The Pediatric Optic Neuritis Prospective Outcomes Study: Two-Year Results.

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).

Secondary 12-Month Ocular Outcomes of a Phase 1 Dosing Study of Bevacizumab for Retinopathy of Prematurity.

Importance: Lower bevacizumab dosages are being used for type 1 retinopathy of prematurity, but there are limited data on long-term ocular outcomes with lower doses. Objective: To evaluate ocular outcomes at 12 months' corrected age for eyes that received a dose of 0.625 mg, 0.25 mg, 0.125 mg, 0.063 mg, or 0.031 mg of bevacizumab for type 1 retinopathy of prematurity. Design, Setting, and Participants: This prospective cohort study used a masked, multicenter, phase 1 dose de-escalation study design and was conducted from April 2016 to October 2017. Study eyes were treated with a dose of 0.25, 0.125, 0.063, or 0.031 mg of bevacizumab; fellow eyes were treated with a dosage 1 level higher than the study eye. Additional treatment after 4 weeks was at investigator discretion. Data analysis occurred from November 2018 to March 2019. Interventions: Intravitreous bevacizumab injections of 0.625 mg to 0.031 mg. Main Outcomes and Measures: Visual fixation, amblyopia, alignment, nystagmus, cycloplegic refraction, and ocular examinations were assessed at 12 months' corrected age as preplanned secondary outcomes. The primary outcome 4 weeks after treatment and secondary outcomes after 6 months' corrected age have been previously reported. Results: Forty-six of 61 infants (75%) had a 12-month follow-up examination (46 study eyes and 43 fellow eyes; median [interquartile range] birth weight, 650 [590-760] g). Of 87 eyes with a cycloplegic refraction, 12 (14% [95% CI, 7%-27%]) had myopia of more than -5.00 D spherical equivalent; 2 (2%; [95% CI, 0%-8%]) had hyperopia greater than 5.00 D spherical equivalent; and 5 infants (11% [95% CI, 4%-24%]) had anisometropia greater than 1.50 D spherical equivalent. Abnormalities of the cornea, lens, or anterior segment were reported in 1 eye (1% [95% CI, 0%-6%]), 3 eyes (3% [95% CI, 1%-10%]), and 3 eyes (3% [95% CI, 1%-10%]), respectively. Optic nerve atrophy was identified in 11 eyes (13% [95% CI, 6%-26%]), and 1 eye (1% [95% CI, 0%-6%]) had total retinal detachment. Strabismus was reported in 13 infants (30% [95% CI, 17%-45%]), manifest nystagmus in 7 infants (15% [95% CI, 6%-29%]), and amblyopia in 3 infants (7% [95% CI, 1%-18%]). Overall, 98% of infants had central fixation in each eye (44 of 45 eyes). Conclusions and Relevance: In this study of low-dose bevacizumab, the secondary outcomes of high myopia, strabismus, retinal detachment, nystagmus, and other ocular abnormalities at 1 year were consistent with rates reported in other studies with higher dosages. Trial Registration: ClinicalTrials.gov identifier: NCT02390531.

Outcome of pediatric patients referred for papilledema.

PURPOSE: To determine the prevalence of papilledema versus pseudopapilledema among children referred for suspected papilledema and to identify clinical factors differentiating the two diagnoses. METHODS: This is a prospective, cross-sectional analysis of patients <18 years old referred to a pediatric ophthalmology clinic for suspected papilledema by ophthalmoscopic examination between April 2012 and February 2014. Patients underwent detailed ophthalmologic and, when indicated, neurologic evaluation to determine the presence or absence of papilledema. RESULTS: A total of 34 patients were identified. Of these, 26 patients were diagnosed with pseudopapilledema or a normal variant; 2, with papilledema; and 6, with unrelated or indeterminate etiology. Headache was a presenting symptom in 25 patients. Five patients complained of additional symptoms suggestive of increased intracranial pressure, of whom 2 were patients diagnosed with papilledema. CONCLUSIONS: The incidence of true papilledema among children referred for suspected papilledema based on fundus examination is very low. Headache is a common nonspecific symptom in most patients, whether or not they have papilledema. If children have no additional signs and/or symptoms suggestive of elevated ICP or vision loss, the need for evaluation of such children is not urgent. A detailed history and examination coupled with noninvasive testing, such as ultrasonography, will generally distinguish pseudopapilledema from other abnormal-appearing optic nerves.

Update in pediatric optic neuritis.

PURPOSE OF REVIEW: Pediatric optic neuritis is an uncommon disorder with significant distinctions from its adult counterpart. Recognizing the features of this disorder and the potential association with progressive demyelinating processes is important for patients' evaluation and prognosis. RECENT FINDINGS: In the last few years, studies have expanded our understanding of demographic and presenting features for optic neuritis in the pediatric population. Emerging research on biomarkers and optical coherence tomography utility offers potential prognostic value in patient management. In addition, pooled research data have allowed for better understanding of the risks factors for progression from isolated optic neuritis to systemic demyelinating processes, such as multiple sclerosis. Although definitive evidence is lacking, corticosteroids remain the cornerstone of treatment. Various other immunosuppressive therapy studies have also reported success, particularly in refractory cases. SUMMARY: A comprehensive understanding of pediatric optic neuritis and its management remains elusive. A randomized clinical trial would potentially increase our knowledge and benefit the afflicted patients.

Expression of tissue plasminogen activator during eye development.

Tissue plasminogen activator (tPA) is a serine protease responsible for the activation of plasminogen to plasmin as well as extracellular matrix remodeling. While tPA is used clinically to treat some retinal disorders and it is expressed at low levels in the adult eye, its expression pattern during eye development had never been determined. tPA protein is broadly dispersed in the lens placode and optic vesicle of the mouse eye and it becomes highly localized to the apical surfaces of both the lens pit and the optic cup as they invaginate. In the lens, tPA remains at the apical tips of both lens epithelial and fiber cells from the lens vesicle stage until birth in the mouse, when it begins to downregulate to barely detectable levels in adults. In humans, tPA is found in a similar pattern in the lens vesicle and early lens, however, appreciable protein is also detected in the cytoplasm of lens epithelial cells until adulthood. In the retina, tPA is found at the apical interface between the developing retinal pigmented epithelium and neural retina, then begins to downregulate once the photoreceptors have differentiated. In conclusion, tPA protein is found in a different pattern in embryonic versus adult eyes and may be involved in remodeling of the extracellular environment during eye development.