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Abstract：
BACKGROUND: The pathophysiology of toxico-nutritional optic neuropathies remains debated, with no clear understanding of the respective roles played by the direct alcohol toxicity, smoking and the often associated vitamin deficiencies, which are risk factors for optic neuropathy. Our aim was to investigate genetic susceptibility in patients with bilateral infraclinical optic neuropathy associated with chronic alcohol use disorder.
METHODS: This retrospective cohort study included 102 visually asymptomatic patients with documented alcohol use disorder from a French reference center. Optic neuropathy was identified with optical coherence tomography (OCT), after which genetic susceptibility in the group of affected patients was investigated. Genetic testing was performed using panel sequencing of 87 nuclear genes and complete mitochondrial DNA sequencing.
RESULTS: Optic neuropathy was detected in 36% (37/102) of the included patients. Genetic testing of affected patients disclosed two patients (2/30, 6.7%) with optic neuropathy associated with pathogenic variants affecting the SPG7 gene and five patients (5/30, 16.7%) who harbored variants of uncertain significance close to probable pathogenicity in the genes WFS1, LOXL1, MMP19, NR2F1 and PMPCA. No pathogenic mitochondrial DNA variants were found in this group.
CONCLUSIONS: OCT can detect presence of asymptomatic optic neuropathy in patients with chronic alcohol use disorder. Furthermore, genetic susceptibility to optic neuropathy in this setting is found in almost a quarter of affected patients. Further studies may clarify the role of preventative measures in patients who might be predisposed to avoidable visual loss and blindness.
METHODS: This retrospective cohort study included 102 visually asymptomatic patients with documented alcohol use disorder from a French reference center. Optic neuropathy was identified with optical coherence tomography (OCT), after which genetic susceptibility in the group of affected patients was investigated. Genetic testing was performed using panel sequencing of 87 nuclear genes and complete mitochondrial DNA sequencing.
RESULTS: Optic neuropathy was detected in 36% (37/102) of the included patients. Genetic testing of affected patients disclosed two patients (2/30, 6.7%) with optic neuropathy associated with pathogenic variants affecting the SPG7 gene and five patients (5/30, 16.7%) who harbored variants of uncertain significance close to probable pathogenicity in the genes WFS1, LOXL1, MMP19, NR2F1 and PMPCA. No pathogenic mitochondrial DNA variants were found in this group.
CONCLUSIONS: OCT can detect presence of asymptomatic optic neuropathy in patients with chronic alcohol use disorder. Furthermore, genetic susceptibility to optic neuropathy in this setting is found in almost a quarter of affected patients. Further studies may clarify the role of preventative measures in patients who might be predisposed to avoidable visual loss and blindness.
摘要：
背景：毒性营养性视神经病变的病理生理学仍存在争议，由于对直接酒精毒性的作用没有明确的了解，吸烟和经常伴随的维生素缺乏，这是视神经病变的危险因素。我们的目的是调查与慢性饮酒相关的双侧下视神经病变患者的遗传易感性。
方法：这项回顾性队列研究包括来自法国参考中心的102名视觉无症状的饮酒障碍患者。用光学相干断层扫描（OCT）确定视神经病变，之后，研究了受影响患者组中的遗传易感性。使用87个核基因的组测序和完整的线粒体DNA测序进行基因检测。
结果：纳入患者中有36%（37/102）的患者发现视神经病变。对受影响患者的基因检测显示，两名视神经病变患者（2/30，6.7％）与影响SPG7基因的致病性变异相关，五名患者（5/30，16.7％）具有不确定意义的变异，接近可能的致病性基因WFS1，LOXL1，MMP19，NR2F1和PMPCA。在该组中未发现致病性线粒体DNA变异。
结论：OCT可检测慢性酒精使用障碍患者是否存在无症状视神经病变。此外，在这种情况下，视神经病变的遗传易感性在近四分之一的受影响患者中被发现。进一步的研究可能会阐明预防措施在可能容易避免视力丧失和失明的患者中的作用。
方法：这项回顾性队列研究包括来自法国参考中心的102名视觉无症状的饮酒障碍患者。用光学相干断层扫描（OCT）确定视神经病变，之后，研究了受影响患者组中的遗传易感性。使用87个核基因的组测序和完整的线粒体DNA测序进行基因检测。
结果：纳入患者中有36%（37/102）的患者发现视神经病变。对受影响患者的基因检测显示，两名视神经病变患者（2/30，6.7％）与影响SPG7基因的致病性变异相关，五名患者（5/30，16.7％）具有不确定意义的变异，接近可能的致病性基因WFS1，LOXL1，MMP19，NR2F1和PMPCA。在该组中未发现致病性线粒体DNA变异。
结论：OCT可检测慢性酒精使用障碍患者是否存在无症状视神经病变。此外，在这种情况下，视神经病变的遗传易感性在近四分之一的受影响患者中被发现。进一步的研究可能会阐明预防措施在可能容易避免视力丧失和失明的患者中的作用。
