Optical coherence tomography of the macular ganglion cell layer in children with neurofibromatosis type 1 is a useful tool in the assessment for optic pathway gliomas.

BACKGROUND: Optic pathway glioma (OPG) is a feared complication to neurofibromatosis type 1 (NF1) since it can cause visual impairment in young children. The main goal of screening is to detect symptomatic OPGs that require treatment. Optical coherence tomography (OCT) has been suggested as a tool for detection of neuro-retinal damage. AIMS: To investigate whether the ganglion cell layer assessed by OCT is a reliable measure to identify and detect relapses of symptomatic OPGs in children with NF1. METHODS: Children (3-6 years) with NF1, with and without known OPG and children with sporadic OPG (S-OPG) resident in the Stockholm area, were invited and followed in a prospective study during a three-year period. Brain magnetic resonance tomography (MRI) had been performed in children with symptoms of OPG. Outcome measures were VA in logMAR, visual field index (VFI), average thicknesses of the ganglion cell-inner plexiform layer (GC-IPL), and peripapillary retinal nerve fiber layer (pRNFL). RESULTS: There were 25 children with MRI-verified OPG and 52 with NF1 without symptomatic OPG. Eyes from NF1 patients without symptoms of OPG showed significantly better results in all four analyzed parameters compared to eyes with NF1-associated OPG. Mean GC-IPL measurements seemed stable and reliable, significantly correlated to pRNFL (correlation coefficient (r) = 0.662, confidence interval (CI) = .507 to .773 p<0.001), VA (r = -0.661, CI = -7.45 to -.551, p<0.001) and VFI (r = 0.644, CI = .452 to .774, p<0.001). GC-IPL measurements were easy to obtain and acquired at considerably younger age than pRNFL (5.6±1.5 vs 6.8±1.3; p<0.001). CONCLUSIONS: The mean GC-IPL thickness could distinguish well between eyes with OPG and eyes without symptomatic OPG in children with NF1. As thinning of GC-IPL assessed with OCT could indicate underlying OPG, it should be included in the screening protocol of children with questionable VA measurements and in particular in children with NF1.

Treatment evaluation by volumetric segmentation in pediatric optic pathway glioma: evaluation of the effect of bevacizumab on intra-tumor components.

PURPOSE: Progressive pediatric optic pathway gliomas (OPGs) are treated by diverse systemic antitumor modalities. Refined insights on the course of intra-tumoral components are limited. METHODS: We performed an exploratory study on the longitudinal volumetric course of different (intra-)tumor components by manual segmentation of MRI at the start and after 3, 6 and 12 months of bevacizumab (BVZ) treatment. RESULTS: Thirty-one patients were treated with BVZ (median 12 months, range: 2-39 months). During treatment the total tumor volume decreased with median 19.9% (range: - 62.3 to + 29.7%; n = 30) within the first 3 months, decreased 19.0% (range: - 68.8 to + 96.1%; n = 28) between start and 6 months and 27.2% (range: -73.4 to + 36.0%; n = 21) between start and 12 months. Intra-tumoral cysts were present in 12 OPGs, all showed a decrease of volume during treatment. The relative contrast enhanced volume of NF1 associated OPG (n = 11) showed an significant reduction compared to OPG with a KIAA1549-BRAF fusion (p < 0.01). Three OPGs progressed during treatment, but were not preceded by an increase of relative contrast enhancement. CONCLUSION: Treatment with BVZ of progressive pediatric OPGs leads to a decrease of both total tumor volume and cystic volume for the majority of OPGs with emphasis on the first three months. NF1 and KIAA1549-BRAF fusion related OPGs showed a different (early) treatment effect regarding the tumor enhancing component on MRI, which did not correlate with tumor volume changes. Future research is necessary to further evaluate these findings and its relevance to clinical outcome parameters.