Optic neuritis (ON) is an inflammatory, demyelinating disease of the optic nerve that causes visual impairment. It is the most common cause of vision loss due to optic nerve dysfunction in people aged 20–40, with an annual incidence of 0.56–14 per 100,000. It typically occurs between ages 15 and 45 and is more common in women.
ON is clinically divided into typical and atypical forms.
Typical ON is often associated with multiple sclerosis (MS) and presents with acute monocular vision loss. Atypical ON is characterized by onset outside the typical age range (under 15 or over 45), simultaneous bilateral involvement, progression beyond two weeks, or steroid dependence, and may be associated with neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), systemic lupus erythematosus (SLE), or Sjögren’s syndrome.
The exact prevalence during pregnancy is unknown, but there is a clear temporal association between pregnancy and ON onset. An analysis of 54 pregnancy-related ON cases in Chinese women (Bai et al. 2022) found that only 16.4% occurred during pregnancy, while 83.6% occurred within one year postpartum, with 49.3% within the first three months after delivery. In that cohort, 50.0% were anti-AQP4 antibody-positive, 11.6% were anti-MOG antibody-positive, and 38.9% were idiopathic [¹].
The relatively lower incidence during pregnancy may be due to an increase in regulatory T cells, leading to a Th2-dominant immune-tolerant state. Conversely, women with a history of ON may have an increased risk of preeclampsia and preterm birth.
83.6% of cases occur within one year after delivery, with the highest risk period being within three months after childbirth (49.3%). During pregnancy, a Th2-dominant immune tolerance state suppresses the onset of ON, whereas after delivery, the rapid decrease in estrogen and progesterone reactivates the Th1/Th17 system, leading to increased autoimmune activity.
The symptoms of ON that develop during pregnancy are essentially the same as those in non-pregnant individuals.
Idiopathic autoimmune mechanisms account for the majority of cases. Approximately 30% of MS patients present with visual impairment at onset, and ON can be the initial symptom of MS. In patients with ON, the 15-year conversion rate to MS is about 25% without brain lesions, and 72–78% with brain lesions.
The increase in postpartum onset is thought to involve reactivation of Th1/Th17 pathways due to rapid decline of estrogen and progesterone. During pregnancy, viral diseases may also trigger bilateral ON attacks.
Typical ON
Common age: 15–45 years, more common in women
Cause: Mainly autoimmune (idiopathic) mechanisms
Features: Acute monocular onset
MS conversion: 72–78% at 15 years with brain lesions
Prognosis: About 80% begin improvement within 3 weeks. At 1 year, 93% have visual acuity ≥0.5
Atypical ON
Causes: NMOSD, MOGAD, infectious, autoimmune diseases
Features: Bilateral, progressive, steroid-dependent
NMOSD: Anti-AQP4 antibody positive. Steroid-resistant, poor visual prognosis
MOGAD: Anti-MOG antibody positive. A new disease entity
Caution: Infectious causes must be ruled out before using steroids
ON can be the first symptom of MS. The 15-year conversion rate to MS is about 25% if there are no brain MRI lesions, and 72-78% if brain lesions are present. If ON occurs during pregnancy, it is important to undergo a thorough evaluation including brain MRI by a neurologist and ophthalmologist to assess the risk of developing MS.
Performed when necessary to differentiate from infectious or inflammatory diseases.
| Disease | Key points for differentiation |
|---|---|
| Compressive optic neuropathy | Pituitary adenoma, meningioma, etc. Excluded by imaging. |
| Pituitary apoplexy | Occurs during pregnancy and mimics acute optic neuropathy. |
| Leber hereditary optic neuropathy | Bilateral optic neuropathy in young to middle-aged adults. |
| Infectious optic neuritis | Fungal, viral, syphilis. Exclude before steroids. |
| NAION | Differentiation from non-arteritic anterior ischemic optic neuropathy. |
Even without treatment, about 80% of cases begin to improve within 3 weeks of onset. One year after onset, visual acuity of 0.5 or better is achieved in 93% and 1.0 or better in 70%.
First-line: Steroid pulse therapy
Side effects to watch for include hyperglycemia, peptic ulcer, and infection.
Methylprednisolone, prednisone, and prednisolone are inactivated by placental 11-β-hydroxysteroid dehydrogenase, and typically only about 10% of the total dose reaches the fetal circulation. Therefore, they are considered relatively safe at appropriate doses.
When approved, the regimen is IVMP 500–1,000 mg/day for 3 days[²]. However, the following points require attention:
First-line acute treatment is steroid pulse therapy. If there is no improvement with steroid pulse therapy, plasma exchange therapy is performed. Plasma exchange during pregnancy is considered a feasible alternative and has been reported to result in better long-term visual outcomes[³][⁴]. For chronic phase (relapse prevention), oral steroid therapy (low-dose prednisolone) is used, but the first-line treatment is not established.
The risk of using DMTs during pregnancy varies by medication.
| Medication | Fetal toxicity | Breastfeeding compatibility |
|---|---|---|
| Glatiramer acetate | Low | Yes |
| IFN-β | Risk of low birth weight and preterm birth | Probably yes |
| Teriflunomide | Teratogenic | No |
| Fingolimod | Fetal toxicity present | No |
Methylprednisolone and similar drugs are inactivated by placental enzymes, and typically only about 10% of the total dose reaches the fetus. Short-term standard doses are considered to have relatively little effect on the fetus. However, long-term high-dose administration can saturate placental enzymes and pose a risk of fetal adrenal insufficiency, so careful judgment in collaboration with an obstetrician is necessary.
It varies greatly by medication. Glatiramer acetate and prednisolone are considered safe for breastfeeding. IFN-β is probably safe, but teriflunomide and fingolimod are not. When resuming DMT postpartum, the risk of drug transfer through breast milk should be considered, and the decision should be made in consultation with a neurologist and obstetrician.
Through autoimmune mechanisms, inflammatory cells such as microglia infiltrate the optic nerve and cause inflammation. Demyelinating and axonal damage due to inflammation leads to death and apoptosis of retinal ganglion cells. Repeated inflammatory episodes progress to optic atrophy.
Anti-AQP4 antibodies bind to complement and selectively attack astrocytes. Astrocytes in the optic nerve and chiasm express abundant AQP4, making them vulnerable targets, leading to severe inflammatory changes and optic nerve damage.
Anti-MOG antibodies are autoantibodies targeting MOG, a component of myelin. Complement pathway activation (weaker than AQP4-IgG) and infiltration of CD4+ T cells and macrophages are involved in the pathogenesis.
During pregnancy, high levels of estrogen and progesterone induce a Th2-dominant state, preventing fetal rejection and suppressing autoimmunity. Additionally, an increase in regulatory T cells contributes to this immune tolerance.
After delivery, estrogen and progesterone levels drop rapidly, reactivating Th1/Th17 responses. This immune rebound is thought to enhance autoimmune activity and contribute to the increased onset of ON within three months postpartum [²][⁶].
Exclusive breastfeeding has been reported to potentially have a protective effect against early postpartum MS relapses. The mechanism is speculated to involve prolactin or immune modulation associated with lactation, but established evidence is lacking.
Women with a history of ON have been reported to have a significantly lower likelihood of pregnancy and childbirth. It is suggested that underlying autoimmune mechanisms or medications may affect fertility, but further research is needed to clarify causality.
In 2023, new international diagnostic criteria for MOGAD were established, and the disease concepts and diagnostic criteria for MOGAD and NMOSD are being refined. This is expected to improve the diagnostic accuracy of atypical ON, which was previously difficult to classify.
Bai W, Sun M, Song H, et al. Serial analyses of clinical spectra and outcomes in Chinese women with pregnancy-induced optic neuritis. Front Med (Lausanne). 2022;9:1067277. doi:10.3389/fmed.2022.1067277. PMID: 36507533
Moss HE. Neuro-ophthalmology and Pregnancy. Continuum (Minneap Minn). 2022;28(1):147-161. doi:10.1212/CON.0000000000001059. PMID: 35133315
D’Souza R, Wuebbolt D, Andrejevic K, et al. Pregnancy and Neuromyelitis Optica Spectrum Disorder - Reciprocal Effects and Practical Recommendations: A Systematic Review. Front Neurol. 2020;11:544434. doi:10.3389/fneur.2020.544434. PMID: 33178102
Mao-Draayer Y, Thiel S, Mills EA, et al. Neuromyelitis optica spectrum disorders and pregnancy: therapeutic considerations. Nat Rev Neurol. 2020;16(3):154-170. doi:10.1038/s41582-020-0313-y. PMID: 32080393
Gal RL, Vedula SS, Beck R. Corticosteroids for treating optic neuritis. Cochrane Database Syst Rev. 2015;(8):CD001430. doi:10.1002/14651858.CD001430.pub4. PMID: 26273799
Mahale RR, Varghese N, Mailankody P, Padmanabha H, Mathuranath PS. Postpartum Optic Neuropathy: Think of Myelin Oligodendrocyte Glycoprotein Immunoglobulin G-Associated Optic Neuritis - Report of Two Cases. Ann Indian Acad Neurol. 2021;24(2):274-276. doi:10.4103/aian.AIAN_317_20. PMID: 34220089
