Characterization of retinal thickness in children with neurofibromatosis type 1 and optic pathway gliomas

using optical coherence tomography

David Wolf, MD, PhDPediatric 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 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

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 micronsMean (OPG): 90 micronsSD (controls): 30SD (OPG): 30Alpha: 0.05Power: 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 micronsMean (OPG): 90 micronsSD (controls): 30SD (OPG): 30Alpha: 0.05Power: 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