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Lenadogene nolparvovec is a gene therapy which has been developed to treat Leber hereditary optic neuropathy (LHON) caused by a point mutation in the mitochondrial NADH dehydrogenase 4 (ND4) gene. Clinical trials have demonstrated a significant improvement of visual acuity up to 5 years after treatment by lenadogene nolparvovec but, surprisingly, unilateral treatment resulted in bilateral improvement of vision. This contralateral effect – similarly observed with other gene therapy products in development for MT-ND4-LHON – is supported by the migration of viral vector genomes and their transcripts to the contralateral eye, as reported in animals, and post-mortem samples from two patients. In this study, we used an AAV2 encoding fluorescent proteins targeting mitochondria to investigate whether these organelles themselves could transfer from the treated eye to the fellow one. We found that mitochondria travel along the visual system (optic chiasm and primary visual cortex) and reach the contralateral eye (optic nerve and retina) in physiological conditions. We also observed that, in a rotenone-induced model of retinal damage mimicking LHON, mitochondrial transfer from the healthy to the damaged eye was accelerated and enhanced. Our results thus provide a further explanation for the contralateral beneficial effect observed during clinical studies with lenadogene nolparvovec.

Objective: The aim of this study was to evaluate the effects of rapid maxillary expansion on the optic nerve sheath diameter and to examine its possible effects on intracranial pressure. Design: 20 patients with bilateral crossbite were selected. Hyrax Expander was applied and activated twice daily until the overcorrection was achieved. The optic nerve sheath diameter (ONSD) was measured via ultrasonography before the first activation (T0), then repeated after 1 (T1) and 10 min (T2). At the end of the expansion, ONSD was measured (T3) again, then the screw was activated for the last time, and measurements were repeated after 1 (T4) and 10 min (T5). The Friedman test was performed to compare the changes, and The Wilcoxon Signed-Rank test was done to determine the significant intergroup changes (p

المخلص: أهداف البحث: يعد فهم تشريح الجيوب الأنفية أمرا بالغ الأهمية لتخطيط الجراحة قبل العملية. تهدف هذه الدراسة إلى تقييم العلاقة بين التغيرات التشريحية للجيوب الجبهية والتهاب الجيوب الأنفية المزمن باستخدام الأشعة المقطعية. طرق البحث: أجريت دراسة وصفية على المرضى الذين يعانون من التهاب الجيوب الأنفية المزمن، والذين أحيلوا لإجراء الأشعة المقطعية إلى قسم التشخيص بالأشعة والتصوير، وتمت مقارنة المعلمات بين مجموعات الدراسة والسيطرة. النتائج: من بين التغيرات التشريحية، كانت وجود أجزاء مساعدة مكررة داخل الجيب الجبهي، وانحسار وبروز الشريان السباتي الداخلي والعصب البصري مرتفعة في الذكور والإناث من الحالات مقارنة بالمجموعة المرجعية. بين التغيرات التشريحية في منطقة الجيوب الأنفية للمشاركين الذكور في مجموعات الدراسة، كان هناك ارتباط كبير مع بروز العصب البصري وانحساره. أظهر بروز العصب البصري في الذكور خطرا أعلى للإصابة بالتهاب الجيوب الأنفية المزمن بين مجموعة الدراسة. الاستنتاجات: توفر المعرفة حول التغيرات التشريحية في الجيوب الجبهية فهما أفضل لحدود الاستئصال الجراحي خلال علاج جراحات الجيوب الجبهية. Abstract: Computerized tomography (CT) of the skull base region has become an indispensable tool for endoscopic sinonasal surgery. Objectives: Fundamental knowledge of the sinus anatomy is crucial for preoperative surgical planning. The aim of this research was to evaluate associations between the anatomical variations sphenoidal sinuses and chronic rhinosinusitis (CRS) by using CT. Methods: A descriptive study was performed on patients with CRS, who were referred to the department of radiodiagnosis and imaging for CT scanning. Parameters were compared between the study and control groups. Results: Among the anatomical variations, the presence of bilateral accessory septa within the sphenoidal sinus, and dehiscence and protrusion of the internal carotid artery and optic nerve (ON), were high in men and women in the case group compared with the control group. Among the anatomical variations in the sinonasal region of the male participants, a significant association (p

The manuscript describes a case of Cavernous Malformation in the optic pathway which is extremely rare, accounting for less than 1% of central nervous system cavernomas. This case report highlights a patient initially diagnosed with a glioma, but subsequent MRI changes and extensive analysis ruled in favor of a hemorrhagic optic neuropathy caused by an optic nerve cavernoma. The patient experienced temporary vision loss but fully regained her vision within a week. Based on clinical, biochemical, and radiological findings, it was confirmed as a rare case of optic nerve cavernoma, and the patient was managed expectantly due to her complete recovery of vision. Follow-up imaging after 1 year indicated a stable lesion with evolving characteristics consistent with a cavernoma. This study provides an informative review of the condition and highlights the key radiologic features of this disease.

Introduction: Determining whether a neurovascular conflict (NVC) involving the anterior visual pathway (AVP) and a non-diseased intracranial artery is amenable for microvascular decompression is challenging. Moreover, it is unclear whether microvascular decompression of the optic nerve is an effective therapy. Research question: What are the outcomes of different treatment strategies for NVCs involving the AVP and a non-diseased intracranial artery? Material and methods: Data on patients with symptomatic NVCs involving the AVP and a non-diseased intracranial artery was collected and included treatment and outcome parameters. The case series was drafted in accordance with the CARE guidelines. Results: Three patients aged 53,53 and 55 visited our out-patient clinic with a suspected symptomatic NVC between the optic nerve and a non-diseased intracranial artery. A conservative treatment was opted for in the first patient aimed at treating her glaucoma, with temporary improvement of symptoms. Microvascular decompression of the optic nerve was performed in two patients. One operated patient developed post-operative complications resulting in posterior circulation perfusion decline, while the other experienced a worse tunnel vision with a decrease in visual acuity. Discussion and conclusion: The diagnosis of a symptomatic NVC between the AVP and a non-diseased intracranial artery should be considered with caution, i.e. after exclusion of all other causes. Microvascular decompression can be performed but does not necessarily improve symptoms. A better understanding of the pathophysiological mechanisms underlying these NVCs is warranted to determine the benefit of microvascular decompression of the optic nerve.

Purpose: To describe a case of linezolid toxic optic neuropathy in a 71-year-old female and review the relevant literature. Observations: An adult female with progressive, symmetric vision loss was hypothesized to have linezolid toxic optic neuropathy. Following cessation of linezolid, the patient experienced improvement in visual function over two months. Conclusions and importance: Patients diagnosed with linezolid toxic optic neuropathy can expect some return of visual function after cessation. The degree of return does not correlate to the cumulative dose of the drug. The goal of this study was to summarize and add to the current body of literature on the topic.

Pilocytic astrocytoma (PA) is categorized as grade I gliomas with a good prognosis. Although PA mostly occurs in the cerebellum, it also can occur in the orbital and mostly presents as a cystic tumor with a mural nodule. PA often presents in the second decade of life, with 75% occurring under the age of 20 years. This case report describes a 10-year-old boy presented a left eye tumor for over 3 years. MRI examination showed unrestricted intraconal lesions in the optic nerve, visible from the optic canal to the anterior with well-defined borders. The excised tumor specimen depicted a nodular tumor tissue, measuring 35 × 28 × 20 mm, weighing 11 grams, solid with gray and white. The microscopic examination showed a classical biphasic pattern including combinations of loose glial tissue and compact pyloid tissue. Hispathology result revealed a pilocytic astrocytoma.

Objective: Pediatric glaucoma is a rare disease that is potentially more severe than adult glaucoma because it is more challenging to diagnose and more difficult to treat. The segmented retinal layer has been shown to have excellent capability in assessing adult glaucoma. However, there is limited information regarding the benefits of spectral domain-optical coherence tomography (SD-OCT) in children. Thus, our study aims to investigate the role of circumpapillary (cp) OCT analysis in examining pediatric glaucoma and characterizing the changes in the fellow eyes of glaucomatous children. Methods: SD-OCT was used to investigate the optic nerve head (ONH) and retinal morphology of 18 patients with pediatric glaucoma and 14 matched healthy controls. Results: As predicted, pediatric patients with glaucoma had a wider disk diameter, cup diameter, and cup-to-disk ratio (CDR). Pediatric glaucoma also resulted in a thinner retinal nerve fiber layer (RNFL), ganglion cell layer – inner plexiform layer (GCL-IPL), photoreceptor layer – retinal pigment epithelium (PRL-RPE), and total retinal layer (TRL). Similarly, these observations were found in the fellow eyes of glaucomatous children. Our finding also indicated that cpRNFL, GC-IPL, and PRL-RPE thickness were useful for the early identification of pediatric glaucoma. Conclusion: In conclusion, SD-OCT could be implemented in managing glaucoma in young children. Moreover, retinal layer damage at the corresponding locations of the fellow eye is similarly detected in the glaucomatous eye.

Zebrafish (Danio rerio) have the capacity for successful adult optic nerve regeneration. In contrast, mammals lack this intrinsic ability and undergo irreversible neurodegeneration seen in glaucoma and other optic neuropathies. Optic nerve regeneration is often studied using optic nerve crush, a mechanical neurodegenerative model. Untargeted metabolomic studies within successful regenerative models are deficient. Evaluation of tissue metabolomic changes in active zebrafish optic nerve regeneration can elucidate prioritized metabolite pathways that can be targeted in mammalian systems for therapeutic development. Female and male (6 month to 1 year old wild type) right zebrafish optic nerves were crushed and collected three days after. Contralateral, uninjured optic nerves were collected as controls. The tissue was dissected from euthanized fish and frozen on dry ice. Samples were pooled for each category (female crush, female control, male crush, male control) and pooled at n = 31 to obtain sufficient metabolite concentrations for analysis. Optic nerve regeneration at 3 days post crush was demonstrated by microscope visualization of GFP fluorescence in Tg(gap43:GFP) transgenic fish. Metabolites were extracted using a Precellys Homogenizer and a serial extraction method: (1) 1:1 Methanol/Water and (2) 8:1:1 Acetonitrile/Methanol/Acetone. Metabolites were analyzed by untargeted liquid chromatography-mass spectrometry (LC MS-MS) profiling using a Q-Exactive Orbitrap instrument coupled with Vanquish Horizon Binary UHPLC LC-MS system. Metabolites were identified and quantified using Compound Discoverer 3.3 and isotopic internal metabolites standards.

Prolonged infusion of a high dose of kynurenic acid (KYNA) reduces the myelin content in the rat spinal cord with preservation of the axonal integrity and without inducing an inflammatory response. We hypothesized that subdural infusion of a high concentration of KYNA can induce myelin loss in the optic nerves (ONs) of chickens. However, existing methods to deliver agents to the ON are inefficient, unlocalized and provide only acute exposure. Thus, we developed a surgical approach for sustained delivery of KYNA to the chicken ON. In brief, the novel surgical technique, which does not include excision of the extraocular muscles, involves incision of the skin and underlying fascial sheath to access the optic nerve within the muscle cone, implantation of a catheter in the dura of the optic nerve, the other end of which exits the orbit under the skin. The catheter runs under the skin near the lateral canthus, over the ears to the back of the neck, where a second incision is made to both implant the osmotic pump and to attach the catheter to the osmotic pump. India ink was used to confirm prolonged sustained administration to the optic nerves and across the chiasm. This surgical model was used to investigate KYNA's effect(s) on myelin loss in the ON. ONs of 7-day old chickens were infused with 50 mM KYNA or phosphate buffered saline (PBS) for seven days. Analysis of KYNA-infused contralateral ON g-ratios and protein levels indicated a reduction in myelin. These findings demonstrate the utility of our surgical approach for sustained delivery of KYNA into the ON and suggest a role for KYNA in modulating CNS myelination.

Malignant optic gliomas are an uncommon pathology, with around 67 cases reported worldwide in the literature. We present the case of a 77-year-old-male with a two-month history of progressive vision loss, ultimately leading to bilateral blindness. The initial clinical suspicion was a non-inflammatory ischemic optic neuropathy. Stereotactic biopsy was performed on the optic chiasm, and the histopathological diagnosis was confirmed as Glioblastoma.

It has been proposed that eye movements could be related to glaucoma development. This research aimed to compare the impact of intraocular pressure (IOP) versus horizontal duction on optic nerve head (ONH) strains. Thus, a tridimensional finite element model of the eye including the three tunics of the eye, all of the meninges, and the subarachnoid space (SAS) was developed using a series of medical tests and anatomical data. The ONH was divided into 22 subregions, and the model was subjected to 21 different eye pressures, as well as 24 different degrees of adduction and abduction ranging from 0.5° to 12°. Mean deformations were documented along anatomical axes and in principal directions. Additionally, the impact of tissue stiffness was assessed. The results show no statistically significant differences between the lamina cribrosa (LC) strains due to eye rotation and IOP variation. However, when assessing LC regions some experienced a reduction in principal strains following a 12° duction, while after the IOP reached 12 mmHg, all LC subzones showed an increase in strains. From an anatomical perspective, the effect on the ONH following 12° duction was opposite to that observed after a rise in IOP. Moreover, high strain dispersion inside the ONH subregions was obtained with lateral eye movements, which was not observed with increased IOP and variation. Finally, SAS and orbital fat stiffness strongly influenced ONH strains during eye movements, while SAS stiffness was also influential under ocular hypertension. Even if horizontal eye movements cause large ONH deformations, their biomechanical effect would be markedly distinct from that induced by IOP. It could be predicted that, at least in physiological conditions, their potential to cause axonal injury would not be so relevant. Thus, a causative role in glaucoma does not appear likely. By contrast, an important role of SAS would be expectable.

The anterior optic pathway (AOP) is a system of three structures (optic nerves, optic chiasma, and optic tracts) that convey visual stimuli from the retina to the lateral geniculate nuclei. A successful reconstruction of the AOP using tractography could be helpful in several clinical scenarios, from presurgical planning and neuronavigation of sellar and parasellar surgery to monitoring the stage of fiber degeneration both in acute (e.g., traumatic optic neuropathy) or chronic conditions that affect AOP structures (e.g., amblyopia, glaucoma, demyelinating disorders or genetic optic nerve atrophies). However, its peculiar anatomy and course, as well as its surroundings, pose a serious challenge to obtaining successful tractographic reconstructions. Several AOP tractography strategies have been adopted but no standard procedure has been agreed upon.We performed a systematic review of the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 guidelines in order to find the combinations of acquisition and reconstruction parameters that have been performed previously and have provided the highest rate of successful reconstruction of the AOP, in order to promote their routine implementation in clinical practice. For this purpose, we reviewed data regarding how the process of anatomical validation of the tractographies was performed. The Cochrane Handbook for Systematic Reviews of Interventions was used to assess the risk of bias and thus the study quality We identified thirty-nine studies that met our inclusion criteria, and only five were considered at low risk of bias and achieved over 80% of successful reconstructions.We found a high degree of heterogeneity in the acquisition and analysis parameters used to perform AOP tractography and different combinations of them can achieve satisfactory levels of anterior optic tractographic reconstruction both in real-life research and clinical scenarios. One thousand s/mm2 was the most frequently used b value, while both deterministic and probabilistic tractography algorithms performed morphological reconstruction of the tract satisfactorily, although probabilistic algorithms estimated a more realistic percentage of crossing fibers (45.6%) in healthy subjects. A wide heterogeneity was also found regarding the method used to assess the anatomical fidelity of the AOP reconstructions. Three main strategies can be found: direct visual direct visual assessment of the tractography superimposed to a conventional MR image, surgical evaluation, and computational methods. Because the latter is less dependent on a priori knowledge of the anatomy by the operator, computational methods of validation of the anatomy should be considered whenever possible.

Vascular compression of the optic nerve in a patient with rapid monocular vision loss with otherwise negative diagnostic workup is a rare, but controversial dilemma. The literature is conflicted, advocating for either timely surgical decompression to preserve vision 1-6 or observation only given the prevalence of asymptomatic vascular compression and observed arrest of visual decline. 7-10 The most frequently reported sources of symptomatic compression are unruptured aneurysms and dolichoectatic vasculature, 1-6 with recent consensus reached over a need for extensive perioperative ophthalmologic evaluations and follow-up. We present an illustrative case for microvascular decompression of the prechiasmatic optic nerve. Video footage of the operative management of microvascular optic nerve compression is exceedingly rare. 5 A 50-year-old man with a past medical history of hypertension and substance use presented with a 1-week history of progressive right nasal hemianopsia (Video 1). After a negative stroke workup, magnetic resonance imaging of the brain showed prechiasmatic displacement of the right optic nerve by the right supraclinoid internal carotid artery. Formal cerebral arteriography showed a left-sided fetal posterior cerebral artery and patent vasculature without a causative lesion. Given isolated right eye symptoms and rapid progression, a right orbitozygomatic craniotomy for microvascular decompression was recommended. The patient consented to the procedure and to the publication of his image. Intraoperatively, a right calcified dolichoectatic supraclinoid internal carotid artery was found to be severely displacing and tethering its ipsilateral optic nerve. Optic canal deroofing, detethering of the optic nerve, and polytetrafluoroethylene (Teflon) patch placement was performed to achieve this decompression. His postoperative course was uncomplicated; only mild improvement of his visual symptoms was noted at 1- and 3-month follow-up. Formal acuity and computerized assessments of vision and extensive follow-up are critical for evaluating the true clinical outcome of patients with microvascular optic nerve compression., 6 A 50-year-old man with a past medical history of hypertension and substance use presented with a 1-week history of progressive right nasal hemianopsia (Video 1). After a negative stroke workup, magnetic resonance imaging of the brain showed prechiasmatic displacement of the right optic nerve by the right supraclinoid internal carotid artery. Formal cerebral arteriography showed a left-sided fetal posterior cerebral artery and patent vasculature without a causative lesion. Given isolated right eye symptoms and rapid progression, a right orbitozygomatic craniotomy for microvascular decompression was recommended. The patient consented to the procedure and to the publication of his image. Intraoperatively, a right calcified dolichoectatic supraclinoid internal carotid artery was found to be severely displacing and tethering its ipsilateral optic nerve. Optic canal deroofing, detethering of the optic nerve, and polytetrafluoroethylene (Teflon) patch placement was performed to achieve this decompression. His postoperative course was uncomplicated; only mild improvement of his visual symptoms was noted at 1- and 3-month follow-up. Formal acuity and computerized assessments of vision and extensive follow-up are critical for evaluating the true clinical outcome of patients with microvascular optic nerve compression., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Optic nerves are part of the craniospinal irradiation (CSI) target volume. Modern radiotherapy techniques achieve highly conformal target doses while avoiding organs-at-risk such as the lens. The magnitude of eye movement and its influence on CSI target- and avoidance volumes are unclear. We aimed to evaluate the movement-range of lenses and optic nerves and its influence on dose distribution of several planning techniques. Methods: Ten volunteers underwent MRI scans in various gaze directions (neutral, left, right, cranial, caudal). Lenses, orbital optic nerves, optic discs and CSI target volumes were delineated. 36-Gy cranial irradiation plans were constructed on synthetic CT images in neutral gaze, with Volumetric Modulated Arc Therapy, pencil-beam scanning proton therapy, and 3D-conventional photons. Movement-amplitudes of lenses and optic discs were analyzed, and influence of gaze direction on lens and orbital optic nerve dose distribution. Results: Mean eye structures’ shift from neutral position was greatest in caudal gaze; −5.8±1.2 mm (±SD) for lenses and 7.0±2.0 mm for optic discs. In 3D-conventional plans, caudal gaze decreased Mean Lens Dose (MLD). In VMAT and proton plans, eye movements mainly increased MLD and diminished D98 orbital optic nerve (D98OON) coverage; mean MLD increased up to 5.5 Gy [total ΔMLD range −8.1 to 10.0 Gy], and mean D98OON decreased up to 3.3 Gy [total ΔD98OON range −13.6 to 1.2 Gy]. VMAT plans optimized for optic disc Internal Target Volume and lens Planning organ-at-Risk Volume resulted in higher MLD over gaze directions. D98OON became ≥95% of prescribed dose over 95/100 evaluated gaze directions, while all-gaze bilateral D98OON significantly changed in 1 of 10 volunteers. Conclusion: With modern CSI techniques, eye movements result in higher lens doses and a mean detriment for orbital optic nerve dose coverage of

Optic nerve tuberculoma is a rare extra-pulmonary manifestation of mycobacterial infection. It is usually associated with HIV infected patients. Due to its clinical polymorphism, the diagnosis and management of the disease either in immunocompetent patients and immunocompromised ones remains challenging. Herein, we discuss a case of a 32-year-old patient with no history of immunodeficiency admitted for multifocal tuberculosis with a reduced visual acuity as an extra-pulmonary manifestation, and radiologically revealed the presence of tuberculoma in the optic nerve in the cerebral MRI.

Purpose: IgG4-related ophthalmic disease (IgG4-ROD) is a lymphoproliferative disorder with representative symptoms including lacrimal gland enlargement (Mikulicz disease), masses around the trigeminal nerves, and extraocular muscle swelling. Herein, we describe cases of IgG4-ROD with lesions surrounding the optic nerve. Methods: Of the 56 consecutive patients (35 men and 21 women) with a “definite case” of IgG4-ROD diagnosed from November 2004 through December 2019 at Kanazawa University hospital, seven patients presented with mass lesions around the optic nerve based on magnetic resonance imaging, and four patients showed symptoms of optic neuropathy. The clinical courses of these seven cases were reviewed. Results: Among the 56 cases of IgG4-ROD, seven cases had lesions surrounding the optic nerve and all of these patients were male. The male dominance in the patient group with lesions surrounding the optic nerve was statistically significant based on a Chi-squared test (p

Background: Optic neuritis (ON) is one of the first manifestations of multiple sclerosis, a disabling disease with rising prevalence. Detecting optic nerve lesions could be a relevant diagnostic marker in patients with multiple sclerosis. Objectives: We aim to create an automated, interpretable method for optic nerve lesion detection from MRI scans. Materials and Methods: We present a 3D convolutional neural network (CNN) model that learns to detect optic nerve lesions based on T2-weighted fat-saturated MRI scans. We validated our system on two different datasets (N = 107 and 62) and interpreted the behaviour of the model using saliency maps. Results: The model showed good performance (68.11% balanced accuracy) that generalizes to unseen data (64.11%). The developed network focuses its attention to the areas that correspond to lesions in the optic nerve. Conclusions: The method shows robustness and, when using only a single imaging sequence, its performance is not far from diagnosis by trained radiologists with the same constraint. Given its speed and performance, the developed methodology could serve as a first step to develop methods that could be translated into a clinical setting.

Disruption or loss of oligodendrocytes (OLs) and myelin has devastating effects on CNS function and integrity, which occur in diverse neurological disorders, including Multiple Sclerosis (MS), Alzheimer’s disease and neuropsychiatric disorders. Hence, there is a need to develop new therapies that promote oligodendrocyte regeneration and myelin repair. A promising approach is drug repurposing, but most agents have potentially contrasting biological actions depending on the cellular context and their dose-dependent effects on intracellular pathways. Here, we have used a combined systems biology and neurobiological approach to identify compounds that exert positive and negative effects on oligodendroglia, depending on concentration. Notably, next generation pharmacogenomic analysis identified the PI3K/Akt modulator LY294002 as the most highly ranked small molecule with both pro- and anti-oligodendroglial concentration-dependent effects. We validated these in silico findings using multidisciplinary approaches to reveal a profoundly bipartite effect of LY294002 on the generation of OPCs and their differentiation into myelinating oligodendrocytes in both postnatal and adult contexts. Finally, we employed transcriptional profiling and signalling pathway activity assays to determine cell-specific mechanisms of action of LY294002 on oligodendrocytes and resolve optimal in vivo conditions required to promote myelin repair. These results demonstrate the power of multidisciplinary strategies in determining the therapeutic potential of small molecules in neurodegenerative disorders.

Eyesight is the most important of our sensory systems for optimal daily activities and overall survival. Patients who experience visual impairment due to elevated intraocular pressure (IOP) are often those afflicted with primary open-angle glaucoma (POAG) which slowly robs them of their vision unless treatment is administered soon after diagnosis. The hallmark features of POAG and other forms of glaucoma are damaged optic nerve, retinal ganglion cell (RGC) loss and atrophied RGC axons connecting to various brain regions associated with receipt of visual input from the eyes and eventual decoding and perception of images in the visual cortex. Even though increased IOP is the major risk factor for POAG, the disease is caused by many injurious chemicals and events that progress slowly within all components of the eye-brain visual axis. Lowering of IOP mitigates the damage to some extent with existing drugs, surgical and device implantation therapeutic interventions. However, since multifactorial degenerative processes occur during aging and with glaucomatous optic neuropathy, different forms of neuroprotective, nutraceutical and electroceutical regenerative and revitalizing agents and processes are being considered to combat these eye-brain disorders. These aspects form the basis of this short review article.

Objective: To objectively correlate distortions of optic apparatus morphology in patients with pituitary adenomas undergoing trans-sphenoidal surgery., Methods: In this retrospective analysis, visual acuity (VA), visual field (VF), and total visual (TV) function were objectively scored in patients selected from an institutional cohort of pituitary adenomas. The following imaging measures of optico-chiasmatic morphology were recorded preoperatively, and at 3 months after surgery: chiasm area, mid-chiasm height (CH), optic nerve-canal bending angle (BA), and optic nerve kinking angle (ONKA). Receiver operator characteristic analysis was performed to establish optimal thresholds for achieving a "normal" TV score of 200 at 1-year follow-up., Results: Seventy-one eyes were individually studied. VA, VF, and TV scores significantly improved after surgery, both at the 3-month and at the 1-year follow-up visits (P < 0.001). Cranio-caudal tumor dimension was significantly associated with VA, VF, and TV scores, both preoperatively and postoperatively. There were significant changes in CH (P < 0.001), BA (P < 0.001), and ONKA (P < 0.001) at 3 months after surgery, but not in chiasm area (P = 0.061). Baseline VA, VF, and TV scores were positively correlated with preoperative CH and ONKA, while VF and TV scores also demonstrated significant negative correlations with preoperative BA. VF scores at 1-year follow-up were significantly correlated with preoperative and change in BA values, as well as with preoperative and change in ONKA values. Receiver operator characteristic analysis revealed that only the preoperative ONKA was found to have acceptable discrimination (area under the curve >0.7) for predicting "normal" TV score. Chiasm sag was noted in 45.8% of patients at 1-year follow-up, but was not associated with delayed visual deterioration in any case., Conclusions: Anatomic realignment of the optic apparatus 3 months following trans-sphenoidal surgery predicts VF scores, but not VA or TV scores at 1-year follow-up. Patients with preoperative ONKA values of more than 139.3° have a 76% chance of achieving normal TV scores 1 year after surgery. Postoperative chiasm sag appears to be clinically irrelevant at short-term follow-up., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To examine the relationship between systemic arterial blood pressure (BP) and the rate of change in standard automated perimetry (SAP) in eyes with glaucoma and suspected glaucoma., Design: Prospective cohort study., Participants: One hundred twenty-four eyes (91 eyes with glaucoma, 33 eyes with suspected glaucoma) of 64 patients (mean age, 68.4 ± 7.6 years) followed up at the Bascom Palmer Eye Institute, Palm Beach Gardens, Florida., Methods: Participants underwent ophthalmic examination, BP measurement, and SAP at 4-month intervals. At the baseline visit, 24-hour ambulatory blood pressure monitoring (ABPM) was acquired. Linear mixed models (adjusted for inclusion of both eyes, age, sex, race, intraocular pressure, baseline severity, and central corneal thickness) were used to investigate the effect of BP on the rates of SAP mean deviation (MD) change over time., Main Outcome Measures: Effect of baseline 24-hour and follow-up mean arterial pressure (MAP), systolic BP (SBP), and diastolic BP on change in SAP MD., Results: Eyes underwent an average of 8.9 ± 1.5 SAP examinations over 28.3 ± 6.0 months of follow-up. The median rate of MD change was 0.14 dB/year (range, -1.21 to 0.96 dB/year) with 9 eyes (7%) showing moderate to fast progression (MD change, ≤ -0.50 dB/year). Each 10 mmHg lower in 24-hour average MAP and SBP were associated with -0.171 dB/year (P = 0.045) and -0.137 dB/year (P = 0.023) faster rates of MD loss. Lower mean SBP during follow-up was associated significantly (P = 0.003) with MD progression., Conclusions: Lower baseline 24-hour ABPM measurements, as well as low SBP during follow-up, were associated significantly with faster rates of glaucomatous SAP progression and may be used as a predictor of risk of glaucomatous progression., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: 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., Methods: 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., Results: 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., Conclusions: 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Management of patients with optic nerve sheath meningiomas (ONSMs) is controversial and the treatment strategy in this patient group is still up for discussion. Transnasal endoscopic orbital and optic nerve decompression aims to reduce the pressure in the orbit and on the optic nerve and thereby prevent vision loss. This article presents material from 7 cases of transnasal endoscopic orbital decompression., Methods: The study design is a retrospective cohort study. The aim was to include all patients with a meningioma residing along the nerve sheath and who were operated using endoscopic transnasal decompression of the orbit and if needed the optic canal at Odense University Hospital. Data from the medical records were collected and pre- and postoperative eye examinations were compared. In addition, it was recorded whether there were complications to the procedure and whether additional treatments were given., Results: In total, 4 women and 3 men were included in the study. Four out of 7 patients experienced improvement in vision after the operation. One patient experienced unchanged vision and 2 patients experienced deterioration of vision after surgery., Conclusions: The current report of 7 patients with ONSM shows promising results for this surgical procedure as 4 out of 7 patients experienced improvement in their vision at follow-up examinations. The 2 patients who experienced deterioration of vision already had severely reduced vision preoperatively, which indicates that surgery should be considered before the vision becomes significantly reduced., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Mitochondrial diseases are among the most prevalent groups of inherited neurological disorders, affecting up to 1 in 5000 adults. Despite the progress achieved on the identification of gene mutations causing mitochondrial pathologies, they cannot be cured so far. Harlequin mice, a relevant model of mitochondrial pathology due to apoptosis inducing factor depletion, suffer from progressive disappearance of retinal ganglion cells leading to optic neuropathy. In our previous work, we showed that administering adeno-associated virus encompassing the coding sequences for neuroglobin, (a neuroprotective molecule belonging to the globin family) or apoptosis-inducing factor, before neurodegeneration onset, prevented retinal ganglion cell loss and preserved visual function.One of the challenges to develop an effective treatment for optic neuropathies is to consider that by the time patients become aware of their handicap, a large amount of nerve fibers has already disappeared.Gene therapy was performed in Harlequin mice aged between 4 and 5 months with either a neuroglobin or an apoptosis-inducing factor vector to determine whether the increased abundance of either one of these proteins in retinas could preserve visual function at this advanced stage of the disease.We demonstrated that gene therapy, by preserving the connectivity of transduced retinal ganglion cells and optic nerve bioenergetics, results in the enhancement of visual cortex activity, ultimately rescuing visual impairment.This study demonstrates that: (a) An increased abundance of neuroglobin functionally overcomes apoptosis-inducing factor absence in Harlequin mouse retinas at a late stage of neuronal degeneration; (b) The beneficial effect for visual function could be mediated by neuroglobin localization to the mitochondria, thus contributing to the maintenance of the organelle homeostasis.

The right optic nerve of adult, 6 month to 1 year old, female and male Danio rerio were crushed and collected three days after. Matching controls of uninjured left optic nerves were also collected. The tissue was dissected from euthanized fish and frozen on dry ice. Samples were pooled for each category (female crush, female control, male crush, male control) n = 24 to obtain sufficient tissue for analysis. The brain from one male fish was also collected for control/calibration. Lipid extraction was done with the Bligh and Dyer [1] method, followed by untargeted liquid chromatography-mass spectrometry (LC MS-MS) lipid profiling using a Q-Exactive Orbitrap instrument coupled with Vanquish Horizon Binary UHPLC LC-MS system. The lipids were identified and quantified with LipidSearch 4.2.21 and the statistical analysis was conducted through Metaboanalyst 5.0. This data is available at Metabolomics Workbench, Study ID ST001725.

Oxidative stress contributes to degeneration of retinal ganglion cells and their axons in glaucoma, a leading cause of irreversible blindness worldwide, through sensitivity to intraocular pressure (IOP). Here, we investigated early elevations in reactive oxygen species (ROS) and a role for the NRF2-KEAP1-ARE endogenous antioxidant response pathway using microbead occlusion to elevate IOP in mice. ROS levels peaked in the retina at 1- and 2-wks following IOP elevation and remained elevated out to 5-wks. Phosphorylation of NRF2 and antioxidant gene transcription and protein levels increased concomitantly at 2-wks after IOP elevation, along with phosphorylation of PI3K and AKT. Inhibiting PI3K or AKT signaling prevented NRF2 phosphorylation and reduced transcription of antioxidant-regulated genes. Ocular hypertensive mice lacking Nrf2 had elevated ROS and a diminished increase in antioxidant gene expression. They also exhibited earlier axon degeneration and loss of visual function. In conclusion, the NRF2-KEAP1-ARE pathway is endogenously activated early in ocular hypertension due to phosphorylation of NRF2 by the PI3K/AKT pathway and serves to slow the onset of axon degeneration and vision loss in glaucoma. These data suggest that exogenous activation of this pathway might further slow glaucomatous neurodegeneration.

The optic nerve is part of the mammalian adult central nervous system (CNS) and has limited capability to regenerate after injury. Deletion of phosphatase and tensin homolog (PTEN), a negative regulator of the PI3 kinase/Akt pathway, has been shown to promote regeneration in retinal ganglion cells (RGCs) after optic nerve injury [1]. We present the lipidome of adult PTENloxP/loxP mice subjected to intravitreal injection of adeno-associated viruses expressing Cre (AAV-Cre) as a model of CNS neuroregeneration. At 4 weeks old, PTENloxP/loxP mice were intravitreally-injected with 2–3 μl of either AAV-Cre (KO) or AAV-PLAP (control), and two weeks later optic nerve crush was performed. At indicated time-points after crush (0 days, 7 days, 14 days), mice were euthanized and optic nerves were immediately dissected out, and then flash frozen on dry ice. A modified Bligh and Dyer [2] method was used for lipid extraction from the optic nerves, followed by liquid chromatography-mass spectrometry (LC MS-MS) lipid profiling using a Q-Exactive Orbitrap instrument coupled with Accela 600 HPLC. The raw scans were analysed with LipidSearch 4.2 and the statistical analysis was conducted through Metaboanalyst 4.0. This data is available at Metabolomics Workbench, study ID ST001477.

Purpose: To report a patient with post-operative gas migration into the optic nerve and lateral ventricles after retinal detachment repair. Observations: A 78-year-old pseudophakic man developed a temporal visual field cut in his non-operative, right eye 3 weeks after repair of a recurrent, shallow, macula-involving retinal detachment with perfluoropropane intraocular gas in the left eye. Visual acuity in the right eye measured 20/40, and static perimetry demonstrated temporal visual field loss that respected the vertical midline. Dilated fundus examination of the right eye was unrevealing for any retinal cause, raising suspicion for an intracranial etiology. An urgent CT scan of the brain demonstrated gas in all segments of the left optic nerve and lateral ventricles, consistent with intracranial gas migration along the optic nerve. Given the absence of systemic neurologic symptoms, cautious observation was advised on consultation with neuroradiology and neurosurgery, and follow-up CT scan 1 week later showed resolution of the intracranial gas. By 10-weeks post-operatively, vision returned to 20/20 in the right eye with persistent temporal field loss, and the left eye was hand motions (20/70 pre-operatively) with evidence of optic nerve atrophy and severe cupping. Conclusions: Intracranial gas migration is a rare complication of retinaldetachment repair with intraocular gas and may occur in the setting of structural defects of the optic nerve and high post-operative intraocular pressure. Clinicians should be alert to this rare but serious complication, which can cause neurologic symptoms and result in vision loss in both the operative and non-operative eyes.

Optic neuropathies, such as glaucoma, are due to progressive retinal ganglion cells (RGCs) degeneration, result in irreversible vision loss. The promising RGCs replacement therapy for restoring vision are impeded by insufficient RGC-like cells sources. The present work was enriched one new type RGC-like cells using two surface markers CD184 and CD171 from human induced pluripotent stem cells (hiPSCs) by FACS sorting firstly. These new kind cells have well proliferation ability and possessed passage tolerance in vitro 2D or 3D spheroids culture, which kept expressing Pax6, Brn3b and βIII-Tubulin and so on. The transplanted CD184 + CD171 + RGC-like cells could survive and integrate into the normal and optic nerve crush (ONC) mice retina, especially they were more inclined to across the optic nerve head and extend to the damaged optic nerve. These data support the feasible application for cell replacement therapy in RGC degenerative diseases, as well as help to develop new commercial cells sorting reagents and establish good manufacturing practice (GMP) grade RGC-like donor cells for further clinical application., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Optic chiasm cavernoma (OCC) is an uncommon lesion. A limited number of case reports have been published. We report a case of OCC with 48 months follow-up after complete microsurgical resection. Additionally, we provide a pertinent literature review. Case description: A 44-year-old female presented with headaches and decreased visual acuity and visual fields in both eyes for 2 months duration. A complete neurological and ophthalmological exams, as well as preoperative optical coherence tomography (OCT) images, were performed. Magnetic resonance imaging (MRI) showed a suprasellar mass lesion involving the optic chiasm. An inter-hemispheric transbasal approach was performed and complete excision was achieved. Postoperative follow-up showed marked improvement of visual deficits. Histopathologic examination revealed a lesion consistent with a cavernoma. Follow-up brain MRI at 3, 11, 20, 26 and 48 months showed no residual or recurrence. Conclusions: The current case emphasizes that OCC can be completely excised with the dramatic improvement of the visual deficits. Furthermore, MRI is the modality of choice to detect such lesions. Additionally, preoperative OCT can be a good adjuvant technique to predict postoperative-visual-outcome. Moreover, OCC should be included in the differential diagnosis of a space-occupying lesion of the optic chiasm.

Purpose: To describe a case of leukemic infiltration of bilateral optic nerves and retina as a site of relapse in a child with T-Cell Acute Lymphoblastic Leukemia (ALL). Observations: We report a 7 year old female who presented one year following initial treatment for T-Cell ALL with visual acuity impairment, bilateral optic nerve infiltration and infiltration of the retina of both eyes. OCT demonstrated subretinal fluid in both eyes, which eventually resolved, and perivascular hyperreflectivity within the inner retinal layers. She was treated with systemic and intrathecal chemotherapy, total body and orbital radiation and eventual bone marrow transplantation with notable improvement in vision and regression of retinal and optic nerve findings. With continued remission, there was notable outer retinal thinning, specifically of the photoreceptors in the right eye. Conclusions and importance: Leukemic abnormalities of the eye are not uncommon, however optic nerve and retinal infiltration are rare manifestations. Leukemic infiltrates of the retina can be detected by OCT despite normal funduscopic examination and monitored for improvement. The optic nerve and other ocular tissues are considered a pharmacologic sanctuary and thus, the optic nerve can be a site of relapse in leukemia. The use of radiation therapy is a helpful adjunct with systemic, intrathecal chemotherapy and stem cell transplantation in obtaining clinical remission and visual acuity improvement.

Blindness and vision impairment are unpredictable complications of tuberculous meningitis (TBM) that are often unrecognized in the acute stages of illness due to inability to assess vision in patients with depressed levels of consciousness or confusion. We present a patient with definite TBM confirmed by positive Xpert MTB/RIF assay of cerebrospinal fluid (CSF) who developed binocular blindness two weeks after diagnosis and initiation of standard anti-tuberculosis treatment (ATT). Ophthalmological exam demonstrated complete bilateral abducens nerve palsies, impaired pupillary responses to light, normal optic discs, and visual acuity of hand motion only in each eye. Brain CT showed progressive enlargement of the third and lateral ventricles. We managed the patient medically with dexamethasone, acetazolamide, and substitution of moxifloxacin for ethambutol. Serial brain CTs confirmed gradual resolution of hydrocephalus. The patient had complete neurological recovery at six months except for residual blindness in the right eye. Visual acuity in the left eye recovered to normal (20/20). The assessment and management of vision impairment in TBM is discussed.

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

Central nervous system (CNS) neurons fail to regrow injured axons, often resulting in permanently lost neurologic function. Tacrolimus is an FDA-approved immunosuppressive drug with known neuroprotective and neuroregenerative properties in the CNS. However, tacrolimus is typically administered systemically and blood levels required to effectively treat CNS injuries can lead to lethal, off-target organ toxicity. Thus, delivering tacrolimus locally to CNS tissues may provide therapeutic control over tacrolimus levels in CNS tissues while minimizing off-target toxicity. Herein we show an electrospun poly(ester urethane) urea and tacrolimus elastomeric matrix (PEUU-Tac) can deliver tacrolimus trans-durally to CNS tissues. In an acute CNS ischemia model in rat, the optic nerve (ON) was clamped for 10s and then PEUU-Tac was used as an ON wrap and sutured around the injury site. Tacrolimus was detected in PEUU-Tac wrapped ONs at 24 h and 14 days, without significant increases in tacrolimus blood levels. Similar to systemically administered tacrolimus, PEUU-Tac locally decreased glial fibrillary acidic protein (GFAP) at the injury site and increased growth associated protein-43 (GAP-43) expression in ischemic ONs from the globe to the chiasm, consistent with decreased astrogliosis and increased retinal ganglion cell (RGC) axon growth signaling pathways. These initial results suggest PEUU-Tac is a biocompatible elastic matrix that delivers bioactive tacrolimus trans-durally to CNS tissues without significantly increasing tacrolimus blood levels and off-target toxicity.

Si-Wei You,1 Ming-Mei Wu,2 Fang Kuang,2 Kin-Sang Cho,3 Kwok-Fai So4,5 1Department of Ophthalmology, Xijing Hospital, 2Institute of Neurosciences, The Fourth Military Medical University, Xi’an, China; 3Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA; 4GHM Institute of CNS Regeneration, Key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou, 5Department of Ophthalmology, The State Key laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong SAR, China Abstract: Optic neuropathy refers to disorders involving the optic nerve (ON). Any damage to ON or ON-deriving neurons, the retinal ganglion cells (RGCs), may lead to the breakdown of the optical signal transmission from the eye to the brain, thus resulting in a partial or complete vision loss. The causes of optic neuropathy include trauma, ischemia, inflammation, compression, infiltration, and mitochondrial damages. ON injuries include primary and secondary injuries. During these injury phases, various factors orchestrate injured axons to die back and become unable to regenerate, and these factors could be divided into two categories: extrinsic and intrinsic. Extrinsic inhibitory factors refer to the environmental conditions that influence the regeneration of injured axons. The presence of myelin inhibitors and glial scar, lack of neurotrophic factors, and inflammation mediated by injury are regarded as these extrinsic factors. Extrinsic factors need to trigger the intracellular signals to exert inhibitory effect. Proper regulation of these intracellular signals has been shown to be beneficial to ON regeneration. Intrinsic factors of RGCs are the pivotal reasons that inhibit ON regeneration and are closely linked with extrinsic factors. Intracellular cyclic adenosine monophosphate (cAMP) and calcium levels affect axon guidance and growth cone response to guidance molecules. Many genes, such as Bcl-2, PTEN, and mTOR, are crucial in cell proliferation, axon guidance, and growth during development, and play important roles in the regeneration and extension of RGC axons. With transgenic mice and related gene regulations, robust regeneration of RGC axons has been observed after ON injury in laboratories. Although various means of experimental treatments such as cell transplantation and gene therapy have achieved significant progress in neuronal survival, axonal regeneration, and restoration of the visual function after ON injury, many unresolved scientific problems still exist for their clinical applications. Therefore, we still need to overcome hurdles before developing effective therapy to treat optic neuropathy diseases in patients. Keywords: retinal ganglion cells, optic nerve injury, neuronal survival, axonal regeneration, vision restoration

Objective: For unilateral Dodge Class Ⅰ optic pathway glioma (OPG-uDCⅠ) without neurofibromatosis type 1, unilateral isolated optic nerve gliomas before the optic chiasm have been confirmed to possibly cause visual deterioration and poor prognosis. For this type of highly selective localized tumor, we explored surgery as the only treatment method. This article retrospectively analyzed and summarized the clinical data of this case series, with the aim of exploring the main technical details and clinical prognosis., Methods: Included were patients with OPG-uDCⅠ without neurofibromatosis type 1 and experiencing vision loss on the affected side. The fronto-orbital approach was used, which was mainly divided into 3 parts: intraorbital, optic canal, and intracranial. All patients underwent prechiasmatic resection without any adjuvant treatments. The follow-up period was 3 months after surgery, and magnetic resonance imaging and contralateral visual acuity were reviewed annually after surgery., Results: All OPG-uDCⅠ cases were completely removed without any adjuvant treatments, and there was no recurrence during the follow-up period. Pathological results showed that, except for 1 adult patient with pilomyxoid astrocytoma (World Health Organization grade Ⅱ), the others all had pilocytic astrocytoma (World Health Organization grade Ⅰ). Five patients experienced transient ptosis, and all recovered 3 months after surgery., Conclusions: For OPG-uDCⅠ without neurofibromatosis type 1, radical prechiasmatic resection of the tumor is possible, without the need for postoperative radiotherapy and chemotherapy., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The ophthalmic artery normally travels with the optic nerve through the optic canal. However, sometimes, the ophthalmic artery travels through a foramen within the optic strut named an accessory optic canal, double optic canal, or ophthalmic canal. This variant puts individuals at an increased risk for blindness or death during anterior clinoidectomy due to unforeseen hemorrhage of the ophthalmic artery or internal carotid artery when the optic strut is separated from the body of the sphenoid bone. Several features make the accessory optic canal difficult to recognize on imaging: its variant nature, small size, and ability to masquerade as a caroticoclinoid foramen or a pneumatized sphenoidal structure. Hence, improved methods of presurgical identification are warranted. The aim of this study was to assess the size and shape of the optic canal, with and without a concomitant accessory optic canal, to determine whether measurement of the optic canal may provide useful information regarding the presence of an accessory optic canal., Methods: In 191 dry crania, optic canals with and without concomitant accessory optic canals were assessed for the following parameters: canal area, canal perimeter, circularity, solidity, the axes and aspect ratio of a best-fit ellipse, and roundness., Results: Normal optic canals were found to have a larger area (P = 0.036), perimeter (P = 0.043), and minor axis of a best-fit ellipse (P = 0.031) than the optic canals that occurred alongside accessory optic canals., Conclusions: Asymmetry in optic canal size can help indicate the presence of a unilateral accessory optic canal before surgery., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Orbital apex syndrome due to spread of infectious sinusitis is a serious disease, often with an insidious presentation with few ophthalmic signs and symptoms. Failure to recognize and treat infectious orbital apex syndrome early portends a grave prognosis, including profound, permanent visual loss and potentially death. Herein we describe a representative case and discuss the relevant aspects of prompt diagnosis and treatment. Observations: An unusual case of infectious orbital apex syndrome due to contiguous spread of Streptococcus viridans sphenoethmoiditis in a hospitalized, immunosuppressed patient with acute myelogenous leukemia is presented. Given the few clinic signs and subtle imaging findings, a delay in diagnosis occurred resulting in vision loss to light perception and internal carotid artery occlusion within the cavernous sinus. A brief literature review of orbital apex syndromes is presented. Conclusion and importance: A high clinical suspicion for orbital apex syndrome must be maintained in the appropriate circumstance given the subtle clinical signs and imaging, as well as the potential devastating morbidity of the disease process. Prompt diagnosis and treatment is crucial to patient survival and preservation of vision.

Purpose: To determine the effects of cardiopulmonary bypass surgery on retinal nerve fiber layer, ganglion cell layer, and macula by optic coherens tomography (OCT)., Method: Sixty-six eyes of 33 patients aged between 44 and 74 who were indicated for cardiopulmonary bypass surgery in the cardiovascular surgery clinic were included in the study. Routine ophthalmologic examinations of all patients were performed before and 1 week after surgery. In addition, 3D(H) Macula+5 Line Cross 12 × 9 mm mod and Peripapilar 3D Disk 6 × 6 mm mod data were analyzed with OCT (Topcon, Triton Swept Source-OKT, Tokyo, Japan) device. Peripapillary total, superior, inferior retinal nerve fiber layer (RNFL), optic disc cavity volume, cup-to-disc ratio, macular ganglion cell layer (GCL), macular thickness were compared before and after surgery., Results: After cardiopulmonary bypass surgery, thickening was detected in the total RNFL (p<0.001), superior RNFL (p = 0.01) and inferior RNFL (p<0.001) layers. There was no change in the values of GCL, macular thickness, optic disc cupping volume, cup-to-disc ratio after surgery (p>0.05). There was a positive correlation (r = 0.392 p<0.05) between the patients' blood oxygen (PO2) values during bypass surgery with their post-surgical GCL+ values, and a negative correlation between optic disc cup volumes (r=-0.349 p<0.05)., Conclusion: RNFL thickening has been detected in patients undergoing cardiopulmonary bypass surgery. This thickening may occur secondary to ischemic edema that occurs during surgery. Considering the late complications of ischemic edema in the RNFL, oxygen levels should be kept at an optimum level during surgery and long-term ophthalmologic follow-ups should be performed., Competing Interests: Declaration of Competing Interest None of the authors has any conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Glaucoma is a neurodegenerative disease and the leading cause of irreversible blindness worldwide. Vision deficits in glaucoma result from the selective loss of retinal ganglion cells (RGC). Glial cell-mediated neuroinflammation has been proposed to contribute to disease pathophysiology, but whether this response is harmful or beneficial for RGC survival is not well understood. To test this, we characterized the role of ibudilast, a clinically approved cAMP phosphodiesterase (PDE) inhibitor with preferential affinity for PDE type 4 (PDE4). Here, we demonstrate that intraocular administration of ibudilast dampened macroglia and microglia reactivity in the retina and optic nerve hence decreasing production of proinflammatory cytokines in a rat model of ocular hypertension. Importantly, ibudilast promoted robust RGC soma survival, prevented axonal degeneration, and improved anterograde axonal transport in glaucomatous eyes without altering intraocular pressure. Intriguingly, ocular hypertension triggered upregulation of PDE4 subtype A in Müller glia, and ibudilast stimulated cAMP accumulation in these cells. Co-administration of ibudilast with Rp-cAMPS, a cell-permeable and non-hydrolysable cAMP analog that inhibits protein kinase A (PKA), completely blocked ibudilast-induced neuroprotection. Collectively, these data demonstrate that ibudilast, a safe and well-tolerated glial cell modulator, attenuates gliosis, decreases levels of proinflammatory mediators, and enhances neuronal viability in glaucoma through activation of the cAMP/PKA pathway. This study provides insight into PDE4 signaling as a potential target to counter the harmful effects associated with chronic gliosis and neuroinflammation in glaucoma.

Multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), are often accompanied by optic neuritis associated with neurofilament disruption. In this study, the stiffness of the optic nerve was investigated by atomic force microscopy (AFM) in mice with induced EAE in the successive phases of the disease: onset, peak, and chronic. AFM results were compared with the intensity of the main pathological processes in the optic nerve: inflammation, demyelination, and axonal loss, as well as with the density of astrocytes, assessed by quantitative histology and immunohistochemistry. Optic nerve tissue and serum levels of neurofilament light chain protein (NEFL) were also examined by immunostaining and ELISA, respectively. The stiffness of the optic nerve in EAE mice was lower than that in control and naïve animals. It increased in the onset and peak phases and sharply decreased in the chronic phase. Serum NEFL level showed similar dynamics, while tissue NEFL level decreased in the onset and peak phases, indicating a leak of NEFL from the optic nerve to body fluids. Inflammation and demyelination gradually increased to reach the maximum in the peak phase of EAE, and inflammation slightly declined in the chronic phase, while demyelination did not. The axonal loss also gradually increased and had the highest level in the chronic phase. Among these processes, demyelination and especially axonal loss most effectively decrease the stiffness of the optic nerve. NEFL level in serum can be regarded as an early indicator of EAE, as it rapidly grows in the onset phase of the disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could influence the study presented in this manuscript., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Glaucoma is a chronic disorder that harms the optic nerves and causes irreversible blindness. The calculation of optic cup (OC) to optic disc (OD) ratio plays an important role in the primary screening and diagnosis of glaucoma. Thus, automatic and precise segmentations of OD and OC is highly preferable. Recently, deep neural networks demonstrate remarkable progress in the OD and OC segmentation, however, they are severely hindered in generalizing across different scanners and image resolution. In this work, we propose a novel domain adaptation-based framework to mitigate the performance degradation in OD and OC segmentation. We first devise an effective transformer-based segmentation network as a backbone to accurately segment the OD and OC regions. Then, to address the issue of domain shift, we introduce domain adaptation into the learning paradigm to encourage domain-invariant features. Since the segmentation-based domain adaptation loss is insufficient for capturing segmentation details, we further propose an auxiliary classifier to enable the discrimination on segmentation details. Exhaustive experiments on three public retinal fundus image datasets, i.e., REFUGE, Drishti-GS and RIM-ONE-r3, demonstrate our superior performance on the segmentation of OD and OC. These results suggest that our proposal has great potential to be an important component for an automated glaucoma screening system., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Anterior skull base meningioma produces symptoms as a result of mass effect and neurovascular compression. The bony anatomy of the anterior skull base is complex and houses the critical cranial nerves and vessels. Traditional microscopic approaches remove these tumors effectively but require extensive brain retraction and bone drilling. Endoscope assistance offers the advantages of a smaller incision, less brain retraction, and bone drilling. The most significant advantage of endoscope-assisted microneurosurgery for lesions invading the sella and optic foramen is the complete resection of the sellar and foraminal components frequently responsible for recurrence., Objective: In this report, we describe the technique of endoscope-assisted microneurosurgical resection of anterior skull base meningiomas invading the sella and foramen., Methods: We present 10 cases and 3 case examples of endoscope-assisted microneurosurgery for meningiomas invading the sella and optic foramen. This report presents the operating room setup and surgical details to resect sellar and foraminal tumors. The surgical procedure is presented as a video., Results: Endoscope-assisted microneurosurgery yielded excellent clinical and radiologic results and no recurrence at the last follow-up of meningiomas invading the sella and optic foramen. The present article discusses the challenges faced with endoscope-assisted microneurosurgery, techniques, and challenges in the procedure., Conclusions: Endoscope assistance enables complete tumor excision under vision with less retraction and bone drilling in anterior cranial fossa meningioma, invading the chiasmatic sulcus, optic foramen, and sella. The mixed use of microscope and endoscope makes it safer and saves time and is like bringing out the best of both worlds., (Copyright © 2023 Elsevier Inc. All rights reserved.)