Microcystic macular oedema in multiple sclerosis is associated with disease severity
Microcystic macular oedema in multiple sclerosis is associated with disease severity
复制标题
DOI：
10.1093/brain/aws098
复制
发表时间：
2012-06-01
期刊：
影响因子：
14.5
通讯作者：
Green, Ari J.
中科院分区：
文献类型：
--
作者：
Gelfand, Jeffrey M.;Nolan, Rachel;Green, Ari J.
黄斑水肿通常是由血-视网膜屏障破坏引起的。最近有报道称，使用FTY-720(Fingolimod)治疗多发性硬化症的患者可能会出现黄斑水肿。多发性硬化症并不被认为与黄斑水肿有关，除非是在临床葡萄膜炎的情况下。尽管缺乏髓鞘，但在多发性硬化症中，视网膜是炎症和小胶质细胞激活的部位，并显示出显著的神经元和轴突丢失。在多发性硬化症患者中，我们意外地使用光谱域光学相干断层扫描观察到微囊性黄斑水肿，这些患者没有其他原因导致黄斑水肿。因此，我们评估了连续患有多发性硬化症的患者的光谱域光学相干断层扫描图像中的微囊性黄斑水肿，并在横断面分析中检查了黄斑水肿与视力和行走障碍之间的相关性。如果存在可以解释黄斑水肿的共病，如葡萄膜炎、糖尿病或其他视网膜疾病，则将参与者排除在外。在318例多发性硬化症患者中，15例(4.7%)在光学相干断层扫描上观察到黄斑水肿的微囊型。在同一时期评估的52名健康对照组中，没有发现黄斑水肿。微囊性水肿主要累及视网膜内核层，并倾向于以小的、离散的斑块形式出现。有微囊性黄斑水肿的多发性硬化患者的残疾程度[扩展功能评分中位数4分(四分位数范围3~6)]明显低于无黄斑水肿者[扩展功能能力评分中位数2分位数(四分位数范围1.5~3.5)]，P=0.0002。有微囊性黄斑水肿者的多发性硬化严重程度评分也高于无水肿者[中位数分别为6.47(四分位数范围4.96-7.98)和3.65(四分位数范围1.92-5.87)，P=0.0009]。微囊性黄斑水肿在有视神经炎病史的眼中比无视神经炎病史的眼更常见(50%比27%)，并与较低的视力(对数平均视力0.17比-0.1)和较薄的视网膜神经纤维层有关。多发性硬化症患者出现的黄斑微囊性水肿症提示，神经系统中缺乏髓鞘的部分可能存在血-视网膜屏障的破坏和紧密连接的完整性。除了神经纤维层丢失外，微囊性黄斑水肿也可能导致视觉功能障碍。在评估黄斑体积作为视网膜神经节细胞存活标志的临床试验中，需要评估微囊性改变，并可能对其进行调整。这些发现对多发性硬化症患者使用1-磷酸鞘氨醇受体调节剂进行临床监测也有一定的意义。
Macular oedema typically results from blood-retinal barrier disruption. It has recently been reported that patients with multiple sclerosis treated with FTY-720 (fingolimod) may exhibit macular oedema. Multiple sclerosis is not otherwise thought to be associated with macular oedema except in the context of comorbid clinical uveitis. Despite a lack of myelin, the retina is a site of inflammation and microglial activation in multiple sclerosis and demonstrates significant neuronal and axonal loss. We unexpectedly observed microcystic macular oedema using spectral domain optical coherence tomography in patients with multiple sclerosis who did not have another reason for macular oedema. We therefore evaluated spectral domain optical coherence tomography images in consecutive patients with multiple sclerosis for microcystic macular oedema and examined correlations between macular oedema and visual and ambulatory disability in a cross-sectional analysis. Participants were excluded if there was a comorbidity that could account for the presence of macular oedema, such as uveitis, diabetes or other retinal disease. A microcystic pattern of macular oedema was observed on optical coherence tomography in 15 of 318 (4.7%) patients with multiple sclerosis. No macular oedema was identified in 52 healthy controls assessed over the same period. The microcystic oedema predominantly involved the inner nuclear layer of the retina and tended to occur in small, discrete patches. Patients with multiple sclerosis with microcystic macular oedema had significantly worse disability [median Expanded Disability Score Scale 4 (interquartile range 3-6)] than patients without macular oedema [median Expanded Disability Score Scale 2 (interquartile range 1.5-3.5)], P = 0.0002. Patients with multiple sclerosis with microcystic macular oedema also had higher Multiple Sclerosis Severity Scores, a measure of disease progression, than those without oedema [median of 6.47 (interquartile range 4.96-7.98) versus 3.65 (interquartile range 1.92-5.87), P = 0.0009]. Microcystic macular oedema occurred more commonly in eyes with prior optic neuritis than eyes without prior optic neuritis (50 versus 27%) and was associated with lower visual acuity (median logMAR acuity of 0.17 versus -0.1) and a thinner retinal nerve fibre layer. The presence of microcystic macular oedema in multiple sclerosis suggests that there may be breakdown of the blood-retinal barrier and tight junction integrity in a part of the nervous system that lacks myelin. Microcystic macular oedema may also contribute to visual dysfunction beyond that explained by nerve fibre layer loss. Microcystic changes need to be assessed, and potentially adjusted for, in clinical trials that evaluate macular volume as a marker of retinal ganglion cell survival. These findings also have implications for clinical monitoring in patients with multiple sclerosis on sphingosine 1-phosphate receptor modulating agents.