Microvascular alterations detected by optical coherence tomography angiography in non-arteritic anterior ischaemic optic neuropathy: a meta-analysis.

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.

Comparative Topographical Analysis of Choroidal Microvascular Dropout Between Glaucoma and Nonarteritic Anterior Ischemic Optic Neuropathy.

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 ß-zone peripapillary atrophy (ßPPA). We recorded the presence of MvD and compared between the peripapillary topographical measures of MvD, retinal nerve fiber layer (RNFL) defect, and ßPPA 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 ßPPA 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 ßPPA-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.

Inhibition of Retinal Ganglion Cell Loss By a Novel ROCK Inhibitor (E212) in Ischemic Optic Nerve Injury Via Antioxidative and Anti-Inflammatory Actions.

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.

The Benefits and Hazards of Intravitreal Mesenchymal Stem Cell (MSC) Based-Therapies in the Experimental Ischemic Optic Neuropathy.

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.

Follow-Up of Nonarteritic Anterior Ischemic Optic Neuropathy With Optical Coherence Tomography Angiography.

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.

Dual Specific Phosphatase 14 Deletion Rescues Retinal Ganglion Cells and Optic Nerve Axons after Experimental Anterior 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.

Analysis of Macular Microperimetry Characteristics in Non-Arteritic Anterior Ischemic Optic Neuropathy.

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.

Abnormal Regional Spontaneous Neural Activity in Nonarteritic Anterior Ischemic Optic Neuropathy: A Resting-State Functional MRI Study.

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.

Peripapillary Retinal and Choroidal Perfusion in Nonarteritic Ischemic Optic Neuropathy Using Optical Coherence Tomography Angiography.

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.

Evaluation of enhanced external counterpulsation therapy for nonarteritic anterior ischemic optic neuropathy.

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.

Young Adults With Anterior Ischemic Optic Neuropathy: A Multicenter Optic Disc Drusen Study.

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.

Automated Evaluation of Parapapillary Choroidal Microvasculature in Ischemic Optic Neuropathy and Open Angle Glaucoma.

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.

Controversies on neuroprotection therapy in non-arteritic anterior ischaemic optic neuropathy.

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.

Macular Vascularity in Ischemic Optic Neuropathy Compared to Glaucoma by Projection-Resolved Optical Coherence Tomography Angiography.

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.

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.

Unraveling the Enigma of Nonarteritic Anterior Ischemic Optic Neuropathy.

Non-arteritic anterior ischemic optic neuropathy (NAON) is the second most common optic neuropathy in adults. Despite extensive study, the etiology of NAION is not definitively known. The best evidence suggests that NAION is caused by an infarction in the region of the optic nerve head (ONH), which is perfused by paraoptic short posterior ciliary arteries (sPCAs) and their branches. To examine the gaps in knowledge that defies our understanding of NAION, a historical review was performed both of anatomical investigations of the ONH and its relevant blood vessels and the evolution of clinical understanding of NAION. Notably, almost all of the in vitro vascular research was performed prior our current understanding of NAION, which has largely precluded a hypothesis-based laboratory approach to study the etiological conundrum of NAION. More recent investigative techniques, like fluorescein angiography, have provided valuable insight into vascular physiology, but such light-based techniques have not been able to image blood vessels located within or behind the dense connective tissue of the sclera and laminar cribrosa, sites that are likely culpable in NAION. The lingering gaps in knowledge clarify investigative paths that might be taken to uncover the pathogenesis of NAION and possibly glaucoma, the most common optic neuropathy for which evidence of a vascular pathology also exists.