;=\u0026thinsp;2.63, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0171) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC), in the inferior sector (Estimate: 1.0125, t\u0026thinsp;=\u0026thinsp;5.04, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD) respectively.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssociation analysis between intraretinal vessel densities and structural parameters including average peripapillary retinal nerve fiber layer thickness and average ganglion cell-inner plexiform layer thickness (significant values are indicated in bold. RPC, radial peripapillary capillary; pRNFL, peripapillary retinal nerve fiber layer; GCIPL, ganglion cell-inner plexiform layer; SRCP, superficial retinal capillary plexus; DRCP, deep retinal capillary plexus. \u003csup\u003e*\u003c/sup\u003e, \u003cem\u003eP\u003c/em\u003e-value by Spearman\u0026rsquo;s correlation analysis).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eEstimate\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003et value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eP-\u003c/em\u003evalue\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"8\" nameend=\"c8\" namest=\"c1\"\u003e \u003cp\u003eRPC vessel density\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSuperior\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003epRNFL thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e1.1371\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e2.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.0171\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eGCIPL thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0.1488\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e0.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.6976\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eInferior\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003epRNFL thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e1.0125\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e5.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eGCIPL thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0.1338\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.5677\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTemporal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003epRNFL thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e1.0929\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e2.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.0092\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eGCIPL thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0.2632\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e0.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.4388\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNasal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003epRNFL thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0.1716\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.7485\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eGCIPL thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e-0.1852\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e-0.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.6410\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"8\" nameend=\"c8\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSRCP vessel density\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSuperior\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003epRNFL thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0.9877\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e1.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.1372\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eGCIPL thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0.6815\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e1.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.1380\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eInferior\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003epRNFL thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e1.0853\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e1.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.1864\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eGCIPL thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0.5228\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e0.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.3654\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTemporal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003epRNFL thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0.9723\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e1.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.2750\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eGCIPL thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0.5087\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e0.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.4132\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNasal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003epRNFL thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e1.2619\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e1.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.2804\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eGCIPL thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0.7905\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e1.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.3300\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"8\" nameend=\"c8\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDRCP vessel density\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSuperior\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003epRNFL thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e1.0658\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e1.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.1575\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eGCIPL thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0.7232\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e1.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.1659\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eInferior\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003epRNFL thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0.9780\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e1.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.3177\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eGCIPL thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0.6211\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.3601\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTemporal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003epRNFL thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0.8389\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.3350\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eGCIPL thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0.2455\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e0.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.6874\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNasal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003epRNFL thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e1.1356\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e0.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.4197\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eGCIPL thickness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0.6146\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e0.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.5296\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn 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 [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan additionalcitationids=\"CR22 CR23 CR24 CR25\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Medierios et al. [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] and L\u0026oacute;pez-de-Eguileta et al. [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] have reported cases of gradual RNFL loss, ganglion cell complex loss, and Bruch\u0026rsquo;s membrane opening-minimum rim width loss measured with OCT in TON patients. Cunha et al. [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] have reported progressive thinning of RNFL and macular thickness in three TON patients. Sung et al. [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] and Lee et al. [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] have studied OCT measurements of TON patients showing both reductions in RNFL and GCIPL thicknesses. Chan et al. [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] reported thinning of RNFL and ganglion cell complex, and also subfoveal choroidal thinning in TON patients with chronic mild traumatic brain injury.\u003c/p\u003e \u003cp\u003eIn 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 [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] and found that vessel densities in macular and peripapillary areas are significantly lower in TON eyes than in fellow eyes [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. 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 [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. 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 [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. 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 [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. 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 [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Furthermore, Shi et al. have reported decreased perfusion of the central retinal artery in TON eyes [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. 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 [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Results of the present study are in line with previous studies showing a significant reduction of intraocular blood flow in TON.\u003c/p\u003e \u003cp\u003eIn 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 [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] and GCIPL [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] in TON patients have also reported significant correlations between OCT parameters and visual functional parameters such as visual acuity [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], color vision [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], visual evoked potential (VEP) results [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], and the degree of visual field defect [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. 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\u0026rsquo; post-injury eyesight is weak [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. They reported that a preserved vision was not associated with time-dependent alteration in retinal thickness or vascular attenuation [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. 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 [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] 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 [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. 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.\u003c/p\u003e \u003cp\u003eTo 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 [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e], optic disc drusen [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e], glaucoma [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], and neuromyelitis optica spectrum disorders [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], 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.\u003c/p\u003e \u003cp\u003eThis 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.\u003c/p\u003e \u003cp\u003eDespite 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.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no funding or sponsorship.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eS.Y.O and K.A.P designed and conducted the study. G.I.L, M.C.K and J.H collected the data, managed the study, and and interpreted the data. K.A.P contributed to the review of the manuscript. M.C.K and J.H drafted and revised the manuscript. S.Y.O and K.A.P have reviewed and approved the final version of the manuscript.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWarner N, Eggenberger E. Traumatic optic neuropathy: a review of the current literature. Curr Opin Ophthalmol. 2010;21:459-62.\u003c/li\u003e\n\u003cli\u003eWang BH, Robertson BC, Girotto JA, Liem A, Miller NR, Iliff N, et al. Traumatic optic neuropathy: a review of 61 patients. Plast Reconstr Surg. 2001;107:1655-64.\u003c/li\u003e\n\u003cli\u003eal-Qurainy IA, Stassen LF, Dutton GN, Moos KF, el-Attar A. The characteristics of midfacial fractures and the association with ocular injury: a prospective study. Br J Oral Maxillofac Surg. 1991;29:291-301.\u003c/li\u003e\n\u003cli\u003eHolt GR, Holt JE. Incidence of eye injuries in facial fractures: an analysis of 727 cases. 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Yan Ke Xue Bao. 2002;18:80-3.\u003c/li\u003e\n\u003cli\u003eSteinsapir KD, Goldberg RA. Traumatic optic neuropathy. Surv Ophthalmol. 1994;38:487-518.\u003c/li\u003e\n\u003cli\u003eLiu J, Chen C, Li L, Yi Z, Zheng H. Peripapillary and Macular Flow Changes in Nonarteritic Anterior Ischemic Optic Neuropathy (NAION) by Optical Coherence Tomography Angiography (OCT-A). J Ophthalmol. 2020;2020:3010631.\u003c/li\u003e\n\u003cli\u003eWright Mayes E, Cole ED, Dang S, Novais EA, Vuong L, Mendoza-Santiesteban C, et al. Optical Coherence Tomography Angiography in Nonarteritic Anterior Ischemic Optic Neuropathy. J Neuroophthalmol. 2017;37:358-64.\u003c/li\u003e\n\u003cli\u003eEngelke H, Shajari M, Riedel J, Mohr N, Priglinger SG, Mackert MJ. OCT angiography in optic disc drusen: comparison with structural and functional parameters. Br J Ophthalmol. 2020;104:1109-13.\u003c/li\u003e\n\u003cli\u003eLeal-Gonz\u0026aacute;lez M, Pessanha F, Azevedo Gonz\u0026aacute;lez-Oliva M, P\u0026eacute;rez-Fern\u0026aacute;ndez E, Gili P. Study of peripapillary vascular flow using optical coherence tomography angiography in optic nerve head drusen. Clin Exp Ophthalmol. 2020;48:775-82.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"eye","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"eye","sideBox":"Learn more about [Eye](http://www.nature.com/eye/)","snPcode":"41433","submissionUrl":"https://mts-eye.nature.com/cgi-bin/main.plex","title":"Eye","twitterHandle":"@eye_journal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"optical coherence tomography angiography, vessel density, traumatic optic neuropathy, superficial retinal capillary plexus, deep retinal capillary plexus, radial peripapillary capillary segment ","lastPublishedDoi":"10.21203/rs.3.rs-2376086/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2376086/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePURPOSE\u003c/h2\u003e \u003cp\u003eTo quantitatively evaluate macular and peripapillary microvascular alterations in patients with indirect traumatic optic neuropathy (TON) compared to normal controls using optical coherence tomography angiography (OCT-A [Topcon DRI OCT; Triton]) and determine their associations with other ocular parameters.\u003c/p\u003e\u003ch2\u003eMETHODS\u003c/h2\u003e \u003cp\u003eWe enrolled 33 eyes of 33 patients with TON and 34 eyes of 34 healthy controls. OCT-A was used to generate microvascular structure images of the superficial retinal capillary plexus (SRCP), deep retinal capillary plexus (DRCP), and radial peripapillary capillary (RPC) segment in the macula and peripapillary area. Age, gender, and spherical equivalent refractive errors were statistically adjusted for the analysis.\u003c/p\u003e\u003ch2\u003eRESULTS\u003c/h2\u003e \u003cp\u003eOCT-A revealed a significant reduction of the average vessel density in the RPC segment in TON patients compared to controls (48.5% \u0026plusmn; 6.28 vs. 57.88% \u0026plusmn; 3.06%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001, corrected \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). 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 inferior sector vessel density of the RPC segment was significantly associated with visual field defects (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0253) and visual acuity (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0369). The temporal sector vessel density of DRCP was also associated with visual field defects (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0377). The RPC segment in the temporal, superior, and inferior sector vessel density had a significant association with the average pRNFL thickness (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0092, 0.0171, and \u0026lt;\u0026thinsp;0.0001, respectively).\u003c/p\u003e\u003ch2\u003eCONCLUSIONS\u003c/h2\u003e \u003cp\u003ePatients with indirect TON show significant microvascular alterations compared to controls. This study confirms that TON can induce intraretinal microvascular changes and suggests that OCTA can be a useful biomarker for visual functional and structural changes.\u003c/p\u003e","manuscriptTitle":"Intraretinal microvascular alterations in indirect traumatic optic neuropathy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-01-23 15:13:40","doi":"10.21203/rs.3.rs-2376086/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2023-02-20T09:41:22+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2023-02-07T16:18:26+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2023-02-07T15:27:28+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2023-01-19T17:35:47+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-01-10T12:00:22+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2022-12-15T17:36:32+00:00","index":"","fulltext":""},{"type":"submitted","content":"Eye","date":"2022-12-14T03:42:37+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"eye","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"eye","sideBox":"Learn more about [Eye](http://www.nature.com/eye/)","snPcode":"41433","submissionUrl":"https://mts-eye.nature.com/cgi-bin/main.plex","title":"Eye","twitterHandle":"@eye_journal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"da3c5580-af7f-4d32-bf59-c4d5ed1a7287","owner":[],"postedDate":"January 23rd, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":18291131,"name":"Biological sciences/Neuroscience/Visual system"},{"id":18291132,"name":"Health sciences/Biomarkers"}],"tags":[],"updatedAt":"2023-12-01T08:41:04+00:00","versionOfRecord":{"articleIdentity":"rs-2376086","link":"https://doi.org/10.1038/s41433-023-02839-8","journal":{"identity":"eye","isVorOnly":false,"title":"Eye"},"publishedOn":"2023-11-30 05:00:00","publishedOnDateReadable":"November 30th, 2023"},"versionCreatedAt":"2023-01-23 15:13:40","video":"","vorDoi":"10.1038/s41433-023-02839-8","vorDoiUrl":"https://doi.org/10.1038/s41433-023-02839-8","workflowStages":[]},"version":"v1","identity":"rs-2376086","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2376086","identity":"rs-2376086","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}