Effects of Myopia on Rates of Change in Optical Coherence Tomography Measured Retinal Layer Thicknesses in People with Multiple Sclerosis and Healthy Controls

To quantify the associations of myopia with longitudinal changes in retinal layer thicknesses in people with multiple sclerosis (PwMS) and healthy controls (HC). A cohort of PwMS and HC with recorded refractive error (RE) prospectively scanned on Cirrus HD-OCT at the Johns Hopkins MS Center was assessed for inclusion. Exclusion criteria included OCT follow-up &lt; 6 months, ocular comorbidities, incidental OCT pathologies, and inadequate scan quality. Eyes were classified as having high myopia (HM) (RE≤ −6 diopters), low myopia (LM) (RE&gt; −6 and ≤ −3 diopters), or no myopia (NM) (RE&gt; −3 and ≤ +2.75). Linear mixed-effects regression models were used in analyses. A total of 213 PwMS (eyes: 67 HM, 98 LM, 207 NM) and 80 HC (eyes: 26 HM, 37 LM, 93 NM) were included. Baseline average ganglion cell/inner plexiform (GCIPL) and peri-papillary retinal nerve fiber layer (pRNFL) thicknesses were lower in MS HM compared with MS NM (diff: −3.2 µm, 95% CI: −5.5 to −0.8, <i>p</i> = 0.008 and −5.3 µm, 95% CI: −9.0 to −1.7, <i>p</i> = 0.004, respectively), and similarly in HC HM, as compared with HC NM. Baseline superior, inferior, and nasal pRNFL thicknesses were lower in HM compared with NM, while temporal pRNFL thickness was higher, both in MS and HC (MS: 7.1 µm, 95% CI: 2.7–11.6, <i>p</i> = 0.002; HC: 4.7 µm, 95% CI: −0.3 to 9.7, <i>p</i> = 0.07). No longitudinal differences in rates of GCIPL change were noted between HM and LM <i>vs.</i> NM, either in MS or HC. Cross-sectional differences in average GCIPL and pRNFL thicknesses are commonly seen in people with HM as compared to reference normative values from people with NM and can lead to false attribution of pathology if RE is not taken into account. However, our study suggests that longitudinal changes in average GCIPL thickness in PwMS with myopia are similar in magnitude to PwMS with NM, and therefore are appropriate for monitoring disease-related pathology.

本研究旨在量化多发性硬化患者（people with multiple sclerosis, PwMS）与健康对照者（healthy controls, HC）的近视状态与视网膜层厚度纵向变化之间的关联。本研究纳入在约翰·霍普金斯多发性硬化中心（Johns Hopkins MS Center）接受前瞻性Cirrus HD-OCT扫描且记录有屈光不正（refractive error, RE）的多发性硬化患者与健康对照者队列，开展入组筛选工作。排除标准包括光学相干断层扫描（optical coherence tomography, OCT）随访时长不足6个月、眼部合并症、偶然发现的OCT病理改变以及扫描质量不合格。按眼部屈光状态将受试者分为三组：高度近视（high myopia, HM，屈光度≤−6 D）、低度近视（low myopia, LM，屈光度>−6且≤−3 D）以及无近视（no myopia, NM，屈光度>−3且≤+2.75 D）。本研究采用线性混合效应回归模型进行统计分析。最终共纳入213例多发性硬化患者（对应眼部：高度近视67眼、低度近视98眼、无近视207眼）与80例健康对照者（对应眼部：高度近视26眼、低度近视37眼、无近视93眼）。基线状态下，与无近视的多发性硬化患者相比，伴高度近视的多发性硬化患者的平均神经节细胞/内丛状层（ganglion cell/inner plexiform layer, GCIPL）厚度与视盘周围视网膜神经纤维层（peri-papillary retinal nerve fiber layer, pRNFL）厚度均显著更低，差值分别为−3.2 μm（95%置信区间：−5.5~−0.8，p=0.008）与−5.3 μm（95%置信区间：−9.0~−1.7，p=0.004）；健康对照者中伴高度近视者与无近视者也呈现出相似的统计学差异。基线时，无论在多发性硬化患者还是健康对照者中，伴高度近视者的上方、下方及鼻侧视盘周围视网膜神经纤维层厚度均低于无近视者，而颞侧视盘周围视网膜神经纤维层厚度则更高（多发性硬化患者：7.1 μm，95%置信区间：2.7~11.6，p=0.002；健康对照者：4.7 μm，95%置信区间：−0.3~9.7，p=0.07）。无论在多发性硬化患者还是健康对照者中，高度近视、低度近视组与无近视组的神经节细胞/内丛状层厚度纵向变化速率均未观察到显著差异。相较于无近视人群的参考正常值，高度近视人群的平均神经节细胞/内丛状层与视盘周围视网膜神经纤维层厚度常存在横断面差异，若未考虑屈光不正状态，可能会将此类差异错误归因于病理改变。但本研究结果显示，伴近视的多发性硬化患者的平均神经节细胞/内丛状层厚度纵向变化幅度与无近视患者相近，因此该指标仍可适用于监测疾病相关的病理改变。