Outcome of patients with pediatric optic neuritis characterized in 2-year study

The Pediatric Optic Neuritis Prospective Outcomes Study (PON1) observed children and teenagers with pediatric optic neuritis (PON) for 2 years to characterize the etiologies, associated neurologic conditions that could develop, and risk of recurrence.

Study design

This nonrandomized observational study at 23 pediatric ophthalmology or neuro-ophthalmology clinics in the United States and Canada included children and teenagers (aged 3–15 years) with an initial episode of optic neuritis in 1 or both eyes with vision loss or painful eye movements for ≤2 weeks. Monocular distance high-contrast visual acuity (HCVA) and low-contrast VA (LCVA) were tested via the electronic Amblyopia Treatment Study HOTV protocol for participants aged <7 years while those aged ≥7 years underwent the Electronic Early Treatment Diabetic Retinopathy Study protocol. Enrollment also included blood testing for aquaporin-4 (AQP4) antibody testing for neuromyelitis optica spectrum disease. For each participant, a masked examiner analyzed images from magnetic resonance imaging (MRI) of the brain with and without intravenous gadolinium taken either at enrollment or within 2 weeks of presentation to confirmed findings of optic nerve enhancement and associated white matter lesions, as well as images taken 2 years after presentation. Cases with white matter lesions were considered as stemming from autoimmune dysfunction. At follow-up visits at 1 month, 6 months, 1 year, and 2 years after enrollment, monocular HCVA and LCVA and anterior and posterior segments were assessed.

Outcomes

PON1 was conceived to generate prospective data on PON by evaluating the outcomes and etiologies associated with PON. Twenty-eight (64%) of the 44 children initially enrolled in PON1 completed the 2-year study. The causes of PON were isolated for 40%, myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease for 29%, multiple sclerosis for 14%, neuromyelitis optica spectrum disorder for 11%, and acute disseminated encephalomyelitis for 7%. Children diagnosed with an isolated case were less likely to experience recurrence or development of an associated neurological condition. The mean presenting visual acuity (VA) at nadir was ∼20/125, improving to ∼20/25-2 at 6 months, which was unchanged at 2 years. Recurrent optic neuritis occurred in 5 (18%) of patients during the 2-year follow-up.

Limitations

Limitations include a loss of follow-up in 1/3 of patients originally enrolled in the study. In addition, patients were mostly recruited at academic centers so there could have been a bias toward more severe disease or patients with underlying demyelinating diseases. Lastly, MOG antibody testing was not performed routinely on all patients at the time of enrollment.

Clinical significance

Despite these limitations, PON1 is the longest longitudinal study evaluating the visual outcomes in PON. The study demonstrates that despite poor vision at presentation, recovery tends to be good following PON with most children having marked improvement in VA by 6 months, which was maintained for at least 2 years. Associated neurologic diseases are common, especially MOG antibody-associated disease.