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Purpose: To investigate the global and regional correlations between longitudinal structure-function (S-F) and vasculature-function (V-F) using circumpapillary retinal nerve fiber layer (cpRNFL) thickness measurements, circumpapillary vessel density (cpVD) and the corresponding/final visual outcomes at different stages of nonarteritic anterior ischemic optic neuropathy (NAION)., Methods: Thirty eyes of 30 patients with acute NAION were included. LogMAR best-corrected visual acuity(BCVA), mean deviation (MD) and visual field index (VFI), cpRNFL thickness and cpVD across different retinal layers were examined at baseline, 2 weeks and 1 month after diagnosis. Potential correlations between the Optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) parameters and visual outcomes were investigated in both acute and sub-acute NAION., Results: Significant global and regional correlations in S-F relationship were identified exclusively in sub-acute stage (p < 0.05). However, among the OCTA parameters for the acute NAION, the temporal cpVD in superficial vessel complex (SVC) and inner retinal layer (IRL) exhibited positive correlations with corresponding and final visual acuity and visual field outcomes. In the sub-acute stage of NAION, the cpVD of global or temporal section in radial peripapillary capillary (RPC), SVC and IRL were positively correlated with visual outcomes., Conclusion: Significant longitudinal V-F relationships exist both globally and regionally, in acute and sub-acute NAION. The cpVD parameters of the SVC and IRL are potentially valuable for evaluating corresponding and final visual outcomes and highlights the importance of monitoring cpVD over cpRNFL thickness in acute NAION., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: The objective of this study was to analyze the nycthemeral variations in blood pressure (BP) in individuals who presented with non-arteritic anterior ischemic optic neuropathy (NAION)., Methods: BP was recorded for 24 h (ambulatory blood pressure monitoring, ABPM) in 65 patients with acute NAION. Three definitions of nighttime periods were used: definition 1, 1 a.m.-6 a.m.; definition 2, 10 p.m.-7 a.m.; and definition 3, 10 p.m.-8 a.m. For each of these definitions, patients were classified according to the value of nocturnal reduction in BP into dippers (10-20%), mild dippers (0-10%), reverse dippers (< 0%), and extreme dippers (> 20%)., Results: The proportions of dippers, mild dippers, reverse dippers, and extreme dippers varied significantly depending on the definition chosen. We found the highest number of patients with extreme dipping (23%) when using the strictest definition of nighttime period (definition 1, 1 a.m.-6 a.m.), as compared with 6.2% and 1.5% for the other definitions, respectively. Overall, 13 of 33 patients without known systemic hypertension (39%) were diagnosed with hypertension after ABPM. No risk factor for NAION was associated with the extreme-dipping profile. Finally, the prevalence of systemic hypertension was high (69%)., Conclusion: In our population of patients who had an episode of NAION, the proportion of extreme dippers was higher than that usually found in the literature. However, extreme dipping is not a frequent feature of patients with NAION as compared to patients with systemic hypertension. ABPM is recommended for all patients with NAION and unknown history of systemic hypertension., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To review treatment modalities that have been studied in acute non arteritic anterior ischemic optic neuropathy (NAION)., Methods: We performed a comprehensive literature search of English language publications in the last 5 years, with human species and NAION. Articles were reviewed to identify those that described original research on treatment of acute NAION. Study type, setting, duration, interventions, and results were extracted and articles were reviewed for biases and limitations., Results: We identified 22 kinds of treatment varying by compound and modality. These include topical, intravitreal, and systemic drugs as well as surgical approaches. Evidence for efficacy ranges from expert opinion to randomized control trials., Conclusions: Although several treatments are utilized in practice, none of these have high quality evidence of efficacy to improve visual outcomes.  Continued collaborative research is necessary to complete high quality studies in order identify effective therapies for this rare and blinding disease., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: We describe the baseline ophthalmic and cardiovascular risk factors across countries, race, and sex for the Quark207 treatment trial for acute nonarteritic anterior ischemic optic neuropathy (NAION)., Design: Prospective, randomized controlled clinical trial., Participants: Adults 50 to 80 years of age with acute NAION recruited from 80 sites across 8 countries., Main Outcome Measures: Ophthalmic features of NAION and cardiovascular risk factors., Methods: We evaluated demographics and clinical and ophthalmologic data, including best-corrected visual acuity (BCVA) and average visual field total deviation (TD), in affected eyes and cup-to-disc ratio in fellow eyes at enrollment. We report the prevalence (mean and standard devition, and median and interquartile range [IQR]) of ophthalmic features and cardiovascular risk factors, stratified by country, race, and sex. We corrected for multiple comparisons using Dunn's test with Bonferroni correction for continuous variables and chi-square testing with Holm-Bonferroni correction for categorical variables., Results: The study enrolled 500 men and 229 women with a median age of 60 and 61 years (P = 0.027), respectively. Participants were predominantly White (n = 570) and Asian (n = 149). The study eye BCVA was 71 characters (IQR, 53-84 characters; approximately 0.4 logarithm of the minimum angle of resolution), and the TD was -16.5 dB (IQR, -22.2 to -12.6 dB) for stimulus III and -15.7 dB (IQR, -20.8 to -10.9 dB) for stimulus V. The vertical and horizontal cup-to-disc ratio was 0.1 (IQR, 0.1-0.3) for unaffected fellow eyes. The prevalence of cardiovascular risk factors varied among countries. The most notable differences were in the baseline comorbidities and ophthalmologic features, which differed between Asian and White races. Men and women differed with respect to a few clinically meaningful features., Conclusions: The cardiovascular risk factors in the NAION cohort varied among the 7 countries, race, and sex, but were not typically more prevalent than in the general population. Ophthalmic features, typical of NAION, generally were consistent across countries, race, and sex, except for worse BCVA and TD in China. Men have a frequency of NAION twice that of women. Having a small cup-to-disc ratio in the fellow eye was the most prevalent risk factor across all demographics. This study suggests that factors, not yet identified, may contribute to the development of NAION., 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.)

Purpose: To evaluate microvascular alterations with optical coherence tomography angiography (OCTA) in eyes with non-arteritic anterior ischaemic optic neuropathy (NAION) and the unaffected fellow eyes., Design: Systematic review and meta-analysis., Methods: A comprehensive literature search was conducted in the PubMed and Embase databases through 6 September 2020, to identify the studies on NAION and the unaffected fellow eyes using OCTA. Eligible studies and data of interest were extracted and analysed by RevMan Software v. 5.4 and Stata Software v.14.0. The weighted mean differences and 95% confidence intervals were used to assess the strength of the association., Results: Seventeen observational comparative studies, including 379 eyes with NAION, 175 unaffected contralateral eyes and 470 eyes of healthy controls, were identified. Compared to those of the healthy controls, the perfusion density (PD) of radial peripapillary capillary (RPC) and peripapillary superficial capillary plexus (ppSCP) of NAION were significantly lower. Moreover, the PD of the macular SCP (mSCP) in NAION was significantly reduced in the whole image, superior quadrant and temporal quadrant, while the macular deep capillary plexus (mDCP) showed a decreasing PD only within the whole image. Between unaffected fellow eyes and healthy eyes, significant differences of PD were demonstrated in the whole image and some peripapillary regions of the RPC and ppSCP., Conclusion: Our results suggested that compared to those of healthy controls, the eyes affected by NAION and unaffected fellow eyes demonstrated significant microvascular impairments in different regions. Between acute and non-acute NAION, macular OCTA parameters showed different characteristic patterns., (© 2021 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To identify the presence of choroidal microvascular dropout (MvD) in nonarteritic anterior ischemic optic neuropathy (NAION) eyes and to characterize the topographical distribution for the mechanistic interpretation of MvD development., Methods: We performed optical coherence tomography angiography on 47 open-angle glaucoma (OAG) and 19 NAION eyes with β-zone peripapillary atrophy (βPPA). We recorded the presence of MvD and compared between the peripapillary topographical measures of MvD, retinal nerve fiber layer (RNFL) defect, and βPPA in angular width and location., Results: MvD was present in both diseases, marginally more frequently in NAION eyes (19/19, 100.0%) than in OAG eyes (38/47, 80.6%, P = 0.050), without a discernable difference in appearance. NAION eyes also showed wider MvD and RNFL defects compared to OAG eyes (both P < 0.001). In topographical measurements, the distribution of MvD showed a strong correspondence to superimposition areas of βPPA and RNFL defects, more distinctly than to RNFL defects (all P < 0.001). The outline of superimposition area also remarkably resembled the MvD area., Conclusions: MvD was present in both the OAG and NAION groups. The βPPA-RNFL defect superimposition area topographically and morphologically matched MvD. Further investigations are needed to elucidate the role of RNFL defects in the pathogenesis of MvD and the clinical significance.

Purpose: This study investigated the neuroprotective effects of administration of ROCK inhibitor E212 on ischemic optic neuropathy., Methods: Rats received an intravitreal injection of either E212 or PBS immediately after optic nerve infarct. The oxidative stress in the retina was detected by performing superoxide dismutase activity and CellROX assays. The integrity of retinal pigment epithelium was determined by staining of zona occludens 1. The visual function, retinal ganglion cell (RGC) density, and RGC apoptosis were determined by using flash visual-evoked potential analysis, retrograde FluoroGold labeling, and TdT-dUTP nick end-labeling assay. Macrophage infiltration was detected by staining for ED1. The protein levels of TNF-α, p-CRMP, p-AKT1, p-STAT3, and CD206 were evaluated using Western blotting., Results: Administration of E212 resulted in a 1.23-fold increase in the superoxide dismutase activity of the retina and 2.28-fold decrease in RGC-produced reactive oxygen species as compared to the levels observed upon treatment with PBS (P < 0.05). Moreover, E212 prevented the disruption of the blood-retinal barrier (BRB) in contrast to PBS. The P1-N2 amplitude and RGC density in the E212-treated group were 1.75- and 2.05-fold higher, respectively, than those in the PBS-treated group (P < 0.05). The numbers of apoptotic RGCs and macrophages were reduced by 2.93- and 2.54-fold, respectively, in the E212-treated group compared with those in the PBS-treated group (P < 0.05). The levels of p-AKT1, p-STAT3, and CD206 were increased, whereas those of p-PTEN, p-CRMP2, and TNF-α were decreased after treatment with E212 (P < 0.05)., Conclusions: Treatment with E212 suppresses oxidative stress, BRB disruption, and neuroinflammation to protect the visual function in ischemic optic neuropathy.

Purpose: Understanding molecular changes is essential for designing effective treatments for nonarteritic anterior ischemic optic neuropathy (AION), the most common acute optic neuropathy in adults older than 50 years. We investigated changes in the mitogen-activated protein kinase (MAPK) pathway after experimental AION and focused on dual specificity phosphatase 14 (Dusp14), an atypical MAPK phosphatase that is downstream of Krüppel-like transcription factor (KLF) 9-mediated inhibition of retinal ganglion cell (RGC) survival and axonal regeneration., Materials and Methods: We induced severe AION in a photochemical thrombosis model in adult C57BL/6 wild-type and Dusp14 knockout mice. For comparison, some studies were performed using an optic nerve crush model. We assessed changes in MAPK pathway molecules using Western blot and immunohistochemistry, measured retinal thickness using optical coherence tomography (OCT), and quantified RGCs and axons using histologic methods., Results: Three days after severe AION, there was no change in the retinal protein levels of MAPK ERK1/2, phosphorylated-ERK1/2 (pERK1/2), downstream effector Elk-1 and phosphatase Dusp14 on Western blot. Western blot analysis of purified RGCs after a more severe model using optic nerve crush also showed no change in Dusp14 protein expression. Because of the known importance of the Dusp14 and MAPK pathway in RGCs, we examined changes after AION in Dusp14 knockout mice. Three days after AION, Dusp14 knockout mice had significantly increased pERK1/2 + , Brn3A + RGCs on immunohistochemistry. Three weeks after AION, Dusp14 knockout mice had significantly greater preservation of retinal thickness, increased number of Brn3A + RGCs on whole mount preparation, and increased number of optic nerve axons compared with wild-type mice., Conclusions: Genetic deletion of Dusp14, a MAPK phosphatase important in KFL9-mediated inhibition of RGC survival, led to increased activation of MAPK ERK1/2 and greater RGC and axonal survival after experimental AION. Inhibiting Dusp14 or activating the MAPK pathway should be examined further as a potential therapeutic approach to treatment of AION., Abbreviations: AION: anterior ischemic optic neuropathy; Dusp14: dual specific phosphatase 14; ERK1/2: extracellular signal-regulated kinases 1/2; Elk-1: ETS Like-1 protein; GCC: ganglion cell complex; GCL: ganglion cell layer; inner nuclear layer; KO: knockout; MAPK: mitogen-activated phosphokinase; OCT: optical coherence tomography; RGC: retinal ganglion cell; RNFL: retinal nerve fiber layer.

Competing Interests: The authors report no conflicts of interest.

Mesenchymal stem cell (MSC) therapy has been investigated intensively for many years. However, there is a potential risk related to MSC applications in various cell niches., Methods: The safety of intravitreal MSC application and the efficacy of MSC-derived conditioned medium (MDCM) were evaluated in the normal eye and the diseased eye, respectively. For safety evaluation, the fundus morphology, visual function, retinal function, and histological changes of the retina were examined. For efficacy evaluation, the MDCM was intravitreally administrated in a rodent model of anterior ischemic optic neuropathy (rAION). The visual function, retinal ganglion cell (RGC) density, and neuroinflammation were evaluated at day 28 post-optic nerve (ON) infarct., Results: The fundus imaging showed that MSC transplantation induced retinal distortion and venous congestion. The visual function, retinal function, and RGC density were significantly decreased in MSC-treated eyes. MSC transplantation induced astrogliosis, microgliosis, and macrophage infiltration in the retina due to an increase in the HLA-DR-positive MSC proportion in vitreous. Treatment with the MDCM preserved the visual function and RGC density in rAION via inhibition of macrophage infiltration and RGC apoptosis., Conclusions: The vitreous induced the HLA-DR expression in the MSCs to cause retinal inflammation and retina injury. However, the MDCM provided the neuroprotective effects in rAION.

Purpose: The purpose of this study was to describe capillary changes in patients with nonarteritic anterior ischemic optic neuropathy (NAION) using optical coherence tomography-angiography (OCT-A) and correlate the results with best corrected visual acuity (BCVA), visual field, OCT retinal nerve fiber layer (RNFL), and combined thickness of ganglion cell and inner plexiform layers (GCIPL) thicknesses., Methods: We enrolled 22 eyes with acute NAION and 30 normal control (NC) subjects in this study. Whole en face image vessel density (WiVD) was measured in the radial peripapillary capillary plexus (RPC), superficial capillary plexus (SCP), and deep vascular complex (DVC) using OCT-A. The examination was repeated at 1 (M1), 3 (M3), 6 (M6), and 9 (M9) months after presentation for NAION., Results: The initial RPC WiVD was significantly reduced in the acute NAION group compared to the NC group (P < 0.0001). Over the course of NAION follow-up, RPC WiVD was significantly reduced at M1 (P < 0.001 compared to M0) and M3 (P < 0.0001 compared to M1). However, there was no significant further decrease at M6 and M9. The initial SCP WiVD was significantly reduced in the NAION group compared to the NC group (P < 0.0001 for both). Over the course of NAION follow-up, a significant decrease was observed for SCP WiVD at M1 (P < 0.001 compared to M0), but no significant change was seen at M3, M6, or M9. DVC was normal in the NAION group. Correlations were found between GCIPL and SCP WiVD in the NAION acute phase (R = 0.604, P = 0.003) and in the M9 atrophic stage (R = 0.551, P = 0.009). At M9, RPC WiVD was correlated with BCVA (R = -0.562, P = 0.007), mean deviation (R = 0.518, P = 0.01), and RNFL (R = 0.655, P = 0.001)., Conclusions: Over the course of NAION, OCT-A provided detailed visualization of retinal capillary plexus involvement.

BACKGROUND The aim of this study was to analyze the correlation of macular micro-field characteristics with vision and visual field in patients with non-arteritic anterior ischemic optic neuropathy. MATERIAL AND METHODS Retrospective case analysis was performed. Fifty-eight NAION patients with 62 affected eyes were included in the study. In addition, 54 eyes not affected by NAION from 54 patients among the 58 patients were included as controls. All eyes underwent best corrected visual acuity (BCVA) test, slit lamp biomicroscopy, indirect ophthalmoscopy, visual field examination, and microperimetry. BCVA was converted into logarithm of minimum angle of resolution (LogMAR) for statistical analysis. There was no significant difference in age, sex, eye type, or intraocular pressure between the 2 groups. The macular integrity assessment (MAIA) instrument was used for microperimetry. Mean light sensitivity (microMS) in the 10° macular region and the fixation rates for macular fovea 2° and 4° were recorded. Spearman correlation analysis was performed. RESULTS The microMS values were significantly different between the control group and the affected eye group (t=-2.427, P=0.036). MicroMS was significantly correlated with logMAR BCVA (r=-0.802, P=-0.005) and with mean sensitivity (MS) and mean deviation (MD) (r=0.912, P=0.002; r=-0.905, P=0.002; P<0.05). MS and MD were not correlated with logMAR BCVA (r=-0.465, P=0.245; r=0.437, P=0.278). CONCLUSIONS The present study demonstrates that microMS of macular micro-visual field in NAION patients was significantly decreased at early stage, and was significantly correlated with and consistent with visual acuity and visual field.

Objective: To explore altered regional neuronal activity in patients with nonarteritic anterior ischemic optic neuropathy (NAION) and its correlation with clinical performances using the regional homogeneity (ReHo) method, which is based on resting-state functional magnetic resonance imaging (fMRI)., Method: Thirty-one patients with NAION (20 males, 11 females) and 31 age- and sex-matched normal controls (NCs) (20 males, 11 females) were enrolled in the study. All patients underwent ophthalmic examination, including eyesight, intraocular pressure measurement, optimal coherence tomography (OCT), visual field analysis, and fMRI scans. After ReHo was calculated, we investigated group differences in results between the patients and NCs. We analyzed the relationship between ReHo values for different brain regions in patients with NAION and intraocular pressure, visual field analysis, and OCT. A receiver operating characteristic (ROC) curve was used to assess the diagnostic ability of the ReHo method., Results: Compared with NCs, patients with NAION exhibited higher ReHo values in the left middle frontal gyrus, left middle cingulate gyrus, left superior temporal gyrus, and left inferior parietal lobule. Additionally, they exhibited lower ReHo values in the right lingual gyrus, left putamen/lentiform nucleus, and left superior parietal lobule. ReHo values in the left superior parietal lobule were negatively correlated with right retinal nerve fiber layer values ( r = -0.462, P = 0.01). The area under the ROC curve for each brain region indicated that the ReHo method is a credible means of diagnosing patient with NAION., Conclusion: NAION was primarily associated with dysfunction in the default mode network, which may reflect its underlying neural mechanisms., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Pengde Guo et al.)

Purpose: Optic disc drusen (ODD), present in 2% of the general population, have occasionally been reported in patients with nonarteritic anterior ischemic optic neuropathy (NA-AION). The purpose of this study was to examine the prevalence of ODD in young patients with NA-AION., Design: Retrospective, cross-sectional multicenter study., Methods: All patients with NA-AION 50 years old or younger, seen in neuro-ophthalmology clinics of the international ODDS (Optic Disc Drusen Studies) Consortium between April 1, 2017, and March 31, 2019, were identified. Patients were included if ODD were diagnosed by any method, or if ODD were excluded by enhanced-depth imaging optical coherence tomography (EDI-OCT) using ODDS Consortium guidelines. NA-AION eyes with ODD were termed "ODD-AION"; those without were termed "NODD-AION"., Results: A total of 65 patients (127 eyes) with NA-AION were included (mean 41 years old). Of the 74 eyes with NA-AION, 51% had ODD-AION, whereas 43% of fellow eyes without NA-AION had ODD (P = .36). No significant differences were found between ODD-AION and NODD-AION eyes in terms of Snellen best-corrected VA or perimetric mean deviation. According to EDI-OCT results, 28% of eyes with NODD-AION had peripapillary hyperreflective ovoid mass-like structures (PHOMS); 7% had hyperreflective lines, whereas 54% with ODD-AION had PHOMS; and 66% had hyperreflective lines (P = .006 and P < .001, respectively)., Conclusions: Most of these young NA-AION patients had ODD. This indicates that ODD may be an independent risk factor for the development of NA-AION, at least in younger patients. This study suggests ODD-AION be recognized as a novel diagnosis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Significance: Nonarteritic ischemic optic neuropathy (NAION) has been linked with vascular insufficiency, although the pathophysiology remains elusive. Optical coherence tomography angiography (OCTA) is a promising technology that noninvasively evaluates optic disc perfusion and that may help to characterize peripapillary vascular changes in NAION., Purpose: This study aimed to evaluate peripapillary vascularity in NAION eyes and to compare it with fellow unaffected eyes and healthy control eyes using OCTA., Methods: In this cross-sectional study, OCTA of the optic nerve head was obtained in 10 nonacute unilateral NAION and 12 healthy age-matched controls using ZEISS Angioplex. Quantitative analysis of peripapillary retinal and choroidal vascularity of NAION eyes was done using the instrument's inbuilt algorithm and ImageJ software and compared with fellow and control eyes., Results: Mean total peripapillary superficial retinal vessel and perfusion density as calculated by the instrument was significantly reduced in NAION eyes compared with fellow eyes (13.93 ± 4.27 mm/0.36 ± 0.07 for NAION eyes; 17.77 ± 1.26 mm/0.43 ± 0.08 for fellow eyes; P = .01/P = .05). Using the ImageJ software technique, the mean superficial retinal perfusion was found to be significantly reduced in NAION eyes (0.17 ± 0.07) compared with fellow eyes (0.25 ± 0.06; P < .01) and control eyes (0.25 ± 0.04; P < .01). At the level of choriocapillaris, it was not significantly affected in NAION eyes (0.37 ± 0.13) versus fellow (0.34 ± 0.14; P = .1) and control eyes (0.31 ± 0.34; P = .83). Analysis with the two techniques yielded differing results: the ImageJ analysis technique found a 32% reduction in superficial retinal perfusion in NAION eyes, whereas the instrument's inbuilt algorithm found a 16% reduction compared with fellow and control eyes (P ≤.01)., Conclusions: Peripapillary vascularity can be estimated both at the retinal and choroidal levels using ImageJ software to analyze OCTA images. Retinal peripapillary vascularity is compromised in NAION eyes, but vascularity is not significantly affected at the choroidal level.

Background: To explore the effects of enhanced external counterpulsation (EECP) and its underlying influencing factors in nonarteritic anterior ischemic optic neuropathy (NAION) patients., Methods: Patients at Zhongshan Ophthalmic Center with recent-onset (< 8 weeks) NAION were retrospectively recruited. The patients had decided whether or not they would undergo EECP treatment, and the patients who declined were included in the control group. The effectiveness of EECP was evaluated by comparing the visual function and fellow eye involvement in patients with and without EECP treatment., Results: In total, 61 patients (76 eyes) were included. Twenty-nine patients (37 eyes) underwent EECP treatment, while 32 patients (39 eyes) were included in the control group. Mean time from NAION onset to EECP initiation was 27.59 ± 16.70 days. In the EECP group, the mean EECP duration was 31.57 ± 18.45 days. EECP was well tolerated by all patients. However, there was no significant difference in visual function between the EECP and control groups. Furthermore, there was no evidence of the effectiveness of EECP in the subgroup analysis of patients with different systemic health conditions. Among the 42 patients with monocular NAION, the sequential attack rate was comparable between the EECP (27.78%) and control (25.00%) groups., Conclusion: This study is the first nonrandomized controlled study to evaluate the effectiveness of EECP in NAION patients. Unfortunately, we failed to demonstrate the effectiveness of EECP in NAION at the 6-month follow-up. Any further application of EECP in NAION patients should be cautious.

Purpose: To determine whether parapapillary choroidal microvasculature (PPCMv) density as measured by optical coherence tomography angiography differs between nonarteritic anterior ischemic optic neuropathy (NAION) and primary open angle glaucoma (POAG)., Methods: Thirty-seven eyes with chronic NAION, 34 unaffected fellow eyes with NAION, 47 moderate and severe POAG eyes, and 54 healthy control subjects were evaluated. Automated PPCMv density was calculated using custom Matlab software in inner and outer annuli around the optic nerve region in addition to peripapillary superficial retinal vessels., Results: Linear models showed no difference in peripapillary retinal nerve fiber layer between NAION and POAG eyes. Mean peripapillary superficial small vessels in the NAION and POAG groups were 36.62 ± 7.1% and 39.72 ± 8.18% without a statistically difference between them (P = 0.16). Mean inner and outer annular region PPCMv densities in the NAION group were 26.55 ± 9.2% and 17.81 ± 6.9%, which were not different from unaffected fellow eyes and the control group. However, the POAG group had significantly reduced PPCMv density in both inner and outer annuli with values of 15.84 ± 6.5% and 12.80 ± 5.0%, respectively, compared with normal subjects (both P < 0.001). Inner and outer circle PPCMv densities were also significantly reduced in the POAG group compared with the NAION group., Conclusions: Reduced PPCMv density in POAG eyes shows that deep optic nerve head ocular blood flow may contribute to axonal damage in patients with glaucoma.

Objective: There has long been a great interest in neuroprotection therapy for ischaemic stroke and various types of optic neuropathies. In view of that, I reviewed the literature on the role of neuroprotection for non-arteritic anterior ischaemic optic neuropathy (NA-AION)., Methods: The review is based on a PubMed search of literature about the use of neuroprotectors in stroke and optic neuropathies and about current clinical trials of RPh201 and QPI-1007 in NA-AION., Results: Several neuroprotection agents for ischaemic stroke and various types of optic neuropathies have been evaluated extensively in experimental studies in animals and benefits claimed. However, translation of therapeutic strategies for neuroprotection from experimental research to humans has invariably been fraught with failure. Two currently ongoing studies dealing with neuroprotection by RPh201 and QPI-1007 in NA-AION may have limitations in their rationale and study designs., Conclusions: Unfortunately, in spite of all the experimental and clinical research on neuroprotection agents in NA-AION so far, we have no scientifically proven evidence of neuroprotection agents showing any benefit in the human clinical studies so far., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To compare macular vasculature in patients with primary open-angle glaucoma (POAG) and atrophic nonarteritic anterior ischemic optic neuropathy (NAION)., Design: Prospective, cross-sectional study., Methods: Thirty-seven eyes with moderate and advanced POAG, 19 eyes with atrophic NAION, and 40 eyes of normal subjects were imaged using optical coherence tomography angiography (OCT-A). Macular ganglion cell complex (GCC) and peripapillary retinal nerve fiber layer (RNFL) thicknesses were measured in addition to macular superficial and deep vasculature after projection removal using custom software., Results: Linear models showed that while averaged peripapillary RNFL and macular GCC were not different between NAION and POAG eyes, both were significantly thinner than control eyes. Whole image macular superficial vessel density was significantly lower in NAION and glaucoma eyes (P = .003 and <.001, respectively) than in normal eyes, with lower vessel density in glaucoma than in NAION eyes (P = .01). Whole image and parafoveal deep macular vessels in glaucoma eyes (21.0%±8.7%, 24.4%±9.6%) were significantly lower than in control eyes (27.4%±8.6%, 31.9%±10.6%) (P = .01 and P = .01, respectively). No significant differences in deep vessels were observed between NAION and control eyes. Glaucomatous eyes had lower temporal and inferior parafoveal deep vasculature values than NAION eyes (P = .007 and .03, respectively)., Conclusions: In NAION and POAG with similar RNFL and macular damage, macular OCT-A shows less involvement of superficial and deep vascular plexus in NAION in contrast to POAG, which might show a primary vascular insult in addition to secondary vascular damage due to ganglion cell damage., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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 (r 2 =0.32; P=0.03) and RNFL at 6 months of follow-up (r 2 =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., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Purpose: The pathophysiology of nonarteritic anterior ischemic optic neuropathy (NAION) is not completely understood. Studies of the retinal vasculature phenotype in patients with NAION could help us to understand vascular abnormalities associated with the disease., Design: Retrospective case series with matched control subjects., Methods: Study population: 57 patients with NAION and 57 control subjects matched to NAION patients for sex, age, systemic hypertension, diabetes, and obstructive sleep apnea syndrome between September 2007 and July 2017., Main Outcome Measures: All patients and control subjects underwent a complete ocular examination and 45° funduscopic color photographs. The widths of the 6 largest arteries in zone B (between 0.5 and 1 optic disc diameter from the optic disc), summarized by the central retinal artery equivalent (CRAE), the widths of the 6 largest veins in zone B, summarized by the central retinal vein equivalent (CRVE), the arteriole to venule ratio, tortuosity, and fractal dimension were measured on the 2 groups using Vessel Assessment and Measurement Platform for Images of the Retina, a software tool for efficient semiautomatic quantification of the retinal vasculature morphology in fundus camera images. The Wilcoxon signed-rank test and MacNemar χ 2 test for paired sample and generalized estimating equations for modeling the Vessel Assessment and Measurement Platform for Images of the Retina parameters as dependent variables were used., Results: CRVE and fractal dimension (D0a) were significantly higher in the NAION group when compared with the control group, whereas the arteriole to venule ratio and vascular tortuosity were significantly lower. Compared with control subjects, acute NAION yielded an increased CRAE value (174 ± 33 vs 160 ± 13 μm) while resolution NAION yielded a decreased CRAE value (152 ± 12 vs 156 ± 33 μm). Acute NAION yielded an increased CRVE value (244 ± 35 vs 210 ± 21 μm) while resolution NAION yielded an unchanged CRVE value. We found no difference between groups for age, refraction, optic disc diameter, CRAE, or fractal dimension., Conclusions: Retinal vascular parameters were different in our sample between NAION and control patients, especially at the acute stage of the disease. Our results suggest a normalization of the same parameters at the resolution stage., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: No proven treatment exists for nonarteritic anterior ischemic optic neuropathy (NAION), either in the acute or late phase., Objective: To assess safety and changes in visual function and structure after RPh201/placebo treatment in participants with previous NAION., Design and Setting: Phase 2a, single-site, prospective, randomized, placebo-controlled, double-masked trial (registration NCT02045212)., Main Outcomes Measures: Early Treatment Diabetic Retinopathy Study best-corrected visual acuity (BCVA), visual fields, retinal nerve fiber layer, and visual evoked potential at weeks 13, 26, and after a 13-week wash-out ("off-drug") period; and safety., Study Population: Twenty-two participants aged 18 years or older with previous NAION., Intervention(s): RPh201 (20 mg) or placebo (cottonseed oil vehicle) administered subcutaneously twice weekly at the study site., Results: Thirteen men and 9 women were randomized, of which 20 completed all visits. The mean (±SD) age was 61.0 ± 7.6 years. In a post hoc analysis, after 26 weeks of treatment, BCVA improved by ≥15 letters in 4/11 (36.4%) eyes with RPh201, compared to 1/8 (12.5%) eyes with placebo (P = 0.24). Overall, 7/11 (63.6%) of participants on RPh201 showed some improvement in BCVA, compared with 3/8 (37.5%) on placebo (P = 0.26). Improvement in BCVA from a calculated baseline was 14.8 ± 15.8 letters for RPh201 and 6.6 ± 15.3 for placebo (P = 0.27). Of the 154 adverse effects (AEs), 52 were considered related to the study procedures/treatment. Across the study and 1,017 injections, the most frequently reported AE was injection site pain (23 events in 5 participants). There were no clinically significant changes in vital signs or laboratory values., Conclusions: This Phase 2a was designed to assess safety, feasibility, and explore potential efficacy signals in treating previous NAION with RPh201. No safety concerns were raised. The results support a larger trial in patients with previous NAION.

Purpose: To evaluate whether treatment with Citicoline in oral solution (OS-Citicoline) would increase visual function, retinal ganglion cells (RGCs) function, and neural conduction along visual pathways (neuroenhancement), and/or induce preservation of RGCs fibers' loss (neuroprotection) in non-arteritic ischemic optic neuropathy (NAION), a human model of neurodegeneration., Methods: Thirty-six patients with NAION and 20 age-matched controls were enrolled. Nineteen NAION patients received 500 mg/day of OS-Citicoline for a 6-month period followed by 3-month of wash-out (NC Group); 17 NAION patients were not treated (NN Group) from baseline to 9 months. In all subjects at baseline, and in NC and NN eyes at 6 and 9 months of follow-up, we assessed Visual Acuity (VA), Pattern Electroretinogram (PERG), Visual Evoked Potentials (VEP), retinal nerve fiber layer thickness (RNFL-T), and Humphrey 24-2 visual field mean deviation (HFA MD). Mean differences were statistically evaluated with ANOVA between Groups, and linear correlations were analysed with Pearson's test., Results: At 6 months, significant differences between groups for all parameters were observed (ANOVA, p<0.01). In NC eyes, VA increased, PERG responses increased, VEP recordings improved and were significantly correlated with increases in HFA MD (p<0.01), and RNFL-T was unmodified or improved. In contrast, in NN eyes, VA, PERG, VEP responses, RNFL-T, and HFA MD were further worsened. Significant differences were still present at 9-month follow-up in the NN Group and after 3 months of OS-Citicoline wash-out in NC eyes., Conclusions: OS-Citicoline treatment induced neuroenhancement (improvement in RGCs function and neural conduction along visual pathways related to improvement of visual field defects) and neuroprotection (unmodified or improved RNFL morphological condition) in a human model of NAION involving fast RGCs degeneration., Trial Registration: ClinicalTrials.gov NCT03758118., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To investigate the effect of posterior ocular hemodynamics on the retinal nerve fiber layer (RNFL), choroid thickness (CT) and central macular thickness (CMT) in patients with obstructive sleep apnea syndrome (OSAS) and to reveal the association with glaucomatous optic neuropathy., Methods: The research was planned as a prospective, randomized study. The ophthalmic, retinal and posterior ciliary artery pulsatile index (PI) and resistive index (RI) were measured by colored Doppler sonography. RNFL thickness, CMT and CT were then measured by spectral-domain optical coherence tomography., Results: Sixty subjects were divided into four groups-mild, moderate and severe OSAS and a control group. There were 16 subjects in the control group, 14 in the mild OSAS group, 15 in the moderate OSAS group and 15 in the severe OSAS group. Ophthalmic artery and central retinal artery PI and RI values of the OSAS patients did not show statistically significant difference than those of the control group, but posterior ciliary artery (PCA) PI and RI values were significantly higher. In addition, mean, superior and inferior RNFL thickness values were significantly lower than those in the control group. Moreover, the glaucoma prevalence of the OSAS patients in this study was 6.8% and all of these patients were in the severe OSAS group., Conclusion: PI and RI values of the PCA, which supplies the optic nerve, show a linear increase as the apnea hypoxia index values in OSAS. As the grade of OSAS improves, this situation leads to a more serious ischemic optic neuropathy. Furthermore, the prevalence of glaucoma in this study is found to be higher in the severe OSAS group.

Purpose: The purpose of this study was to evaluate ocular hemodynamics in patients with a disease believed to be related to a chronic vascular damage [ie, normal tension glaucoma (NTG)] in comparison with an entity with an acute ischemic impact on the optic nerve [ie, acute nonarteritic anterior ischemic optic neuropathy (NAION)]., Materials and Methods: Blood-flow velocities [peak systolic velocity (PSV), enddiastolic velocity (EDV)] of the ophthalmic artery (OA), central retinal artery (CRA), and nasal and temporal posterior ciliary arteries were measured using color Doppler imaging. Resistive index (RI) of all vessels was calculated (PSV-EDV/PSV). A total of 41 patients suffering from acute NAION (onset of symptoms <10 d) and 64 age-matched patients suffering from NTG were included in this prospective study., Results: No significant differences were recorded for either age or intraocular pressure inbetween the 2 groups. Systolic blood pressure was significantly higher in the NAION group, whereas no significant differences were recorded for the diastolic blood pressure. Only 3 color Doppler imaging parameters were found to differ significantly. The PSV (P<0.005) and EDV (P<0.02) in the CRA were significantly higher in NTG patients. Furthermore, the RI in the OA was significantly higher in the NAION patients (P<0.005)., Conclusions: Decreased blood-flow velocities in the CRA and a higher RI in the OA can be recorded in NAION patients as compared with NTG. No differences with regard to the posterior ciliary arteries' velocities were recorded. Ocular hemodynamics are suspected to play a critical role in NAION and NTG, whereas the blood-flow disturbances seem to be more severe in NAION than in NTG.

Purpose: Evaluation of ocular haemodynamics in patients with acute non-arteritic anterior ischaemic optic neuropathy (NAION) by colour Doppler imaging and fluorescein angiography and correlation of blood flow parameters to visual field loss and visual acuity., Methods: Blood flow velocities (peak systolic velocity (PSV), end-diastolic velocity (EDV)) of the ophthalmic artery (OA), central retinal artery (CRA) and nasal and temporal posterior ciliary arteries (PCAs) were measured via colour Doppler imaging. Resistive index (RI) of all vessels was calculated (PSV-EDV/PSV). Retinal arteriovenous passage times (AVP) were evaluated using fluorescein angiography (scanning laser ophthalmoscope) and digital image analysis. The visual field global index mean deviation (MD, 30-2 programme, Humphrey Field Analyzer) and visual acuity (logMar) was used for analysis of functional impairment after NAION., Results: Twenty patients (age: 64.62 ± 11.63 years) with acute NAION were included. Mean duration of symptoms was 7.6 ± 6.9 days. Mean defect was 15.4 ± 8.9 dB, AVP was determined with 1.66 ± 0.37 s. EDV of the CRA was significantly correlated to visual field MD (r = 0.52, p = 0.017) and AVP (r = - 0.49, p = 0.025). The RI of the OA was significantly correlated to visual acuity (r = 0.493, p < 0.037). No significant correlations were recorded for the PCAs. A significant correlation was found between AVP and the EDV of the CRA (r = - 0.49, p = 0.025)., Conclusion: Decreased EDV in the CRA and increased RI in the OA seem to be linked to the functional damage in NAION. An improvement of the retrobulbar circulation might be beneficial in the treatment of NAION.

Background: While often idiopathic, anterior ischemic optic neuropathy occasionally may occur from an identifiable cause., Methods: Observational case report., Results: A 19-year-old woman with unremarkable medical and ophthalmic histories developed visual loss from nonarteritic anterior ischemic optic neuropathy in her right eye after otherwise uneventful dental extraction of the inferior third molars., Conclusions: Anterior ischemic optic neuropathy may rarely occur after dental extraction. Potential pathophysiologic mechanisms of this rare occurrence are discussed.

Introduction: Blindness after orthognathic surgery may be the result of the surgical procedure itself or the consequence of factors induced by general anesthesia. However, the exact mechanism between is not known. The purpose of this article is to present a case of a postoperative visual loss after orthognathic surgery under general anesthesia concluding with a brief literature review about this topic., Report of Case: We report the case of a patient who suffered unilateral blindness with homolateral frontal paresthesia after orthognathic procedure in 2 steps. He presented intraoperative bradycardia with a potential undiagnosed hypertension, associated with significant blood loss and volume resuscitation by colloids and cristalloids.Postoperative examination concluded to posterior ischemic optic neuropathy., Discussion and Conclusion: By a systematic literature review, we discuss about surgical and anesthesic causes of postoperative visual loss, and particularly pathophysiology mechanism of posterior ischemic optic neuropathy. Some predisposition and risk factors have been identified and need to be taken into account.

Purpose : The presence of the so called disc at risk (a small disc with no cupping) has been considered the main risk factor for the development of non-arteritic anterior ischemic optic neuropathy (NAION). However its role as a prognostic factor has not been studied. Our aim was to determine the weight of disc configuration as a risk and a prognostic factor for NAION. Methods : Case control study. Forty eyes of 40 patients who were diagnosed with NAION between 2008 and 2017, and 120 controls (3 controls for each patient) were included in the study. Disc diameter (DD), cup to disc ratio (CDR), and peripapillar retinal nerve fiber layer thickness (RNFLT) of the non-affected eye were measured using optic coherence tomography (3D OCT 2000, Topcon). Crowding index (CI) was defined as the quotient of average RNFLT and disc area. Mean deviation (MD) at the time of diagnosis and at least three months later was determined using a Humphrey Visual Field Analyzer (SITA standard 24-2 strategy). Visual acuity (VA) was measured using Snellen charts and transformed into LogMAR values. Results : Only CDR was found to be a risk factor for NAION. No correlationship was found between CI and visual loss. Conclusions : DD and CI did not show value as either prognostic or risk factors. Glial tissue may be a part of the content of the optic disc as important as axons. Our results are in line with the latest studies about NAION pathophysiology. Contrary to classic thinking, these papers have not found smaller disc diameters, but smaller values of lamina cribosa depth in NAION patients.

Objective To assess the in vivo dynamic blood flow features of posterior optic nerve head (ONH) in rat model of nonarteritic anterior ischemic optic neuropathy (rNAION). Methods rNAION was established with Rose Bengal and argon green laser in Sprague-Dawley rats. Fundus photography and fundus fluorescein angiography (FFA) were performed to assess the dynamic changes of optic disc in morphology in 90 days and in blood perfusion in 3 hours after the induction of disease. Histological examinations were performed to evaluate the success of modeling. The dynamic blood flow kinetics of posterior ONH in rNAION were measured by Laser Doppler Flowmetry (LDF) on the day 3, 7, 14, 21, and 40 after the disease induction. One-way ANOVA, Student's t-test and Bonferroni adjustment were used for multiple comparisons of kinetic measurements of blood flow. Results Optic disc edema and subsequent resolution associated with the development of optic disc pallor were observed in rNAION. FFA showed that the optic disc was hypofluorescence in the early phase and hyperfluorescence in the late phase. Histological studies suggested edema and loosened tissues of ONH, loss of retinal ganglion cells (RGCs), optic nerve substance and gliosis. Compared to the naive rats, the blood flow kinetics of posterior ONH in rNAION significant reduced at each time point after modeling (F=175.06, P<0.0001). The reductions were specifically remarkable in 14 days after the disease induction (All P<0.01). Conclusions Continuous blood perfusion reduction was found in rNAION, with significant alteration in 14 days after disease induction. Our results provided important information for understanding the hemodynamic changes in rNAION.

Background: This study aimes to characterize the fundus structural changes in patients with nonarteritic anterior ischemic optic neuropathy (NAION) and the correlation between macular vessel density, retinal nerve fibre layer (RNFL) parameters and visual field sensitivity (VFS) in NAION patients., Methods: A retrospective case control study was performed using 37 eyes with NAION, 30 uninvolved contralateral eyes, and 27 eyes of healthy age-matched subjects. Data on the retinas and choroidal vessel densities and VFS were compared among the three groups., Results: The NAION group exhibited significantly lower RNFL thicknesses, lower ganglion cell complexes (GCC), larger global loss volume (GLV) values and focal loss volume (FLV) values when compared with both uninvolved eyes and healthy eyes (p < 0.01 for all comparisons). The superficial vessel density (SVD) valus (whole, parafovea, superior-hemi and inferior-hemi) were significantly lower in NAION eyes, followed by uninvolved eyes and healthy eyes (p < 0.01; LSD, p < 0.05 for all comparisons). The deep vessel density (DVD) values (parafovea, superior-hemi and inferior-hemi) were the lowest by a significant value in NAION eyes, followed by uninvolved eyes and healthy eyes (p < 0.01; LSD, p < 0.05 for all comparisons). However, DVD value measurements (whole and fovea) of healthy and uninvolved eyes were not significantly different. The average threshold deviation (TD) was - 11.02 ± 3.75 dB for the overall field region, - 6.01 ± 2.21 dB for the affected superior field region and - 9.98 ± 3.34 dB for the affected inferior field region in NAION eyes. A statistically significant correlation was found between the RNFL thickness and visual field(VF) loss (r = - 0.788, p < 0.001)., Conclusion: In addition to peripapillary vascular changes occurring in NAION eyes, macular vessel density is also involved. Furthermore, NAION-uninvolved eyes exhibited abnormalities compared with healthy eyes. This indicates that vascular changes may occur before changes in retinal thickness at the early stages of NAION.

Purpose: Optic nerve head (ONH) parameters as well as circumpapillary retinal nerve fibre layer (RNFL) thickness values measured with two different spectral domain optical coherence tomography (SD-OCT) machines (Spectralis ® and Cirrus ® OCT) have been compared between two patient groups, primary open-angle glaucoma (POAG), nonarteritic anterior ischaemic optic neuropathy (NAION) and healthy controls. A comparison of the performance of the two OCT machines was made., Methods: Twenty healthy controls, 20 POAG and 20 NAION patients with comparable visual field defects were included. Comparison between groups was made using anova and post hoc t-tests. To evaluate the diagnostic power of OCT to differentiate POAG from NAION, a stepwise linear regression analysis of the rim-RNFL correlation with adjusting covariates (optic disc area and age) was performed. Based on the regression formula, the area under the receiver operator characteristic (AUROC) was calculated., Results: Both glaucoma and NAION patients showed significantly smaller global RNFL thickness values compared to healthy subjects in t-tests (p < 0.001), while only patients with glaucoma showed significantly smaller global ONH parameters for both devices compared to healthy subjects (p < 0.001). Correlation between global ONH parameters was highly statistically significant (r = 0.93), whereas in t-test a statistically significant difference between the two machines was detected (p < 0.001). Area under the receiver operator characteristic revealed a similarly good discrimination between glaucoma and NAION for Spectralis ® (0.980) and Cirrus ® OCT (0.945)., Conclusion: NAION patients have similar RNFL thickness values as do glaucomatous eyes, whereas ONH parameters in NAION eyes were similar to those seen in healthy controls. This difference might help discriminating between these two different disease conditions in a chronic disease stadium, and in this regard, none of the two OCT machines performed better., (© 2018 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Introduction: The management of nonarteritic anterior ischemic optic neuropathy centers around prevention of second eye involvement, without a uniformly accepted therapy for the involved eye. Several researchers have assessed the benefit of steroids with conflicting results. This experimental study was designed to evaluate the efficacy of a single intravitreal triamcinolone acetonide injection (IVTA) in preserving retinal ganglion cells (RGCs) in a rodent model of anterior ischemic optic neuropathy (rAION)., Methods: The rAION was induced in female Wistar rats. Animals were randomized into 3 groups: 1) untreated, 2) treated with 56 μg IVTA, and 3) intravitreal saline (placebo). Procedures were performed in the left eye, with the right eye serving as control. After 30 days, animals were sacrificed and eyes were assessed histologically for RGC number., Results: The average number of RGC was significantly lower in rAION subgroups when compared with the control group (P < 0.001). No significant difference was seen between rAION eyes treated with IVTA, placebo, and untreated eyes (P > 0.05%)., Conclusions: In this rodent model for AION, no therapeutic benefit of intravitreal steroid injection was identified.

Background: A rodent model of photodynamic AION resulting from intravenous verteporfin is presented. The analysis of the morphological function, the pathological changes and the potential mechanism of action were further investigated., Methods: Photodynamic treatment was conducted on the optic nerve head (ONH) following administration of the photosensitizer. The fellow eye was considered as sham control. Fundus Fluorescein angiography (FFA), spectral domain optical coherence tomography (SD-OCT) and Flash-visual evoked potential (F-VEP) recordings were conducted at different time points. Immunohistochemistry was used to observe apoptotic cell death (TUNEL) and macrophage infiltration (ED-1/Iba-1). Retrograde labeling of retinal ganglion cells (RGCs) was used to evaluate the loss of RGCs., Results: After laser treatment, SD-OCT indicated optic nerve edema, while FFA indicated late leakage of the ONH. F-VEPs were distinctly reduced compared to control eyes. The number of apoptotic RGCs peaked on day 14 (5.71 ± 0.76, p < 0.01). The infiltration of ED-1 and Iba-1 increased on the 3rd day following PDT, while it peaked on day 14 (67.5 ± 9.57 and 77.5 ± 12.58 respectively, p < 0.01). Following 3 weeks of AION, the densities of RGCs in the central retinas of the normal and AION eyes were 3075 ± 298/mm 2 and 2078 ± 141/mm 2 (p < 0.01), respectively., Conclusions: Verteporfin photodynamic treatment on rodents ONH can lead to functional, histological, and pathological changes. This type of animal model of AION is easy to establish and stable. It can be used for studying the mechanism and neuroprotective medicine of AION injury.

Background: Mechanisms of peri-operative ischaemic optic neuropathy remain poorly understood. Both specific pre-operative and intra-operative factors have been examined by retrospective studies, but no animal model currently exists., Objectives: To develop a rodent model of peri-operative ischaemic optic neuropathy. In rats, we performed head-down tilt and/or haemodilution, theorising that the combination damages the optic nerve., Design: Animal study., Setting: Laboratory., Animals: A total of 36 rats, in four groups, completed the functional examination of retina and optic nerve after the interventions., Interventions: Anaesthetised groups (n>8) were supine (SUP) for 5 h, head-down tilted 70° for 5 h, head-down tilted/haemodiluted for 5 h or SUP/haemodiluted for 5 h. We measured blood pressure, heart rate, intra-ocular pressure and maintained constant temperature., Main Outcome Measurements: Retinal function (electroretinography), scotopic threshold response (STR) (for retinal ganglion cells) and visual evoked potentials (VEP) (for transmission through the optic nerve). We imaged the optic nerve in vivo and evaluated retinal histology, apoptotic cells and glial activation in the optic nerve. Retinal and optic nerve function were followed to 14 and 28 days after experiments., Results: At 28 days in head down tilted/haemodiluted rats, negative STR decreased (about 50% amplitude reduction, P = 0.006), VEP wave N2-P3 decreased (70% amplitude reduction, P = 0.01) and P2 latency increased (35%, P = 0.003), optic discs were swollen and glial activation was present in the optic nerve. SUP/haemodiluted rats had decreases in negative STR and increased VEP latency, but no glial activation., Conclusion: An injury partly resembling human ischaemic optic neuropathy can be produced in rats by combining haemodilution and head-down tilt. Significant functional changes were also present with haemodilution alone. Future studies with this partial optic nerve injury may enable understanding of mechanisms of peri-operative ischaemic optic neuropathy and could help discover preventive or treatment strategies.

Purpose: To use spectral-domain optical coherence tomography (SD-OCT) to assess whether epipapillary vitreous traction from evolving posterior vitreous detachment (PVD) is mechanistically involved in the pathogenesis of nonarteritic anterior ischemic optic neuropathy (NAION)., Design: Retrospective cohort study., Methods: Setting: Single academic center. Patient or Study Population: Eighty eyes in 74 subjects presenting within 2 weeks of symptom onset of NAION. Intervention or Observation Procedures: SD-OCT imaging of the optic nerve head, macula, and peripapillary retinal nerve fiber layer (pRNFL) were reviewed for PVD and vitreopapillary traction (VPT)., Main Outcome Measures: Prevalence and incidence of PVD and VPT, logMAR best-corrected visual acuity (BCVA), mean deviation (MD) on automated perimetry, and pRNFL thickness at presentation and final follow-up., Results: The co-prevalence of PVD at the time of acute presentation for NAION was 30% (n = 24/80). This was similar to the prevalence of PVD in contralateral uninvolved eyes (34.5%, n = 19/55). In 8 NAION eyes, PVD had been documented prior to the onset of NAION. No eyes had SD-OCT evidence of VPT on presentation or final follow-up. Only 5 eyes developed a PVD following the development of NAION, and this typically occurred months after resolution of optic disc edema. When comparing eyes with PVD and without PVD, there was no significant difference in BCVA, MD, and pRNFL thickness at baseline, final follow-up, or the change from baseline to final follow-up (all P > .10)., Conclusions: VPT was not mechanistically related to the development of classic NAION. Preexisting PVD did not preclude the future development of NAION. The co-prevalence of PVD with acute NAION had no impact on final visual outcome., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To examine the role of oral steroid therapy in the treatment of nondiabetic cases of acute nonarteritic anterior ischemic optic neuropathy (NAAION)., Design: Randomized double-blind clinical trial., Participants: Thirty-eight patients with acute nondiabetic NAAION divided into 2 arms of 19 patients each. One arm constituted the cases and the other constituted the controls., Methods: Cases received oral steroid therapy and were designated the steroid group, whereas controls received placebo and were designated the nonsteroid group. Best-corrected visual acuity (BCVA), visual evoked response (VER), and OCT were performed at baseline, 1 month, 3 months, and 6 months after recruitment into the trial., Main Outcome Measures: Best-corrected visual acuity, VER, and retinal nerve fiber layer changes on OCT., Results: Both groups showed significant improvement in BCVA, VER latency, and resolution of disc edema on OCT parameters over 6 months. Final outcome showed no statistically significant difference with regard to visual acuity, although VER was better in the steroid group (P = 0.011). Best-corrected visual acuity, VER amplitude, and VER latency (P = 0.02, P = 0.02, and P = 0.04, respectively) showed a greater percentage improvement in the steroid group, which also saw a faster resolution of disc edema on OCT (1-month follow-up)., Conclusions: Oral steroids in acute NAAION did not improve the visual acuity significantly at 6 months. However, they improved resolution of disc edema significantly and enabled a greater improvement in VER parameters. This subtle benefit of oral steroids in NAAION is clinically unimportant and does not provide support for its use., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Non-arteritic anterior ischemic optic neuropathy (NAION) is a common cause of acute optic neuropathy in the elderly. The role of the genetic polymorphisms of Atonal Homolog 7 (ATOH7), Endothelin-1 (ET-1) and Angiotensin Converting Enzyme (ACE) in NAION and the combined effects of the gene-gene and gene-medical comorbidities on NAION were not clear. We conducted a perspective, case-control study. 71 NAION patients and 142 age and sex-matched healthy controls were enrolled. Single nucleotide polymorphisms of ATOH7 (rs1900004), ET-1 (rs5370) and ACE (rs1799752) were identified by polymerase chain reaction (PCR) method and all PCR products were screened with Sanger sequencing. The prevalence of genetic factors in NAION patients were compared to normal people, and assessed in conditional logistic regression models. The modified effects of gene-gene or gene-medical comorbidities on NAION development were assessed with a multiplicative model. A significant high risk was found in the T allele of ATOH7 in NAION, with an odds ratio (OR) of 1.55 (P = 0.04). Conditional logistic regression analysis, including diabetes and hypertension, revealed that ATOH7 TT genotype carriers conferred a significantly increased risk of NAION (TT/CC + CT, OR = 3.32, 95% confidence interval (CI) = 1.16-9.53, P = 0.03). Interaction analysis showed that ET-1 (P = 0.01), ACE (P = 0.046) and hypertension (P = 0.02) have modified effects on NAION development. Our results showed that the polymorphism of optic disc associated gene-ATOH7 conferred a significant risk of NAION. Combination of ATOH7 and ET-1, ATOH7 and ACE, as well as ATOH7 and hypertension, increased the susceptibility of NAION. Our data may be useful for NAION predicting., (Copyright © 2018. Published by Elsevier Ltd.)

Aims: We set out to determine the optical coherence tomographic angiography (OCT-A) characteristics of arteritic anterior ischaemic optic neuropathy (AAION) in the context of giant cell arteritis (GCA)., Methods: This is an observational case series of four patients with AAION secondary to GCA, three with unilateral AAION and one with bilateral AAION. We reviewed the charts, fundus photography, visual fields, fluorescein angiography (FA) and OCT-A images for all patients to identify a unifying theme in a range of AAION clinical severity. Imaging of two healthy control eyes from two patients of similar age to the patients in our series were used for comparison., Results: Superficial peripapillary capillary dilation was seen in eyes with acute AAION. It was also noted in the fellow eyes of two patients. Retinal capillary perfusion defects corresponded to visual field loss. Dense optic disc oedema and cotton-wool spots imparted blockage effects. OCT-A laminar analysis did not highlight the choroidal/choriocapillaris perfusion defects seen on FA in two patients. Follow-up OCT-A was obtained in two patients and revealed progression to superficial peripapillary capillary attenuation that corresponded with visual field loss., Conclusions: There are acute and chronic vascular changes in AAION that are detectable by OCT-A that correspond with visual function. Though the microvascular changes seen in GCA and AAION are not specific, the nearly ubiquitous findings among preclinical and clinically affected eyes in this series of patients with GCA support OCT-A as a potentially useful adjunctive diagnostic test in the work-up of ambiguous cases of suspected ischaemic optic neuropathy., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: Non-arteritic anterior ischemic optic neuropathy (NAION) is the most common cause of non-glaucomatous optic neuropathy in older adults. Optical coherence tomographic angiography (OCT-A) is an emerging, non-invasive method to study the microvasculature of the posterior pole, including the optic nerve head. The goal of this study was to assess the vascular changes in the optic nerve head and peripapillary area associated with NAION using OCT-A., Design: Retrospective comparative case series., Methods: We performed OCT-A in 25 eyes (7 acute and 18 non-acute) in 19 patients with NAION. Fellow, unaffected eyes were analyzed for comparison. Patent macro- and microvascular densities were quantified in the papillary and peripapillary regions of unaffected, acutely affected, and non-acutely affected eyes and compared across these groups according to laminar segment and capillary sampling region, and with respect to performance on automated visual field testing., Results: In acutely affected eyes, OCT-A revealed a reduction in the signal from the major retinal vessels and dilation of patent superficial capillaries in the peripapillary area. By contrast, non-acutely affected eyes showed attenuation of patent capillaries. The peripapillary choriocapillaris was obscured by edema in acute cases, but was similar between non-acute and unaffected eyes. The degree of dilation of the superficial microvasculature in the acute phase and attenuation in the non-acute phase each correlated inversely with visual field performance. The region of reduced patent capillary density correlated with the location of visual field defects in 80% of acute cases and 80% of non-acute cases., Conclusions: OCT-A reveals a dynamic shift in the superficial capillary network of the optic nerve head with strong functional correlates in both the acute and non-acute phases of NAION. Further study may validate OCT-A as a useful adjunctive diagnostic tool in the evaluation of ischemic optic neuropathy., Competing Interests: The authors have declared that no competing interests exist.