Vision improvement in indirect traumatic optic neuropathy treated by endoscopic transnasal optic canal decompression.

BACKGROUND: Indirect Traumatic optic neuropathy (ITON) is a severe disease characterized by a sudden decline of visual function after craniofacial injury. However, the best treatment for ITON is unknown. Endoscopic transnasal optic canal decompression (ETOCD) has gradually been used for ITON treatment worldwide in recent years. OBJECTIVE: To assess the effect of ETOCD on visual acuity in patients with ITON and identify factors that affect prognosis. METHODS: In this study, clinical characteristics of 44 ITON patients who underwent ETOCD in Qilu Hospital of Shandong University were retrospectively analyzed. Factors affecting prognosis were also evaluated. RESULTS: ETOCD treatment improved the vision of 20 (45.5%) patients with no patient suffering from vision deterioration. The mean value of visual acuity (VA) scores improved from 1.57 to 2.39 (P < 0.001). Patients with residual vision had a better VA improvement percent than those without light perception (66.67% versus 34.48%, χ2 = 4.13, P = 0.042). Although shorter duration before ETOCD was associated with better improvement score in ITON patients (r = -0.30, P = 0.044), optic canal fracture (OCF) and optic nerve sheath incision did not affect the prognosis of these patients. Five ITON patients with cerebrospinal fluid rhinorrhea were treated with free nasal mucosal flap during the surgery, and no other severe surgical complication occurred. CONCLUSIONS: ETOCD can effectively and safely improve the vision of ITON patients, patients with residual vision and those treated earlier may benefit more from this surgery.

JNK/c-Jun-driven NLRP3 inflammasome activation in microglia contributed to retinal ganglion cells degeneration induced by indirect traumatic optic neuropathy.

BACKGROUND: Indirect traumatic optic neuropathy (ITON) is a major cause of permanent loss of vision after blunt head trauma. Neuroinflammation plays a crucial role in neurodegenerative diseases. The present study concentrated on JNK/c-Jun-driven NLRP3 inflammasome activation in microglia during the degeneration of retinal ganglion cells (RGCs) in ITON. METHODS: An impact acceleration (IA) model was employed to induce ITON, which could produce significant neurodegeneration in the visual system. Pharmacological approaches were employed to disrupt JNK and to explore whether JNK and the microglial response contribute to RGC death and axonal degeneration. RESULTS: Our results indicated that the ITON model induced significant RGC death and axonal degeneration and activated JNK/c-Jun signaling, which could further induce the microglial response and NLRP3 inflammasome activation. Moreover, JNK disruption is sufficient to suppress NLRP3 inflammasome activation in microglia and to prevent RGC death and axonal degeneration. CONCLUSIONS: ITON could promote JNK/c-Jun signaling, which further activates the NLRP3 inflammasome in microglia and contributes to the degeneration of axons and death of RGCs. JNK inhibition is able to suppress the inflammatory reaction and improve RGC survival. Although further work is needed to determine whether pharmacological inhibition of the NLRP3 inflammasome can prevent ITON, our findings indicated that such intervention could be promising for translational work.

The retinal vasculature pathophysiological changes in vision recovery after treatment for indirect traumatic optic neuropathy patients.

PURPOSE: To evaluate the retinal vasculature pathophysiological changes of indirect traumatic optic neuropathy (ITON) patients after effective surgery. METHODS: Monocular ITON patients who underwent endoscopic trans-ethmosphenoid optic canal decompression (ETOCD) or conservative treatments in Zhongshan Ophthalmic Center from January 2017 to June 2020 were recruited. Visual acuity (VA), visual evoked potential (VEP), oxygen saturation of retinal blood vessels (SO2), and optical coherence tomography angiography (OCT-A) were measured. All patients were followed up at least 3 months after treatments. RESULTS: A total of 95 ITON patients were recruited, including 77 patients who underwent ETOCD and 18 patients who underwent conservative treatments. After treatments, more patients received ETOCD (59/77 = 76.6%) presented with improved VA compared with the patients with conservative treatments (6/18 = 33.3%). Compared with the pre-therapeutic measurements, VEP were significantly improved after surgery in ETOCD-treated patients (P < 0.05). Latent periods of P1 and N2, as well as amplitude of P2 of VEP parameters, showed more sensitive to vision recovery (P < 0.05). Retinal artery SO2 and the differences between arteries and veins were improved in ETOCD-treated patients (P < 0.05). Meanwhile, with OCT-A examination, the retinal thickness and retinal vessel density were notably better in ETOCD-treated patients after surgery than that in patients received conservative treatments (P < 0.05). CONCLUSIONS: Vision recovery after effective treatment of ITON patients was associated with the increased oxygen saturation of retinal vessels, better availability of oxygen in the retina, greater vessel density, and thicker retinas, which might further underlie the vasculature mechanism of vision recovery in ITON patients.

Galantamine protects against synaptic, axonal, and vision deficits in experimental neurotrauma.

Our goal was to investigate the neuroprotective effects of galantamine in a mouse model of blast-induced indirect traumatic optic neuropathy (bITON). Galantamine is an FDA-approved acetylcholinesterase inhibitor used to treat mild-moderate Alzheimer's disease. We exposed one eye of an anesthetized mouse to repeat bursts of over-pressurized air to induce traumatic optic neuropathy. Mice were given regular or galantamine-containing water (120 mg/L) ad libitum, beginning immediately after blast and continuing for one month. Electroretinograms and visual evoked potentials were performed just prior to endpoint collection. Histological and biochemical assessments were performed to assess activation of sterile inflammation, axon degeneration, and synaptic changes. Galantamine treatment mitigated visual function deficits induced by our bITON model via preservation of the b-wave of the electroretinogram and the N1 of the visual evoked potential. We also observed a reduction in axon degeneration in the optic nerve as well as decreased rod bipolar cell dendritic retraction. Galantamine also showed anti-inflammatory and antioxidant effects. Galantamine may be a promising treatment for blast-induced indirect traumatic optic neuropathy as well as other optic neuropathies.

Indirect Traumatic Optic Neuropathy Induced by Primary Blast: A Fluid-Structure Interaction Study.

Current knowledge of traumatic ocular injury is still limited as most studies have focused on the ocular injuries that happened at the anterior part of the eye, whereas the damage to the optic nerve known as traumatic optic neuropathy (TON) is poorly understood. The goal of this study is to understand the mechanism of the TON following the primary blast through a fluid-structure interaction model. An axisymmetric three-dimensional (3D) eye model with detailed orbital components was developed to capture the dynamics of the eye under the blast wave. Our numerical results demonstrated a transient pressure elevation in both vitreous and cerebrospinal fluid (CSF). A high strain rate over 100 s-1 was observed throughout the optic nerve during the blast with the most vulnerable part located at the intracanalicular region. The optic nerve deforming at such a high strain rate may account for the axonal damage and vision loss in patients subjected to the primary blast. The results from this work would enhance the understanding of indirect TON and provide guidance in the design of protective eyewear against such injury.

Outcome of endoscopic trans-ethmosphenoid optic canal decompression for indirect traumatic optic neuropathy in children.

BACKGROUND: To evaluate the safety and outcomes of endoscopic trans-ethmosphenoid optic canal decompression (ETOCD) for children with indirect traumatic optic neuropathy (ITON). METHODS: From July 1st, 2008 to July 1st, 2015, 62 children diagnosed with ITON who underwent ETOCD were reviewed. Main outcome measure was improvement in visual acuity after treatment. RESULTS: Altogether 62 children (62 eyes) with a mean age of 11.26 ± 4.14 years were included. Thirty-three (53.2%) of them had residual vision before surgery while 29 (46.8%) had no light perception (NLP). The overall visual acuity improvement rate after surgery was 54.84%. The improvement rate of patients with residual vision (69.70%) was significant higher than that of patients with no light perception (NLP) (37.9%) (P = 0.012). However, no significant difference was shown among patients with different residual vision (P = 0.630). Presence of orbital and/ or optic canal fracture and hemorrhage within the post-ethmoid and/or sphenoid sinus resulted in poor postoperative visual acuity, duration of presenting complaints did not affect final visual acuity or did not effect outcomes. Intervention performed in children presenting even after 7 days from the injury did not influence the final visual outcome. Three patients developed cerebrospinal fluid rhinorrhea and one encountered cavernous sinus hemorrhage during surgery. No other severe complications were observed. CONCLUSION: Children with residual vision had better postoperative visual prognosis and benefited more from ETOCD than children with NLP. Intervention performed in children presenting even after 7 days from the injury did not influence the final visual outcome, however, this needs to be reassessed in children presenting long after the injury.Treatment should still be recommended even for cases of delayed presentation to hospital.

Factors predictive of poor visual outcome in indirect traumatic optic neuropathy: A retrospective cohort study.

INTRODUCTION: The gold standard treatment for indirect traumatic optic neuropathy (ITON) has not yet been conclusively established, and it is essential to gain an understanding of visual prognosis and to counsel patients regarding the predictive risk factors of poor visual outcomes. Currently, there is limited information regarding ITON in Thai populations; therefore, this study aimed to determine the risk factors of poor visual outcome in patients with this condition. METHODS: A retrospective review was conducted of all ITON cases diagnosed at Rajavithi Hospital and Sawanpracharak Hospital between January 2016 and December 2022 in order to determine clinical characteristics and evaluate associated risk factors of poor visual prognosis using binary logistic regression analysis. RESULTS: The mean age of this cohort of 101 patients was 36.17 years, with a male predominance of 73.3 %. Motor vehicle accidents were the most common cause of ITON, with a statistically significant 79.2 % of cases. The patients were categorized into an "improved group" of 29 patients and an "unimproved group" of 72. The unimproved group had a significantly older mean age and poorer initial visual acuity of 20/200 (p-values 0.001 and p < 0.001 respectively). There was no significant difference between Computed Tomography (CT) findings in the two groups. The improved group had significantly better visual acuity (VA) at 1-month and final follow-up visit than the unimproved group (both p < 0.001). Differences between gender, Glasgow coma score, associated underlying diseases, and duration from trauma to intravenous glucocorticoids therapy in the two groups were not statistically significant. Multivariable logistic regression analysis identified patient age of 40 years or more (Odds ratio (OR) 3.447, 95 % CI, 1.085-10.955, p = 0.036) and poor baseline VA (OR 6.628, 95 % Confidence Interval (CI), 2.308-19.036, p < 0.001) as significant risk factors for poor visual outcome in ITON patients. CONCLUSIONS: No clear benefit was found of intravenous glucocorticoids in treatment of ITON. Patients aged 40 years or more and/or with poor baseline visual status should be advised that they are at increased risk of poor final visual outcomes.

Retinal peripapillary microvasculature in indirect traumatic optic neuropathy predicted prognosis of endoscopic trans-ethmosphenoid optic canal decompression.

PURPOSES: The purpose of this study is to quantify the alteration of retinal peripapillary microvasculature and structure in unilateral indirect traumatic optic neuropathy (ITON) and figure out predicted factors of visual improvement for ITON patients with endoscopic trans-ethmosphenoid optic canal decompression (ETOCD) after one month. METHODS: Twenty healthy controls and 72 unilateral ITON patients were included. Optical coherence tomography angiography was used to analyse radial peripapillary capillary (RPC) density, peripapillary retinal nerve fibre layer (pRNFL) thickness, superficial retinal capillary plexus (SRCP) and deep retinal capillary plexus (DRCP) density. Associations between preoperative parameters and postoperative best-corrected visual acuity (BCVA) were determined. The receiver operating characteristic (ROC) curves were used to figure out predicted factors of visual improvement for ITON after ETOCD one month. RESULTS: In ITON eyes, the preoperative global RPC density, pRNFL thickness and SRCP density were reduced compared with unaffected eyes (p ≤ 0.001). Multivariate linear regression showed that preoperative global RPC density (Standardized ß = -0.273), SRCP density (Standardized ß = -0.183), DRCP density (Standardized ß = -0.098) and preoperative BCVA (Standardized ß = 0.795) were associated with the postoperative BCVA (All p < 0.001). The area under the curve (AUC) of preoperative global RPC density to predict visual improvement after ETOCD was 0.816, while the AUCs of preoperative BCVA, global pRNFL thickness, SRCP and DRCP density were 0.575, 0.756, 0.516 and 0.615, respectively. CONCLUSIONS: The alteration of peripapillary area, especially the reduced RPC density, occurred in ITON eyes. The preoperative RPC density was associated with postoperative BCVA and was shown to be highly predictive for visual improvement after ETOCD one month.

Prognosticators for Visual Outcome in Indirect Traumatic Optic Neuropathy: A Prospective Cohort Study.

Introduction Traumatic optic neuropathy (TON), with indirect TON as its more prevalent form, is a dreadful cause of severe visual dysfunctions. The condition is known to have a contentious treatment plan and poor visual sequelae; hence, the assessment of prognostic signs becomes valuable. Prospective studies evaluating important predictors of visual recovery after traumatic optic nerve injury can particularly be helpful in a longitudinal observation. The possible roles of clinical variables need to be assessed. Absent visual evoked potential (VEP) records as a crucial finding associated with TON has reportedly valuable prognostic significance. This also needs to be explored. Hence, the study sought to determine the role of prognosticators in the visual outcome of the patients, with a focus on evaluating the role of VEPs in the severity and prognosis of indirect TON. Methods A prospective observational study involving 40 patients with indirect TON was conducted. Ocular, neuro-ophthalmological, radiological, and neurophysiological variables, including flash VEP, were investigated at their initial visit and followed up until the end of six months. Final visual acuity was the primary outcome variable studied. Paired t-test was used to perform the comparison between the flash VEP variables for normal and affected eyes at the initial visit. Pearson correlation coefficient was computed for obtaining the association of initial visual acuity and flash VEP variables with the outcome variable. Relative risk was calculated and analysed for the prognosticators in univariate analysis. Statistical significance was defined as p < 0.05. Results Statistically significant variations in mean P100 latency, N75-P100, and P100-N145 amplitudes compared between normal and affected eyes in the patients at the initial visit were obtained (p < 0.0001; paired t-test). Pearson correlation coefficient for initial visual acuity and flash VEP variable as independent variables and final visual acuity as the dependent variable were statistically significant (p < 0.05). The relative risks for prognosticators with a statistically significant range of confidence intervals were poor initial visual acuity, greater relative afferent pupillary defect (RAPD) grades, deranged flash VEP variables (absent VEP, reduction in amplitude ratio (>50%), and increased interocular latency differences), loss of consciousness during injury, age greater than 40 years, and lack of improvement after 48 hours of steroid treatment. Conclusion The identified negative prognosticators may be helpful in deciding the kind of therapeutic approach and predicting the visual outcome in patients with indirect TON.

Analysis of retinal vasculature changes in indirect traumatic optic neuropathy using optic coherence tomography angiography.

AIM: To assess the retinal vasculature alterations in indirect traumatic optic neuropathy (ITON) patients following craniofacial trauma by optic coherence tomography angiography (OCTA). METHODS: Patients diagnosed of monocular ITON were recruited from August 2016 to May 2020. OCTA was performed using the AngioVue OCT-A system for two cube scans centered at the optic nerve head and fovea. OCTA data included thicknesses of peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell complex (GCC), as well as proportion of capillary perfusion and data were analyzed for correlation with post-injury timepoints: within 7, 8-30, 31-90, and 91-365d. RESULTS: A total of 73 ITON patients were studied. Significant thinning of RNFL and GCC layers and attenuation of microvascular perfusion were observed in ITON eyes as compared to contralateral unaffected eyes (for most of the analyzed sectors and quadrants, P<0.05). Without respect to surgical intervention and vision recovery, the decrease in retinal layer thicknesses and microvascular perfusion was time-dependent, and most significant within three months (P<0.001). CONCLUSION: ITON presents with time-dependent thinning of retinal layers and attenuation of microvasculature, indicating possible degeneration of retinal ganglion cells due to reduced retinal blood supply.

Newly onset indirect traumatic optic neuropathy-surgical treatment first versus steroid treatment first.

AIM: To investigate the efficacy and safety of the treatment of endoscopic trans-ethmosphenoid optic canal decompression (ETOCD) with combination of steroid in patients with newly onset indirect traumatic optic neuropathy (ITON) and compare the outcome between immediate ETOCD treatment and ETOCD with preoperative steroid treatment. METHODS: Patients presented as newly onset ITON (suffered trauma within 3d) at a tertiary medical center between Mar 1st, 2016 and Mar 1st, 2018 were enrolled in this study. All patients were equally and randomly divided into 2 groups. Cases in group A were performed ETOCD immediately after admition while cases in group B were prescribed by methylprednisolone (20 mg/kg · d) for 3d before ETOCD. Methylprednisolone (20 mg/kg · d) was used after surgery for 6d in group A and 3d in group B. Follow-up was up to 3mo in all cases. Visual acuity (VA) before and after treatment between the two groups were taken into comparison. RESULTS: Complete postoperative data were acquired from 34 patients in group A and from 32 patients in group B. Group A had significantly higher effective rate in VA than group B (χ 2=4.905, P=0.027). CONCLUSION: For patients with newly onset ITON, combination treatment of ETOCD with high-dose steroid is an effective and safe way. Immediate surgery will lead to better prognosis for these cases.

Progression and Pathology of Traumatic Optic Neuropathy From Repeated Primary Blast Exposure.

Indirect traumatic optic neuropathy (ITON) is a condition that is often associated with traumatic brain injury and can result in significant vision loss due to degeneration of retinal ganglion cell (RGC) axons at the time of injury or within the ensuing weeks. We used a mouse model of eye-directed air-blast exposure to characterize the histopathology of blast-induced ITON. This injury caused a transient elevation of intraocular pressure with subsequent RGC death and axon degeneration that was similar throughout the length of the optic nerve (ON). Deficits in active anterograde axon transport to the superior colliculus accompanied axon degeneration and first appeared in peripheral representations of the retina. Glial area in the ON increased early after injury and involved a later period of additional expansion. The increase in area involved a transient change in astrocyte organization independent of axon degeneration. While levels of many cytokines and chemokines did not change, IL-1α and IL-1ß increased in both the ON and retina. In contrast, glaucoma shows distal to proximal axon degeneration with astrocyte remodeling and increases in many cytokines and chemokines. Further, direct traumatic optic neuropathies have a clear site of injury with rapid, progressive axon degeneration and cell death. These data show that blast-induced ITON is a distinct neuropathology from other optic neuropathies.

Prognostic factors of trans-ethmosphenoid optic canal decompression for indirect traumatic optic neuropathy.

AIM: To investigate a possible correlation between visual acuity (VA) prognosis and the presence at baseline of various orbital and ocular signs in patients affected by indirect traumatic optic neuropathy (ITON). METHODS: From July 1st, 2012 to July 1st, 2015, 224 adults diagnosed with ITON who underwent endoscopic trans-ethmosphenoid optic canal decompression (ETOCD) were reviewed. Visual outcome before and after treatment were taken into comparison. RESULTS: Accompanied older in age, longer time to medical treatment and existence of optic canal fracture (OCF) were the independent predictors for poor postoperative VA and lower improvement degree of visual acuity (IDVA), while worse preoperative VA was predictive factor for poor postoperative VA only. Mean value of IDVA in patients with OCF was 0.19±0.30. Mean value of IDVA in patients without OCF was 0.29±0.35. IDVA in cases without OCF was significant higher than those with OCF (t=2.272, P<0.05). CONCLUSION: Patients suffered from ITON without OCF before ETOCD have better surgical outcome than those with OCF. Older in age, longer time to medical treatment and existence of OCF are independent factors for poor VA prognosis and lower IDVA. Preoperative VA is independent factor for VA prognosis only.