Objective To establish an rat model of the Anterior Isc hemic Optic Neuropathy (rAION), and identify its reliability by observing the fundus, fluorescein fundus angiography (FFA),optical coherence tomography (OCT), v isually evoked potential (VEP) and histopathology. Methods Thirty male Sprague-Dawley rats were randomly divided into group Naive with 5 rats, group Laser with 5 rats, group hematoporphyrin derivative(HPD) with 5 rats, group rAION with 15 rats. All of the right eyes were the experimental eyes and the left ones were the control. after administration of HPD in rats` vena caudalis. The rats in group Laser were treated with a krypton red 647nm/2/3disc spot laser for 120 seconds, the rats in group HPD were treated by administration of HPD in rats` vena caudalis, and the rats in group Na?ve were not treated. Results From 1 day to 6 day s after rAION induction, the ON was pale and swollen in the superior part. The ON at 90 days after induction was pale and shrunken.30 minutes after rAION induction, hyperfluoresc ence appeared in the superior part of the optic disc, and the hypofluorescence in the 23rd day. In early FFA, hypofluorescence appeared at the ischemic area of the optic disc, and in midst and later stage the ischemic area revealed hyperflu orescence in the 1st day after rAION induction, the hypofluorescence in midst and later stage in the sixth day after r-AION model. The latent period of F-VEP expanded. The amplitude cut down in the 1-2 days after r-AION induction and did not changed in 35nd day. The surface of optic disc showed higher and rougher tha n the surface of retina in the 6th day after r-AION induction in OCT. After fixation and hematoxylineosin staining of 6-mu;m sections, in high power field the o pt ic disc showed edema with the displacement of retina surrounding the disc 1 day after treatment. Rarefaction and degeneration in the nerve fiber of retina and r eduction of the number of nuclei of ganglion cells in the 23st day after the mod el induction, and the thinning of nerve fiber of the optic disc and its surround ings. In contrast, there was no change in group Na?ve, group Laser and group HPD. Conclusions The r-AION model is like the human AION in fundus, FFA, OCT, VEP and histopathology. The rAION model provides the ischemic changes of occurrence of AION, and is helpful for the fundamental study of the AION. (Chin J Ocul Fundus Dis,2008,24:90-94)
ObjectiveTo observe the blood perfusion of optic nerve and macular areas and investigate its relationship with visual field defect in nonarteritic anterior ischemic optic neuropathy (NAION).MethodsTwelve consecutive unilateral NAION patients (course of disease ＜3 months) and 12 healthy Chinese adults were enrolled in the study. The affected eyes and fellow eyes from 12 NAION patients were defined as group A and group B; 12 eyes from 12 healthy adults were defined as group C. Best corrected visual acuity (BCVA), intraocular pressure (IOP), indirect ophthalmoscope and computer optometry were performed on all of the three groups of patients. Visual field (VF) and optical coherence tomography (OCT) were performed on NAION patients. Logarithm of the minimum angle of resolution (logMAR) was used to calculate visual acuity. Compared to group B, logMAR BCVA, mean deviation (MD) and pattern standard deviation (PSD) in group A were significant decreased (t=3.278, −4.909, 4.130, P＜0.05). There was no significant difference in spherical equivalent, IOP, peripapillary retinal nerve fibre layer (pRNFL) between group A and group B (t=0.000, 0.890, 1.215; P＞0.05). OCT angiography (OCTA) was used to measure the flow area (FA) at optic disc, flow area at radial peripapillary capillaries (RCFA) and FA, non-perfusion area (NFA), parafoveal vessel density (PVD) and parafoveal vascular index (PVI) in macular area. Pearson correlations between the deficiency of optic blood flow and visual field were analyzed.ResultsThe differences of FA at optic disc and peripapillary RCFA among 3 groups were significant (F=4.162, 3.357; P＜0.050). Compared to group B (t=−5.822, −7.467; P＜0.001) and C (t=9.435, 4.615, P＜0.05), FA at optic disc and peripapillary RCFA in group A was significantly reduced. There is several NAION showed quadrantal FA decreased in optic nerve. However, there was no significant difference in optic disc FA and peripapillar RCFA between group B and C (F=0.004, 0.030; P＞0.050). There was no differences of FA, NFA, PVD and PVI among 3 groups (F=0.488, 1.107, 0.493, 1.086, 1.098, 0.093, 1.093, 1.221; P＞0.05). Positive correlation between optic disc FA, peripapillary RCFA and MD (r=0.542, 0.585; P＜0.05) were observed. However, there was no significant correlation between optic disc FA, peripapillary RCFA and PSD (r=−0.404, −0.430; P＞0.05), and negatively correlated to BCVA (r=−0.617, −0.596; P＜0.05). PRNFL was negatively correlated to optic disc FA (r=−0.643, P＜0.05), but not correlated to peripapillary RCFA (r=−0.377, P＞0.05).ConclusionsThe optic disc blood flow reduced in affected eyes of unilateral NAION whose disease course was less than 3 months, while the macular perfusion was normal. There was a positive correlation between optic disc flow and visual field.
Tumor immunotherapy includes immune checkpoint inhibitor (ICI), tumor vaccines, and adoptive cell therapy. Immunotherapy, as the main systemic treatment for advanced malignant tumors, kills tumor cells by activating the immune system and prolongs the survival of patients. However, excessive immune responses can cause immune-related adverse events (irAE), causing damage to systemic tissues. ICI are the main tumor immunotherapy drugs that cause optic nerve irAE. The most common optic nerve irAE are optic neuritis, only a few patients appeared arteritic anterior ischemic optic neuropathy. Sudden painless loss of bilateral vision is the most common clinical manifestation. In severe cases, the vision decrease to no light perception. Early diagnosis and early adequate glucocorticoid treatment can improve the symptoms. Therefore, neuro-ophthalmologists and oncologists should know the clinical characteristics of optic nerve irAE, in order to diagnose and treat early and improve the prognosis.
ObjectiveTo analyze retrospectively the risk factors of nonarteritic anterior ischemic optic neuropathy (NAION). MethodsThe complete clinical data of 116 patients (134 eyes) were collected. All patients were asked in detail about the disease history and symptoms and were examined for the visual acuity, intraocular pressure, fundus, visual field and fundus fluorescein angiography (FFA), blood pressure, blood glucose, blood fat and head MRI or CT. Suspicious cases and patients with incomplete clinical data were excluded. The relationship between NAION and age, visual field, FFA, systemic and ocular factors, onset seasons were retrospectively analyzed. Results80 patients (68.97%) were 55 to 70 years old. 97 patients (83.7%) had systemic diseases, including 38 patients (39.2) with diabetes mellitus, 32 patients (32.9%) with hypertension (8 patients had low blood pressure at night), 28 patients (28.9%) with hyperlipidemia, 16 patients (16.5%) with cerebrovascular diseases (mainly lacunar cerebral infarction), 6 patients (6.2%) with coronary heart disease. There were 8 patients with ocular factors, including 3 patients (2.6%) with cataract surgery history, 5 patients (4.2%) with small optic discs. The difference of percentage of with or without diabetes mellitus and hypertension was significant (χ2=362, 259; P < 0.05). There were 27.6% patients with disease onset at March to April, 24.1% patients with disease onset at September to October, much higher than other months (χ2=580, P < 0.05). Visual field test results showed that 49 eyes (36.5%) had inferior visual field defect, 12 eyes (9.0%) had superior visual field defect. FFA showed that in the early stage 103 eyes (76.9%) had optic weak fluorescence, 13 eyes (9.7%) had strong fluorescence; in the late stage, 110 eyes (82.1%) had strong fluorescence, 8 eyes (6.0%) had weak fluorescence. ConclusionsDiabetes mellitus, hypertension may be the system risk factors of NAION. The seasonal variation from spring to summer and from autumn to winter may also be another risk factor for the onset of NAION.
Objective To observe the efficiency and security of enhanced external counter pulsation (EECP) as an adjunctive therapy for nonarteritic anterior ischemic optic neuropathy (NAION). Methods This was a retrospective casecontrol study. Forty-eight patients (48 eyes) with NAION were enrolled in this study. Thirty-two patients (32 eyes) who had been treated with blood vessel dilation and nerve nutrition drugs comprised the medicated group. Sixteen of the patients (16 eyes) in the medicated group were treated with EECP combined with blood vessel dilating and nerve nutrition drugs as EECP group. The differences were not statistically significant between groups in gender(chi;2=0.000), age (t=1.096), course (t=1.613) and visual acuity (chi;2=0.000,P＞0.05). EECP was done once a day, one hour per time, five times a week. Fourteen eyes were treated 12 times EECP and two eyes were treated 36 times EECP within the EECP group. Systemic and ocular side effects were observed during EECP treatment. Corrected visual acuity was examined after treatment and the differences of visual acuity between medicated group and EECP group treated six times and or 12 times with EECP treatment were analyzed. The correlation of visual acuity level, and course, and acuity before treatment were analyzed. A significant improvement in visual acuity was defined as a sustained improvement of three or more visual acuity gradations. An effective of treatment was defined as a sustained improvement of two or less visual acuity gradations. No effective of treatment was defined as visual acuity dropped or showed no progress. Results After six treatments of EECP, within the 16 eyes of EECP group, two eyes achieved significant improvement, five eyes had effective improvement, and nine eyes did not show any improvement. Within the 32 eyes of medicated group, three eyes achieved significant improvement, eight eyes had effective improvement, and 21 eyes did not show any improvement. There was no statistically significant difference in vision between the two groups (chi;2=0.404,P＞0.05). After 12 treatments of EECP, within the 16 eyes of EECP group, six eyes achieved significant improvement, nine eyes had effective improvement, and one eye did not show any improvement. Within the 32 eyes of medicated group, four eyes achieved significant improvement, 10 eyes had effective improvement, and 28 eyes did not show any improvement. The difference was statistically significant comparing the vision level between the two groups (chi;2=11.621,P＜0.05）. The curative effect of patients negatively correlated with course of the disease (r=-0.860，P＜0.05), but positively correlated with visual acuity before treatment (r=1.380,P＜0.05). Skin bruises, hematoma, new retinal bleeding and other side effects did not occur in patients during EECP treatment. Conclusions Many time therapy of EECP can improve vision of NAION patients. There is no local and general complications after a certain number of therapy.
ObjectiveTo observe the blood perfusion changes of peripapillary and macular vessels in patients with nonarteritic anterior ischaemic optic neuropathy (NAION).MethodsRetrospective cohort study. Thirty-six eyes (19 affected eyes and 17 fellow eyes) of 19 patients with NAION diagnosed in People’s Hospital of Wuhan University from November 2017 to January 2019 were included in this study. There were 10 males and 9 females, with the mean age of 55.05±7.11 years. Forty eyes of 20 normal subjects matched with NAION patients were included as controls. BCVA, fundus color photography, SD-OCT and OCT angiography were performed in normal controls and repeated in NAION affected eyes at 1-2 weeks, 1-2 months, 3-5 months intervals. OCT quantitative measurements: average retinal nerve fiber layer thickness (aRNFL) of the disc and its superior values (sRNFL) and the inferior values (iRNFL), average ganglion cell complex thickness (aGCC) in macular region and its superior values (sGCC) and the inferior values (iGCC). OCTA quantitative measurements: average radial peripapillary capillary density (aRPC) and its superior values (sRPC) and the inferior values (iRPC), average vascular density of superficial retina (aSVD) in macular region and its superior values (sSVD) and the inferior values (iSVD), average vascular density of deep layer retina (aDVD), areas of foveal avascular zone (FAZ). The differences of OCT and OCTA quantitative measurements between NAION eyes and the fellow eyes and normal controls were comparatively analyzed. Independent sample t test, paired sample t test or nonparametric rank sum test were performed for comparison among three groups. Pearson or Spearman correlation analysis were used to analyze the correlation between RNFL and RPC, GCC and SVD, RNFL and GCC, RPC and SVD.ResultsAt baseline, the aRNFL, aRPC and aDVD of NAION patients were significantly higher than those of normal controls. Compared with the fellow eyes, the aRNFL increased significantly and the aRPC decreased significantly in NAION affected eyes. The overall differences of aRNFL, aRPC, aGCC and aSVD at four intervals within NAION affected eyes were statistically significant (P＜0.05). The average sRNFL, sRPC, sGCC and sSVD at 1-2 months interval were significantly lower than the average iRNFL, iRPC, iGCC and iSVD (P＜0.05). Correlation analysis: at 1-2 months interval, aGCC was positively correlated with aSVD (r=0.482, P=0.037); at 3-5 months interval, aRNFL was positively correlated with aRPC (r=0.631, P=0.037).ConclusionThere is a sectorial reduction of vascular density of peripapillary RPC and macular SVD with the disease progression of NAION.
Objective To observe the characteristics of multifocal microperimetry and its relationship with visual acuity and multifocal ganglion cell complex (GCC) in nonarteritic anterior ischemic optic neuropathy (NAION). Methods A retrospective case study. A total of 38 patients (54 eyes) with NAION were enrolled in this study. 25 NAION eyes (25 patients) and 29 contralateral health eyes (29 patients) were randomly selected into case group and control group respectively. All eyes underwent best corrected visual acuity (BCVA), slit lamp microscope, indirect ophthalmoscope, color fundus photography, optical coherence tomography (OCT), visual field and multifocal microperimetry. Logarithm of the minimum angle of resolution (logMAR) was used to calculate BCVA. There were no significantly differences on age (t=−0.647), gender, dominant eyes ( χ2=0.128, 0.099), intraocular pressure (t=0.376) between two groups (P>0.05). Macular GCC thickness, superior and inferior GCC thickness were measured by OCT, focal loss volume (FLV) and global loss volume (GLV) were obtained at the same time. Microperimetry were measured by macular integrity assessment instrument (MAIA microperimetry), and mean retinal sensitivities (MS) in macular area 10° and fixation rate in the macular central 2° and 4° were determined. The relationship between MS, macular GCC and BCVA were analyzed by Spearman correlation analysis. Results The mean logMAR BCVA of case group and control group were 0.68±0.79 and 0.07±0.06, respectively. There was significantly statistical difference in MS between two groups (t=−2.507, P=0.037). There were no significantly statistical difference in mean GCC (t=−1.245, P=0.259), superior and inferior GCC (t=−1.336, −1.024; P=0.230, 0.346), FLV (t=1.058, P=0.331) and GLV (P=0.182) between two groups. The correlation between BCVA and MS (r=−0.809, P=−0.005) was observed. However, there were no correlation between BCVA and GCC, superior and inferior GCC, FLV, GLV (r=−0.98, −0.466, −0.061, 0.442, 0.442; P=0.817, −0.244, 0.885, 0.273, 0.273). And also, there were no correlation between MS and GCC, superior and inferior GCC, FLV, GLV (r=0.238, 0.524, 0.286, 0.643, −0.619; P=0.570, 0.183, 0.493, 0.086, 0.102). Conclusions MS reduced in early stage NAION eyes, which did not correlate with macular GCC.
ObjectiveTo analyze the protein expression changes in the retina of non-arteritic anterior ischemic optic neuropathy (NAION) in rats.MethodsThe rat NAION (rNAION) model was established by Rose Bengal and laser. Twenty Sprague-Dawley rats were randomly divided into 4 groups, the normal control group, the laser control group, the RB injection control group, and the rNAION model group, with 5 rats in each group. The right eye was used as the experimental eye. The retina was dissected at the third day after modeling. Enzyme digestion method was used for sample preparation and data collection was performed in a non-dependent collection mode. The data were quantitatively analyzed by SWATH quantitative mass spectrometry, searching for differential proteins and performing function and pathway analysis.ResultsCompared with the other three control groups, a total of 184 differential proteins were detected in the rNAION group (expression fold greater than 1.5 times and P＜0.05), including 99 up-regulated proteins and 85 down-regulated proteins. The expressions of glial fibrillary acidic protein, guanine nucleotide binding protein 4, laminin 1, 14-3-3γ protein YWHAG were increased. Whereas the expressions of Leucine-rich glioma-inactivated protein 1, secretory carrier-associated membrane protein 5, and Clathrin coat assembly protein AP180 were decreased. The differential proteins are mainly involved in biological processes such as nerve growth, energy metabolism, vesicle-mediated transport, the regulation of synaptic plasticity, apoptosis and inflammation. Pathway enrichment analysis showed that PI3K-Akt signaling pathway and complement and thrombin reaction pathway was related to the disease.ConclusionThe protein expressions of energy metabolism, nerve growth, synaptic vesicle transport and PI3K-Akt signaling pathway can regulate the neuronal regeneration and apoptosis in NAION.
Objectives To evaluate the risk factors of nonarteritic a nterior ischemic optic neuropathy（NAION）in a population of China and to provide theory basis for clinical decision. Methods Demographic features and clinical data of NAION were recorded. Cerebral infarction (CI) patients were also collected as control group. Systemic evaluations including whole blood chemical test, brain MRI, carotid artery ultrasound and fundus photography were perfor med in NAION and CI patients. The fundus photography and cup/disk ratio were als o acquired in a healthy controlgroup with matched age and gender. Statistical a nalysis was done by SPSS11.5 software. Results Thirtyeight N AION patients and 40 CI patients with intact data were included. Fundus photography and cup/disk ratio were acquired in 41 healthy individuals. No statistically significant difference regard to incidences of diabetes, male gender and lipid metabolic abnormalities was found between NAION and CI patients (Pgt;0.05). H ypertension, clinical and subclinical cerebral vascular disease and carotid ar tery stenosis were statistically more commonin CI patients than in NAION patien ts (Plt;0.01, 0.05). Cup/disk ratio was statistically significant smaller in NAION than in CI patients while no statistical difference (Pgt;0.05) was fo und between the CI group and healthy individuals. Conclusions NAION shared similar risk factors with cerebral infarction, but exposure of these risk factors was different between NAION and cerebral infarction. Hypertension , cerebral vascular disease and carotid artery stenosis were more common in cere bral infarction while diabetes, male gender and lipid metabolic abnormalities were similar. Small cup/disk ratio was an independent and the most important risk factor for NAION. (Chin J Ocul Fundus Dis,2008,24:86-89)
Objective To observe the relationship between shallow optic cup，small disc and occurrence in patients with nonarteritic anterior ischemic optic neuropathy (NAION).Methods Ninetysix patients（96 diseased eyes）who accorded with the diagnosis criteria for NAION，with duration ge; three months and optic disc edema in paracmasis were selected. The fellow eyes of 96 NAION patients and 80 normal eyes were selected in our study. The horizontal and vertical disc and cup diameters，optic cup depth, and peripapillary retinal nerve fiber layer (RNFL) thickness were measured by quot;crossquot; and quot;ringquot; scan of optical coherence tomography (OCT，Humphrey 2000，German Carl Zeiss Company) inspection system. The cup depth were classified four grades by cup shape according to OCT images：GradeⅠ，bottom of optic cup above the anterior plane of peripapillary neuroepithelial layer（PNL）；GradeⅡ，bottom of optic cup above the plane of PNL；Grade Ⅲ，bottom of optic cup between the plane of PNL and choroidal pigment epithelium；Grade Ⅳ，bottom of optic cup under the plane of choroidal pigment epithelium connection. The grades of optic cup and value in three groups were statistically analyzed. The follow up ranged from six months to three years.Results The disc diameter in horizontal scanning of diseased eyes，fellow eyes and normal eyes were (1.29plusmn;0.19), (1.32plusmn;0.17), (1.40plusmn;0.15) mm，and diameters in vertical scanning were (1.52plusmn;0.14), (1.49plusmn;0.17), (1.60plusmn;0.22) mm, respectively. Compared the diseased eyes and fellow eyes with normal eyes，the difference were statistically significant in horizontal scanning (t=4.291,3.315; P＜0.05) and in vertical scanning (t=2.812, 3.654; P＜0.05). Compared the diseased eyes with fellow eyes，the difference of average diameter were not statistically significant in horizontal and vertical scanning (t=1.153,1.335; P＞0.05). Of the diseased eyes，GradeⅠoptic cup in 36 eyes（37.50），Grade Ⅱ-Ⅲoptic cup in 52 eyes（54.17%），Grade Ⅳoptic cup in eight eyes（8.33%），and GradeⅠ-Ⅲ optic cup in 88 eyes（91.67%）were found. Of the fellow eyes，GradeⅠoptic cup in 18 eyes（18.75%），Grade Ⅱ-Ⅲoptic cup in 69 eyes（71.88%），Grade Ⅳoptic cup in nine eyes（9.34%），and GradeⅠ-Ⅲ optic cup in 87 eyes（9066%）were found. Compared the average RNFL thickness of diseased eyes with the fellow eyes and normal eyes，the differences were statistically significant in temporal, upper, nasal, lower quadrant(t=12.862，10.147，15.046，8.180，12.859，9.562，12.174，8.632；P＜0.001). Compared the average RNFL thickness of the fellow eyes and normal eyes，the differences were not statistically significant in all quadrants（t=1.040，1.576，1.062，1.192；P＞0.05）. During the followup，eight eyes with recurrence which optic cup were GradeⅠand Ⅱin diseased eyes；44 eyes（45.8%）occurred NAION. Correlation analysis showed that there was negative correlation between incidence of fellow eye and optic cup depth(t=-0.757, P=0.000). Conclusion Optic cup and disk in NAION patients are smaller than that in the normal，the anatomical characteristics of shallow cup and small disc was one of the NAION pathogenesis.