Characterization of retinal thickness in children with neurofibromatosis type 1 and optic pathway gliomas using optical coherence tomography David Wolf, MD, PhD Pediatric Neurology Group 4

Neurofibromatosis Type 1 Autosomal dominant neurocutaneous disorder Incidence of 1:3500 Diagnosis based primarily on clinical criteria

Optic Pathway Gliomas and NF1 15% of children with NF1 (Listernick et al, J Pediatr 1994) Age <6 years – Can be seen into early adulthood Present with: – Diminished visual acuity Difficult to assess – Proptosis – Precocious puberty Tumor causes compressive damage to optic nerve

Current Guidelines Yearly ophthalmologic exam – Acuity – Visual fields – Color vision Follow growth curves closely If optic pathway glioma suspected, MRI indicated – No indication for “screening” neuroimaging

Post-contrast T2

Problems with MRI Can follow size, enhancement over time Changes not associated with visual acuity Requires general anesthesia – May be needed up to 8 times over 2 years

Other testing modalities? Noninvasive Fast Can be performed on children Quantitative Correlates with standard visual acuity testing

Optical Coherence Tomography

Noninvasive, no ionizing radiation Gives quantitative, reproducible measurement of retinal thickness Decreased retinal thickness correlates with poorer visual acuity Tumors that compress the optic nerve decrease retinal thickness – OPGs have not been specifically examined

Hypothesis Retinal nerve layer thickness will be decreased in children with optic pathway glioma relative to children without optic pathway glioma This is a feasibility study. In the future, we hope to use OCT as a tool to follow progression of OPGs

Study design Cross sectional study of children seen in the Johns Hopkins Outpatient Center

Inclusion and Exclusion Criteria Inclusion: Children aged 6-19 years Exclusion – History of optic neuritis, papilledema – Chemotherapy for optic glioma – Glioma regression – Foster children – Unable to sit for exam Myopia and hyperopia are NOT exclusion criteria

Definition of three comparison groups Neurofibromatosis Type 1 with OPG – First occurrence of OPG as assessed by MRI – Recruited through referral from neuro-oncology and neuro-ophthalmology Neurofibromatosis Type 1 without OPG – Based on clinical diagnosis – Matched to cases with OPG on age (+/- 3 years) – Recruited through neurofibromatosis clinic Non-NF1 controls recruited from general pediatric neurology clinic

Assessment of Retinal Thickness OCT performed by one person (me) on one machine Complete retinal thickness measured in each eye once Average retinal thickness will be used in analysis

Additional Testing Visual acuity – Snellen visual acuity testing – Sloan low contrast visual acuity – Will be used for secondary analysis Demographic factors, medical history collected at time of exam – Prior imaging studies – Prior ophthalmologic exams

Power calculation Mean (controls): 100 microns Mean (OPG): 90 microns SD (controls): 30 SD (OPG): 30 Alpha: 0.05 Power: 0.8 Sample size: 19 subjects per group

Analytical Plan ANOVA comparing retinal thickness between three groups General linear regression to compare differences in retinal thickness between all three groups (using non-NF1 as reference group) while adjusting for age, sex, and other potential confounders Correlation matrix of retinal thickness, visual acuity, and tumor size

Power calculation Mean (controls): 100 microns Mean (OPG): 90 microns SD (controls): 30 SD (OPG): 30 Alpha: 0.05 Power: 0.8 Sample size: 19 subjects per group

Significance Children with OPGs require frequent MR imaging to monitor tumor progression – In young children requires general anesthesia OCT can serve as non-invasive method to follow OPG and assess progression of tumor