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Traumatic optic neuropathy (TON) consists of damage to the optic nerve following head injury and affects about 0.5–5% of patients with closed head injuries. It is characterized by a sudden decrease in visual acuity and/or visual field loss. Surgical treatment is usually warranted when ongoing compression occurs at the level of the optic canal. We describe the technical nuances of endoscopic endonasal approach for compressive TON and add evidence supporting this approach as a valid option to treat this condition. [ABSTRACT FROM AUTHOR]

Optic nerve (ON) injury causes blindness in adult mammals as their retinal ganglion cells (RGCs) cannot regenerate axons. However, amphibian RGC axons do not experience the same regenerative failure. Studying the regeneration process of the ON in amphibians holds profound implications for regenerative medicine and human health. Using transgenic tadpoles and laser micro-optics, we developed a reproducible ON transection and regeneration model. Through microscopy of axon dynamics, functional testing to assess visual pathway recovery, TUNEL cell death and EdU cell proliferation assays, and RNA-seq of the retina and optic nerve, we characterized the optic nerve injury response and subsequent recovery. Our model suggests no chemoattractant gradient exists early in regeneration, with defasciculated axons sprouting in random directions from the globe-proximal cut end. Once individual axons reach the appropriate targets in the brain, their tract is reinforced by other regenerating axons, restoring normal ON morphology. Thus, guidance cues or scaffolding from brain-innervating axons likely support later stages of regeneration. After 14 days, the regenerated ON is morphologically indistinguishable from the naïve ON, and visual function is restored. We found no evidence of RGC death or new RGC formation in the model, suggesting that ON regeneration involves remodeling of injured axons of pre-existing RGCs. [ABSTRACT FROM AUTHOR]

Optic nerve regeneration remains challenging worldwide due to the limited intrinsic regenerative capacity of retinal ganglion cells (RGCs) and the inhibitory microenvironment. Oxidative stress, induced by excessive reactive oxygen species (ROS) following optic nerve injury, is associated with prolonged neuroinflammation, resulting in a secondary injury of RGCs and the impairment of axon regeneration. Herein, we developed a bionic nanocomposite scaffold (GA@PDA) with immunoregulatory ability for enhanced optic nerve regeneration. The ice-templating method was employed to fabricate biopolymer-based scaffolds with a directional porous structure, mimicking the optic nerve, which effectively guided the oriented growth of neuronal cells. The incorporation of bioinspired polydopamine nanoparticles (PDA NPs) further confers excellent ROS scavenging ability, thereby modulating the phenotype transformation of microglia/macrophages from pro-inflammatory M1 to anti-inflammatory M2. In a rat optic nerve crush model, the implantation of GA@PDA scaffold enhanced survival of RGCs and promoted axonal regeneration. Our study offers novel insights and holds promising potential for the advancement of engineered biomaterials in facilitating optic nerve regeneration. [ABSTRACT FROM AUTHOR]

Background: Endoscopic Endonasal Decompression for Traumatic Optic Nerve Injury has become an established endoscopic technique. However, Poor sphenoid sinus pneumatization often obscures landmarks, elevating the risk to vital neurovascular structures. Method: By decompressing the orbital apex region and determining the contour of the optic nerve, sequential decompression of the medial wall, superomedial wall, and inferomedial wall of the optic canal. Conclusion: This surgical technique can gradually reveal the contour of the optic canal when the anatomical landmarks on the lateral wall of the sphenoid sinus are unclear, ensuring the surgery can be completed safely and effectively. [ABSTRACT FROM AUTHOR]

Axon-to-soma signaling events drive the changes in gene expression required for the injured axon to shift from non-elongating to growth-competent. Genetic reprogramming of adult neurons back to a growth-compatible state relies on the activation and coordinated actions of several transcription factors and epigenetic modifiers. Local translation supplies the injured axon with the necessary proteins to carry out the regenerative program. Neurons activate intrinsic energetic repair mechanisms to remobilize axonal mitochondria and meet the high energy demands of the regenerative process. Several intrinsic barriers to axonal regeneration have been identified, including the presence of functional presynaptic active zones, transcriptional repressors, and inhibitors of critical regenerative signaling pathways. Injury to the central nervous system (CNS) often results in permanent neurological impairments because axons fail to regenerate and re-establish lost synaptic contacts. By contrast, peripheral neurons can activate a pro-regenerative program and regenerate following a nerve lesion. This relies on an intricate intracellular communication system between the severed axon and the cell body. Locally activated signaling molecules are retrogradely transported to the soma to promote the epigenetic and transcriptional changes required for the injured neuron to regain growth competence. These signaling events rely heavily on intra-axonal translation and mitochondrial trafficking into the severed axon. Here, we discuss the interplay between these mechanisms and the main intrinsic barriers to axonal regeneration. We also examine the potential of manipulating these processes for driving CNS repair. [ABSTRACT FROM AUTHOR]

Schlemm's canal (SC) is a small circular canal in the deep part of the sclera at the junction of the sclera and cornea. As an integral component of the aqueous humor outflow, its structure and function are essential in regulating intraocular pressure (IOP). If SC develops lesions, the drainage of aqueous humor would be obstructed, leading to increased intraocular pressure and injury to the optic nerve. With the rapid development of minimally invasive glaucoma surgery, an increasing number of surgeons became familiar with SC, and the area generated substantial academic attention. The pathological mechanism and the therapy for SC that had been studied in recent years are summarized in this article, hoping to provide ideas for the treatment of glaucoma in the future. [ABSTRACT FROM AUTHOR]

Modulating inflammation is critical to enhance nerve regeneration after injury. However, clinically applicable regenerative therapies that modulate inflammation have not yet been established. Here, we demonstrate synergistic effects of the combination of an HMG-CoA reductase inhibitor, statin/fluvastatin and critical components of the extracellular matrix, Matrix-Bound Nanovesicles (MBV) to enhance axon regeneration and neuroprotection after mouse optic nerve injury. Mechanistically, co-intravitreal injections of fluvastatin and MBV robustly promote infiltration of monocytes and neutrophils, which lead to RGC protection and axon regeneration. Furthermore, monocyte infiltration is triggered by elevated expression of CCL2, a chemokine, in the superficial layer of the retina after treatment with a combination of fluvastatin and MBV or IL-33, a cytokine contained within MBV. Finally, this therapy can be further combined with AAV-based gene therapy blocking anti-regenerative pathways in RGCs to extend regenerated axons. These data highlight novel molecular insights into the development of immunomodulatory regenerative therapy. [ABSTRACT FROM AUTHOR]

AIM: This study aimed to investigate the mechanism by which celoside I enhances mitophagy in a model of optic nerve injury through regulation of reactive oxygen species（ ROS）-mediated c-Jun N-terminal kinase（ JNK）/c-Jun signaling pathway. METHODS: Twenty-four New Zealand white rabbits were randomly divided into four groups: sham surgery, model, mecobalamin, and experimental group. Optic nerve injury was induced in the model, mecobalamin, and experimental groups, while the sham surgery group underwent a sham procedure. The mecobalamin group received mecobalamin, the experimental group received celoside I, and the sham surgery and model groups received saline. Interventions were administered daily for 28 d. Various techniques including endoscopy, hematoxylin-eosin （HE） staining, TUNEL method, immunofluorescence staining and Western blot were used to assess fundus condition, retinal morphology, apoptosis, ROS expression, and protein levels in the retina. RESULTS: Fundus examination revealed improved blood flow in the mecobalamin and experimental groups compared to the model group. Retinal morphology showed enhanced retinal ganglion cells （RGCs） in the mecobalamin and experimental groups. Apoptosis index was lower in the mecobalamin group compared to the experimental group. Immunofluorescence staining indicated reduced ROS and P62 expression and increased parkin and microtubule-associated protein light chain 3 （LC3） expression in the experimental group compared to the mecobalamin group. Protein analysis showed decreased JNK, c-Jun, and P62 levels, and increased parkin and LC3 levels in the mecobalamin and experimental groups compared to the model group. CONCLUSION: Celoside I reduces ROS expression, inhibits the JNK/c-Jun pathway, enhances mitophagy, reduces apoptosis, and protects RGCs in optic nerve injury models. [ABSTRACT FROM AUTHOR]

The integrated stress response (ISR) is a conserved pathway in eukaryotic cells that is activated in response to multiple sources of cellular stress. Although acute activation of this pathway restores cellular homeostasis, intense or prolonged ISR activation perturbs cell function and may contribute to neurodegeneration. DNL343 is an investigational CNS-penetrant small-molecule ISR inhibitor designed to activate the eukaryotic initiation factor 2B (eIF2B) and suppress aberrant ISR activation. DNL343 reduced CNS ISR activity and neurodegeneration in a dose-dependent manner in two established in vivo models - the optic nerve crush injury and an eIF2B loss of function (LOF) mutant - demonstrating neuroprotection in both and preventing motor dysfunction in the LOF mutant mouse. Treatment with DNL343 at a late stage of disease in the LOF model reversed elevation in plasma biomarkers of neuroinflammation and neurodegeneration and prevented premature mortality. Several proteins and metabolites that are dysregulated in the LOF mouse brains were normalized by DNL343 treatment, and this response is detectable in human biofluids. Several of these biomarkers show differential levels in CSF and plasma from patients with vanishing white matter disease (VWMD), a neurodegenerative disease that is driven by eIF2B LOF and chronic ISR activation, supporting their potential translational relevance. This study demonstrates that DNL343 is a brain-penetrant ISR inhibitor capable of attenuating neurodegeneration in mouse models and identifies several biomarker candidates that may be used to assess treatment responses in the clinic. [ABSTRACT FROM AUTHOR]

Objectives: To characterize the epidemiology of simultaneous traumatic brain injury (TBI) and ocular trauma. Materials and Methods: In this retrospective, observational study, de-identified data from patients admitted with ocular trauma and TBI was extracted from the National Trauma Data Bank (2008-2014) using International Classification of Diseases 9th Revision, Clinical Modification diagnostic codes and E-codes relating to injury circumstances. Mechanisms, types of ocular and head injuries, intention, and demographic distribution were determined. Association of variables was calculated with Student's t and chi-squared tests and logistic regression analysis. Results: Of 316,485 patients admitted with ocular trauma, 184,124 (58.2%) also had TBI. The mean (standard deviation [SD]) age was 41.8 (23) years. Most were males (69.8%). Race/ethnicity distribution was 68.5% white, 13.3% black, and 11.4% Hispanic patients. The mean (SD) Glasgow Coma Score (GCS) was 12.4 (4.4) and Injury Severity Score (ISS) was 17 (10.6). Frequent injuries were orbital fractures (49.3%) and eye/adnexa contusions (38.3%). Common mechanisms were falls (27.7%) and motor vehicle-occupant (22.6%). Firearm-related trauma (5.2%) had the greatest odds of very severe injury (ISS >24) (odds ratio [OR]: 4.29; p<0.001) and severe TBI (GCS <8) (OR: 5.38; p<0.001). Assault injuries were associated with the greatest odds of mild TBI (OR: 1.36; p<0.001) and self-inflicted injuries with severe TBI (OR: 8.06; p<0.001). Eye/adnexal contusions were most associated with mild TBI (OR: 1.25; p<0.001). Optic nerve/visual pathway injuries had greater odds of severe TBI (OR: 2.91; p<0.001) and mortality (OR: 2.27; p<0.001) than other injuries. Of associated head injuries, the odds of severe TBI were greatest with skull base fractures (OR: 4.07; p<0.001) and mortality with intracerebral hemorrhages (OR: 4.28; p<0.001). Mortality occurred in 5.9% of patients. Conclusion: TBI occurred in nearly two-thirds of ocular trauma admissions. The mortality rate was low with implications for challenging rehabilitation and long-term disability in survivors. [ABSTRACT FROM AUTHOR]

Neurosurgical interventions and trauma are common causes of damage to the optic nerve. This determines the relevance of research for solutions aimed at restoration of the nerve's anatomical integrity, electrical conductivity, and subsequently – restoration of its function. Restore a damaged (cut) optic nerve using n. suralis autograft in vivo. The experiment involved reconstruction of the optic nerve through injury modulation, graft placement and restored nerve harvest and evaluation. Injury modulation included removal of a fragment of the optic nerve. Autograft harvesting and placement involved resection of a fragment of the sural (sensory) nerve and its subsequent anastomosis in place of the removed fragment of the optic nerve. As an experimental model, a rabbit of the "Burgundy" breed was used. The animal was previously examined for the presence of infectious and other diseases to confirm its health. Four months post operatively when stimulating the operated right eye, low-amplitude components altered in shape are registered. Thus, signs of mild restoration of electrical conductivity on the treated optic nerve were seen. Our initial experience shows the technical feasibility of reconstructing the optic nerve using an autograft, the possibility of axonal growth through the graft and, in the future, using this method for direct optic nerve reconstruction, as well as a bypass method for damage to the optic nerve with various tumor diseases of the optic nerve, tumors of the chiasmatic-sellar localization, orbital injuries. [ABSTRACT FROM AUTHOR]

Carotid-cavernous fistula (CCF) is a rare condition. However, it should be suspected when there are traumatic facial fractures, because if not diagnosed, it can lead to permanent damage such as blindness. Traumatic CCF often presents delayed symptoms, and delayed diagnosis without prompt treatment can lead to permanent injuries in optic and cranial nerves III, IV, V, and VI as well as intracranial hemorrhage. The routine initial modality for patients with suspected facial bone fractures is noncontrast computed tomography (CT) to identify any fracture lines and check for intracranial hemorrhage. We report a post-traumatic CCF case with a 4-day symptom delay, where left superior ophthalmic vein (SOV) enlargement was observed on the routine noncontrast facial CT with ipsilateral orbital wall fracture. When the patient first presented to the emergency room (ER), we did not detect vein enlargement on CT. Afterwards, the patient developed delayed symptoms of CCF and was readmitted to the ER. When we reanalyzed the first CT scan, an enlarged SOV was confirmed. The diagnosis was confirmed via magnetic resonance imaging angiography, and the patient was successfully treated with embolization of the fistula. Thus, we recommend reviewing ophthalmic vein enlargement that is readily identifiable through noncontrast CT for patients injured by craniofacial trauma to suspect the presence of delayed CCF at their initial presentation. [ABSTRACT FROM AUTHOR]

Background: Activated microglia release harmful substances to retinal ganglion cells (RGCs), but may also benefit by removing cellular debris and secreting neurotrophic factors. These paradoxical roles remain controversial because the nature and time-course of the injury that defines their role is unknown. The aim of this study was to determine if pharmacological manipulation of microglia to acquire a pro-inflammatory or pro-survival phenotype will exacerbate or enhance neuronal survival after injury.Material and methods: Treated HAP I (highly aggressively proliferating immortalized) microglia were injected into the vitreous or tail vein (T V) of female Sprague-Dawley rats. Retinas were examined at 4-14 days following optic nerve crush (ONC) and the number of surviving RGCs was determined.Results: Injection of untreated HAP I cells resulted in the greater loss of RGCs early after ONC when injected into the vitreous and later after ONC when injected into the T V. LP S activated HAP I cells injected into the vitreous resulted in greater RGC loss with and without injury. When injected into the T V with ONC there was no loss of RGCs 4 days after ONC but greater loss afterwards. Minocycline treated HAP I cells injected into the vitreous resulted in greater RGC survival than untreated HAP I cells. However, when injected into the T V with ONC there was greater loss of RGCs. These results suggest that optic nerve signals attract extrinsic microglia to the retina, resulting in a proinflammatory response.Conclusion: Neuroprotection or cytotoxicity of microglia depends on the type of activation, time course of the injury, and if they act on the axon or cell body. HAPI microglia migrate to the retina or optic nerve following optic nerve injury when injected into the vitreous or tail vein, respectively. Pretreatment with LPS or minocycline differentially effects retinal ganglion cell survival. In most cases, the result late in the injury process is greater retinal ganglion cell loss. We show here that neuroprotection is not solely determined by the microglial activation state but factors such as the environment and time-course of the injury. Culture microglia can be treated in vitro and then injected in vivo. The cells migrate to the site of injury, cell body of retinal ganglion cells if in the vitreous or to the optic nerve if injected in the tail vein. Retinal ganglion cell death is dependent on the location the microglia act, time-course of injury, and activation state. Proinflammatory microglia can be neuroprotective early in the injury when the primary site of action is on the axons whereas hypoactivated microglia are neuroprotective early in injury when they act on the soma. Later in the injury, both become detrimental. [ABSTRACT FROM AUTHOR]

A 6‐month‐old intact female mixed‐breed kitten presented with severe exophthalmos of the left eye. Periocular lesions, including subconjunctival haemorrhage, third eyelid protrusion, and left eyelid oedema, were detected in the absence of globe retropulsion. The left intraocular pressure was increased, and ocular ultrasonography revealed ipsilateral retrobulbar fluid. Coagulation panels were markedly prolonged and severe anaemia was detected. Ultrasound‐guided retrobulbar centesis performed to decrease intraocular pressure yielded blood. Based on the history and clinical findings, anticoagulant rodenticide intoxication was suspected. Treatment included partial tarsorrhaphy and the administration of topical antibiotics, artificial tears, and vitamin K1. Fresh whole blood and fresh frozen plasma were transfused for supportive therapy. Coagulation parameters improved after 7 days of hospitalisation. The periocular lesions resolved within 14 days, despite persistent optic nerve damage and blindness. This case report raises the possibility that anticoagulant rodenticide toxicity may result in retrobulbar haemorrhage in the absence of other typical cavitary bleeding. Although uncommon, anticoagulant rodenticide toxicity should be considered in cats with retrobulbar haemorrhage. [ABSTRACT FROM AUTHOR]

This document provides information on a condition called Superior Segmental Optic Nerve Hypoplasia (SSONH), also known as topless disc syndrome. It explains that SSONH is a congenital anomaly of the optic nerve head, characterized by underdeveloped superior nerve fibers. The article presents two cases of patients who were initially misdiagnosed with glaucoma but were later found to have SSONH. It emphasizes the importance of careful evaluation of the optic nerve in ophthalmic examinations and raises awareness about biases that can influence medical decision-making. The document also discusses the clinical features and diagnostic challenges of SSONH, highlighting the need for careful observation and consideration of all clinical features to accurately identify optic nerve abnormalities. [Extracted from the article]

BAX plays an essential role in retinal ganglion cell (RGC) death induced by optic nerve injury. Recently, we developed M109S, an orally bioactive and cytoprotective small compound (CPSC) that inhibits BAX-mediated cell death. We examined whether M109S can protect RGC from optic nerve crush (ONC)-induced apoptosis. M109S was administered starting 5 h after ONC for 7 days. M109S was orally administered in two groups (5 mg/kg twice a day or 7.5 mg/kg once a day). The retina was stained with anti-BRN3A and cleaved Caspase-3 (active Caspase-3) that are the markers of RGC and apoptotic cells, respectively. ONC decreased the number of BRN3A-positive RGC and increased the number of active Caspase-3-expressing apoptotic cells. In ONC-treated retina, there were cells that were double stained with anti-BRN3A and ant-cleaved Caspase-3, indicating that apoptosis in BRN3A-positive RGCs occurred. M109S inhibited the decrease of BRN3A-positive cells whereas it inhibited the increase of active Caspase-3-positive cells in the retina of ONC-treated mice, suggesting that M109S inhibited apoptosis in RGCs. M109S did not induce detectable histological damage to the lungs or kidneys in mice, suggesting that M109S did not show toxicities in the lung or kidneys when the therapeutic dose was used. The present study suggests that M109S is effective in rescuing damaged RGCs. Since M109S is an orally bioactive small compound, M109S may become the basis for a portable patient-friendly medicine that can be used to prevent blindness by rescuing damaged optic nerve cells from death. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) represents a complex pathology within the central nervous system (CNS), leading to severe sensory and motor impairments. It activates various signaling pathways, notably the mitogen‐activated protein kinase (MAPK) pathway. Present treatment approaches primarily focus on symptomatic relief, lacking efficacy in addressing the underlying pathophysiological mechanisms. Emerging research underscores the significance of the MAPK pathway in neuronal differentiation, growth, survival, axonal regeneration, and inflammatory responses post‐SCI. Modulating this pathway post‐injury has shown promise in attenuating inflammation, minimizing apoptosis, alleviating neuropathic pain, and fostering neural regeneration. Given its pivotal role, the MAPK pathway emerges as a potential therapeutic target in SCI management. This review synthesizes current knowledge on SCI pathology, delineates the MAPK pathway's characteristics, and explores its dual roles in SCI pathology and therapeutic interventions. Furthermore, it addresses the existing challenges in MAPK research in the context of SCI, proposing solutions to overcome these hurdles. Our aim is to offer a comprehensive reference for future research on the MAPK pathway and SCI, laying the groundwork for targeted therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Glaucoma stands as a prominent global cause of irreversible blindness and the primary treatment approach involves reducing intraocular pressure (IOP). However, around one-third of patients exhibit disease progression despite effective IOP reduction. Microvascular endothelial function, chronic inflammation, and oxidative stress are known to affect retinal neuronal networks and have been associated with disease severity and progression. Exercise training has the potential to counteract these mechanisms as add-on treatment to usual care. Aims: The HIT-GLAUCOMA study will investigate the effects of a 6-month highintensity interval training (HIIT) on intermediate endpoints such as local retinal microvascular and systemic large artery function, inflammation, and oxidative stress as well as clinical endpoints such as visual field indices, optic nerve rim assessment, retinal nerve fiber layer thickness, IOP, number of eye drops, visionrelated quality of life and ocular surface disease symptomatology. Methods: The study is a multi-center randomized controlled clinical trial in patients with both normal tension and high-tension primary open angle glaucoma. Across two study centers, 128 patients will be enrolled and randomized on a 1:1 basis into an exercise intervention group and a usual care control group. The primary microvascular endpoints are retinal arteriolar and venular flicker light-induced dilation at 6 months. The primary endpoint in the systemic circulation is brachial artery flow-mediated dilation at 6 months. Anticipated results: We hypothesize that exercise therapy will improve retinal microvascular function and thus ocular blood flow in patients with glaucoma. As clinical outcomes, we will investigate the effect of exercise on visual field indices, optic nerve rim assessment, retinal nerve fiber layer thickness, IOP, number of eye drops, vision-related quality of life and ocular surface disease symptomatology. Discussion: HIT-GLAUCOMA is a blueprint trial design to study the effect of exercise training on neurodegenerative and cardiovascular diseases. Importantly, patients are also expected to benefit from improvements in general health and cardiovascular co-morbidities. If proven effective, exercise may offer a new add-on treatment strategy to slow glaucoma progression. [ABSTRACT FROM AUTHOR]

The complex nature of the retina demands well-organized signaling to uphold signal accuracy and avoid interference, a critical aspect in handling a variety of visual stimuli. A-kinase anchoring proteins (AKAPs), known for binding protein kinase A (PKA), contribute to the specificity and efficiency of retinal signaling. They play multifaceted roles in various retinal cell types, influencing photoreceptor sensitivity, neurotransmitter release in bipolar cells, and the integration of visual information in ganglion cells. AKAPs like AKAP79/150 and AKAP95 exhibit distinct subcellular localizations, impacting synaptic transmission and receptor sensitivity in photoreceptors and bipolar cells. Furthermore, AKAPs are involved in neuroprotective mechanisms and axonal degeneration, particularly in retinal ganglion cells. In particular, AKAP6 coordinates stressspecific signaling and promotes neuroprotection following optic nerve injury. As our review underscores the therapeutic potential of targeting AKAP signaling complexes for retinal neuroprotection and enhancement, it acknowledges challenges in developing selective drugs that target complex protein--protein interactions. Overall, this exploration of AKAPs provides valuable insights into the intricacies of retinal signaling, offering a foundation for understanding and potentially addressing retinal disorders. [ABSTRACT FROM AUTHOR]

This article presents a study on optic neuritis (ON) induced by COVID-19, a condition characterized by inflammation of the optic nerve. The study included 13 hospitalized patients who experienced vision loss after a mild COVID-19 infection. The patients had an initial attack of ON but did not experience a relapse. The study found that involvement of certain segments of the optic nerve was associated with better visual recovery. Treatment with corticosteroids and plasmapheresis improved visual acuity and prognosis for most patients. However, the study had limitations due to a small sample size and short follow-up period, and further research is needed to confirm the significance of certain antibodies in these patients. [Extracted from the article]

Retinal neurodegenerative disease is a leading cause of blindness among the elderly in developed countries, including glaucoma, diabetic retinopathy, traumatic optic neuropathy and optic neuritis, etc. The current clinical treatment is not very effective. We investigated indirubin, one of the main bioactive components of the traditional Chinese medicine Danggui Longhui Pill, in the present study for its role in retinal neurodegeneration. Indirubin exhibited no detectable tissue toxicity in vivo or cytotoxicity in vitro. Moreover, indirubin improved visual function and ameliorated retinal neurodegeneration in mice after optic nerve crush injury in vivo. Furthermore, indirubin reduced the apoptosis of retinal ganglion cells induced by oxidative stress in vitro. In addition, indirubin significantly suppressed the increased production of intracellular reactive oxygen species and the decreased activity of superoxide dismutase induced by oxidative stress. Mechanically, indirubin played a neuroprotective role by regulating the PI3K/AKT/BAD/BCL-2 signaling. In conclusion, indirubin protected retinal ganglion cells from oxidative damage and alleviated retinal neurodegeneration induced by optic nerve crush injury. The present study provides a potential therapeutic medicine for retinal neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

This case series aims to report the manifestation of acute secondary optic neuropathy attributed to optic nerve injury associated with a singular episode of markedly elevated intraocular pressure (IOP) during an acute glaucoma attack. The correlation between acute primary angle-closure (APAC) and non-arteritic anterior ischemic optic neuropathy (NAION) remains uncertain within the context of current knowledge. Definitive conclusions regarding the causal relationship between APAC and NAION or their mutual influence cannot be established based on the current evidence. The association between these conditions is recognized as a potential link, and comprehensive research is imperative to elucidate their interrelationship thoroughly. This case series emphasizes the importance of promptly addressing acute optic nerve injury and neuropathy associated with elevated intraocular pressure (IOP) in patients with crowded disc anatomical risk factors. It underscores the need for proactive interventions to prevent irreversible damage, highlighting the infrequent yet vision-compromising occurrence of non-arteritic anterior ischemic optic neuropathy (NAION) in acute primary angle-closure (APAC). [ABSTRACT FROM AUTHOR]

To report a case of choroidal effusion and exudative retinal detachment following a non perforating Yttrium-Aluminium-Garnett (YAG)-laser iridotomy. Case report. A 53-year-old woman complains of sudden onset of blurred vision in her left eye 15 days after the attempt of YAG-laser peripheral iridotomy. Clinical examination revealed 3+ flare and 1+ cells in the anterior chamber, 2+ vitreous cells, swollen optic nerve, ciliochoroidal effusion, and exudative retinal detachment involving macular area in the left eye. After starting treatment with prednisone 25 mg once daily, choroidal effusion and retinal detachment were managed successfully without any surgical approach. Serous choroidal and exudative retinal detachments are rare complications following YAG-laser procedure. In our case, this clinical presentation occurs after a non perforating iridotomy. In medical practice, exudative retinal detachment should be always considered after YAG-laser iridotomy. [ABSTRACT FROM AUTHOR]

Background: The worldwide mortality and morbidity rates are highest for traumatic brain injury (TBI), which frequently involves damage to the cranial nerves (CNs). The occurrence of CN injury (CNI) in craniocerebral trauma ranges from 5 to 23%. Aims and Objectives: The objective of this study is to evaluate the occurrence of CNI in TBI patients within our population and determine the association between CN involvement and the severity of head injuries. In addition, we aim to assess the outcomes of patients who experience CNI in cases of head trauma. Materials and Methods: In our institution, a prospective observational analytical study was conducted from July 2022 to June 2023. The study included 100 patients aged over 1 year who had sustained head injuries. These patients were followed up for a period of 6 months. Results: Our study included a total of 100 patients, revealing that the highest number of head injuries occurred within the age range of 20-60 years, with an average age of 46 years. Among the study population, males accounted for 74%. Of these patients, 66 had mild head injuries, 22 had moderate head injuries, and 12 were admitted with severe head injuries. We discovered that 15% of TBI patients experienced CNIs. Specifically, five patients had a single CN palsy, while three patients had multiple CN palsies. Road traffic accidents accounted for 78% of the cases, making them the most common cause of injury, while low-velocity injuries only made up 22% of the cases. The facial nerve was the CN most frequently affected, followed by the olfactory nerve, optic nerve, and vestibulocochlear nerve. Among the 15 patients with CNI, seven had delayed symptoms, whereas eight patients presented with immediate symptoms. Conclusion: A substantial proportion of patients experience a delayed onset of CNI symptoms. Therefore, it is essential to perform a comprehensive neurological examination of all CNs during follow-up for all TBI patients. [ABSTRACT FROM AUTHOR]

Glaucoma is a complex and progressive disease that primarily affects the optic nerve axons, leading to irreversible vision loss. Although the exact molecular mechanisms underlying glaucoma pathogenesis are not fully understood, it is believed that except increased intraocular pressure, a combination of genetic and environmental factors play a role in the development of the disease. Animal models have been widely used in the study of glaucoma, allowing researchers to better understand the underlying mechanisms of the disease and test potential treatments. Several molecular pathways have been implicated in the pathogenesis of glaucoma, including oxidative stress, inflammation, and excitotoxic-induced neurodegeneration. This review summarizes the most important knowledge about molecular mechanisms involved in the glaucoma development. Although much research has been done to better understand the molecular mechanisms underlying this disease, there is still much to be learned to develop effective treatments and prevent vision loss in those affected by glaucoma. [ABSTRACT FROM AUTHOR]

Neural progenitor cells (NPCs) derived from human pluripotent stem cells(hPSCs) provide major cell sources for repairing damaged neural circuitry and enabling axonal regeneration after spinal cord injury (SCI). However, the injury niche and inadequate intrinsic factors in the adult spinal cord restrict the therapeutic potential of transplanted NPCs. The Sonic Hedgehog protein (Shh) has crucial roles in neurodevelopment by promoting the formation of motorneurons and oligodendrocytes as well as its recently described neuroprotective features in response to the injury, indicating its essential role in neural homeostasis and tissue repair. In this study, we demonstrate that elevated SHH signaling in hNPCs by inhibiting its negative regulator, SUFU, enhanced cell survival and promoted robust neuronal differentiation with extensive axonal outgrowth, counteracting the harmful effects of the injured niche. Importantly, SUFU inhibition in NPCs exert non-cell autonomous effects on promoting survival and neurogenesis of endogenous cells and modulating the microenvironment by reducing suppressive barriers around lesion sites. The combined beneficial effects of SUFU inhibition in hNPCs resulted in the effective reconstruction of neuronal connectivity with the host and corticospinal regeneration, significantly improving neurobehavioral recovery in recipient animals. These results demonstrate that SUFU inhibition confers hNPCs with potent therapeutic potential to overcome extrinsic and intrinsic barriers in transplantation treatments for SCI. [ABSTRACT FROM AUTHOR]

Microglia-mediated neuroinflammatory responses are recognized as a predominant factor during high intraocular pressure (IOP)-induced retinal and optic nerve injury along with potential therapeutic targets for the disease. Our previous research indicated that mesenchymal stem cell (MSC) treatment could reduce high IOP-induced neuroinflammatory responses through the TLR4 pathway in a rat model without apparent cell replacement and differentiation, suggesting that the anti-neuroinflammatory properties of MSCs are potentially mediated by paracrine signaling. This study aimed to evaluate the anti-neuroinflammatory effect of human adipose tissue-derived extracellular vesicles (ADSC-EVs) in microbead-induced ocular hypertension (OHT) animals and to explore the underlying mechanism since extracellular vesicles (EVs) are the primary transporters for cell secretory action. The anti-neuroinflammatory effect of ADSC-EVs on LPS-stimulated BV-2 cells in vitro and OHT-induced retinal and optic nerve injury in vivo was investigated. According to the in vitro research, ADSC-EV treatment reduced LPS-induced microglial activation and the TLR4/NF-κB proinflammatory cascade response axis in BV-2 cells, such as CD68, iNOS, TNF-α, IL-6, and IL-1β, TLR4, p-38 MAPK, NF-κB. According to the in vivo data, intravitreal injection of ADSC-EVs promoted RGC survival and function, reduced microglial activation, microglial-derived neuroinflammatory responses, and TLR4/MAPK/NF-κB proinflammatory cascade response axis in the OHT mice. Our findings provide preliminary evidence for the RGC protective and microglia-associated neuroinflammatory reduction effects of ADSC-EVs by inhibiting the TLR4/MAPK/NF-κB proinflammatory cascade response in OHT mice, indicating the therapeutic potential ADSC-EVs or adjunctive therapy for glaucoma. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) have been recognized as prevalent contributors to the development of inner retinal injuries including optic neuropathies such as glaucoma, non‐arteritic anterior ischemic optic neuropathy, traumatic optic neuropathy, and Leber hereditary optic neuropathy, among others. This underscores the pivotal significance of oxidative stress in the damage inflicted upon retinal tissue. To combat ROS‐related challenges, this study focuses on creating an injectable and tissue‐adhesive hydrogel with tailored antioxidant properties for retinal applications. GelCA, a gelatin‐modified hydrogel with photo‐crosslinkable and injectable properties, is developed. To enhance its antioxidant capabilities, curcumin‐loaded polydopamine nanoparticles (Cur@PDA NPs) are incorporated into the GelCA matrix, resulting in a multifunctional nanocomposite hydrogel referred to as Cur@PDA@GelCA. This hydrogel exhibits excellent biocompatibility in both in vitro and in vivo assessments, along with enhanced tissue adhesion facilitated by NPs in an in vivo model. Importantly, Cur@PDA@GelCA demonstrates the potential to mitigate oxidative stress when administered via intravitreal injection in retinal injury models such as the optic nerve crush model. These findings underscore its promise in advancing retinal tissue engineering and providing an innovative strategy for acute neuroprotection in the context of inner retinal injuries. [ABSTRACT FROM AUTHOR]

Background: Klippel–Feil syndrome is a rare congenital bone disorder characterized by an abnormal fusion of two or more cervical spine vertebrae. Individuals with Klippel–Feil syndrome exhibit diverse clinical manifestations, including skeletal irregularities, visual and hearing impairments, orofacial anomalies, and anomalies in various internal organs, such as the heart, kidneys, genitourinary system, and nervous system. Case presentation: This case report describes a 12-year-old Pashtun female patient who presented with acute bilateral visual loss. The patient had Klippel–Feil syndrome, with the typical clinical triad symptoms of Klippel–Feil syndrome, along with Sprengel's deformity. She also exhibited generalized hypoalgesia, which had previously resulted in widespread burn-related injuries. Upon examination, bilateral optic disc swelling was observed, but intracranial pressure was found to be normal. Extensive investigations yielded normal results, except for hypocalcemia and low vitamin D levels, while parathyroid function remained within the normal range. Visual acuity improved following 2 months of calcium and vitamin D supplementation, suggesting that the visual loss and optic nerve swelling were attributed to hypocalcemia. Given the normal parathyroid function, it is possible that hypocalcemia resulted from low vitamin D levels, which can occur after severe burn scarring. Furthermore, the patient received a provisional diagnosis of congenital insensitivity to pain on the basis of the detailed medical history and the findings of severe and widespread loss of the ability to perceive painful stimuli, as well as impaired temperature sensation. However, due to limitations in genetic testing, confirmation of the congenital insensitivity to pain diagnosis could not be obtained. Conclusion: This case highlights a rare presentation of transient binocular vision loss and pain insensitivity in a patient with Klippel–Feil syndrome, emphasizing the importance of considering unusual associations in symptom interpretation. [ABSTRACT FROM AUTHOR]

Glaucoma is a leading cause of blindness worldwide, with a marked increase in prevalence with advancing age. Due to the multifactorial nature of glaucoma pathogenesis, dissecting how ageing impacts upon glaucoma risk requires analysis and synthesis of evidence from a vast literature. While there is a wealth of human clinical studies examining glaucoma pathogenesis and why older patients have increased risk, many aspects of the disease such as adaptations of retinal ganglion cells to stress, autophagy and the role of glial cells in glaucoma, require the use of animal models to study the complex cellular processes and interactions. Additionally, the accelerated nature of ageing in rodents facilitates the longitudinal study of changes that would not be feasible in human clinical studies. This review article examines evidence derived predominantly from rodent models on how the ageing process impacts upon various aspects of glaucoma pathology from the retinal ganglion cells themselves, to supporting cells and tissues such as glial cells, connective tissue and vasculature, in addition to oxidative stress and autophagy. An improved understanding of how ageing modifies these factors may lead to the development of different therapeutic strategies that target specific risk factors or processes involved in glaucoma. [ABSTRACT FROM AUTHOR]

Two recent cases of central retinal artery occlusion under otherwise uncomplicated sub-Tenon's block that resulted in significant visual loss after cataract surgery prompted us to undertake a literature review of such cases. We identified 97 cases of retinal artery occlusion after ophthalmic surgery under regional anaesthesia that had no immediate signs of block-related complications. These occurred after various intraocular (87%) and extraocular (13%) operations, across a wide range of ages (19–89 years) on patients with (59%) or without (39%) known risk factors. The anaesthetic techniques included 40 retrobulbar blocks, 36 peribulbar blocks, 19 sub-Tenon's blocks, one topical anaesthetic and one unspecified local anaesthetic. Different strengths of lidocaine, bupivacaine, mepivacaine and ropivacaine, either alone or in various combinations, were used. The details of the anaesthetic techniques were often incomplete in the reports, which made comparison and analysis difficult. Only nine cases had their cause (optic nerve sheath injury) identified, while the mechanism of injury was unclear in the remaining patients. Various mechanisms were postulated; however, the cause was likely to be multifactorial due to patient, surgical and anaesthetic risk factors, especially in those with compromised retinal circulation. As there were no definite risk factors identified, no specific recommendations could be made to avoid this devastating outcome. We have provided rationales for some general considerations, which may reduce this risk, and propose anaesthetic options for ophthalmic surgery on the fellow eye if required, based both on our literature review and our personal experience. [ABSTRACT FROM AUTHOR]

Introduction: The inflammatory response after spinal cord injury (SCI) is an important contributor to secondary damage. Infiltrating macrophages can acquire a spectrum of activation states, however, the microenvironment at the SCI site favors macrophage polarization into a pro-inflammatory phenotype, which is one of the reasons why macrophage transplantation has failed. Methods: In this study, we investigated the therapeutic potential of the macrophage secretome for SCI recovery. We investigated the effect of the secretome in vitro using peripheral and CNS-derived neurons and human neural stem cells. Moreover, we perform a pre-clinical trial using a SCI compression mice model and analyzed the recovery of motor, sensory and autonomic functions. Instead of transplanting the cells, we injected the paracrine factors and extracellular vesicles that they secrete, avoiding the loss of the phenotype of the transplanted cells due to local environmental cues. Results: We demonstrated that different macrophage phenotypes have a distinct effect on neuronal growth and survival, namely, the alternative activation with IL- 10 and TGF-β1 (M(IL-10+TGF-β1)) promotes significant axonal regeneration. We also observed that systemic injection of soluble factors and extracellular vesicles derived from M(IL-10+TGF-β1) macrophages promotes significant functional recovery after compressive SCI and leads to higher survival of spinal cord neurons. Additionally, the M(IL-10+TGF-β1) secretome supported the recovery of bladder function and decreased microglial activation, astrogliosis and fibrotic scar in the spinal cord. Proteomic analysis of the M(IL-10+TGF-β1)-derived secretome identified clusters of proteins involved in axon extension, dendritic spine maintenance, cell polarity establishment, and regulation of astrocytic activation. Discussion: Overall, our results demonstrated that macrophages-derived soluble factors and extracellular vesicles might be a promising therapy for SCI with possible clinical applications. [ABSTRACT FROM AUTHOR]

Regulatory programs governing neuronal death and axon regeneration in neurodegenerative diseases remain poorly understood. In adult mice, optic nerve crush (ONC) injury by severing retinal ganglion cell (RGC) axons results in massive RGC death and regenerative failure. We performed an in vivo CRISPR-Cas9-based genome-wide screen of 1,893 transcription factors (TFs) to seek repressors of RGC survival and axon regeneration following ONC. In parallel, we profiled the epigenetic and transcriptional landscapes of injured RGCs by ATAC-seq and RNA-seq to identify injury-responsive TFs and their targets. These analyses converged on four TFs as critical survival regulators, of which ATF3/CHOP preferentially regulate pathways activated by cytokines and innate immunity and ATF4/C/EBPγ regulate pathways engaged by intrinsic neuronal stressors. Manipulation of these TFs protects RGCs in a glaucoma model. Our results reveal core transcription programs that transform an initial axonal insult into a degenerative process and suggest novel strategies for treating neurodegenerative diseases.

In this issue of Neuron, three studies establish new strategies to uncover mediators of retinal neuroprotection and optic nerve regeneration. Tian et al. (2022) carry out a multi-omics screen and identify transcriptional regulators of axon injury signaling leading to cell death; Jacobi et al. (2022) and Li et al. (2022) combine retrograde tracing and single-cell RNA-seq (scRNA-seq) to uncover molecular targets for axon regeneration.

Optic neuropathies, characterized by injury of retinal ganglion cell (RGC) axons of the optic nerve, cause incurable blindness worldwide. Mesenchymal stem cell–derived small extracellular vesicles (MSC-sEVs) represent a promising “cell-free” therapy for regenerative medicine; however, the therapeutic effect on neural restoration fluctuates, and the underlying mechanism is poorly understood. Here, we illustrated that intraocular administration of MSC-sEVs promoted both RGC survival and axon regeneration in an optic nerve crush mouse model. Mechanistically, MSC-sEVs primarily targeted retinal mural cells to release high levels of colony-stimulating factor 3 (G-CSF) that recruited a neural restorative population of Ly6Clow monocytes/monocyte-derived macrophages (Mo/MΦ). Intravitreal administration of G-CSF, a clinically proven agent for treating neutropenia, or donor Ly6Clow Mo/MΦ markedly improved neurological outcomes in vivo. Together, our data define a unique mechanism of MSC-sEV-induced G-CSF-to-Ly6Clow Mo/MΦ signaling in repairing optic nerve injury and highlight local delivery of MSC-sEVs, G-CSF, and Ly6Clow Mo/MΦ as therapeutic paradigms for the treatment of optic neuropathies [ABSTRACT FROM AUTHOR]

Background: Visual field defect (VFD) refers to the phenomenon that the eye is unable to see a certain area within the normal range of vision, which may be caused by eye diseases, neurological diseases and other reasons. Transcranial direct current stimulation (tDCS) is expected to be an effective treatment for the recovery or partial recovery of VFD. This paper describes the potential for tDCS in combination with visual retraining strategies to have a positive impact on vision recovery, and the potential for neuroplasticity to play a key role in vision recovery. Methods: This case report includes two patients. Patient 1 was diagnosed with a right occipital hemorrhage and homonymous hemianopia. Patient 2 had multiple facial fractures, a contusion of the right eye, and damage to the optic nerve of the right eye, which was diagnosed as a peripheral nerve injury (optic nerve injury). We administered a series of treatments to two patients, including transcranial direct current stimulation; visual field restoration rehabilitation: paracentric gaze training, upper and lower visual field training, VR rehabilitation, and perceptual training. One time per day, 5 days per week, total 6 weeks. Results: After 6 weeks of visual rehabilitation and tDCS treatment, Patient 1 Humphrey visual field examination showed a significant improvement compared to the initial visit, with a reduction in the extent of visual field defects, increased visual acuity, and improvement in most visual functions. Patient 2 had an expanded visual field, improved visual sensitivity, and substantial improvement in visual function. Conclusion: Our case reports support the feasibility and effectiveness of tDCS combined with visual rehabilitation training in the treatment of occipital stroke and optic nerve injury settings. [ABSTRACT FROM AUTHOR]

Glaucoma is a complex neurodegenerative disorder characterized by the progressive loss of retinal ganglion cells (RGC) and optic nerve axons, leading to irreversible visual impairment. Despite its clinical significance, the underlying mechanisms of glaucoma pathogenesis remain poorly understood. In this study, we aimed to unravel the multifaceted nature of glaucoma by investigating the interaction between T cells and retinas. By utilizing clinical samples, murine glaucoma models, and T cell transfer models, we made several key findings. Firstly, we observed that CD4+ T cells from glaucoma patients displayed enhanced activation and a bias towards T helper (Th) 1 responses, which correlated with visual impairment. Secondly, we identified the infiltration of Th1 cells into the retina, where they targeted RGC and integrated into the pro-inflammatory glial network, contributing to progressive RGC loss. Thirdly, we discovered that circulating Th1 cells upregulated vascular cell adhesion protein 1 (VCAM-1) on retinal microvessels, facilitating their entry into the neural retina. Lastly, we found that Th1 cells underwent functional reprogramming before reaching the retina, acquiring a phenotype associated with lymphocyte migration and neurodegenerative diseases. Our study provides novel insights into the role of peripheral CD4+ T cells in glaucoma pathogenesis, shedding light on the mechanisms underlying their infiltration into the retina and offering potential avenues for innovative therapeutic interventions in this sight-threatening disease. [ABSTRACT FROM AUTHOR]

This article discusses the importance of the falciform ligament (FL) in decompression procedures. The FL is a dural extension that covers the optic nerve and ophthalmic artery. In certain pathological conditions, such as ICA dilatation and optic nerve meningiomas, the optic nerve can be compressed against the FL, leading to visual deficits. The study found that stenotic proximal optic canals, which can cause optic nerve compression, were due to ossification of the FL. The authors emphasize the need for knowledge of the FL's histological composition to ensure its safe release during surgery. [Extracted from the article]

Retinal ganglion cells (RGCs) are specialized projection neurons that constitute part of the retina, and the death of RGCs causes various eye diseases, but the mechanism of RGC death is still unclear. Here, we induced cell death in human induced pluripotent stem cell (hiPSC)-derived RGC-rich retinal tissues using hypoxia–reoxygenation in vitro. Flow cytometry, immunochemistry, and Western blotting showed the apoptosis and necrosis of RGCs under hypoxia–reoxygenation, and they were rescued by an apoptosis inhibitor but not by a necrosis inhibitor. This revealed that the cell death induced in our model was mainly due to apoptosis. To our knowledge, this is the first model to reproduce ischemia–reperfusion in hiPSC-derived RGCs. Thus, the efficacy of apoptosis inhibitors and neuroprotective agents can be evaluated using this model, bringing us closer to clinical applications. [ABSTRACT FROM AUTHOR]

This document is a collection of abstracts from the Asian Journal of Ophthalmology. The first abstract discusses a retrospective study conducted at a tertiary eye care center in South India, analyzing the prevalence, clinical presentation, and treatment modalities of childhood glaucoma. The study found that secondary glaucoma was the most common type, with glaucoma associated with acquired conditions being the most prevalent. Trabeculectomy was the most common surgery performed for primary childhood glaucoma. The second abstract presents a case series on the successful outcomes of MicroPulse laser trabeculoplasty (MLT) in primary open-angle glaucoma patients who had previously undergone glaucoma surgery. MLT was found to reduce the need for antiglaucoma eye drops and maintain stable intraocular pressure. [Extracted from the article]

Aims: Nerve growth factor is a well characterised neurotrophic factor that play a critical role in the survival, growth and differentiation of neurons both in central and peripheral nervous system. However, it is difficult for the conventional exogenous nerve growth factor administration delivery to the central nervous system due to the biological barrier in human bodies. Results: We validated a series of cell penetrating peptides and found that L-PenetraMax significantly enhanced the efficiency of recombinant human nerve growth factor entry into the rat retina. In the optic nerve crush mice model, eye drop administration of recombinant human nerve growth factor alone promoted retinal ganglion cell survival and axon regeneration at high dose, while the combination of recombinant human nerve growth factor with L-PenetraMax significantly enhanced the neuroprotective efficacy at lower dose, thus potentially enhancing the availability of recombinant human nerve growth factor eye drops in patients with optic neuropathy. Conclusions: This study provides the evidence that the noncovalent coadministration of recombinant human nerve growth factor with L-PenetraMax could be a potent strategy for the non-invasive and sustained ocular delivery of therapeutic proteins for improving the optic nerve injury. [ABSTRACT FROM AUTHOR]

IgG4-related disease (IgG4-RD) is an immune-mediated multi-system disorder. The nervous system (IgG4-RND) is rarely affected. We describe a short case series. We performed an ambispective analysis of IgG4-RND patients admitted at our centre between January 2016 and December 2022. Eight patients (M: F-2:6) were included with a mean age at presentation of 40.63 ± 17.88 years and disease duration of 5.16 ± 4.08 years. The common diseased sites were pachymeninges (7), orbits (4), paranasal sinuses (3), frontal lobe (1), hypophysis (1), leptomeninges (1), and middle ear (1). Common symptoms were headache and cranial neuropathy. The common nerves involved were the optic nerve, followed by the third, fifth, sixth, and seventh. Cerebrospinal fluid showed lymphocytic pleocytosis. Histopathology showed lymphoplasmacytic infiltrate (8), fibrosis (5), >10 IgG4 + cells (7), and IgG4/IgG >40% (6). Six had a relapsing course. The rituximab-based treatment regimen showed a favourable response. [ABSTRACT FROM AUTHOR]

This article discusses the use of radiation therapy as a treatment strategy for patients with secondary central nervous system lymphoma (SCNSL) who are undergoing CAR T-cell therapy. SCNSL is a rare and aggressive form of lymphoma, and CAR T-cell therapy has shown promise in treating other types of lymphoma. The article presents the early experience of using radiation therapy in combination with CAR T-cell therapy for SCNSL patients and discusses the outcomes and response rates. The study found that radiation therapy resulted in good local control without significant side effects, but more research is needed to determine the best use of radiation therapy in this patient population. [Extracted from the article]

Background: Optical coherence tomography angiography (OCTA) allows noninvasive assessment of retinal vessel structures. Thinning and loss of retinal vessels is evident in eyes of patients with multiple sclerosis (MS) and might be associated with a proinflammatory disease phenotype and worse prognosis. We investigated whether changes of the retinal vasculature are linked to brain atrophy and disability in MS. Material and methods: This study includes one longitudinal observational cohort (n=79) of patients with relapsing-remitting MS. Patients underwent annual assessment of the expanded disability status scale (EDSS), timed 25-foot walk, symbol digit modalities test (SDMT), retinal optical coherence tomography (OCT), OCTA, and brain MRI during a follow-up duration of at least 20 months. We investigated intra-individual associations between changes in the retinal architecture, vasculature, brain atrophy and disability. Eyes with a history of optic neuritis (ON) were excluded. Results: We included 79 patients with a median disease duration of 12 (interquartile range 2 - 49) months and a median EDSS of 1.0 (0 - 2.0). Longitudinal retinal axonal and ganglion cell loss were linked to grey matter atrophy, cortical atrophy, and volume loss of the putamen. We observed an association between vessel loss of the superficial vascular complex (SVC) and both grey and white matter atrophy. Both observations were independent of retinal ganglion cell loss. Moreover, patients with worsening of the EDSS and SDMT revealed a pronounced longitudinal rarefication of the SVC and the deep vascular complex. Discussion: ON-independent narrowing of the retinal vasculature might be linked to brain atrophy and disability in MS. Our findings suggest that retinal OCTA might be a new tool for monitoring neurodegeneration during MS. [ABSTRACT FROM AUTHOR]

Background: Papilledema is thought to be the hallmark sign of increased intracranial pressure (ICP). Distension of the subarachnoid space within the optic nerve sheath is also commonly reported in MR studies as an indirect sign of increased ICP. Hypothesis: General anesthesia and positive pressure ventilation might result in changes in optic sheath diameter (OSD) observed on clinical brain MRI. Study Type: Retrospective. Population: One hundred forty‐five patients (154 MRI scans, 7.3 years ± 5.1); 97 studies in the anesthesia group (4.4 years ± 3.4) of which 22 had papilledema, and 57 in the non‐anesthesia group (12.3 years ± 3.2), of which 28 had papilledema. Field Strength/Sequence: 1.5T or 3.0T volumetric T2 images. T2 images were obtained from different vendors. Assessment: OSD, optic nerve diameter (OND), and peri‐optic cerebrospinal fluid (CSF) were measured manually on T2‐weighted MR images for various population subgroups (with and without anesthesia; with or without papilledema). The correlation between these measurements and the clinical diagnosis of papilledema was evaluated via receiver operating characteristic (ROC) analysis. Statistical Tests: Chi‐square test; Mann–Whitney Test; Spearman's test and ROCs; Interclass correlation coefficient, P = 0.05. Results: General anesthesia resulted in significantly larger mean OSD in patients with or without papilledema (7.3 ± 1.0 mm vs. 6.1 ± 1.1 mm and 6.7 ± 1.0 mm vs. 5.4 ± 0.9 mm, respectively). In the non‐anesthesia group, the average OSD values (6.1 ± 1.1 mm) were significantly higher in papilledema patients compared to non‐papilledema patients (5.4 ± 0.9 mm), with larger peri‐optic CSF rim (1.6 ± 0.4 mm vs. 1.3 ± 0.3 mm). In the anesthesia group, OND was significantly larger in papilledema patients (3.4 ± 0.4 mm vs. 3.1 ± 0.5 mm), though the average peri‐optic CSF rim did not reach a significance in papilledema compared with non‐papilledema patients (2.0 ± 0.3 mm vs. 1.8 ± 0.4 mm, P = 0.06). In patients with general anesthesia, peri‐optic CSF rim had a limited correlation with increased ICP. Data Conclusion: In the pediatric population, imaging findings of increased OSD on brain MRI might be related to general anesthesia rather than increased ICP. The interpretation of optic nerve sheath distention should be reported cautiously in conjunction with anesthesia status, especially in the pediatric population. Evidence Level: 4 Technical Efficacy: 5 [ABSTRACT FROM AUTHOR]

Glaucoma is one of the main causes of irreversible blindness in the world. The most common form, primary open-angle glaucoma, is an optic neuropathy that is characterized by a progressive loss of retinal ganglion cells and their axons, leading to structural changes in the optic nerve head and associated visual field defects. Elevated intraocular pressure remains the most important modifiable risk factor for primary open-angle glaucoma. However, a significant proportion of patients develop glaucomatous damage in the absence of increased intraocular pressure, a condition known as normal-tension glaucoma (NTG). The pathophysiology underlying NTG remains unclear. Several studies have revealed that vascular and cerebrospinal fluid (CSF) factors may play significant roles in the development of NTG. Vascular failure caused by functional or structural abnormalities, and compartmentation of the optic nerve subarachnoid space with disturbed CSF dynamics have been shown to be associated with NTG. In the present article, based on the concept of the glymphatic system and observations in patients with NTG, we hypothesize that failure of fluid transport via the glymphatic pathway in the optic nerve may be involved in the pathogenesis of some if not many cases of NTG. According to this hypothesis, vascular and CSF factors may share reduced glymphatic transport and perivascular waste clearance in the optic nerve as a final common pathway leading to the development of NTG. In addition, we speculate that some cases of NTG may reflect glymphatic dysfunction in natural brain aging and central nervous system diseases, such as Alzheimer's disease. Clearly, further studies are needed to gain additional insight into the relative contribution of these factors and conditions to reduced glymphatic transport in the optic nerve. [ABSTRACT FROM AUTHOR]