The Pediatric Optic Neuritis Prospective Outcomes Study

Purpose Pediatric optic neuritis (ON) is a rare disease that has not been well characterized. The Pediatric ON Prospective Outcomes Study (PON1) was the first prospective study to our knowledge aiming to evaluate visual acuity (VA) outcomes, including VA, recurrence risk, and final diagnosis 2 years after enrollment. Design Nonrandomized observational study at 23 pediatric ophthalmology or neuro-ophthalmology clinics in the United States and Canada. Participants A total of 28 (64%) of 44 children initially enrolled in PON1 (age 3–<16 years) who completed their 2-year study visit. Methods Participants were treated at the investigator's discretion. Main Outcomes Measures Age-normal monocular high-contrast VA (HCVA). Secondary outcomes included low-contrast VA (LCVA), neuroimaging findings, and final diagnoses. Results A total of 28 participants completed the 2-year outcome with a median enrollment age of 10.3 years (range, 5–15); 46% were female, and 68% had unilateral ON at presentation. Final 2-year diagnoses included isolated ON (n = 11, 39%), myelin oligodendrocyte glycoprotein–associated demyelination (n = 8, 29%), multiple sclerosis (MS) (n = 4,14%), neuromyelitis optica spectrum disease (NMOSD) (n = 3, 11%), and acute disseminated encephalomyelitis (n = 2, 7%). Two participants (7%; 95% confidence interval [CI], 1–24) had subsequent recurrent ON (plus 1 participant who did not complete the 2-year visit); all had MS. Two other participants (7%) had a new episode in their unaffected eye. Mean presenting HCVA was 0.81 logarithm of the minimum angle of resolution (logMAR) (∼20/125), improving to 0.14 logMAR (∼20/25-2) at 6 months, 0.12 logMAR (∼20/25-2) at 1 year, and 0.11 logMAR (20/25-1) at 2 years (95% CI, −0.08 to 0.3 [20/20+1–20/40-1]). Twenty-four participants (79%) had age-normal VA at 2 years (95% CI, 60–90); 21 participants (66%) had 20/20 vision or better. The 6 participants without age-normal VA had 2-year diagnoses of NMOSD (n = 2 participants, 3 eyes), MS (n = 2 participants, 2 eyes), and isolated ON (n = 2 participants, 3 eyes). Mean presenting LCVA was 1.45 logMAR (∼20/500-2), improving to 0.78 logMAR (∼20/125+2) at 6 months, 0.69 logMAR (∼20/100+1) at 1 year, and 0.68 logMAR (∼20/100+2) at 2 years (95% CI, 0.48–0.88 [20/50+1–20/150-1]). Conclusions Despite poor VA at presentation, most children had marked improvement in VA by 6 months that was maintained over 2 years. Associated neurologic autoimmune diagnoses were common. Additional episodes of ON occurred in 5 (18%) of the participants (3 relapses and 2 new episodes). Pediatric optic neuritis (ON) is a rare disease that has not been well characterized. The Pediatric ON Prospective Outcomes Study (PON1) was the first prospective study to our knowledge aiming to evaluate visual acuity (VA) outcomes, including VA, recurrence risk, and final diagnosis 2 years after enrollment. Nonrandomized observational study at 23 pediatric ophthalmology or neuro-ophthalmology clinics in the United States and Canada. A total of 28 (64%) of 44 children initially enrolled in PON1 (age 3–<16 years) who completed their 2-year study visit. Participants were treated at the investigator's discretion. Age-normal monocular high-contrast VA (HCVA). Secondary outcomes included low-contrast VA (LCVA), neuroimaging findings, and final diagnoses. A total of 28 participants completed the 2-year outcome with a median enrollment age of 10.3 years (range, 5–15); 46% were female, and 68% had unilateral ON at presentation. Final 2-year diagnoses included isolated ON (n = 11, 39%), myelin oligodendrocyte glycoprotein–associated demyelination (n = 8, 29%), multiple sclerosis (MS) (n = 4,14%), neuromyelitis optica spectrum disease (NMOSD) (n = 3, 11%), and acute disseminated encephalomyelitis (n = 2, 7%). Two participants (7%; 95% confidence interval [CI], 1–24) had subsequent recurrent ON (plus 1 participant who did not complete the 2-year visit); all had MS. Two other participants (7%) had a new episode in their unaffected eye. Mean presenting HCVA was 0.81 logarithm of the minimum angle of resolution (logMAR) (∼20/125), improving to 0.14 logMAR (∼20/25-2) at 6 months, 0.12 logMAR (∼20/25-2) at 1 year, and 0.11 logMAR (20/25-1) at 2 years (95% CI, −0.08 to 0.3 [20/20+1–20/40-1]). Twenty-four participants (79%) had age-normal VA at 2 years (95% CI, 60–90); 21 participants (66%) had 20/20 vision or better. The 6 participants without age-normal VA had 2-year diagnoses of NMOSD (n = 2 participants, 3 eyes), MS (n = 2 participants, 2 eyes), and isolated ON (n = 2 participants, 3 eyes). Mean presenting LCVA was 1.45 logMAR (∼20/500-2), improving to 0.78 logMAR (∼20/125+2) at 6 months, 0.69 logMAR (∼20/100+1) at 1 year, and 0.68 logMAR (∼20/100+2) at 2 years (95% CI, 0.48–0.88 [20/50+1–20/150-1]). Despite poor VA at presentation, most children had marked improvement in VA by 6 months that was maintained over 2 years. Associated neurologic autoimmune diagnoses were common. Additional episodes of ON occurred in 5 (18%) of the participants (3 relapses and 2 new episodes).