Wang Wilson X, Rossmiller Helen, Getahun Henok, Santoki Aditya, Perantie Dana C, Naismith Robert T, Apte Rajendra S
John F. Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri.
Department of Neurology, Washington University School of Medicine, St. Louis, Missouri.
Ophthalmol Sci. 2025 Jul 23;5(6):100893. doi: 10.1016/j.xops.2025.100893. eCollection 2025 Nov-Dec.
Sphingosine-1-phosphate (S1P) plays a pivotal role in cells as a bioactive lipid mediator, with emerging evidence suggesting that it may play a role in retinal ganglion cell survival, axonal growth, retinal pigment epithelium (RPE) barrier function, and photoreceptor function. While previous studies have documented associated ophthalmic effects such as fingolimod-associated macular edema, the specific impact of S1P receptor modulators on inner and outer retinal layer thicknesses requires further elucidation.
Retrospective case series.
A total of 44 patients (86 eyes) with multiple sclerosis (MS) treated with fingolimod between 2011 and 2023 at the John L. Trotter Multiple Sclerosis Center at Washington University in St. Louis.
Eligible participants were those with baseline and follow-up OCT images conducted at or prior to S1P initiation and at the most recent visit. The peripapillary retinal nerve fiber layer (pRNFL), ganglion cell layer (GCL), central subfield thickness (CST), macular volume (MV), RPE, and photoreceptor thickness were determined through OCT segmentation. Generalized estimating equations were constructed incorporating relevant covariates.
Annualized rate of change of specified retinal layer thickness.
The mean age was 49.4 ± 10.8 years and time between baseline and follow-up OCTs ranged from 2 months to 6.4 years with a median of 1 year, interquartile range 0.42 to 2.33. The annualized rate of change of pRNFL and CST were 0.022 [-0.363, 0.406] μm/year, and -1.37 [-3.11, 0.38] μm/year, whereas GCL and MV showed significant thinning of -0.231 [-0.430, -0.032] μm/year and -0.024 [-0.047, -0.001] mm3/year, respectively. Retinal pigment epithelium and photoreceptor layer thickness remained largely stable over time at 0.070 [-0.140, 0.280] μm/year and 0.673 [-0.218, 1.561] μm/year, respectively.
Patients with MS on S1P modulators exhibited significant GCL and MV thinning with outer retina layer thickness preservation, providing insight into the potential retinal effects of S1P modulation in the setting of MS-related neurodegeneration. Prospective studies with standardized imaging intervals and appropriate controls are needed to distinguish the specific retinal effect of S1P modulation from MS neurodegeneration and enable more precise OCT interpretation of the retina in monitoring MS disease progression.
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
鞘氨醇-1-磷酸（S1P）作为一种生物活性脂质介质在细胞中发挥关键作用，越来越多的证据表明它可能在视网膜神经节细胞存活、轴突生长、视网膜色素上皮（RPE）屏障功能和光感受器功能中发挥作用。虽然先前的研究记录了相关的眼科效应，如芬戈莫德相关的黄斑水肿，但S1P受体调节剂对视网膜内、外层厚度的具体影响仍需进一步阐明。
回顾性病例系列。
2011年至2023年期间在圣路易斯华盛顿大学约翰·L·特罗特多发性硬化中心接受芬戈莫德治疗的44例多发性硬化症（MS）患者（86只眼）。
符合条件的参与者为在开始使用S1P之前或之时以及最近一次就诊时进行了基线和随访光学相干断层扫描（OCT）图像检查的患者。通过OCT分割确定视乳头周围视网膜神经纤维层（pRNFL）、神经节细胞层（GCL）、中央子区域厚度（CST）、黄斑体积（MV）、RPE和光感受器厚度。构建纳入相关协变量的广义估计方程。
特定视网膜层厚度的年化变化率。
平均年龄为49.4±10.8岁，基线和随访OCT之间的时间间隔为2个月至6.4年，中位数为1年，四分位间距为0.42至2.33年。pRNFL和CST的年化变化率分别为0.022[-0.363,0.406]μm/年和-1.37[-3.11,0.38]μm/年，而GCL和MV分别显示出显著变薄，为-0.231[-0.430,-0.032]μm/年和-0.024[-0.047,-0.001]mm³/年。视网膜色素上皮和光感受器层厚度随时间基本保持稳定，分别为0.070[-0.140,0.280]μm/年和0.673[-0.218,1.561]μm/年。
使用S1P调节剂的MS患者表现出GCL和MV显著变薄，同时外层视网膜层厚度保持不变，这为了解S1P调节在MS相关神经退行性变背景下对视网膜的潜在影响提供了见解。需要进行具有标准化成像间隔和适当对照的前瞻性研究，以区分S1P调节对视网膜的特定影响与MS神经退行性变，并在监测MS疾病进展时更精确地解读视网膜OCT图像。
本文末尾的脚注和披露中可能会找到专有或商业披露信息。
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