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).

Pathognomonic macular ripples are revealed by polarized infrared retinal imaging.

A pathognomonic macular ripple sign has been reported with scanning laser ophthalmoscopy images in patients with foveal hypoplasia, though the optical basis of this sign is presently unknown. Here we present a case series of seven individuals with foveal hypoplasia (based on spectral domain optical coherence tomography). Each patient underwent infrared scanning laser ophthalmoscopy retinal imaging in both eyes, acquired with and without a polarization filter and assessment for a ripple-like effect in the fovea. On imaging, macular ripples were present in all eyes with foveal hypoplasia when using a polarization filter, but not when imaged without the filter. We conclude that the macular ripple sign is an imaging artifact attributable to the unique pattern of phase retardation of the Henle fiber layer in the setting of foveal hypoplasia. By utilizing a polarization filter with retinal photography, this feature can be exploited to promptly identify foveal hypoplasia in settings where OCT is not possible due to nystagmus.

A Randomized Trial of a Binocular iPad Game Versus Part-Time Patching in Children Aged 13 to 16 Years With Amblyopia.

PURPOSE: To compare visual acuity (VA) improvement in teenagers with amblyopia treated with a binocular iPad game vs part-time patching. METHODS: One hundred participants aged 13 to <17 years (mean 14.3 years) with amblyopia (20/40 to 20/200, mean ∼20/63) resulting from strabismus, anisometropia, or both were enrolled into a randomized clinical trial. Participants were randomly assigned to treatment for 16 weeks of either a binocular iPad game prescribed for 1 hour per day (n = 40) or patching of the fellow eye prescribed for 2 hours per day (n = 60). The main outcome measure was change in amblyopic eye VA from baseline to 16 weeks. RESULTS: Mean amblyopic eye VA improved from baseline by 3.5 letters (2-sided 95% confidence interval [CI]: 1.3-5.7 letters) in the binocular group and by 6.5 letters (2-sided 95% CI: 4.4-8.5 letters) in the patching group. After adjusting for baseline VA, the difference between the binocular and patching groups was -2.7 letters (95% CI: -5.7 to 0.3 letters, P = .082) or 0.5 lines, favoring patching. In the binocular group, treatment adherence data from the iPad device indicated that only 13% of participants completed >75% of prescribed treatment. CONCLUSIONS: In teenagers aged 13 to <17 years, improvement in amblyopic eye VA with the binocular iPad game used in this study was not found to be better than patching, and was possibly worse. Nevertheless, it remains unclear whether the minimal treatment response to binocular treatment was owing to poor treatment adherence or lack of treatment effect.

Silicone spacer repair of medial rectus after iatrogenic orbit fracture.

A 51-year-old woman underwent endoscopic nasal polypectomy and ethmoidectomy with accidental entry into the right orbit causing enophthalmos and transection of the medial rectus muscle (MR). The repair of a fracture and of a damaged MR is technically challenging, particularly when large portions of bone and muscle are missing. We report a rare case of repair of the bony defect with an implant and reattachment of the MR with a silicone retina band, through a combined transcaruncular and transconjunctival approach. Postoperatively, the patient had residual enophthalmos and strabismus; further surgical options are discussed.

The evolutionary history and dynamics of bat rabies virus.

Rabies virus (RABV) is endemic in terrestrial mammals throughout the world and in bats on the American continent. We performed the most extensive phylogenetic analyses of bat RABV sequences undertaken to date using a variety of genes. Our study supported previous suggestions that viral sequences are grouped according to the behaviour of the host species. However, there was more genetic and geographical diversity within each phylogenetic group than previously recognised, including evidence for new groups. Furthermore, three clades of Latin American bat RABV that were distinct from the previously identified "group IV" bat RABV clade and more closely related to North American bat RABV clades, were identified. Strikingly, phylogenetic trees for the G (glycoprotein) gene had a significantly different evolutionary history to those inferred for the N (nucleoprotein) and P (phosphoprotein) genes, and an analysis of these competing topologies revealed that it is not possible on current data to resolve whether bat RABV arose from terrestrial mammal RABV, or vice-versa. Finally, using coalescent approaches, we estimated that RABV had similar rates of population growth and nucleotide substitution (approximately 2.5-4x10(-4) substitutions per site, per year) in both bats and terrestrial mammals, despite underlying differences in epidemiology.

Phylogeography, population dynamics, and molecular evolution of European bat lyssaviruses.

European bat lyssaviruses types 1 and 2 (EBLV-1 and EBLV-2) are widespread in Europe, although little is known of their evolutionary history. We undertook a comprehensive sequence analysis to infer the selection pressures, rates of nucleotide substitution, age of genetic diversity, geographical origin, and population growth rates of EBLV-1. Our study encompassed data from 12 countries collected over a time span of 35 years and focused on the glycoprotein (G) and nucleoprotein (N) genes. We show that although the two subtypes of EBLV-1--EBLV-1a and EBLV-1b--have both grown at a low exponential rate since their introduction into Europe, they have differing population structures and dispersal patterns. Furthermore, there were strong constraints against amino acid change in both EBLV-1 and EBLV-2, as reflected in a low ratio of nonsynonymous to synonymous substitutions per site, particularly in EBLV-1b. Our inferred rate of nucleotide substitution in EBLV-1, approximately 5 x 10(-5) substitutions per site per year, was also one of the lowest recorded for RNA viruses and implied that the current genetic diversity in the virus arose 500 to 750 years ago. We propose that the slow evolution of EBLVs reflects their distinctive epidemiology in bats, where they occupy a relatively stable fitness peak.

Optic nerve head drusen.

Optic disc drusen are congenital and developmental anomalies of the optic nerve head seen commonly in clinical practice, often as an incidental ophthalmologic finding during routine exams. Optic disc drusen are a form of calcific degeneration in some of the axons of the optic nerve. Visual acuity is often not affected but the visual fields of these patients can be abnormal and deteriorate over time. Optic disc drusen are familial and are not uncommon. They are thought to be the result of pathology at the level of the optic nerve head itself. The diagnosis can be made with clinical findings combined with B scan ultrasound and computed tomography. In addition, newer modalities using optic nerve head tomography are proving to be very useful. Since children as well as adults are affected, it is important to consider optic nerve head drusen in the differential diagnosis of papilledema or optic nerve swelling.