Amini Abdullah, Hamann Steffen, Larsen Michael
Department of Ophthalmology, Rigshospitalet, Copenhagen, Denmark.
Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark.
Acta Ophthalmol. 2025 Mar 8. doi: 10.1111/aos.17473.
This review covers a seminal study of the relation between exposure to the glucagon-like peptide 1 (GLP-1) agonist semaglutide and incident non-arteritic anterior ischaemic optic neuropathy (NAION) in a neuro-ophthalmology clinic setting, subsequent studies in unselected populations, a meta-analysis of clinical trials and pathophysiology studies of the optic disc and retina that may help elucidate the relation between semaglutide and NAION in patients with diabetes or obesity. In the matched cohort study of neuro-ophthalmology patients, those treated using agents other than semaglutide had NAION rates, orders of magnitude higher than a background population, presumably because referral patterns led to the enrichment of the study populations with patients at high risk of NAION. With semaglutide, the rates of NAION were 4.28 and 7.64 times higher for type 2 diabetes (T2D) and obesity, respectively, and onset of NAION was within 14 months of treatment initiation, whereas non-semaglutide NAION was evenly distributed over the 3 years of follow-up. Of four health care registry studies, each covering more than 100 000 patients, two found relative rates of NAION two to three times higher with semaglutide than without semaglutide, one found a trend towards semaglutide being associated with NAION in patients with type 2 diabetes only, and one found statistically insignificant imbalances between the two alternatives. The meta-analysis of various GLP-1 receptor agonists versus placebo or active comparator found no significant difference in rates of NAION. Prior reports of long-term glycaemia reduction being associated with early worsening of retinopathy and with NAION indicate that semaglutide may promote such events in proportion to its antihyperglycaemic potency. The association of NAION with small, crowded discs, optic disc oedema and peripapillary exudation suggests that semaglutide-related NAION may result from changes in perfusion that lead to venous dilation and, presumably, to venous congestion during relative hypoglycaemia. Given the retrospective nature of the epidemiological studies, causality cannot be inferred, but a cautious approach to the use of semaglutide and other powerful glycaemia-reducing agents seems warranted, particularly in patients with crowded optic discs, a characteristic that can be identified by proactive eye examination for disc-at-risk characteristics by the use of optical coherence tomography.
本综述涵盖了一项在神经眼科诊所环境中对胰高血糖素样肽1（GLP-1）激动剂司美格鲁肽与非动脉炎性前部缺血性视神经病变（NAION）发生之间关系的开创性研究，以及后续在未选择人群中的研究、对临床试验的荟萃分析，还有对视盘和视网膜的病理生理学研究，这些研究可能有助于阐明司美格鲁肽与糖尿病或肥胖患者的NAION之间的关系。在神经眼科患者的匹配队列研究中，使用司美格鲁肽以外药物治疗的患者，其NAION发生率比背景人群高出几个数量级，推测这是因为转诊模式导致研究人群中富含NAION高风险患者。使用司美格鲁肽时，2型糖尿病（T2D）和肥胖患者的NAION发生率分别高出4.28倍和7.64倍，且NAION在开始治疗后14个月内发病，而未使用司美格鲁肽的NAION在3年随访期内分布均匀。在四项涵盖超过10万名患者的医疗保健登记研究中，两项研究发现使用司美格鲁肽的患者NAION相对发生率比未使用司美格鲁肽的患者高出两到三倍，一项研究仅在2型糖尿病患者中发现司美格鲁肽与NAION存在关联的趋势，另一项研究发现两种情况之间的差异无统计学意义。对各种GLP-1受体激动剂与安慰剂或活性对照进行荟萃分析，未发现NAION发生率有显著差异。先前关于长期血糖降低与视网膜病变早期恶化以及与NAION相关的报道表明，司美格鲁肽可能按其降血糖效力比例促进此类事件发生。NAION与小而拥挤的视盘、视盘水肿和视乳头周围渗出相关，这表明司美格鲁肽相关的NAION可能是由灌注变化导致静脉扩张引起的，并且在相对低血糖期间可能导致静脉充血。鉴于流行病学研究的回顾性性质，无法推断因果关系，但对于司美格鲁肽和其他强效降糖药物的使用似乎应采取谨慎态度，尤其是对于视盘拥挤的患者，这一特征可通过使用光学相干断层扫描对视盘风险特征进行主动眼部检查来识别。
