Protective effects of compound M01 on retinal ganglion cells in experimental anterior ischemic optic neuropathy by inhibiting TXNIP/NLRP3 inflammasome pathway.

Apoptotic death of retinal ganglion cells (RGCs) is a common pathologic feature in different types of optic neuropathy, including ischemic optic neuropathy and glaucoma, ultimately leading to irreversible visual function loss. Potent and effective protection against RGC death is determinative in developing a successful treatment for these optic neuropathies. This study evaluated the neuroprotective effect of a HECT domain-E3 ubiquitin ligase inhibitor, M01, on retinal ganglion cells after ischemic injury. Experimental anterior ischemic optic neuropathy (AION) was induced by photothrombotic occlusion of microvessels supplying optic nerve in rats. M01 was administered (100 mg/Kg and 200 mg/Kg) subcutaneously for three consecutive days after AION induction. Administration of M01 (100 mg/Kg) significantly increased RGC survival and preserved visual function after AION induction. The number of TUNEL-positive cells and ED1-positive cells was significantly decreased, and optic disc edema was reduced considerably after ischemic infarction with M01 treatment. Moreover, M01 effectively ameliorated optic nerve demyelination and enhanced M2 microglial polarization after AION induction. M01 enhanced the expression of nuclear factor erythroid 2-related factor (Nrf2); subsequently, downregulated Thioredoxin interacting protein (TXNIP) expression, inhibited NLR family pyrin domain containing 3 (NLRP3) activation, and further decreased inflammatory factors, interleukin (IL)-1ß and IL-6 in the retina after ischemic injury. These findings suggested that M01 has therapeutic potential by modulating Nrf2 and TXNIP/NLRP3 inflammasome pathways in the retina and optic nerve ischemic damage-related diseases.

Structure-function relationship between magnetic resonance imaging lesion areas and visual field defects in initial optic neuritis with altitudinal hemianopsia.

PURPOSE: To study the spatial association of magnetic resonance imaging (MRI) contrast enhancement (CE) areas with visual field defect (VFD) asymmetry in initial cases of optic neuritis (ON) with altitudinal hemianopsia (AH) with reference to nonarteritic anterior ischemic optic neuropathy (NAION) with AH. STUDY DESIGN: Multicenter, cross-sectional study. METHODS: The present study comprised 19 ON patients and 20 NAION patients with AH who underwent orbital contrast fat-suppressed MRI. The signal-to-intensity ratio (SIR) was calculated by dividing the maximum CE of the optic nerve by the mean CE of the cerebral white matter in 11 coronal sections at 3-mm intervals from immediately posterior to the eyeball to the optic chiasm. Sections in ON patients with an SIR exceeding the mean plus 2 standard deviations of the SIR at the corresponding section in the NAION group were considered abnormal. The correlation between upper-to-lower CE asymmetry in the maximum SIR section and VFD counterpart was determined. RESULTS: The ON group had significantly higher maximum SIR than that of the NAION group (1.77 ± 0.88 vs. 1.25 ± 0.32; P < .01). Seven of the 19 patients had sections with abnormally high CE extending posteriorly beyond the orbital apex. Significant spatial correspondence was observed between CE and VFD asymmetry (rs = 0.563; P = .015) in the ON group but not in the NAION group (rs = - 0. 048; P = .850). CONCLUSIONS: ON patients with AH frequently show CE even in the intracerebral optic nerve, maintaining a moderate structure-function correspondence.

Is the clinical course of non-arteritic ischemic optic neuropathy associated with oxidative damage and the dynamics of the antioxidant response?

PURPOSE: Oxidative stress is known to be a decisive factor in the wide etiopathogenesis of optic neuropathy. This study aimed to comprehensively evaluate the interaction of optic neuropathy's clinical course with systemic oxidative damage and antioxidant response dynamics in a large series. METHODS: This case-controlled clinical study included 33 non-arteritic anterior ischemic optic neuropathy (NAION) patients and 32 healthy individuals. Extensive systemic oxidation profiles were statistically compared between the two groups, and correlations between the clinical and biochemical data in the study group were analyzed. RESULTS: Vitamin E and malondialdehyde (MDA) levels were significantly higher in the study group. Significant correlations were observed in the analyses between clinical findings and oxidative stress parameters. Correlations between vitamin E and intraocular pressure (IOP), between B12 and cup-to-disk ratio (c/d), between antioxidant glutathione and superoxide dismutase (SOD) enzyme systems, and between uric acid (UA) and age were found to be very significant. As significant correlations were found in either clinical and biochemical data or in oxidative stress parameters, correlations between vitamin E and cholesterol, MDA were found to be very significant. CONCLUSIONS: This study not only supplies significant information regarding oxidative damage and antioxidant response in NAION, but also points out the specific interactions of neuromodulators, like vitamin E, in intracellular signaling pathways and regulation mechanisms. A better reading of these connections may help improve diagnosis, follow-ups and treatment criteria and strategies.

MRI signs helpful in the differentiation of patients with anterior ischaemic optic neuropathy and optic neuritis.

BACKGROUND/AIMS: The aim of this study was to identify specific MRI characteristics of anterior ischaemic optic neuropathy (AION) and optic neuritis (ON) that would aid in the differentiation between these two diagnoses. METHODS: We retrospectively analysed a consecutive case series including all patients with an MRI study of brain and orbit and the clinical diagnosis of either ON or AION. We examined the scans for restricted diffusion of the optic nerve, optic sheath diameter, enhancement and location of enhancement of the optic nerve and distribution of the white matter lesions. RESULTS: Fifty patients met the inclusion criteria. We found an accuracy of 0.98 for the discrimination between AION and ON based solely on parameters extracted from MRI data. Dominance analysis to determine the most influential parameters showed that the enhancement pattern of the optic nerve and distribution of the white matter lesions had the biggest impact on the classification and led to a discrimination accuracy of 0.9 when used alone. CONCLUSION: In patients with an inconclusive clinical diagnosis, optic nerve enhancement pattern and distribution of white matter lesions can aid in the diagnosis and differentiation between AION and ON. Diffusion-weighted imaging did not add significant information to the diagnosis or help to differentiate between the two conditions.

Post-cataract surgery optic neuropathy: a chronological narrative review of the literature and speculation on pathogenesis.

PURPOSE OF REVIEW: To appraise the literature on the incidence of an acute anterior optic neuropathy resembling spontaneous nonarteritic anterior ischemic optic neuropathy (NAION) following uncomplicated cataract surgery and to explore the proposed pathogenesis of both immediate and delayed onset post-cataract surgery optic neuropathy (PCSON). RECENT FINDINGS: A number of case reports, case series, and retrospective case-controlled, big data, and population-based studies have identified an apparent association between cataract surgery and the occurrence of an acute anterior optic neuropathy that can either be immediate or delayed in onset. However, a recent study found no link between modern day cataract surgery and an increased risk of an acute anterior optic neuropathy. SUMMARY: Immediate PCSON appears to be related to negative perfusion pressure at the level of the optic disc due to increased intraocular pressure. The pathogenesis of delayed PCSON is unknown but probably multifactorial. Patients who have experienced spontaneous NAION or PCSON in one eye may be at risk of PCSON in the fellow eye.

Diagnosis of giant cell arteritis using clinical, laboratory, and histopathological findings in patients undergoing temporal artery biopsy.

OBJECTIVE: To identify the clinical, laboratory, and histopathological features that may predict the diagnosis of giant cell arteritis (GCA). METHODS: A retrospective chart review was performed on patients who underwent temporal artery biopsy (TAB) between January 1, 2011 and March 31, 2019. Patient demographics, clinical characteristics, laboratory features, histopathological features, and biopsy results were collected. GCA status was determined by a neuro-ophthalmologist (OOA). Stepwise logistic regression analysis was performed to identify features that predict GCA status. RESULTS: Of 101 patients who underwent TAB, 31 (31%) were diagnosed with GCA. Age was found to be statistically significant for the diagnosis of GCA (P = 0.009), with an average age of 74.4 years ( ± 8.1) in those with GCA vs. 68.9 years ( ± 10.0) in those without. The incidence of transient vision loss was higher in GCA than non-GCA patients (P = 0.005). Anterior arteritic ischemic optic neuropathy (n = 3), ophthalmic artery occlusion (n = 2), and posterior ischemic optic neuropathy (n = 1) were seen only in the GCA group. Of the 31 GCA patients, 15 had active GCA (48%), 3 (10%) had healed temporal arteritis (HTA), 8 (26%) had suggested HTA, and 5 (16%) had false negative biopsies. Of the 70 non-GCA patients, 63 (90%) had negative biopsies, 2 (3%) had HTA, and 5 (7%) had suggested HTA. Histopathological analysis revealed that CD68 staining had a sensitivity of 69% and specificity of 86%. Both presence of multinucleated giant cells (MNGC) and transmural inflammation had 100% specificity; however, sensitivity was ≤ 50%. In patients with negative TABs and complete risk factor data available (n = 66), the odds of GCA increased 2.16-fold every 5 years of age, and 1.08-fold every mg/day of oral steroid use. A biopsy result of HTA had an odds ratio of 84.7 and suggested HTA of 49.2 against a negative TAB for diagnosis of GCA. CONCLUSION: Age at time of biopsy, HTA, and suggested HTA are predictive for the diagnosis of GCA. Transient vision loss is more commonly seen in GCA, and anterior arteritic ischemic optic neuropathy, ophthalmic artery occlusion, and posterior ischemic optic neuropathy are important ophthalmic manifestations of GCA. CD68 staining is more sensitive but less specific for diagnosing GCA in comparison to other histopathologic findings such as presence of MNGC and transmural inflammation. Further work is recommended to investigate the importance of the specific histopathologic finding of CD68 staining in the diagnosis of GCA.

Histopathological effects of topical coenzyme q 10 + Vit E TPGS in experimental ischemic optic neuropathy.

We aimed to create a mechanical optic nerve damage model in rats and to investigate the neuroprotective effects of topical Coenzyme Q10 + Vitamin E TPGS (CoQ10+Vit E) molecule on retinal ganglion cells. In our study, 30 eyes of 20 male Wistar rats were used. Three groups, each consisting of 10 eyes, were formed as control, experimental, and treatment groups. The control group was used to test the formation of optic nerve damage. Topical CoQ10 + Vit E TPGS solution was applied to the rats in the treatment group, one drop twice a day for 3 weeks. On the other hand, physiological drops were applied to the experimental group 2 times a day for 3 weeks. After 3 weeks, the optic nerves of the rats were dissected and examined histopathologically. In electron microscopic examination of the treatment group, it was noted that the myelin sheath in the majority of myelinated nerve fibers and the normal structures of mitochondria, neurotubules, and neurofilaments in the axoplasm were preserved. It was observed that the oligodendrocytes surrounded the myelinated axons. In the experimental group, significant degenerative changes were observed in myelinated nerve fibers in many areas. The number of myelinated axons was significantly increased in the treatment group compared to the experimental group (p = .0028). In the light of the data obtained, the neuroprotective effect of the topically used CoQ10 + Vit E TPGS molecule was found to be histopathologically effective in our experimental study.Abbreviations: NAAION: Nonarteritic anterior ischemic optic neuropathy; CoQ10: Coenzyme q10; CG: Control group; EG: Experimental group; TG: Treatment group.

Optic neuropathies post-Covid 19 - review.

The Corona virus infection started at the end of 2019 in Wuhan - China and spread rapidly throughout the world, generating the Covid 19 pandemic. The manifestations of the Covid disease were extremely varied, from a simple flu, with fever, cough, weakness, headache, joint pain, up to severe pneumonia, with severe acute respiratory syndrome (SARS-Cov2) and even death. The symptomatology of the disease, the evolution and the complications that appeared varied, depending on the associated pathology - diabetes mellitus (DM), hypertension (HT), the age and the immune status of the patient. Aim: The ocular manifestations related to Covid 19 were mostly represented by conjunctivitis, but the neurotropic character of Corona virus could justify the appearance of certain neuro-ophthalmological manifestations, such as: optic neuritis (ON), cranial nerve palsies, visual field (VF) anomalies. The aim of this paper was to research the cases of optic neuropathy post-Covid 19, published in the specialty literature between 2020 and 2022. The following were evaluated: risk factors, distribution by age group and gender, evolution and complications, as well as the clinical forms of optic neuropathies. Materials and methods: We used Google Scholar and PubMed databases to find articles on optic neuropathies related to the Covid-19 infection. We followed the articles published during the pandemic and selected 21 cases, belonging to 17 authors, irrespective of their origin and the language in which they were written. Results: 21 patients affected by ON in the Covid-19 disease, 11 women and 10 men, were mentioned. The optic neuropathies described by the authors were: retrobulbar optic neuropathy, only one associated with myelin oligodendrocyte glycoprotein (MOG), papillitis, neuroretinitis, anterior ischemic optic neuropathy (AION), out of which one arteritic anterior ischemic optic neuropathy (AAION) and the others non-arteritic anterior ischemic optic neuropathy (NAAION), one being related to pronation in an oro-tracheal intubated (OTI) patient with acute respiratory distress syndrome (ARDS). Discussions: The neuro-ophthalmological complications associated with Covid 19 disease can be severe, so the patients should be monitored continuously. Many investigations (serological, immunological and imaging exams) are necessary to exclude other etiologies of ON. Conclusions: A complete ophthalmological exam is mandatory for each patient diagnosed with Covid 19 disease, even if they have ocular manifestations or not. Abbreviations: SARS-Cov2 = severe acute respiratory syndrome; DM = Diabetes mellitus; HT = Hypertension; ON = Optic neuritis; VF = Visual field ; NS = Nervous system; CRP = C-reactive Protein; CL = cytokines; IL = interleukins; TNFɑ = tumor necrosis factor; CNS = central nervous system; ACE = angiotensin-converting enzyme; CRVO = central retinal vein occlusion; MOG = myelin oligodendrocyte glycoprotein; MOG-AD = myelin oligodendrocyte glycoprotein antibody disease; BBB = blood-brain barrier; ARDS = acute respiratory distress syndrome; IOP = intraocular pressure; CVP = central venous pressure; MSOF = multiple systems organ failure; AAION = arteritic anterior ischemic optic neuropathy; NAION = non-arteritic anterior ischemic optic neuropathy; AION = anterior ischemic optic neuropathy; OCT = optical coherence tomography; CT = computer tomography; AFG = angiofluorography; MRI = magnetic resonance imaging; ESR = erythrocyte sedimentation rate; RF = rheumatoid factor; ANA = antinuclear antibodies; ANCA = antineutrophil cytoplasmic antibodies; AQP4 = anti aquaporin 4; NMO = neuromyelitis optica; CSF = cerebrospinal fluid; OTI = oro-tracheal intubated; VA = visual acuity; ONTT = optic neuritis treatment trial; RNFL = retinal nerve fiber layer; ICU = intensive care unit; LE = left eye; RE = right eye; MS = multiple sclerosis; ICH = intracranial hypertension; BCVA = best correction visual acuity; LP = light perception; APD = afferent pupillary defect; BM = biomicroscopy; PDN = prednisone; MTX = methotrexate; MTPN = methylprednisolone; NSAID = non-steroidal anti-inflammatory drugs; CGL = cells ganglion layer; VEP = visual evoked potential; CF = counting fingers.

Early diffusion-weighted MRI at 3 Tesla detects ischemic changes of the optic nerve in anterior ischemic optic neuropathy.

OBJECTIVES: To assess the impact of timing from visual symptoms' onset to diffusion-weighted (DW) 3 T MRI completion to detect ischemic changes of the optic disc and optic nerve in AION patients. METHODS: This IRB-approved retrospective single-center study included 3 T MRI data from 126 patients with AION and 111 controls with optic neuritis treated between January 2015 and May 2020. Two radiologists blinded to all data individually analyzed imaging. A senior neuroradiologist resolved any discrepancies by consensus. The primary judgment criterion was the restricted diffusion of the optic disc and/or the optic nerve assessed subjectively on the ADC maps. ADC values were also measured. Spearman rank correlations were used to examine the relationships between timing from visual symptoms' onset to MRI completion and both the restricted diffusion and the ADC values. RESULTS: One hundred twenty-six patients (47/126 [37.3%] women and 79/126 [62.7%] men, mean age 69.1 ± 13.7 years) with AION were included. Restricted diffusion of the optic disc in AION eyes was more frequent in the early MRI group than in the late MRI group: 35/49 (71.4%) eyes versus 3/83 (3.6%) eyes, p < 0.001. ADC values of the pathological optic discs and optic nerves were lower in the early MRI group than in the late MRI group: 0.61 [0.52-0.94] × 10-3 mm2/s versus 1.28 [1.01-1.44] × 10-3 mm2/s, p < 0.001, and 0.74 [0.61-0.88] × 10-3 mm2/s versus 0.89 [0.72-1.10] × 10-3 mm2/s, p < 0.001, respectively. CONCLUSIONS: DWI MRI showed good diagnostic performance to detect AION when performed early after the onset of visual symptoms. KEY POINTS: • Restricted diffusion of the optic disc in eyes affected by AION was significantly more likely to be observed in patients who had undergone MRI within 5 days after onset of visual symptoms. • ADC values of the pathological optic discs and optic nerves were significantly lower in patients who had undergone MRI within 5 days after onset of visual symptoms of AION: 0.61 × 10-3 mm2/s versus 1.28 × 10-3 mm2/s, p < 0.001, and 0.74 × 10-3 mm2/s versus 0.89 × 10-3 mm2/s, p < 0.001, respectively. • The optimal threshold for timing from visual symptoms' onset to MRI completion to detect restricted diffusion of the optic disc and/or optic nerve was 5 days, with an AUC of 0.88 (CI95%: 0.82-0.94).

Characteristics of macrophage-like cells in acute nonarteritic anterior ischemic optic neuropathy and the normal fellow eyes on en face optical coherence tomography.

Purpose: To quantitatively analyze macrophage-like cells (MLCs) at the vitreoretinal interface (VRI) in acute nonarteritic anterior ischemic optic neuropathy (NAION) using en face swept-source optical coherence tomography (OCT). Methods: Twenty-five acute NAION eyes and 25 normal fellow eyes from 25 patients were included in the study. MLCs were visualized in a 3 µm 6 mm×6 mm en face OCT slab above the VRI centered on the optic nerve head (ONH). After semiautomatic binarization and quantification, we evaluated the MLC density between the two groups. We also investigated the relationship between MLC density and other OCT parameters, including the increase in peripapillary retinal nerve fiber layer (RNFL) thickness and loss of vessel density (VD) in radical peripapillary capillary (RPC). Results: The MLC density in the affected eye of the ONH was highly correlated with that in the fellow eye (r=0.612, p=0.001). The MLC density significantly increased in acute NAION eyes (NAION vs. normal, 11.97 ± 6.66 vs. 9.31 ± 6.10 cell/mm2, p=0.028). In sectorial analysis, the increase in MLCs was mainly in the superior regions (4.13 ± 7.49 vs. 0.94 ± 5.21 cell/mm2, p=0.001). The VD of RPC decreased significantly in the affected eyes (NAION vs. normal, 37.54 ± 5.25 vs. 40.56 ± 4.25, p=0.016), and the loss of RPC was predominantly in the superior sectors and the temporal sectors when compared to the inferior sectors and the nasal sectors, respectively (superior vs. inferior, -3.54 ± 6.71 vs. -0.37 ± 8.07, p=0.004; temporal vs. nasal, -2.69 ± 8.72 vs. -1.22 ± 6.06, p=0.005). The loss of RPC and the increase in MLC density were greater in affected sector corresponding to the visual field (VF) defect. Conclision: MLCs located above the VRI increased significantly in acute NAION eyes, especially in subregions corresponding to VF defect, which provides clinical evidence supporting that the inflammatory response participates in the pathological process of NAION. The magnitude of the increase in MLCs corresponds to the RPC loss in the quadrant analysis.

Biomarkers of lesion severity in a rodent model of nonarteritic anterior ischemic optic neuropathy (rNAION).

The rodent model of nonarteritic anterior ischemic optic neuropathy (rNAION) is similar in many of its pathophysiological responses to clinical NAION. Like human NAION, there is significant variability in the severity of the lesion produced, and little is known of the parameters associated with rNAION induction severity or if pre- or early post-induction biomarkers can be identified that enable prediction of lesion severity and ultimate loss of retinal ganglion cells (RGCs). Adult male Sprague-Dawley outbred rats were evaluated for various parameters including physiological characteristics (heart rate, respiratory rate, temperature, hematocrit [Hct]), optic nerve head (ONH) appearance, pre- and post-induction mean diameter, and intravenous fluorescein and indocyanine green angiographic patterns of vascular leakage at 5 hours post-induction, performed using a spectral domain-optical coherence tomography (SD-OCT) instrument. Early changes were correlated with ultimate RGC loss by Brn3a (+) immunohistology. RGC loss also was correlated with the relative level of laser exposure. The severity of ONH edema 2d, but not 5hr, post induction was most closely associated with the degree of RGC loss, revealing a threshold effect, and consistent with a compartment syndrome where a minimum level of capillary compression within a tight space is responsible for damage. RGC loss increased dramatically as the degree of laser exposure increased. Neither physiological parameters nor the degree of capillary leakage 5hr post induction were informative as to the ultimate degree of RGC loss. Similar to human NAION, the rNAION model exhibits marked variability in lesion severity. Unlike clinical NAION, pre-induction ONH diameter likely does not contribute to ultimate lesion severity; however, cross-sectional ONH edema can be used as a biomarker 2d post-induction to determine randomization of subjects prior to inclusion in specific neuroprotection or neuroregeneration studies.

No Evidence of Varicella-Zoster Virus Infection in Temporal Artery Biopsies of Anterior Ischemic Optic Neuropathy Patients With and Without Giant Cell Arteritis.

BACKGROUND: To test the hypothesis that varicella-zoster virus (VZV) infection contributes to temporal arteritis pathogenesis, comprehensive in situ analysis was performed on temporal artery biopsies of 38 anterior ischemic optic neuropathy (AION) patients, including 14 (37%) with giant cell arteritis. METHODS: Biopsies were completely sectioned, and, on average, 146 serial sections per patient were stained for VZV glycoprotein E. RESULTS: Four of 38 AION patients showed VZV glycoprotein E staining, but VZV infection was not confirmed by staining for VZV IE63 protein and VZV-specific polymerase chain reaction on adjacent sections. CONCLUSIONS: This study refutes the premise that VZV is casually related to AION with and without giant cell arteritis.

Therapeutic Targeting of Retinal Immune Microenvironment With CSF-1 Receptor Antibody Promotes Visual Function Recovery After Ischemic Optic Neuropathy.

Retinal ischemia/reperfusion injury (RI) is a common cause of irreversible visual impairment and blindness in elderly and critical unmet medical need. While no effective treatment is available for RI, microglial activation and local immune responses in the retina are thought to play important roles in the pathophysiology of neurodegeneration. While survival and activation of microglia depend critically on colony-stimulating factor receptor (CSF-1R) signaling, it remains unclear if targeting the retinal immune microenvironments by CSF-1RAb after RI is sufficient to rescue vision and present a potentially effective therapy. Here we used rodent models of RI and showed that retinal ischemia induced by acute elevation of intraocular pressure triggered an early activation of microglia and macrophages in the retina within 12 h. This was followed by lymphocyte infiltration and increased production of pro-inflammatory cytokines. Intravitreal injection of CSF-1R neutralizing antibody (CSF-1RAb) after RI significantly blocked microglial activation and the subsequent T cell recruitment. This also led to improved retinal ganglion cell survival and function measured by cell quantification and electroretinogram positive scotopic threshold responses, as well as increased visual acuity and contrast sensitivity as assessed by optomotor reflex-based assays, when compared to the isotype-treated control group. Moreover, the administration of CSF-1RAb efficiently attenuated inflammatory responses and activation of human microglia in culture, suggesting a therapeutic target with human relevance. These results, together with the existing clinical safety profiles, support that CSF-1RAb may present a promising therapeutic avenue for RI, a currently untreatable condition, by targeting microglia and the immune microenvironment in the retina to facilitate neural survival and visual function recovery.

Neuroprotective effects of low-dose G-CSF plus meloxicam in a rat model of anterior ischemic optic neuropathy.

Non-arteritic anterior ischemic optic neuropathy (NAION) causes a sudden loss of vision and lacks effective treatment. Granulocyte colony-stimulating factor (G-CSF) provides neuroprotection against the experimental optic nerve injuries but also induce leukocytosis upon typical administration. We found synergetic neuroprotective effects of meloxicam and low dose G-CSF without leukocytosis in a rat model of anterior ischemic optic neuropathy (rAION). The WBC counts in the low-dose G-CSF-plus meloxicam-treated group were similar to the sham-operated group. Combination treatment of low-dose G-CSF plus meloxicam preserved RGCs survival and visual function, reduced RGC apoptosis and the macrophages infiltration, and promote more M2 phenotype of macrophage/microglial transition than the low-dose GCSF treatment or the meloxicam treatment. Moreover, the combination treatment induced higher serine/threonine kinase 1 (Akt1) expression. The combination treatment of low-dose G-CSF plus meloxicam lessened the leukocytotic side effect and provided neuroprotective effects via Akt1 activation in the rAION model. This approach provides crucial preclinical information for the development of alternative therapy in AION.

Prospective analysis of macular and optic disc changes after non-arteritic anterior ischemic optic neuropathy.

PURPOSE: To prospectively analyse macular and optic disc changes after the occurrence of non-arteritic anterior ischemic optic neuropathy (NAION) and study possible predictors of final visual outcome. METHODS: Patients with NAION underwent a complete ophthalmic examination, including spectral-domain optical coherence tomography of the macula and optic nerve head. The examination was repeated 1, 3, 6, 9 and 12 months after onset. Final visual prognosis was evaluated by visual field (VF) and best-corrected visual acuity (BCVA) at the final visit. Data within the NAION group were analysed over the course of the disease and compared to a disease-free control group at each visit. RESULTS: Twenty-two eyes with NAION and 43 eyes from a control group were included. The retinal nerve fiber layer (RNFL) was significantly thicker in NAION eyes than controls at presentation (P=0.00), and significantly decreased during the next 3 months after presentation (P=0.02). The ganglion cell+inner plexiform layer (GCIPL) was thinner in the NAION group throughout the course of the disease (all P<0.05). Although the acute NAION eyes had significantly lower cup/disc ratios and higher neuroretinal and disc sizes (all P=0.00), there were no significant differences between groups from the third month onwards (all P>0.05). The best predictors of BCVA and VF were GCIPL at 3 months of follow-up (r2=0.32; P=0.03) and RNFL at 6 months of follow-up (r2=0.41; P=0.01) respectively. CONCLUSIONS: RNFL and optic disc changes occur during the first 3 months after the onset of NAION, whereas GCIPL is affected soon after the onset of symptoms. GCIPL and RNFL are useful predictors of final visual outcome.

Three Tesla 3D High-Resolution Vessel Wall MRI of the Orbit may Differentiate Arteritic From Nonarteritic Anterior Ischemic Optic Neuropathy.

BACKGROUND: Anterior ischemic optic neuropathy (AION) is the most common cause of acute optic neuropathy in older patients. Distinguishing between arteritic AION (A-AION) and nonarteritic (NA-AION) is paramount for improved patient management. PURPOSE: The aim of this study was to evaluate 3-dimensional high-resolution vessel wall (HR-VW) magnetic resonance imaging (MRI) at 3 T to discriminate A-AION from NA-AION. MATERIALS AND METHODS: This prospective single-center study was approved by a national research ethics board and included 27 patients (17 A-AION and 10 NA-AION) with 36 AIONs from December 2014 to August 2017 who underwent 3 T HR-VW MRI. Two radiologists blinded to clinical data individually analyzed the imaging separately and in random order. Discrepancies were resolved by consensus with a third neuroradiologist. The primary diagnostic criterion was the presence of inflammatory changes of the ophthalmic artery. Secondary diagnostic criteria included the presence of an enhancement of the optic nerve or its sheath, the optic disc, or inflammatory changes of posterior ciliary or extracranial arteries. A Fisher exact test was used to compare A-AION from NA-AION patients. RESULTS: Inflammatory changes of the ophthalmic artery were present in all patients with A-AION but in none of NA-AION (P < 0.0001). Its sensitivity, specificity, positive predictive value, and negative predictive value were 100%. Inflammatory changes of posterior ciliary arteries were significantly more likely in A-AOIN (82% vs 0%, P < 0.0001). Interreader and intrareader agreements were almost perfect (κ = 0.82-1). CONCLUSIONS: High-resolution vessel wall MRI seems highly accurate when distinguishing A-AION from NA-AION and might be useful to improve patient management.

Increased ER Stress After Experimental Ischemic Optic Neuropathy and Improved RGC and Oligodendrocyte Survival After Treatment With Chemical Chaperon.

Purpose: Increased endoplasmic reticulum (ER) stress is one of the earliest subcellular changes in neuro-ophthalmic diseases. In this study, we investigated the expression of key molecules in the ER stress pathways following nonarteritic anterior ischemic optic neuropathy (AION), the most common acute optic neuropathy in adults over 50, and assessed the impact of chemical chaperon 4-phenylbutyric acid (4-PBA) in vivo. Methods: We induced AION using photochemical thrombosis in adult mice and performed histologic analyses of key molecules in the ER stress pathway in the retina and optic nerve. We also assessed the effects of daily intraperitoneal injections of 4-PBA after AION. Results: In the retina at baseline, there was low proapoptotic transcriptional regulator C/EBP homologous protein (CHOP) and high prosurvival chaperon glucose-regulated protein 78 (GRP78) expression in retinal ganglion cells (RGCs). One day after AION, there was significantly increased CHOP and reduced GRP78 expressions in the ganglion cell layer. In the optic nerve at baseline, there was little CHOP and high GRP78 expression. One day after AION, there was significantly increased CHOP and no change in GRP78 expression. Treatment immediately after AION using daily intraperitoneal injection of chemical chaperone 4-PBA for 19 days significantly rescued Brn3A+ RGCs and Olig2+ optic nerve oligodendrocytes. Conclusions: We showed for the first time that acute AION resulted in increased ER stress and differential expression of ER stress markers CHOP and GRP78 in the retina and optic nerve. Rescue of RGCs and oligodendrocytes with 4-PBA provides support for ER stress reduction as possible treatment for AION.