Indirect Traumatic Optic Neuropathy Research Articles

Diffusion basis spectrum imaging detects subclinical traumatic optic neuropathy in a closed-head impact mouse model of traumatic brain injury.

Traumatic optic neuropathy (TON) is the optic nerve injury secondary to brain trauma leading to visual impairment and vision loss. Current clinical visual function assessments often fail to detect TON due to slow disease progression and clinically silent lesions resulting in potentially delayed or missed treatment in patients with traumatic brain injury (TBI). Diffusion basis spectrum imaging (DBSI) is a novel imaging modality that can potentially fill this diagnostic gap. Twenty-two, 16-week-old, male mice were equally divided into a sham or TBI (induced by moderate Closed-Head Impact Model of Engineered Rotational Acceleration device) group. Briefly, mice were anesthetized with isoflurane (5% for 2.5 min followed by 2.5% maintenance during injury induction), had a helmet placed over the head, and were placed in a holder prior to a 2.1-joule impact. Serial visual acuity (VA) assessments, using the Virtual Optometry System, and DBSI scans were performed in both groups of mice. Immunohistochemistry (IHC) and histological analysis of optic nerves was also performed after in vivo MRI. VA of the TBI mice showed unilateral or bilateral impairment. DBSI of the optic nerves exhibited bilateral involvement. IHC results of the optic nerves revealed axonal loss, myelin injury, axonal injury, and increased cellularity in the optic nerves of the TBI mice. Increased DBSI axon volume, decreased DBSI λ||, and elevated DBSI restricted fraction correlated with decreased SMI-312, decreased SMI-31, and increased DAPI density, respectively, suggesting that DBSI can detect coexisting pathologies in the optic nerves of TBI mice. DBSI provides an imaging modality capable of detecting subclinical changes of indirect TON in TBI mice.

Intraretinal microvascular alterations in indirect traumatic optic neuropathy using optical coherence tomography angiography.

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) and determine their associations with other ocular parameters. 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. Functional and structural parameters such as best-corrected visual acuity, visual field, peripapillary retinal nerve fibre layer (pRNFL) thickness, macular ganglion cell-inner plexiform layer (mGCIPL) thickness, OCT-A variables were compared between TON patients and controls. Age, gender, and spherical equivalent refractive errors were statistically adjusted for the analysis. 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). When comparing sectors, the vessel density of the RPC segment in TON patients was also significantly lower in all four quadrants compared to healthy controls. 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 superior and inferior sector vessel density displayed a significant association with the corresponding regional pRNFL thickness (P = 0.0248 and <0.0001, respectively). Patients with indirect TON exhibit significant microvascular alterations compared to controls. This study confirms that TON can induce intraretinal microvascular changes and suggests that OCT-A may serve as a useful biomarker for assessing visual functional and structural changes.

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

IntroductionThe 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. MethodsA 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. ResultsThe 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. ConclusionsNo 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.

Diffuse Damage in Traumatic Brain Injury and Its Large-Spectrum Implications: Keys on Diffuse Axonal Injury and Indirect Traumatic Optic Neuropathy for Major Eye Diseases. Revisiting the “Eye-Brain Axis”

Diffuse damage is a key characteristic of alpha emitters when they cause internal contamination, because their alpha charge keeps them away from each other, giving birth to “grid” patterns in the brain. The effect was already shown to be characteristic of traumatic brain injury. The push effect of the positive charges onto other positive charges (reverse magnet effect) leads to many comorbidities altogether with the main disease caused by them, beyond TBI. The study of the “eye-brain axis” is a large provider of cases of such comorbidities. The review of eye diseases and their relation with TBI or related diseases, especially thyroid diseases, was done to determine whether they are related or not to this grid effect. The results show that more diseases than what was known until now are found to be dependent on contamination with alpha emitters.

Clinical profile and visual outcome in patients with traumatic optic neuropathy.

To analyze the visual outcome in patients with traumatic optic neuropathy (TON) with respect to different treatment modalities, to study the correlation of initial visual loss with the final visual outcome, and to find out the predictor of final visual outcome in patients with indirect TON. A retrospective analysis of 36 eyes with TON was done. Data on clinical profile, including demographics, mode of trauma, best corrected visual acuity (BCVA), pupillary reflex examination, and anterior and posterior segment examination, was collected. Presence and location of orbital and cranial fractures were identified from computed tomography scan. Visual outcomes following steroid therapy, optic nerve (ON) decompression, and in untreated patients were analyzed. Pre- and post-treatment BCVA were divided into three groups based on logarithm of the minimum angle of resolution (logMAR) as follows: group A: 3, group B: 2.9-1.3, and group C<1.3. BCVA values at follow-up visits were taken as the primary outcome measure. Association between various risk factors and final visual outcome in patients with indirect TON was also analyzed. Out of 34 patients whose 36 eyes were studied, three (8.8%) patients were females and 31 (91.2%) patients were males. Most common mode of trauma was road traffic accident (RTA; 91.2%), which was followed by fall (8.8%) and assault (2.9%). Pre- and post-treatment BCVA values of 36 eyes were compared, and improvement in BCVA after treatment was found to be statistically significant. Also, 28.6% of patients with presenting BCVA of no light perception showed improvement compared to 94.1% and 100% in groups B and C, respectively. Orbital wall fractures were seen in 80.5% (n = 29) of the patients, with lateral wall fracture being the most common (58.3%) followed by medial wall (33.3%), roof (27.7%), floor (27.7%), and optic strut (5%). Baseline BCVA had significant association with final vision improvement. Lateral wall fracture was the most common fracture associated with indirect TON. Patients treated with high-dose corticosteroids, irrespective of the time of presentation, had a better visual outcome.

Clinical Spectrum of Indirect Traumatic Optic Neuropathy in South Indian Subjects Observational Study

Purpose: To report the aetiology, visual outcome, and clinical features of indirect traumatic Optic Neuropathy (TON) patients from the tertiary eye care center in South India. Methods: It is a retrospective and observational study. Details of age, gender, number of days of presentation after injury, Snellen visual acuity at presentation and last follow-up, visual evoked potentials, visual field findings using the Humphrey visual field analyser, associated ocular complications, and mode and time of treatment were obtained from the medical records of all indirect TON patients. Results: Indirect TON patients are mainly young males (94%) and road traffic accident (RTA) (65%) is the main cause of TON, followed by falls (19%) and sport-related activities (11%). Visual acuity loss was severe in more than 50% of the subjects and only 16%% of the patients showed improvement in visual acuity greater than one line. Pattern visual evoked potentials and visual fields are recordable only in 15% of the subjects. Commonly associated ocular complications in indirect TON patients were orbital fracture (43%), lid tear (16%), sub-conjunctival haemorrhage (13.5%), and angle recession (13.5%). Three out of four patients who received methylprednisolone and oral steroids within a week showed an improvement in visual acuity of greater than three lines, while just one patient out of four who received the same medication after a week improved visual acuity of three lines. Conclusion: RTA (road traffic accidents) is the most common cause of indirect TON and mainly young males were the affected individuals. IVMP along with oral steroids within a week, would help TON patients for reasonable visual recovery. Presenting Visual acuity of &gt; 6/600 and recordable pattern VEPs would be the prognostic factors for good visual outcomes in indirect TON patients.

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.

Erythropoietin as a treatment option for indirect traumatic optic neuropathy: A pilot study.

Our study aims to evaluate the effectiveness of intravenous erythropoietin (EPO) in patients with indirect traumatic optic neuropathy (TON), assess the side effects, and compare the visual function results among three groups of patients who had received different treatment options - EPO, steroids, and observation. : Patients with indirect TON presenting to the neuro-ophthalmology clinic from August 2019 to March 2020, were assigned to three groups, with six patients in each group. In group 1, patients were recruited prospectively and received recombinant human erythropoietin, whereas, in groups 2 and 3, patients were recruited retrospectively and received intravenous methylprednisolone followed by oral steroids and multivitamins, respectively. Groups 1 and 2 included patients presenting within 2 weeks of trauma, whereas group 3 included those presenting beyond that. Best-corrected visual acuity, pupillary reaction, color vision, and visual fields following treatment were measured. Initial visual acuity in the EPO group ranged from 20/80 to no perception of light (No PL). The mean initial BCVA (1.82 logMAR, standard deviation [SD] = 0.847) improved to 1.32, SD = 0.93 logMAR after treatment recorded at the third month (P = 0.0375), with no significant adverse effects. The initial BCVA of group 2 ranged from 20/120 to No PL. The mean initial BCVA (1.95, SD = 0.77 logMAR) improved to 1.45 logMAR, SD = 0.97 after treatment (P = 0.0435) but three patients had side effects of steroids. Initial visual acuity in Group 3 ranged from 20/40 to no PL. The mean initial BCVA (1.09 logMAR, SD = 1.10) worsened to 1.19 logMAR, SD = 1.06 after treatment after treatment (P = 0.0193). The improvement in BCVA when compared between the three groups was not significant. Both erythropoietin and steroids are effective in the management of traumatic optic neuropathy. However, erythropoietin shows lesser or no side effects when compared to steroids.

Mitochondrial Triglyceride Dysregulation in Optic Nerves Following Indirect Traumatic Optic Neuropathy.

The purpose of this work is to identify mitochondrial optic nerve (ON) lipid alterations associated with sonication-induced traumatic optic neuropathy (TON). Briefly, a mouse model of indirect TON was generated using sound energy concentrated focally at the entrance of the optic canal using a laboratory sonifier (Branson Digital Sonifier 450, Danbury, CT, USA) with a microtip probe. We performed an analysis of a previously generated dataset from high-performance liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS). We analyzed lipids from isolated mitochondria from the ON at 1 day, 7 days, and 14 days post-sonication compared to non-sonicated controls. Lipid abundance alterations in post-sonicated ON mitochondria were evaluated with 1-way ANOVA (FDR-adjusted significant p-value &lt; 0.01), debiased sparse partial correlation (DSPC) network modeling, and partial least squares-discriminant analysis (PLS-DA). We find temporal alterations in triglyceride metabolism are observed in ON mitochondria of mice following sonication-induced optic neuropathy with notable depletions of TG(18:1/18:2/18:2), TG(18:1/18:1/18:1), and TG(16:0/16:0/18:1). Depletion of mitochondrial triglycerides may mediate ON damage in indirect traumatic optic neuropathy through loss energy substrates for neuronal metabolism.

Traumatic Optic Neuropathy

Traumatic optic neuropathy (TON) refers to optic nerve injury due to direct or indirect head and facial trauma. TON may lead to severe visual disfunction. A wide variety of methods, ranging from simple clinical examination to complicated imaging methods, are used to diagnose this clinical picture. High-dose steroids and surgical interventions have been applied in the indirect TON. Our review of the recent literature aims that discuss how to manage TON.

Effect of orbital volume in unilateral orbital fracture on indirect traumatic optic neuropathy.

This retrospective study aimed to analyze the relationship between the volume of the fractured and the normalorbitin patients with unilateral orbital fractures with and without indirect traumatic optic neuropathy (TON). Data of 25 patients with unilateral orbital fractures who underwent computer tomography between January 2016 and December 2020 were investigated. Emergency imaging was performed within 2hours of arrival at the emergency room.The subjects were categorized into two groups: unilateral orbital fractures with and without TON. The assessment of TON was performed during a comprehensive ophthalmologic examination by an ophthalmologist. The stereographic orbit was reconstructed, and the volume was calculated. Other variables examined included age, sex, and cause of orbital trauma.The variables were compared using paired t-tests. Statistical significance was set at p < 0.05. The orbital volume of the non-fractured orbit was27.50 ± 2.26 and 27.48 ± 2.64cm3 in the groups with and without TON, respectively.The average volume of the fractured orbit in the TON group was27.78 ± 2.56cm3, andthere was no significant volumetric difference between the fractured and non-fractured sides in this group. However, the average volume of the fractured orbit without TON was 28.76 ± 3.18cm3, larger than that of the non-fractured orbit (p = 0.016). Non-expansion of the fractured orbit was a risk factor for indirect TON in patients with unilateral orbital fractures. Volumetric analysis from primary imaging would expedite the diagnosis and treatment of TON, resulting in optimal outcomes.

Temporal Alterations of Sphingolipids in Optic Nerves After Indirect Traumatic Optic Neuropathy

PurposeTo identify optic nerve (ON) lipid alterations associated with sonication-induced traumatic optic neuropathy (TON).DesignExperimental study.SubjectsA mouse model of indirect TON was generated using sound energy concentrated focally at the entrance of the optic canal using a laboratory sonifier with a microtip probe.MethodsAnalyses of datasets generated from high-performance liquid chromatography-electrospray tandem mass spectrometry of ONs dissected from the head of the ON to the optic chiasm at 1 day, 7 days, and 14 days postsonication compared with that in nonsonicated controls.Main Outcome MeasuresLipid abundance alterations in postsonicated ONs were evaluated using 1-way analysis of variance (false discovery rate-adjusted significant P value < 0.01), lipid-related gene sets, biochemical properties, and receiver operating characteristic to identify lipids associated with optic neuropathy.ResultsThere were 28 lipid species with significantly different abundances across the control and postsonication groups. The 2 most significantly upregulated lipids included a sphingomyelin (SM) species, SM(d40:7), and a hexosylceramide (CerG1) species, CerG1(d18:1/24:2). Hexosylceramide (d18:1/24:2) was noted to have a stepwise increasing trend from day 1 to day 14 after sonication-induced optic neuropathy. Investigation of biophysical properties showed notable enrichment of lipids with high and above-average transition temperatures at day 14 after sonication. Lipid-related gene set analysis revealed enrichment in sphingolipid and glycosphingolipid metabolic processes. The best classifier to differentiate day 14 postsonication from controls, based on area under the receiver operating characteristic curve, was CerG1(d18:1/24:2) (area under the receiver operating characteristic curve: 1).ConclusionsTemporal alterations in sphingolipid metabolism and biochemical properties were observed in the ON of mice after sonication-induced optic neuropathy, with notable elevations in sphingomyelin and hexosylceramide species. Hexosylceramide (d18:1/24:2) may be associated with damage after indirect trauma, indicating that lipid membrane abnormalities may be a mediator of pathology due to trauma.

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

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. 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. 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 β= -0.273), SRCP density (Standardized β= -0.183), DRCP density (Standardized β= -0.098) and preoperative BCVA (Standardized β= 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. 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.

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

To assess the retinal vasculature alterations in indirect traumatic optic neuropathy (ITON) patients following craniofacial trauma by optic coherence tomography angiography (OCTA). 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. 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). 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.

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

BackgroundIndirect 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. ObjectiveTo assess the effect of ETOCD on visual acuity in patients with ITON and identify factors that affect prognosis. MethodsIn 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. ResultsETOCD 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. ConclusionsETOCD can effectively and safely improve the vision of ITON patients, patients with residual vision and those treated earlier may benefit more from this surgery.

Prognosticators of Visual Acuity After Indirect Traumatic Optic Neuropathy.

The purpose of this study is to determine whether there are radiographic and systemic clinical characteristics that can predict final visual outcomes in patients with indirect traumatic optic neuropathy (iTON). This study is a retrospective, multicenter case series of adult patients with iTON treated initially at large, urban, and/or academic trauma centers with follow-up at an affiliated ophthalmology clinic. In addition to detailed cranial computed tomography characteristics, demographics, systemic comorbidities, coinjuries, blood products administered, and intracranial pressure, along with other factors, were gathered. LogMAR visual acuity (VA) at the initial presentation to the hospital and up to 12 months follow-up was collected. Twenty patients met inclusion criteria; 16 (80%) were men with a mean age of 40.9 years (±20.9). Mean initial VA was 1.61 logMAR (∼20/800, ± 0.95), and final VA was 1.31 logMAR (∼20/400, ± 1.06). Three patients (4 eyes) had no light perception (NLP) VA at presentation and remained NLP at final follow-up. Of the predictors analyzed, only the initial VA was found to be a significant predictor of visual outcome. The presence of orbital fractures, intraconal and/or extraconal hemorrhage, as well as systemic comorbidities, were not found to significantly affect visual outcome. After evaluating multiple factors, initial VA was the only factor associated with visual prognosis in iTON. This knowledge may better enable clinicians to predict visual prognosis and set reasonable expectations with patients and families at the time of injury.

Indirect Traumatic Optic Neuropathy with Associated Charles Bonnet Syndrome

Indirect Traumatic Optic Neuropathy with Associated Charles Bonnet Syndrome

Chronic Histological Outcomes of Indirect Traumatic Optic Neuropathy in Adolescent Mice: Persistent Degeneration and Temporally Regulated Glial Responses.

Injury to the optic nerve, termed, traumatic optic neuropathy (TON) is a known comorbidity of traumatic brain injury (TBI) and is now known to cause chronic and progressive retinal thinning up to 35 years after injury. Although animal models of TBI have described the presence of optic nerve degeneration and research exploring acute mechanisms is underway, few studies in humans or animals have examined chronic TON pathophysiology outside the retina. We used a closed-head weight-drop model of TBI/TON in 6-week-old male C57BL/6 mice. Mice were euthanized 7-, 14-, 30-, 90-, and 150-days post-injury (DPI) to assess histological changes in the visual system of the brain spanning a total of 12 regions. We show chronic elevation of FluoroJade-C, indicative of neurodegeneration, throughout the time course. Intriguingly, FJ-C staining revealed a bimodal distribution of mice indicating the possibility of subpopulations that may be more or less susceptible to injury outcomes. Additionally, we show that microglia and astrocytes react to optic nerve damage in both temporally and regionally different ways. Despite these differences, astrogliosis and microglial changes were alleviated between 14–30 DPI in all regions examined, perhaps indicating a potentially critical period for intervention/recovery that may determine chronic outcomes.

Effects of intravitreal injection of siRNA against caspase-2 on retinal and optic nerve degeneration in air blast induced ocular trauma

Ocular repeated air blast injuries occur from low overpressure blast wave exposure, which are often repeated and in quick succession. We have shown that caspase-2 caused the death of retinal ganglion cells (RGC) after blunt ocular trauma. Here, we investigated if caspase-2 also mediates RGC apoptosis in a mouse model of air blast induced indirect traumatic optic neuropathy (b-ITON). C57BL/6 mice were exposed to repeated blasts of overpressure air (3 × 2 × 15 psi) and intravitreal injections of siRNA against caspase-2 (siCASP2) or against a control enhanced green fluorescent protein (siEGFP) at either 5 h after the first 2 × 15 psi (“post-blast”) or 48 h before the first blast exposure (“pre-blast”) and repeated every 7 days. RGC counts were unaffected by the b-ITON or intravitreal injections, despite increased degenerating ON axons, even in siCASP2 “post-blast” injection groups. Degenerating ON axons remained at sham levels after b-ITON and intravitreal siCASP2 “pre-blast” injections, but with less degenerating axons in siCASP2 compared to siEGFP-treated eyes. Intravitreal injections “post-blast” caused greater vitreous inflammation, potentiated by siCASP2, with less in “pre-blast” injected eyes, which was abrogated by siCASP2. We conclude that intravitreal injection timing after ocular trauma induced variable retinal and ON pathology, undermining our candidate neuroprotective therapy, siCASP2.

Progression of optic atrophy in traumatic optic neuropathy: retrograde neuronal degeneration in humans.

We used optical coherence tomography (OCT) to document the time course of retrograde neuronal degeneration following indirect optic nerve injury. We retrospectively studied patients diagnosed with unilateral indirect traumatic optic neuropathy (TON). Patients with total or near-total optic atrophy were included. All patients underwent complete ophthalmological examinations, including OCT imaging, within 1day and at 1, 2, 3, 4, 6, 8, 12, 24, and 48weeks after trauma. The mean thicknesses of the circumpapillary retinal nerve fiber layer (cpRNFL) and macular retinal ganglion cell-inner plexiform layer (mGCIPL) decreased significantly at 2weeks after trauma (p = 0.027 and p = 0.043). Changes in mGCIPL thickness preceded changes in cpRNFL thickness. The rates of reduction in mGCIPL and cpRNFL thicknesses were greatest between 2 to 4weeks and 4 to 6weeks after trauma. The reduction in mGCIPL thickness then slowed, and stabilized at 12weeks after trauma. The proportions of cpRNFL and mGCIPL losses at 2, 4, 6, 8, and 12weeks compared to 24weeks were 17.1, 33.7, 59.8, 77.9, and 87.9% and 30.0, 73.3, 76.1, 88.3, and 97.9%, respectively. OCT revealed optic atrophy progression 2weeks after trauma, which was most rapid from 2 to 6weeks, and then gradually stabilized. Loss of retinal ganglion cell bodies and dendrites seemed to precede the axonal degeneration. Observations of morphological changes in retinal layers using OCT in TON patients improve our understanding of retrograde neuronal degeneration of the central nervous system.