Ophthalmic and Systemic Factors of Acute Nonarteritic Anterior Ischemic Optic Neuropathy in the Quark207 Treatment Trial.

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.

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.

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.

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.

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.

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.

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.

Anterior Ischemic Optic Neuropathy After Dental Extraction.

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.

Randomized Controlled Phase 2a Study of RPh201 in Previous Nonarteritic Anterior Ischemic Optic Neuropathy.

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.

Postoperative Visual Loss: A Report of One Patient With Unilateral Blindness After Orthognathic Surgery.

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.

The relation between retrobulbar blood flow and posterior ocular changes measured using spectral-domain optical coherence tomography in patients with obstructive sleep apnea syndrome.

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.

Retrobulbar and intraocular blood flow in anterior ischaemic optic neuropathy are linked to the functional impairment.

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.

Steroids versus No Steroids in Nonarteritic Anterior Ischemic Optic Neuropathy: A Randomized Controlled Trial.

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.

The polymorphisms of ATOH 7, ET-1 and ACE in non-arteritic anterior ischemic optic neuropathy.

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.

Steady-state PERG adaptation: a conspicuous component of response variability with clinical significance.

PURPOSE: To investigate within-test variability of the steady-state PERG (SS-PERG). METHODS: SS-PERGs were recorded in response to black-white horizontal gratings (1.6 cycles/deg, 98% contrast, 15.63 reversals/s, LED display, 25 deg square field, 800 cd/sqm mean luminance) using skin electrodes. PERG and noise (± reference) signals were averaged over 1024 epochs (~ 2.2 min) and Fourier analyzed to retrieve SS-PERG amplitude and phase. SS-PERGs were split into 16 partial averages (samples) of 64 epochs each, and corresponding amplitudes and phases combined in polar coordinates to assess their dispersion (within-test variability). To assess time-dependent variability, samples were clustered in four successive time segments of ~ 33 s each. Amplitude adaptation was defined as amplitude difference between initial and final clusters, and PERG phase adaptation as the corresponding phase difference. To determine the dynamic range of SS-PERG adaptation, recording was performed in normal controls of different age (n = 32) and patients with different severity of optic nerve dysfunction (early manifest glaucoma, EMG, n = 7; non-arteritic ischemic optic neuropathy, NAION, n = 5). RESULTS: Amplitude adaptation was largest in younger controls (amplitude adaptation ÷ noise, SNR = 9.5, 95% CI 13.1, 5.9) and progressively decreased with increasing age (older subjects, SNR = 5.5, 95% CI 9.2, 1.8) and presence of disease (EMG: SNR = 2.4, 95% CI 3.5, 1.4; NAION: SNR = 1.9, 95% CI 6.5,-2.2). In 11 young subjects, amplitude adaptation was repeatable (test-retest in two sessions a week apart; intraclass correlation coefficient = 0.59). Phase adaptation was not significantly different from zero in all groups. CONCLUSIONS: SS-PERG adaptation accounts for a sizeable portion of the within-test variability. As it has robust SNR, sufficient test-retest variability, and is altered in disease, it may have physiological and clinical significance. This study suggests that SS-PERG protocols should include adaptation in addition to SS-PERG amplitude and phase/latency.

A rodent model of anterior ischemic optic neuropathy (AION) based on laser photoactivation of verteporfin.

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/mm2 and 2078 ± 141/mm2 (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.

Macular evaluation of the retinal and choroidal vasculature changes in anterior ischemic optic neuropathy-a case control study.

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.

Intravitreal Triamcinolone Acetonide Injection in a Rodent Model of Anterior Ischemic Optic Neuropathy.

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.

Haemodilution and head-down tilting induce functional injury in the rat optic nerve: A model for peri-operative ischemic optic neuropathy.

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.

Longitudinal Measurement of Hemodynamic Changes within the Posterior Optic Nerve Head in Rodent Nonarteritic Anterior Ischemic Optic Neuropathy.

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.