Ocular Neuromyotonia in Children and Adolescents Following Radiation Treatment of Pediatric Brain Tumors.

PURPOSE: To report five cases of ocular neuromyotonia in children and adolescents following radiation therapy for a variety of pediatric brain tumors. Notably, three cases occurred in children younger than 11 years. METHODS: Case series of five patients with ocular neuromyotonia following proton beam therapy or conventional radiation. RESULTS: Five cases of ocular neuromyotonia were identified following radiation treatment of various pediatric brain tumors. Onset ranged from 5 to 142 months after radiation treatment. The abducens nerve/lateral rectus muscle was affected in three patients, and the trochlear nerve/superior oblique muscle was affected in two patients. Ages at symptom presentation were 4 years (intermittent head tilt), 9 years (intermittent blurry vision and head tilt), 10 years (intermittent blurry vision progressing to intermittent diplopia), 15 years (intermittent diplopia), and 17 years (intermittent diplopia). One patient improved with gabapentin. Two patients experienced spontaneous resolution. One patient died due to meta-static disease, and one patient has planned follow-up. CONCLUSIONS: Ocular neuromyotonia occurs most commonly following radiation to the brain and skull base. Clinicians need to be aware that ocular neuromyotonia presents differently in children (who may not report diplopia) than in adults or adolescents (who typically report diplopia). Two children in this series never reported diplopia, only intermittent head tilt and blurry vision. Ocular neuromyotonia requires a high index of suspicion to diagnose, especially in children. Membrane stabilizers can be used effectively, but observation may be a valid option in children because spontaneous resolution was seen. [J Pediatr Ophthalmol Strabismus. 2022;59(5):338-343.].

Unilateral Abducens Nerve Palsy Following Perinatal Stroke of the Middle Cerebral Artery.

The authors describe a case of unilateral abducens nerve palsy following perinatal stroke of the middle cerebral artery. A 1-year-old boy presented with left eye esotropia but no other ocular abnormalities. The patient's history, examination, and diagnostic tests were consistent with abducens nerve palsy. He underwent left medial rectus recession of 5.5 mm and left lateral rectus resection of 7 mm followed by patching. At 15 months after surgery, primary gaze by prism alternate cover testing revealed a 4 prism diopter (PD) esophoria (small angle in left gaze with essentially no action of lateral rectus) and 2 PD right hyperphoria. Ophthalmologic management of abducens nerve palsy entails addressing neurological sequelae in a timely manner, treating the esotropia and strabismic amblyopia to optimize visual system development. [J Pediatr Ophthalmol Strabismus. 2020;57:e30-e33.].

Long-term visual acuity outcomes after radiation therapy for sporadic optic pathway glioma.

PURPOSE: Children with sporadic optic pathway glioma (OPG) commonly experience a decline in visual acuity (VA). This study aimed to quantify long-term VA outcomes after definitive radiation therapy (RT). METHODS: From 1997 to 2017, 41 patients underwent RT for OPG and had baseline VA testing. All patients underwent serial VA testing every 3-6 months during the first 5 years and annually thereafter. The cumulative incidence of VA decline or improvement (per eye) was estimated using death as a competing risk. RESULTS: Mean follow-up was 5 years. Most tumors (93%) involved the postchiasmatic optic tracts and/or hypothalamus. Of the tumors tested for BRAF alterations (n = 15), 67% had a BRAF fusion. Median time to VA decline was 20 months in the eye with worse vision and 22 months in the better eye. For the worse eye, the 5-year cumulative incidences of VA decline and improvement were 17.9% [95% confidence interval (CI) 7-32.8%] and 13.5% (95% CI 4.7-26.7%), respectively. For the better eye, the 5-year cumulative incidences of VA decline and improvement were 11.5% (95% CI 3.5-30.7%) and 10.6% (95% CI 2.6-25.2%), respectively. Visual outcomes did not correlate with radiographic evidence of tumor progression. CONCLUSIONS: The 5-year cumulative incidence of VA decline was low. VA decline is most likely to occur within the first 2 years after RT and is not associated with radiographic progression of disease, highlighting the need for frequent ophthalmologic exams during this period.

Identification of a therapeutic dose of continuously delivered erythropoietin in the eye using an inducible promoter system.

Erythropoietin (EPO) can protect the retina from acute damage, but long-term systemic treatment induces polycythemia. Intraocular gene delivery of EPO is not protective despite producing high levels of EPO likely due to its bellshaped dose curve. The goal of this study was to identify a therapeutic dose of continuously produced EPO in the eye. We packaged a mutated form of EPO (EPOR76E) that has equivalent neuroprotective activity as wild-type EPO and attenuated erythropoietic activity into a recombinant adeno-associated viral vector under the control of the tetracycline inducible promoter. This vector was injected into the subretinal space of homozygous postnatal 5-7 day retinal degeneration slow mice, that express the tetracycline transactivators from a retinal pigment epithelium specific promoter. At weaning, mice received a single intraperitoneal injection of doxycycline and were then maintained on water with or without doxycycline until postnatal day 60. Intraocular EPO levels and outer nuclear layer thickness were quantified and correlated. Control eyes contained 6.1 ± 0.1 (SEM) mU/ml EPO. The eyes of mice that received an intraperitoneal injection of doxycycline contained 11.8 ± 2.0 (SEM) mU/ml EPO-R76E. Treatment with doxycycline water induced production of 35.9 ± 2.4 (SEM) mU/ml EPO-R76E in the eye. The outer nuclear layer was approximately 8 µm thicker in eyes of mice that received doxycycline water as compared to the control groups. Our data indicates that drug delivery systems should be optimized to deliver at least 36 mU/ml EPO into the eye since this dose was effective for the treatment of a progressive retinal degeneration.