Primary Optic Nerve Research Articles

Combined Whole Eye and Face Transplant: Microsurgical Strategy and 1-Year Clinical Course.

Catastrophic facial injury with globe loss remains a formidable clinical problem with no previous reports of reconstruction by whole eye or combined whole eye and facial transplant. To develop a microsurgical strategy for combined whole eye and facial transplant and describe the clinical findings during the first year following transplant. A 46-year-old man who sustained a high-voltage electrical injury with catastrophic tissue loss to his face and left globe underwent combined whole eye and face transplant using personalized surgical devices and a novel microsurgical strategy at a specialized center for vascularized composite allotransplantation. Reperfusion and viability of the whole eye and facial allografts, retinal function, and incidence of acute rejection. The patient underwent a combined whole eye and face transplant from an immunologically compatible donor with primary optic nerve coaptation and conventional postoperative immunosuppression. Globe and retinal perfusion were maintained throughout the immediate postoperative period, evidenced by fluorescein angiography. Optical coherence tomography demonstrated atrophy of inner retinal layers and attenuation and disruption of the ellipsoid zone. Serial electroretinography confirmed retinal responses to light in the transplanted eye. Using structural and functional magnetic resonance imaging, the integrity of the transplanted visual pathways and potential occipital cortical response to light stimulation of the transplanted eye was demonstrated. At 1 year post transplant (postoperative day 366), there was no perception of light in the transplanted eye. This is the first report of whole eye transplant combined with facial transplant, demonstrating allograft survival including rejection-free graft survival and electroretinographic measurements indicating retinal response to light stimuli. These data highlight the potential for clinical allotransplantation for globe loss.

Targeting DRP1 with Mdivi-1 to correct mitochondrial abnormalities in ADOA+ syndrome.

Autosomal dominant optic atrophy plus (ADOA+) is characterized by primary optic nerve atrophy accompanied by a spectrum of degenerative neurological symptoms. Despite ongoing research, no effective treatments are currently available for this condition. Our study provided evidence for the pathogenicity of an unreported c.1780T>C variant in the OPA1 gene through patient-derived skin fibroblasts and an engineered HEK293T cell line with OPA1 downregulation. We demonstrate that OPA1 insufficiency promoted mitochondrial fragmentation and increased DRP1 expression, disrupting mitochondrial dynamics. Consequently, this disruption enhanced mitophagy and caused mitochondrial dysfunction, contributing to the ADOA+ phenotype. Notably, the Drp1 inhibitor, mitochondrial division inhibitor-1 (Mdivi-1), effectively mitigated the adverse effects of OPA1 impairment. These effects included reduced Drp1 phosphorylation, decreased mitochondrial fragmentation, and balanced mitophagy. Thus, we propose that intervening in DRP1 with Mdivi-1 could correct mitochondrial abnormalities, offering a promising therapeutic approach for managing ADOA+.

Atypical orbital primary optic nerve sheath meningioma with severe disfiguring proptosis: an alternative surgical approach

Primary optic nerve sheath meningioma is generally a benign tumor. In rare instances, however, the growth rate and intraocular and intracranial extensions can be highly aggressive, especially in children, leading to poor prognosis. Here, we reported a case of a 24-year-old woman who presented with left eye swelling for 3 years. This was associated with blurred vision, retrobulbar pain, and redness. On examination, the left eye was severely proptosed with complete ophthalmoplegia. Magnetic resonance imaging showed an extensive tumor occupying the whole left orbital cavity with a disfigured eyeball. However, no intracranial extension was observed. Interestingly, complete surgical excision was feasible via transconjunctival anterior orbitotomy without bone removal. The histopathological examination confirmed the diagnosis of optic nerve sheath meningioma. Adjunct radiotherapy was given. On a follow-up after 2 years, left enophthalmos with esotropia was observed.

Primary Tumours of The Optic Disc and The Optic Disc Sheath

Primary optic nerve and optic nerve sheath tumors constitute approximately 8% of intraorbital tumors and although most of them are benign, they are manifested by findings that significantly affect visual function such as vision loss, visual field defect and proptosis. Tumors originating from the optic nerve trunk are mostly benign optic nerve glioma, but rarer tumors such as ganglioglioma, medulloepithelioma, hemangioblastoma, melanocytoma and high-grade glioblastomas such as malignant optic nerve glioma can also be detected. Tumors originating from the optic nerve sheath usually have optic nerve sheath meningioma (ONSM), of those with intraorbital and intracanalicular origin are classified as primary and intracranial ONSMs are classified as secondary tumors. Optic glioma, ONSM, and hemangioblastomas can be seen sporadically or as a component of Type 1 and Type 2 Neurofibromatosis (NF) and Von Hippel-Lindau (VHL) syndromes, respectively. Treatment with systemic chemotherapy, surgical resection and radiotherapy methods should be considered when progressive vision loss, visual field defect and cosmetically intolerable proptosis develop in optic nerve and nerve sheath tumors, which can have a quiet course for years in terms of visual function. While systemic chemotherapy is accepted as the main treatment method in optic gliomas, more successful results are obtained with specialized treatment methods such as stereotactic fractionated radiotherapy in ONSMs.

Role of hypofractionated stereotactic radiotherapy for primary optic nerve sheath meningioma.

Optic nerve sheath meningiomas (ONSM) are rare tumors potentially causing visual deficits. This study aims to report the anatomic and visual outcomes of patients with primary ONSM treated with hypofractionated stereotactic radiotherapy (HF-SRT). Data of 36 patients treated with HF-SRT between 2008 and 2019 were retrospectively collected. The clinical target volume (CTV) was equal to the gross tumor volume and a 2 mm was added for the planning target volume. All responses other than progression were accepted as local control (LC). The VA grading was performed under 3 groups to provide an even distribution; 20/400 or worse, 20/40-20/400, and 20/40 or better. Median HF-SRT dose was 25 Gy and the median CTV was 1.94 cc. After a median of 106 months of follow-up, the tumor regressed in 23 (64%), was stable in 9 (25%), and progressed in 4 (11%) eyes. The overall rate of LC was 89% with 2-, 5-, 10-, and 15-year rate of 100%, 94%, 84%, and 84%, respectively. Treatment-related late toxicity rate was 11%. The VA was stable in 27 (75%) eyes, improved in 5 (14%) eyes, and worsened in 4 (11%) eyes, respectively, after HF-SRT. Female gender was the only independent predictor of an improved VA. Hypofractionated stereotactic radiotherapy is a safe and satisfactory treatment option for primary ONSM without severe toxicity. It may be advisable to commence treatment before an established visual deficit of 20/400 or worse occurs, to make the most of the functional benefit.

A Patient With Exophytic Primary Optic Nerve Sheath Meningioma: Stratified Risk of Surgery Based on the Morphology.

Primary optic nerve sheath meningioma (pONSM) is one of the most challenging tumors to manage. Although surgical excision may be considered a treatment option to maintain visual function, the safety of surgery remains debatable due to the non-negligible risk of optic nerve injury. pONSM often grows concentrically around the optic nerve; however, it can also demonstrate an exophytic growth from the optic nerve. The risk of surgical excision of pONSM may vary based on the tumor's growth pattern and area of contact with the optic nerve; however, there has been no detailed report on risk stratification to date. The authors present an illustrative case of an exophytic pONSM which was removed surgically without complications, suggesting that tumor morphology may also influence the surgical risk. In this report, the imaging and intraoperative features of exophytic pONSM are presented in detail, and the risk factors for complications are discussed.

Cover Image, Volume 71, Issue 5

Cover Illustration: The immunofluorescent confocal microscopy image shows that the glial fibrillary acidic protein (GFAP, green; nuclei, blue), a specific marker of astrocytes, is robustly expressed by primary optic nerve head astrocytes dissociated from neonatal mice (P3). (See Wan, Y, et al. https://doi.org/10.1002/glia.24334)

Tomography features of the lamina cribrosa and its scleral canal in different types and stages of the diabetic optic neuropathy

AbstractLamina cribrosa morphology is ever changing in health and disease, and its changes might cause primary optic nerve damage and secondary damage due to decreasing of blood supplying and axoplasmic transport. Anatomical narrowing of the lamina cribrosa scleral canal may be a precondition of optic nerve and retina damage in diabetes mellitus (DM).Purpose: to define the tomography changes of lamina cribrosa (LC) and its scleral canal depending on type and stage of diabetic optic neuropathy (DON).Methods: 575 patients (1150 eyes) with type 2 DM and 50 non‐diabetic control persons (100 eyes) aged 55.9 ± 7.8 years were examined. LC thickness was measured with optical coherent tomography (OCT) using LC_Thickness_programm.m and main_low_noise_filters_programm.m. The area of LC scleral canal was measured with SD OCT using the LC_cut_position_programm.m and LC_diameter_calculation_programm.m.Results: A correlation between type and stage of DON and LC thickness in diabetic patients was found. An average index of LC thickness in diabetic patients without DON was 1.4 times higher than in controls; in subclinical stage of axial DON – 1.9 times higher, in initial stage – 2.1 times higher, in severe stage of axial DON and diabetic papillopathy – 2.6 times higher, in anterior ischemic DON – 2.7 times higher, in dystrophic stage – 3.1 times higher than in controls (303 ± 56 μm) (р < 0.001). Scleral canal area in diabetic papillopathy was 35% less and in anterior ischemic DON was 21.6% less than that in controls. A direct correlation between the area of LC scleral canal and the state of optic nerve head was found in diabetic papillopathy and ischemic DON (r = 0.89, р < 0.001 and r = 0.93, р < 0.001 соrrespondingly).Conclusions: A direct correlation between type and stage of DON and scleral LC thickness in patients with DM was revealed. Narrowing of LC scleral canal and thickening of LC were found to change in diabetic papillopathy and ischemic DON.

Long-Term Visual Function After Fractionated Stereotactic Radiotherapy for Primary Optic Nerve Sheath Meningioma: A Retrospective Analysis of 34 Subjects

ObjectiveTo evaluate long-term visual function after fractionated stereotactic radiotherapy (FSRT) for primary optic nerve sheath meningioma (PONSM).MethodsThis 22-year retrospective study included 34 subjects (34 affected eyes) with PONSM who were treated with FSRT exclusively. Subjects with a history of biopsy/resection were excluded. Visual function, including visual acuity (VA) and visual field mean deviation (VF MD), was evaluated at presentation (pre-radiotherapy; pre-RT) and at the final follow-up (post-radiotherapy; post-RT); treatment complications were also evaluated. Treatment success was defined as either stabilization or improvement of visual function.ResultsThe median pre-RT VA and pre-RT VF MD were 0.70 logarithm of the minimum angle of resolution (logMAR; range: 0.0–2.9 logMAR) and −15.4 decibels (dB) (range: −31.4 to −3.2 dB), respectively. The median total dose of FSRT was 50 Gy (range: 45–54 Gy) and the median number of fractions was 25 (range: 25–30). The median follow-up interval was 89 months (range: 6–251 months). The median post-RT VA and post-RT VF MD were 0.48 logMAR (range: 0.0–2.9 logMAR) (p = 0.010) and −6.8 dB (range: −20.6 to −1.6 dB) (p = 0.005), respectively. Among the 34 included eyes, VA was successfully treated in 29 eyes (85.3%) and worsened in 5 eyes (14.7%). Of the 14 eyes with both VA and reliable VF MD at pre-RT and post-RT time points, VF MD was successfully treated in 13 eyes (92.8%) and worsened in one (7.2%); overall visual function was successfully treated in 13 eyes (92.8%) and worsened in 1 eye (7.2%). Complications occurred in one subject (2.9%; radiation retinopathy).ConclusionApproximately 90% of PONSM subjects exhibited long-term treatment success in terms of VA, VF MD, and overall visual function after FSRT. Additionally, the incidence of complications was low. Therefore, FSRT is effective and safe treatment for PONSM.

Photoreceptor Manifestations of Primary Mitochondrial Optic Nerve Disorders.

PurposeTo compare the manifestations of photoreceptors (PRs) in three hereditary optic neuropathies affected by primary mitochondrial dysfunction and discuss whether the retinal ganglion cells (RGCs) or the PRs are preferentially affected.MethodsA retrospective analysis of patients with genetically confirmed diagnoses of optic neuropathies associated with mitochondrial dysfunction was performed. This cohort included Leber's hereditary optic neuropathy (LHON), autosomal dominant optic atrophy type 1 (OPA1), and optic atrophy type 13 (OPA13). Patient chart evaluations included clinical characteristics, best-corrected visual acuity (BCVA), fundus photography, spectral-domain optical coherence tomography (SD-OCT), electroretinogram (ERG), and visual evoked potential data.ResultsThis analysis included seven patients with LHON, six with OPA1, and one with OPA13 from a tertiary medical center. Thirteen of the 14 individuals were male. The average BCVA at diagnosis was 20/285 and 20/500 in the right and left eyes, respectively. Five of the seven patients with LHON, and three of the six patients with OPA1 also showed a mild amplitude reduction or delayed latency on light-adapted ERG and 30-Hz flicker responses; however, SD-OCT imaging did not show correlated PR abnormalities. Notably, a 7-year follow-up of a patient with OPA13 revealed degeneration of RGCs prior to the degeneration of PRs. Follow-up data also demonstrated continuous loss of cone outer segment tips on SD-OCT imaging.ConclusionsRGCs are, in general, affected by mitochondrial dysfunction, whereas variable PR dysfunction exists in patients with LHON and OPA1, especially with respect to the cone responses. Involvement of PRs is particularly evident in OPA13 after RGC degenerations.

Occurrence of Second Primary Malignancies in Patients With Primary Optic Nerve Gliomas: A Surveillance, Epidemiology, and End Results Analysis.

Advanced understanding of screening and therapeutic modalities acts as provision for increased survival in patients diagnosed with optic nerve gliomas. Secondary primary malignancies (SPMs) in patients diagnosed with primary optic nerve glioma (OPG) are currently an uncharacterized frontier. This US national database analysis highlights the incidences of SPMs in patients diagnosed with primary OPG. Standardized incidence ratios (SIR) and excess absolute risk (EAR) for SPMs were calculated using the SEER-specific multiple outcome analysis. 95% SIR confidence intervals were calculated with statistical significance achieved at p<0.05. SPMs originating from soft tissues (including the heart) (SIR=33.23, CI=6.85-97.11; EAR=5.07), breast (SIR=4.99, CI=1.36-12.77; EAR=5.57), female breast (SIR=5.03, CI=1.37-12.89; EAR=5.58), brain (SIR=105.38, CI=65.23-161.08; EAR=36.23), cranial nerves (SIR=103.29, CI=12.51-373.12; EAR=3.45), non-lymphocytic leukemia (SIR=15.05, CI=1.82-54.37; EAR=3.25), myeloid and monocytic leukemia (SIR=16.26, CI=1.97-58.75; EAR=3.27), and Kaposi's sarcoma (SIR=79.88, CI=2.02-445.08; EAR=1.72) demonstrated significantly increased SIR. Overall, the values for cumulative SPM (SIR=6.04, CI=4.33-8.19; EAR=59.60) highlight the overall significance in incidence of SPM in patients diagnosed with OPG. Clinical decision-making should reconcile enhanced propensities for development of SPM.

Mechanosensitive channel inhibition attenuates TGFβ2-induced actin cytoskeletal remodeling and reactivity in mouse optic nerve head astrocytes

Astrocytes within the optic nerve head undergo actin cytoskeletal rearrangement early in glaucoma, which coincides with astrocyte reactivity and extracellular matrix (ECM) deposition. Elevated transforming growth factor beta 2 (TGFβ2) levels within astrocytes have been described in glaucoma, and TGFβ signaling induces actin cytoskeletal remodeling and ECM deposition in many tissues. A key mechanism by which astrocytes sense and respond to external stimuli is via mechanosensitive ion channels. Here, we tested the hypothesis that inhibition of mechanosensitive channels will attenuate TGFβ2-mediated optic nerve head astrocyte actin cytoskeletal remodeling, reactivity, and ECM deposition. Primary optic nerve head astrocytes were isolated from C57BL/6J mice and cell purity was confirmed by immunostaining. Astrocytes were treated with vehicle control, TGFβ2 (5 ng/ml), GsMTx4 (a mechanosensitive channel inhibitor; 500 nM), or TGFβ2 (5 ng/ml) + GsMTx4 (500 nM) for 48 h. FITC-phalloidin staining was used to assess the formation of f-actin stress fibers and to quantify the presence of crosslinked actin networks (CLANs). Cell reactivity was determined by immunostaining and immunoblotting for GFAP. Levels of fibronectin and collagen IV deposition were also quantified. Primary optic nerve head astrocytes were positive for the astrocyte marker GFAP and negative for markers for microglia (F4/80) and oligodendrocytes (OSP1). Significantly increased %CLAN-positive cells were observed after 48-h treatment with TGFβ2 vs. control in a dose-dependent manner. Co-treatment with GsMTx4 significantly decreased %CLAN-positive cells vs. TGFβ2 treatment and the presence of f-actin stress fibers. TGFβ2 treatment significantly increased GFAP, fibronectin, and collagen IV levels, and GsMTx4 co-treatment ameliorated GFAP immunoreactivity. Our data suggest inhibition of mechanosensitive channel activity as a potential therapeutic strategy to modulate actin cytoskeletal remodeling within the optic nerve head in glaucoma.

Новые возможности нейропротекторной терапии при дегенеративных и ишемических поражениях сетчатки и зрительного нерва

The presented literature review highlights the significance of the ischemia as a reason of reducing visual acuity in case of having such diseases as rhegmatogenous retinal detachment, primary open-angle glaucoma, AION and optic nerve atrophy. The expediency of prescribing “Cytoflavin” in the background of ischemia in case of neurodegenerative eye diseases is justified. The evidence of the effectiveness of this medicine in ophthalmological practice is provided.

Primary and Secondary Optic Nerve Sheath Meningioma.

Objective This study was aimed to review issues relating to the recognition, radiographic diagnosis, monitoring, and management of primary and secondary optic nerve sheath meningioma (ONSM). Design This study is a review of peer-reviewed literature combined with illustrative case studies. Participants and Methods A literature search was conducted via the PubMed database using pertinent search terms. Selected articles were limited to those written or translated into English. Additional works cited within articles were also included. Individual cases were drawn from the experience of a tertiary academic neuroophthalmic and orbital practice. Tables summarize radiotherapeutic and surgical studies, excluding single case reports and studies focusing on meningioma of intracranial origin. Main Outcome Measurements Review of reported surgical and radiotherapeutic series is the primary measurement. Results The natural history of optic nerve sheath meningiomas is primarily characterized by progressive ipsilateral vision loss. Diagnosis is typically based on radiographic imaging findings, with biopsy remaining indicated in some patients. Management strategies may include observation, radiation, and/or surgical intervention, or a combination of these approaches. The role of surgery, especially with respect to primary ONSM (pONSM), remains controversial. Advancement of radiotherapy techniques has shifted modern treatment paradigms in pONSM toward radiation as primary treatment, as surgical outcomes are inferior in major studies. Although radiation remains the treatment of choice in many cases, selected patients may benefit from surgery, especially in the setting of secondary ONSM (sONSM). Conclusion A wide variety of radiotherapeutic and surgical treatment modalities for ONSM exist. The specific indications for each management strategy continue to be redefined.

Piezo1 plays a role in optic nerve head astrocyte reactivity

Piezo1 (also known as Fam38A) is a mechanosensing channel required for mechanotransduction in various cell types. In astrocytes, Piezo1 activation is associated with the pathogenesis of central nervous system neurodegeneration. Expression of Piezo1 has been detected in mouse optic nerve head astrocytes, however, the functional role of Piezo1 has not been identified. In this study, we investigated the role of Piezo1 in optic nerve head astrocyte reactivity. Primary mouse optic nerve head astrocytes were cultured and subjected to mechanical stretch. The expression level of Piezo1 was determined by quantitative PCR and immunocytochemistry staining. Astrocytes were further treated with Yoda1, a specific Piezo1 agonist. The intracellular calcium concentration and expression of F-actin and fibronectin were determined in Yoda1 treated cells. We found that mechanical stretch activated Piezo1 in optic nerve head astrocytes. Yoda1 induced robust Ca2+ responses in a dose dependent manner. In addition, Yoda1 treated cells showed a redistribution of F-actin cytoskeleton and an increased expression of fibronectin which indicated astrocyte reactivity. Our results suggest that Piezo1 responses to mechanical stimulation and plays a role in astrocyte reactivity. This study provides new insights into optic nerve head astrocyte mechanotransduction.

Visual evoked potentials (VEP) studies in primary open glaucoma

Background: With increasing prevalance of primary open angle glaucoma and optic nerve damage as a consequence of this, there is a need for early diagnosis and prevention of optic nerve damage. VEP, the potential recorded from the occipital region in response to the visual stimuli can be used for early detection of the primary open angle glaucoma. Visual evoked potential (VEP) is a non invasive method to assess the visual pathway. The present study was done to evaluate the impact of primary open angle glaucoma on central nervous system particularly, visual pathway. Methods: 30 primary open angle glaucoma patients attending outpatient department of ophthalmology department, SS hospital, Davanagere and 30 age matched controls selected randomly from general population were subjected to Visual evoked potential. Parameters for VEP such as latencies of waves N70, P100, and N155 peak-to-peak amplitudes of waves N70-P100 and P100-N155 were assessed and analyzed by using unpaired student-T test for comparison between cases and controls. Results: The present study observed that the there was a statistically significant increase in P100 latency in cases compared to the controls. And also there was a statistically significant decrease in N70 and P100 amplitude in cases compared to the controls. Conclusion: The present study correlates with earlier findings that visual pathway gets involved in primary open angle glaucoma even before the development of neuropathy which can be detected using VEP. Meticulous follow-up is a must to prevent the complications of primary open angle glaucoma, so that further damage can be prevented.

The extracellular matrix composition of the optic nerve subarachnoid space

The meninges not only surround the brain and the spinal cord but also the optic nerve. Meningeal-derived extracellular matrix (ECM) is a crucial component of the pial basement membrane, glia limitans and important for maintenance of optic nerve axon integrity, homeostasis and retinal ganglion cell health. To get closer insight into optic nerve meningeal-derived ECM composition, we performed proteomic analysis of the sheep optic nerve subarachnoid space (SAS). Candidate components were confirmed in cultures of primary human meningothelial cells (phMECs) and human optic nerve samples. Sheep optic nerve SAS samples were analysed by LC-MS, identified proteins were matched to their human orthologs and filtered using gene lists representing all major ECM components. To validate these findings digital droplet PCR (ddPCR) to evaluate mRNA expression of all candidate components identified was performed on cultures of phMECs. In addition, one protein per major ECM group was stained on human optic nerve sections and on phMEC cultures. Employing LC-MS, 1273 proteins were identified and subjected to bioinformatic analysis. Gene ontology analysis revealed six out of forty-four collagen types (1A1, 1A2, 3A1, 6A2, 6A3 and 14A1), three out of eleven laminin subunits (A4, B2, C1) and six out of twenty-seven hyaluronan binding proteins (CD44, versican (VCAN), C1q binding protein, neurocan (NCAN), brevican (BCAN) and hyalaluronan proteoglycan link protein 2 (HAPLN2)) were present in our cohort. DdPCR in phMEC cell culture confirmed presence of all candidate components except NCAN, BCAN and HAPLN2. Immunohistochemistry (IHC) staining on human optic nerve sections and immunofluorescence (IF) staining on in vitro cultured phMECs showed strong immunopositivity for collagen-typeI-α1 (COL1A1), lamininγ1 (LAMC1), and VCAN. Fibronectin (FN1) was exclusively present in cultures of phMECs. Using a combined bioinformatics and immunohistological approach, we describe the ECM composition of the optic nerve subarachnoid space. As this space plays an important role in maintaining optic nerve function, a better understanding of ECM composition in this delicate environment might be key to further pathophysiological insight into optic nerve degeneration and associated disorders.

Differential Activation of Glioprotective Intracellular Signaling Pathways in Primary Optic Nerve Head Astrocytes after Treatment with Different Classes of Antioxidants.

Optic nerve head astrocytes are the specialized glia cells that provide structural and trophic support to the optic nerve head. In response to cellular injury, optic nerve head astrocytes undergo reactive astrocytosis, the process of cellular activation associated with cytoskeletal remodeling, increases in the rate of proliferation and motility, and the generation of Reactive Oxygen Species. Antioxidant intervention has previously been proposed as a therapeutic approach for glaucomatous optic neuropathy, however, little is known regarding the response of optic nerve head astrocytes to antioxidants under physiological versus pathological conditions. The goal of this study was to determine the effects of three different antioxidants, manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin (Mn-TM-2-PyP), resveratrol and xanthohumol in primary optic nerve head astrocytes. Effects on the expression of the master regulator nuclear factor erythroid 2-related factor 2 (Nrf2), the antioxidant enzyme, manganese-dependent superoxide dismutase 2 (SOD2), and the pro-oxidant enzyme, nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), were determined by quantitative immunoblotting. Furthermore, efficacy in preventing chemically and reactive astrocytosis-induced increases in cellular oxidative stress was quantified using cell viability assays. The results were compared to the effects of the prototypic antioxidant, Trolox. Antioxidants elicited highly differential changes in the expression levels of Nrf2, SOD2, and NOX4. Notably, Mn-TM-2-PyP increased SOD2 expression eight-fold, while resveratrol increased Nrf2 expression three-fold. In contrast, xanthohumol exerted no statistically significant changes in expression levels. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) uptake and lactate dehydrogenase (LDH) release assays were performed to assess cell viability after chemically and reactive astrocytosis-induced oxidative stress. Mn-TM-2-PyP exerted the most potent glioprotection by fully preventing the loss of cell viability, whereas resveratrol and xanthohumol partially restored cell viability. Our data provide the first evidence for a well-developed antioxidant defense system in optic nerve head astrocytes, which can be pharmacologically targeted by different classes of antioxidants.

Retrospective analysis of fractionated intensity-modulated radiotherapy (IMRT) in the interdisciplinary management of primary optic nerve sheath meningiomas

BackgroundAs optic nerve sheath meningiomas (ONSM) are rare, there are no prospective studies. Our retrospective analysis focusses on a cohort of patients with uniform disease characteristics all treated with the same radiotherapy regimen. We describe treatment decision making, radiotherapy planning and detailed neuro-ophthalmological outcome of the patients.Methods26 patients with unilateral ONSM extending only to the orbit and the optic canal were evaluated for neuro-ophthalmological outcome. Radiation treatment was planned in a simultaneous integrated boost approach to gross tumor volume (GTV) + 2 mm / 5 mm to 54 Gy / 51 Gy in 1.8 Gy / 1.7 Gy fractions. Follow-up was done by specialized neuro-ophthalmologists. Visual acuity and visual field defects were evaluated after therapy as well as during follow-up.ResultsInterdisciplinary treatment decision for patients with ONSM follows a rather complex decision tree. Radiation treatment planning (equivalent uniform dose (EUD), maximum dose to the optic nerve) improved with experience over time. With this patient selection visual acuity as well as visual field improved significantly at first follow-up after treatment. For visual acuity this also applied to patients with severe defects before treatment. Long term evaluation showed 16 patients with improved visual function, 6 were stable, in 4 patients visual function declined. Interdisciplinary case discussion rated the visual decline as radiation-associated in two patients.ConclusionsWith stringent patient selection radiotherapy for unilateral primary ONSM to 51 Gy / 54 Gy is safe and leads to significantly improved visual function. Interdisciplinary treatment decision and experience of the radiation oncology team play a major role.

Long-term treatment outcomes of patients with primary optic nerve sheath meningioma treated with stereotactic radiotherapy

We analysed the long-term outcomes of patients with primary optic nerve sheath meningioma (ONSM) treated with stereotactic radiotherapy (SRT). 26 patients with primary ONSM were treated with SRT between 2004 and 2013 at a single institution. SRT was delivered with image guidance to a median dose of 50.4 Gy in 28 fractions. 4 patients had prior surgical debulking. At a median radiological follow-up of 68 months, the MRI based tumour control was 100%. Visual acuity improved in 10 (38.4%), remained stable in 10 (38.4%) and was reduced in 6 (23.1%) patients following treatment. Stable or improved vision post-treatment was seen in 92.3% of patients with good pre-treatment vision (best corrected visual acuity 6/18 or better), compared to only 61.5% of patients with poor pre-treatment vision (best corrected visual acuity 6/24 or worse). Overall, the treatment was well tolerated with no Grade 2 or greater acute toxicity. Minimal other ophthalmic complications were seen with only one patient developing late onset Grade 3 radiation retinopathy.