The Clinical Profile And Risk Factors Of Nonarteritic Anterior Ischemic Optic Neuropathy

ObjectiveTo observe the clinical profile of nonarteritic anterior ischemic optic neuropathy (NAION), explore the structure -function relationship on NAION severity, and assess the role of environment risk factors as well as the genetic polymorphisms of Atonal Homolog 7 (ATOH7), Endothelin-1 (ET-1) and Angiotensin Converting Enzyme (ACE) and the combined effects of the gene-gene and gene-environment on NAION.Methods73 NAION patients were consecutively recruited. A detailed history of previous systemic diseases, smoking and drinking was collected, and a comprehensive ophthalmic evaluation was performed, including the visual field (VF) test and retinal nerve fiber layer (RNFL) thickness, optic disc morphology and ganglion cell complex (GCC) measured by the RTVue XR Fourier-domain optical coherence tomography (OCT). Single nucleotide polymorphism of ATOH7 (rs1900004), ET-1(rs5370) and ACE (rs 1799752) was identified by polymerase chain reaction (PCR) method and all PCR products were screened with Sanger sequencing. The non-parametric Wilcoxon test was used for the paired eyes. Spearman’s coefficient was conducted to assess the relationship among VF, RNFL, optic disc and GCC. Receiver operating characteristic (ROC) curves and the area under the ROC curves (AUROC) were calculated to assess the ability of VF and OCT parameters to distinguish NAION eyes from normal eyes. The prevalence of associated environment and genetic factors in NAION patients were compared to 146 normal people, and assessed in multiple logistic regression models. The modified effects of gene-gene or gene-environment on NAION development were assessed by an additive model with synergy index (SI), attributable proportion of interaction (AP) and relative excess risks due to interaction (RERI) and a multiplicative model with odds ratio (OR) and 95% confidence interval (CI).ResultsOf the 73 NAION patients,16 were bilateral and 57 were unilateral. Arcuate visual field defect (31.58%) was the most prevalent defect detected in unilateral NAION and in bilateral NAION, concentric visual field contraction (40.63%) was the most common.In unilateral NAION patients, five suffered the incipient NAION. About the optic disc parameters, there were no significant difference between the affected eyes and unaffected eyes (All P>0.05) and the C/D area ratio, cup volume, horizontal and vertical C/D ratios were signicifantly correlated (All P<0.05). The temporal RNFL was significantly decreased (P=0.004). Among all these paremeters, the GCC focal loss volume (FLV) had the higest levels of AUROC value (0.93), and the cut-off value was 3.331%. The superior hemisphere VF mean defect (MD) and mean sensitivity (MS) were significantly correlated with inferior hemisphere GCC in affected NAION eyes. In bilateral NAION patients, the VF paremeters, GCC FLV and global loss volume (GLV) were strongly correlated. Obesity (OR=8.09,95% CI:2.94-22.23, P<0.001) and diabetes (OR=4.72, 95% CI:1.57-14.25, P=0.006) were significantly associated with NAION. A significant high risk was found in the T allele of ATOH7 in NAION, with an OR of 1.55 (P=0.04). ATOH7 TT genotype carriers conferred a significantly increased risk of developing NAION as compared with carries of CC or CT (P=0.02). Combined analysis showed that ATOH7 and ET-1 genes had multiple interaction (OR=27.31,95%CI=2.96-251.84, P=0.004) and synergy effects on NAION development (SI=35.73 (95%CI=32.21 39.24), AP=0.93 (95%CI=0.78 - 1.09). A positive correlation between hypertension, diabetes and ET-1 gene were found in NAION patients (ET-1 and diabetes:SI=4.03 (95%CI=2.09 - 5.98), AP=0.68 (95%CI=0.17 - 1.18); ET-1 and hypertension:SI=4.51 (95%CI=2.43 - 6.59), AP=0.65 (95%CI=0.17 - 1.12)).ConclusionsWe should pay attention to the fellow eye in case of the incipient NAION in unilateral NAION patients. The optic disc morphology of affected eyes and contralateral unaffected eyes were similar in NAION patients. After NAION, the optic disc morphology were stable. The FLV showed the strongest ability to detect NAION eyes from normal, which could be used as an auxiliary method in NAION diagnosis. The values of VF defect, GCC FLV and GLV were similarity between eyes in bilateral NAION. Diabetes, obesity and ATOH7 are associated with NAION. Combination of ATOH7 and ET-1, as well as ET-1 and diabetes or hypertension, increased the susceptibility of NAION. Our data may be useful for NAION prevention and predicting.