From the Save Sight Institute (A.K., S.K., and Y.Y.), Sydney Medical School, University of Sydney, New South Wales, Australia; Faculty of Medicine and Health Sciences (A.K., Y.Y., and S.L.G.), Macquarie University, Sydney, New South Wales, Australia; Royal North Shore Hospital (S.K., C.Y., and J.P.), Sydney, New South Wales, Australia; Brain and Mind Centre (M.B.), University of Sydney, New South Wales, Australia; and Sydney Neuroimaging Analysis Centre (M.B.), Camperdown, New South Wales, Australia.
Neurol Neuroimmunol Neuroinflamm. 2022 Mar 3;9(3). doi: 10.1212/NXI.0000000000001155. Print 2022 May.
To investigate the long-term effect of permanent demyelination on axonal attrition by examining an association between intereye asymmetry of the multifocal visual evoked potential (mfVEP) latency delay and subsequent thinning of retinal ganglion cell axons in patients with a long-standing history of unilateral optic neuritis (ON).
Only patients with a significant degree of chronic demyelination (intereye latency asymmetry >5 ms) were included in this study. The level of optic nerve demyelination was estimated at baseline by the latency delay of mfVEP, while the degree of axonal loss was assessed by thinning of the retinal nerve fiber layer (RNFL) thickness between baseline and follow-up visits. Low-contrast visual acuity (LCVA) was also evaluated at baseline and follow-up. Patients were examined twice with an average interval of 6.1 ± 1.4 years.
From 85 examined patients with multiple sclerosis, 28 satisfied inclusion criteria. Latency of the mfVEP was delayed, and RNFL thickness was reduced in ON eyes compared with fellow eyes at both visits. There was significant correlation between latency asymmetry and baseline or follow-up intereye RNFL thickness asymmetry. Intereye asymmetry of LCVA at baseline correlated with baseline latency asymmetry of mfVEP and baseline asymmetry of RNFL thickness. Latency of the mfVEP in ON eyes improved slightly during the follow-up period, whereas latency of the fellow eye remained stable. By contrast, RNFL thickness significantly declined in both ON and fellow eyes during the follow-up period. The rate of RNFL thinning in ON eyes, however, was more than 2 times faster compared with the fellow eyes ( < 0.001). Furthermore, baseline latency asymmetry significantly correlated with the rate of RNFL thinning in ON eyes during the follow-up ( < 0.001), explaining almost half of the variability of temporal RNFL progression. For each millisecond of latency delay (i.e., ∼0.5 mm of demyelination along the optic nerve), temporal RNFL thickness was annually reduced by 0.05%.
Our study provides clear in vivo evidence that chronic demyelination significantly accelerates axonal loss. However, because this process is slow and its effect is mild, long-term monitoring is required to establish and confidently measure the neurodegenerative consequences of demyelination.
通过检查多发性视觉诱发电位（mfVEP）潜伏期延迟的双眼间不对称与长期单侧视神经炎（ON）患者的视网膜神经节细胞轴突随后变薄之间的关联，研究永久性脱髓鞘对轴突损耗的长期影响。
仅纳入本研究中存在明显慢性脱髓鞘（双眼间潜伏期不对称>5ms）的患者。在基线时通过 mfVEP 的潜伏期延迟来估计视神经脱髓鞘程度，而通过基线和随访期间视网膜神经纤维层（RNFL）厚度变薄来评估轴突丢失程度。在基线和随访时还评估低对比度视力（LCVA）。患者平均间隔 6.1±1.4 年接受两次检查。
在 85 例多发性硬化症患者中，有 28 例符合纳入标准。在两次检查中，ON 眼的 mfVEP 潜伏期延迟，且与对侧眼相比，RNFL 厚度均变薄。潜伏期不对称与基线或随访时双眼间 RNFL 厚度不对称之间存在显著相关性。基线时 LCVA 的双眼间不对称与 mfVEP 的基线潜伏期不对称和基线时 RNFL 厚度的不对称相关。ON 眼的 mfVEP 潜伏期在随访期间略有改善，而对侧眼的潜伏期保持稳定。相比之下，在随访期间，ON 眼和对侧眼的 RNFL 厚度均显著下降。然而，ON 眼的 RNFL 变薄速度比对侧眼快 2 倍以上（<0.001）。此外，基线潜伏期不对称与 ON 眼在随访期间的 RNFL 变薄速度显著相关（<0.001），解释了时间性 RNFL 进展的近一半变异性。对于每 1 毫秒的潜伏期延迟（即视神经上约 0.5mm 的脱髓鞘），每年 RNFL 厚度减少 0.05%。
本研究提供了明确的体内证据，表明慢性脱髓鞘会显著加速轴突丢失。然而，由于该过程缓慢且影响轻微，需要进行长期监测以建立并可靠地测量脱髓鞘的神经退行性后果。
