Hoshina Yoji, Seay Meagan, Vegunta Sravanthi, Stulberg Eric L, Wright Melissa A, Wong Ka-Ho, Smith Tammy L, Shimura Daisuke, Clardy Stacey L
Departments of Neurology (YH, MS, ELS, MAW, K-HW, TLS, SLC) and Pathology (TLS), University of Utah, Salt Lake City, Utah; Department of Ophthalmology and Visual Sciences (MS, SV), University of Utah Moran Eye Center, Salt Lake City, Utah; Department of Pediatric Neurology (MAW), Primary Children's Hospital, Salt Lake City, Utah; George E. Wahlen Department of Veterans Affairs Medical Center (TLS, SLC), Salt Lake City, Utah; and Nora Eccles Harrison Cardiovascular Research and Training Institute (DS), University of Utah, Salt Lake City, Utah.
J Neuroophthalmol. 2025 Mar 1;45(1):36-43. doi: 10.1097/WNO.0000000000002157. Epub 2024 Apr 22.
The diagnosis and treatment of autoimmune optic neuritis (ON) has improved with the accessibility and reliability of aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) antibody testing, yet autoantibody-negative ON remains common. This study describes the demographic, clinical, and outcome data in patients with isolated ON across the pediatric and adult cohort.
A retrospective chart review of University of Utah Health patients with the International Classification of Diseases ( ICD ) code of ICD-9 377.30 (ON unspecified), ICD-9 377.39 (other ON), or ICD-10 H46 (ON) and at least 2 ophthalmologic evaluations were conducted between February 2011 and July 2023. Only isolated cases of ON without other brain or spinal demyelinating lesions were evaluated. Differences in demographic and clinical characteristics between AQP4, MOG, and Other-ON were determined.
Of the 98 patients (15 children and 83 adults), 9 (9.2%) were positive for AQP4-IgG and 35 (35.7%) tested positive for MOG-IgG. Fifty-four were classified into Other-ON, of which 7 (13.0%) had recurrence or new demyelinating lesions during a median follow-up of 12.5 months-2 were ultimately diagnosed with recurrent isolated ON (RION), 1 with chronic relapsing inflammatory ON (CRION), 2 with multiple sclerosis, 1 with collapsin response-mediator protein (CRMP)-5-ON, and 1 with seronegative neuromyelitis optica spectrum disorder. Four patients were treated with long-term immunosuppressive therapy. No patients with RION or CRION had preceding infections; they had first recurrences of ON within 2 months. At presentation, AQP4-ON (75%) and MOG-ON (48.8%) had more severe vision loss (visual acuity <20/200) than Other-ON (23.2%, P = 0.01). At the 1-month follow-up, 93.0% of patients with MOG-ON and 89.3% of patients with Other-ON demonstrated a visual acuity ≥20/40, compared with only 50% of patients with AQP4-ON ( P < 0.01). By the last follow-up, 37.5% of the AQP4-ON still exhibited visual acuity <20/40, including 25% who experienced severe vision loss (visual acuity <20/200). By contrast, over 95% of patients with MOG-ON and Other-ON maintained a visual acuity of ≥20/40. In our cohort, over a quarter of pediatric cases presented with simultaneous bilateral ON, 40% had a preceding infection, and 44.4% initially presented with a visual acuity <20/200. Two pediatric cases had recurrence, and both were MOG-ON. By their last follow-up, all pediatric cases had achieved a visual acuity of 20/40 or better. In addition, pediatric cases were more likely to exhibit disc edema compared with adult cases (100% vs 64%, P < 0.01).
Despite recent advances in identification and availability of testing for AQP4-IgG and MOG-IgG, over half of patients who presented with isolated ON remained with an "idiopathic" diagnostic label. As more than 1 in 10 patients with AQP4-IgG and MOG-IgG negative ON experienced recurrence or develop new demyelinating lesions, clinicians should provide anticipatory guidance and closely monitor for potential long-term outcomes. In addition, it is crucial to re-evaluate the diagnosis in cases of poor recovery, ON recurrence, and the emergence of new neurological symptoms, as ON can often be the initial presentation of other conditions.
随着水通道蛋白4（AQP4）和髓鞘少突胶质细胞糖蛋白（MOG）抗体检测的可及性和可靠性提高，自身免疫性视神经炎（ON）的诊断和治疗有所改善，但自身抗体阴性的ON仍然常见。本研究描述了儿科和成人队列中孤立性ON患者的人口统计学、临床和结局数据。
对犹他大学健康中心患有国际疾病分类（ICD）代码为ICD - 9 377.30（未特指的ON）、ICD - 9 377.39（其他ON）或ICD - 10 H46（ON）且在2011年2月至2023年7月期间至少进行了2次眼科评估的患者进行回顾性病历审查。仅评估无其他脑或脊髓脱髓鞘病变的孤立性ON病例。确定了AQP4、MOG和其他ON之间人口统计学和临床特征的差异。
在98例患者（15名儿童和83名成人）中，9例（9.2%）AQP4 - IgG呈阳性，35例（35.7%）MOG - IgG检测呈阳性。54例被归类为其他ON，其中7例（13.0%）在中位随访12.5个月期间出现复发或新的脱髓鞘病变——2例最终被诊断为复发性孤立性ON（RION），1例为慢性复发性炎性ON（CRION），2例为多发性硬化，1例为塌陷反应介导蛋白（CRMP）- 5 - ON，1例为血清阴性视神经脊髓炎谱系障碍。4例患者接受了长期免疫抑制治疗。没有RION或CRION患者有先前感染；他们在2个月内首次出现ON复发。就诊时，AQP4 - ON（75%）和MOG - ON（48.8%）的视力丧失比其他ON更严重（视力<20/200）（23.2%，P = 0.01）。在1个月随访时，93.0%的MOG - ON患者和89.3%的其他ON患者视力≥20/40，而AQP4 - ON患者仅为50%（P < 0.01）。到最后一次随访时，37.5%的AQP4 - ON患者视力仍<20/40，其中25%经历了严重视力丧失（视力<20/200）。相比之下，超过95%的MOG - ON和其他ON患者视力维持在≥20/40。在我们的队列中超过四分之一的儿科病例表现为同时双侧ON，40%有先前感染，44.4%最初视力<20/200。2例儿科病例复发，均为MOG - ON。到最后一次随访时，所有儿科病例视力均达到20/40或更好。此外，与成人病例相比，儿科病例更易出现视盘水肿（100%对64%，P < 0.01）。
尽管最近在AQP4 - IgG和MOG - IgG检测的识别和可及性方面取得了进展，但超过一半表现为孤立性ON的患者仍被贴上“特发性”诊断标签。由于超过十分之一的AQP4 - IgG和MOG - IgG阴性ON患者经历复发或出现新的脱髓鞘病变，临床医生应提供预期指导并密切监测潜在的长期结局。此外，在恢复不佳、ON复发和出现新的神经症状的情况下重新评估诊断至关重要，因为ON通常可能是其他疾病的初始表现。
