Managing intraoperative rupture of internal carotid pseudoaneurysms during endoscopic transnasal optic canal decompression: a case report.

Background: Endoscopic transnasal optic canal decompression is widely used in the treatment of traumatic optic neuropathy (TON) following head and craniofacial trauma. Intraoperative hemorrhage is a catastrophic surgical complication during optic canal decompression. Case description: We present two cases of patients with TON who suffered unexpected intra-operative massive bleeding during endoscopic transnasal optic canal decompression. After intraoperative hemostasis was achieved, emergent cerebral angiograms demonstrated the formation of internal carotid pseudoaneurysms, which were immediately embolized with coils combined with or without Onyx with balloon assistance. One of these cases was also complicated by a postoperative cerebrospinal fluid leak, which failed to be treated with lumbar drainage but was successfully repaired with endoscopic transnasal surgery. Conclusion: The intra-operative rupture of ICA pseudoaneurysm is a rare but catastrophic complication in TON patients. Intraoperative massive bleeding indicates rupture of ICA pseudoaneurysm. Postoperative emergency angiography and endovascular therapy should be arranged to evaluate and repair the cerebral vascular injury. Endoscopic trans-nasal surgery repairing CSF leaks resistant to lumbar drainage could be efficient and safe following pseudoaneurysm embolization.

Optic nerve decompression through pterional and supraorbital approaches in the treatment of severe traumatic optic neuropathy.

To investigate the effectiveness of optic nerve decompression (OND) in the treatment of severe traumatic optic neuropathy (TON) through pterional and supraorbital approaches, and to identify the prognostic factor for postoperative visual acuity (VA) following OND. Patients with severe TON treated with OND through either pterional or supraorbital approach in our institute from September 2019 to June 2022 were retrospectively reviewed in this study. Demographic information, trauma factors, the interval between trauma and complete blindness, the interval between trauma and surgery, and the associated craniofacial traumas were recorded. Hospitalization days and the postoperative VA of patients in two groups were compared. There were 54 severe TON patients with NLP included in this study; 21 patients underwent OND through the pterional approach, and the other 33 underwent the supraorbital approach. Respectively, in groups of pterional and supraorbital approaches, the average hospitalization days were 9.8 ± 3.2 and 10.7 ± 2.9 days (p = 0.58), the mean durations of follow-up were 18.9 ± 4.3 and 20.8 ± 3.7 months (p = 0.09), and the average circumference of OND were 53.14 ± 15.89 ◦ (range 220 ◦ -278◦) and 181.70 ± 6.56◦ (range 173 ◦ -193◦) (p<0.001). The overall improvement rates of pterional and supraorbital approaches are 57.1% and 45.5% (p = 0.40), respectively. Optic canal fracture (OCF) was revealed to be significantly associated with postoperative VA in the supraorbital approach (Binary: p = 0.014, CI: 1.573-57.087; Ordinal: p = 0.003, CI: 1.517-5.503), but not in the pterional approach. In the group of supraorbital approach, patients with OFC had a higher rate of a better outcome (78.6%) than those without (21.4%). Patients with severe traumatic TON may benefit from OND through either the pterional or supraorbital approach. OCF is a potential prognostic factor for postoperative VA following OND through the supraorbital approach.

Neuroprotective effects and mechanisms of action of artemisinin in retinal ganglion cells in a mouse model of traumatic optic neuropathy.

Introduction: Traumatic optic neuropathy is known to be a critical condition that can cause blindness; however, the specific mechanism underlying optic nerve injury is unclear. Recent studies have reported that artemisinin, considered vital in malaria treatment, can also be used to treat neurodegenerative diseases; however, its precise role and mechanism of action remain unknown. Therefore, in this study, we aimed to investigate the impact and probable mechanism of action of artemisinin in retinal ganglion cells (RGCs) in a mouse model of traumatic optic neuropathy induced by optic nerve crush (ONC). Methods: ONC was induced in the left eye of mice by short-term clamping of the optic nerve; oral artemisinin was administered daily. The neuroprotective effect of the drug was assessed using Tuj-1 staining in RGCs. In addition, the inflammatory response and the expression levels of phosphorylated tau protein and tau oligomers were observed using RT-qPCR, TUNEL assay, and fluorescence staining to investigate the underlying mechanisms. Results: Artemisinin increased the survival rate of RGCs 14 days after ONC. Artemisinin significantly reduced the levels of inflammatory factors such as CXCL10, CXCR3, and IL-1ß in the retina and decreased the apoptosis of RGCs. Moreover, downregulation of the phosphorylation of tau proteins and the expression of tau oligomers were observed after artemisinin treatment. Conclusion: Our results suggest that artemisinin can increase the survival rate of RGCs after ONC and reduce their apoptosis. This effect may be achieved by inhibiting the inflammatory response it triggers and downregulating tau protein phosphorylation and tau oligomer expression. These findings suggest the potential application of artemisinin as a therapeutic agent for neuropathy.

Diffusion tensor imaging of optic neuropathies: a narrative review.

Background and Objective: Diffusion tensor imaging (DTI) has been implemented in a breadth of scientific investigations of optic neuropathies, though it has yet to be fully adopted for diagnosis or prognosis. This is potentially due to a lack of standardization and weak replication of results. The aim of this investigation was to review DTI results from studies specific to three distinct optic neuropathies in order to probe its current clinical utility. Methods: We reviewed the DTI literature specific to primary open-angle glaucoma (POAG), optic neuritis (ON), and traumatic optic neuropathy (TON) by systematically searching the PubMed database on March 1st, 2023. Four distinct DTI metrics are considered: fractional anisotropy (FA), along with mean diffusivity (MD, axial diffusivity (AD), and radial diffusivity (RD). Results from within-group, between-group, and correlational studies were thoroughly assessed. Key Content and Findings: POAG studies most consistently report a decrease in FA, especially in the optic radiations, followed in prevalence by an increase in RD and then MD, whilst AD yields conflicting results between studies. It is notable that there is not an equal distribution of investigated DTI metrics, with FA utilized the most, followed by MD, RD, and AD. Studies of ON are similar in that the most consistent findings are specific to FA, RD, and MD. These results are specific to the optic nerve and radiation since only one study measured the intermediary regions. More studies are needed to assess the effect that ON has on the tracts of the visual system. Finally, only three studies assessing DTI of TON have been performed to date, displaying low to moderate replicability of results. To improve the level of agreement between studies assessing each optic neuropathy, an increased level of standardization is recommended. Conclusions: Both POAG and ON studies have yielded some prevalent DTI findings, both for contrast and correlation-based assessments. Although the clinical need is high for TON, considering the limitations of the current diagnostic tools, too few studies exist to make confident conclusions. Future use of standardized and longitudinal DTI, along with the foreseen methodological and technical improvements, is warranted to effectively study optic neuropathies.

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.

Comparison of Surgical Decompression and Steroid Therapy for the Management of Traumatic Optic Neuropathy: A Systematic Review and Meta-Analysis.

Study Design: A systematic review and meta-analysis. Objective: Treatment of traumatic optic neuropathy (TON) has been a subject of debate for many decades due to the scarcity of evidence-based treatment protocols. This review compares surgical decompression (SD) and steroid therapy (ST) as treatment approaches in TON patients. Methods: A PRISMA-guided systematic review using PubMed, Embase, Ovid and Scopus databases was performed till the last search date of July 31st 2021. The outcome of interest was an improvement in visual acuity. A meta-analysis of the odds ratio was performed using a random-effect model and sub-group analysis based upon criteria for assessment of improvement in visual acuity. Results: Sixteen studies (including 1046 patients) were included in the review. The review could identify 590 patients treated with SD and 456 treated with ST. In addition, there was a second cohort of patients presenting with NLP (no light perception). A meta-analysis with a sub-group analysis revealed that there was statistically no significant difference between the two treatment approaches in terms of improvement in VA. Conclusions: There is no difference in treatment results of SD or ST for TON. Several treatment protocols and different criteria for assessing visual acuity led to difficulty in generating evidence for selecting the correct treatment approach.

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

Introduction: 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). Methods: 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. Results: 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. Conclusion: DBSI provides an imaging modality capable of detecting subclinical changes of indirect TON in TBI mice.

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

Purpose: 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. Methods: 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. Results: 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%). Conclusion: 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.

Visual-evoked potential predicts the efficacy of the optical canal decompression for traumatic optic nerve neuropathy showing blindness: A case report.

Background: The indication for surgical optic canal decompression (OCD) for traumatic optic neuropathy (TON) remains controversial because there is no reliable predictor of a good outcome. We report the case of a blind patient with TON whose remaining visual-evoked potential (VEP) suggested recovery potential of the injured optic nerve after OCD. Case Description: A 48-year-old man had fallen from a height of 7 m, striking his head. He immediately complained of right-eye blindness. He had no light perception and the direct light reflex disappeared from the right pupil, although there was no fracture or traumatic lesion on computed tomography and magnetic resonance imaging. Because the amplitude of the VEP with the right eye stimulation remained unchanged, we performed the right OCD. During surgical OCD, the amplitude and latency of VEP began to improve. Finally, the visual field improved in almost all directions, and eyesight improved to 0.2. Conclusion: The retained VEP activity in TON may suggest the recovery potential of the injured optic nerve, even in cases of blindness. It is possible that VEP is an indicator of aggressive treatment for TON such as OCD.

Erythropoietin Protects against Retinal Damage in A Rat Model of Optic Neuropathy via Glial Suppression.

OBJECTIVE: Traumatic optic neuropathy (TON) causes partial or complete blindness because death of irreplaceable retinal ganglion cells (RGCs). Neuroprotective functions of erythropoietin (EPO) in the nervous system have been considered by many studies investigating effectiveness of this cytokine in various retinal disease models. It has been found that changes in retinal neurons under conditions of glial cells are effective in vision loss, therefore, the present study hypothesized that EPO neuroprotective effect could be mediated through glial cells in TON model. MATERIALS AND METHODS: In this experiment study, 72 rats were assessed in the following groups: intact and optic nerve crush which received either the 4000 IU EPO or saline. Visual evoked potential and optomotor response and RGC number were assessed and regenerated axons evaluated by anterograde test. Cytokines gene expression changes were compared by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Density of astrocytes cells, assessed by fluorescence intensity, in addition, possible cytotoxic effect of EPO was measured on mouse astrocyte culture in vitro. RESULTS: in vitro data showed that EPO was not toxic for mouse astrocytes. Intravenous injection of EPO improved vision, in terms of visual behavioral tests. RGCs protection was more than two times in EPO, compared to the vehicle group. More regenerated axons were determined by anterograde tracing in the EPO group compared to the vehicle. Moreover, GFAP immunostaining showed while the intensity of reactive astrocytes was increased in injured retina, systemic EPO decreased it. In the treatment group, expression of GFAP was down-regulated, while CNTF was upregulated as assessed by qRT-PCR in the 60th day post-crush. CONCLUSION: Our study showed that systemic administration of EPO can protect degenerating RGCs. Indeed, exogenous EPO exerted neuroprotective and neurotrophic functions by reducing reactive astrocytic gliosis. Therefore, reduction of gliosis by EPO may be considered as therapeutic targets for TON.

Diagnosis and treatment of transnasal endoscopic optic canal decompression for traumatic optic neuropathy.

Objective: To investigate the clinical efficacy and prognostic factors of transnasal endoscopic optic decompression in the treatment of traumatic optic neuropathy (TON). Methods: A retrospective analysis was performed on 13 TON patients in The Seventh Affiliated Hospital of Sun Yat-sen University and Shenzhen Eye Hospital in Shenzhen City (China) from June 2020 to April 2022. These patients had received transnasal endoscopic optic decompression, and hormonal and neurotrophic drugs were given after surgery. Visual acuity (VA) improvement was used as the criterion to judge clinical efficacy. Results: In a total of 13 patients, 13 injured eyes (12 men and 1 woman; mean age, 28.0 ± 11.8 years) received transnasal endoscopic optic decompression. After surgery, nine patients had improved VA, whereas four patients failed to show any improvement, resulting in a total effective rate of 69.2%. Of the six patients with no light perception preoperatively, three had effective results after the operation, giving an effective rate of 50.0%. Of the seven patients with residual light sensation preoperatively, six had effective results after the operation, giving an effective rate of 85.7%. Of the 10 patients operated on within 7 days after injury, seven had effective results, giving an effective rate of 70%. Of the three patients injured and operated on after 7 days, two had effective results, giving an effective rate of 66.7%. Conclusion: Transnasal endoscopic optic nerve decompression is an effective treatment method for TON. The presence of residual light perception and the timing of surgery within 7 days are crucial to the prognosis.

Brief Oxygen Exposure after Traumatic Brain Injury Hastens Recovery and Promotes Adaptive Chronic Endoplasmic Reticulum Stress Responses.

Traumatic brain injury (TBI) is a major public health concern, particularly in adolescents who have a higher mortality and incidence of visual pathway injury compared to adult patients. Likewise, we have found disparities between adult and adolescent TBI outcomes in rodents. Most interestingly, adolescents suffer a prolonged apneic period immediately post-injury, leading to higher mortality; therefore, we implemented a brief oxygen exposure paradigm to circumvent this increased mortality. Adolescent male mice experienced a closed-head weight-drop TBI and were then exposed to 100% O2 until normal breathing returned or recovered in room air. We followed mice for 7 and 30 days and assessed their optokinetic response; retinal ganglion cell loss; axonal degeneration; glial reactivity; and retinal ER stress protein levels. O2 reduced adolescent mortality by 40%, improved post-injury visual acuity, and reduced axonal degeneration and gliosis in optical projection regions. ER stress protein expression was altered in injured mice, and mice given O2 utilized different ER stress pathways in a time-dependent manner. Finally, O2 exposure may be mediating these ER stress responses through regulation of the redox-sensitive ER folding protein ERO1α, which has been linked to a reduction in the toxic effects of free radicals in other animal models of ER stress.

Human amnionic progenitor cell secretome mitigates the consequence of traumatic optic neuropathy in a mouse model.

Traumatic optic neuropathy (TON) is a condition in which acute injury to the optic nerve from direct or indirect trauma results in vision loss. The most common cause of TON is indirect injury to the optic nerve caused by concussive forces that are transmitted to the optic nerve. TON occurs in up to 5% of closed-head trauma patients and there is currently no known effective treatment. One potential treatment option for TON is ST266, a cell-free biological solution containing the secretome of amnion-derived multipotent progenitor (AMP) cells. We investigated the efficacy of intranasal ST266 in a mouse model of TON induced by blunt head trauma. Injured mice treated with a 10-day regimen of ST266 showed an improvement in spatial memory and learning, a significant preservation of retinal ganglion cells, and a decrease in neuropathological markers in the optic nerve, optic tract, and dorsal lateral geniculate nucleus. ST266 treatment effectively downregulated the NLRP3 inflammasome-mediated neuroinflammation pathway after blunt trauma. Overall, treatment with ST266 was shown to improve functional and pathological outcomes in a mouse model of TON, warranting future exploration of ST266 as a cell-free therapeutic candidate for testing in all optic neuropathies.

Intravitreal injection of Huperzine A promotes retinal ganglion cells survival and axonal regeneration after optic nerve crush.

Traumatic optic neuropathy (TON) is a condition that causes massive loss of retinal ganglion cells (RGCs) and their axonal fibers, leading to visual insufficiency. Several intrinsic and external factors can limit the regenerative ability of RGC after TON, subsequently resulting in RGC death. Hence, it is important to investigate a potential drug that can protect RGC after TON and enhance its regenerative capacity. Herein, we investigated whether Huperzine A (HupA), extracted from a Chinese herb, has neuroprotective effects and may enhance neuronal regeneration following the optic nerve crush (ONC) model. We compared the three modes of drug delivery and found that intravitreal injection of HupA could promote RGC survival and axonal regeneration after ONC. Mechanistically, HupA exerted its neuroprotective and axonal regenerative effects through the mTOR pathway; these effects could be blocked by rapamycin. To sum up, our findings suggest a promising application of HupA in the clinical treatment of traumatic optic nerve.

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.

A hypothermia mimetic molecule (zr17-2) reduces ganglion cell death and electroretinogram distortion in a rat model of intraorbital optic nerve crush (IONC).

Introduction: Ocular and periocular traumatisms may result in loss of vision. Our previous work showed that therapeutic hypothermia prevents retinal damage caused by traumatic neuropathy. We also generated and characterized small molecules that elicit the beneficial effects of hypothermia at normal body temperature. Here we investigate whether one of these mimetic molecules, zr17-2, is able to preserve the function of eyes exposed to trauma. Methods: Intraorbital optic nerve crush (IONC) or sham manipulation was applied to Sprague-Dawley rats. One hour after surgery, 5.0 µl of 330 nmol/L zr17-2 or PBS, as vehicle, were injected in the vitreum of treated animals. Electroretinograms were performed 21 days after surgery and a- and b-wave amplitude, as well as oscillatory potentials (OP), were calculated. Some animals were sacrificed 6 days after surgery for TUNEL analysis. All animal experiments were approved by the local ethics board. Results: Our previous studies showed that zr17-2 does not cross the blood-ocular barrier, thus preventing systemic treatment. Here we show that intravitreal injection of zr17-2 results in a very significant prevention of retinal damage, providing preclinical support for its pharmacological use in ocular conditions. As previously reported, IONC resulted in a drastic reduction in the amplitude of the b-wave (p < 0.0001) and OPs (p < 0.05), a large decrease in the number of RGCs (p < 0.0001), and a large increase in the number of apoptotic cells in the GCL and the INL (p < 0.0001). Interestingly, injection of zr17-2 largely prevented all these parameters, in a very similar pattern to that elicited by therapeutic hypothermia. The small molecule was also able to reduce oxidative stress-induced retinal cell death in vitro. Discussion: In summary, we have shown that intravitreal injection of the hypothermia mimetic, zr17-2, significantly reduces the morphological and electrophysiological consequences of ocular traumatism and may represent a new treatment option for this cause of visual loss.

Neuroprotective Effects of Erinacine A on an Experimental Model of Traumatic Optic Neuropathy.

Erinacine A (EA), a natural neuroprotectant, is isolated from a Chinese herbal medicine, Hericium erinaceus. The aim of this study was to investigate the neuroprotective effects of EA in a rat model of traumatic optic neuropathy. The optic nerves (ONs) of adult male Wistar rats were crushed using a standardized method and divided into three experimental groups: phosphate-buffered saline (PBS control)-treated group, standard EA dose-treated group (2.64 mg/kg in 0.5 mL of PBS), and double EA dose-treated group (5.28 mg/kg in 0.5 mL of PBS). After ON crush, each group was fed orally every day for 14 days before being euthanized. The visual function, retinal ganglion cell (RGC) density, and RGC apoptosis were determined using flash visual-evoked potentials (fVEP) analysis, retrograde Fluoro-Gold labelling, and TdT-dUTP nick end-labelling (TUNEL) assay, respectively. Macrophage infiltration of ON was detected by immunostaining (immunohistochemistry) for ED1. The protein levels of phosphor-receptor-interacting serine/threonine-protein kinase1 (pRIP1), caspase 8 (Cas8), cleaved caspase 3 (cCas3), tumour necrosis factor (TNF)-α, tumour necrosis factor receptor1 (TNFR1), interleukin (IL)-1ß, inducible nitric oxide synthase (iNOS), nuclear factor erythroid 2-related factor 2 (Nrf2), haem oxygenase-1 (HO-1), and superoxide dismutase 1 (SOD1) were evaluated by Western blotting. When comparing the standard EA dose-treated group and the double EA dose-treated group with the PBS-treated group, fVEP analysis showed that the amplitudes of P1−N2 in the standard EA dose group and the double EA dose-treated group were 1.8 and 2.4-fold, respectively, higher than that in the PBS-treated group (p < 0.05). The density of RGC in the standard EA dose-treated group and the double EA dose-treated group were 2.3 and 3.7-fold, respectively, higher than that in the PBS-treated group (p < 0.05). The TUNEL assay showed that the standard EA dose-treated group and the double EA dose-treated group had significantly reduced numbers of apoptotic RGC by 10.0 and 15.6-fold, respectively, compared with the PBS-treated group (p < 0.05). The numbers of macrophages on ON were reduced by 1.8 and 2.2-fold in the standard EA dose-treated group and the double EA dose-treated group, respectively (p < 0.01). On the retinal samples, the levels of pRIP, Cas8, cCas3, TNF-α, TNFR1, IL-1ß, and iNOS were decreased, whereas those of Nrf2, HO-1, and SOD1 were increased in both EA-treated groups compared to those in the PBS-treated group (p < 0.05). EA treatment has neuroprotective effects on an experimental model of traumatic optic neuropathy by suppressing apoptosis, neuroinflammation, and oxidative stress to protect the RGCs from death as well as preserving the visual function.

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

Purpose: 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. Methods: : 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. Results: 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. Conclusion: 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.

Traumatic Optic Neuropathy: Update on Management.

Traumatic optic neuropathy is one of the causes of visual loss caused by blunt or penetrating head trauma and is classified as both direct and indirect. Clinical history and examination findings usually allow for the diagnosis of traumatic optic neuropathy. There is still controversy surrounding the management of traumatic optic neuropathy; some physicians advocate observation alone, while others recommend steroid therapy, surgery, or both. In this entry, we tried to highlight traumatic optic neuropathy's main pathophysiologic mechanisms with the most available updated treatment. Recent research suggests future therapies that may be helpful in traumatic optic neuropathy cases.

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

PURPOSE: This retrospective study aimed to analyze the relationship between the volume of the fractured and the normal orbit in patients with unilateral orbital fractures with and without indirect traumatic optic neuropathy (TON). SUBJECTS: 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 2 hours of arrival at the emergency room. The subjects were categorized into two groups: unilateral orbital fractures with and without TON. METHODS AND MEASURES: 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. RESULTS: The orbital volume of the non-fractured orbit was 27.50 ± 2.26 and 27.48 ± 2.64 cm3 in the groups with and without TON, respectively. The average volume of the fractured orbit in the TON group was 27.78 ± 2.56 cm3, and there 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 ± 3.18 cm3, larger than that of the non-fractured orbit (p = 0.016). CONCLUSIONS: 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.