Backgrounds: Bevacizumab (BVZ) is used as a subsequent line of treatment for pediatric optic pathway glioma (OPG) in the case of progression. Data on the treatment effect concerning tumor progression and visual function are scarce and nationwide studies are lacking. Methods: We performed a retrospective, nationwide, multicentre cohort study including all pediatric patients with OPG treated with BVZ in the Netherlands (2009–2021). Progression-free survival, change in visual acuity and visual field, MRI-based radiologic response, and toxicity were evaluated. Results: In total, 33 pediatric patients with OPG were treated with BVZ (median 12 months). Visual acuity improved in 20.5%, remained stable in 74.4%, and decreased in 5.1% of 39 of all analysed eyes. The monocular visual field improved in 73.1%, remained stable in 15.4%, and decreased in 7.7% of 25 analysed eyes. Radiologic response at the end of therapy showed a partial response in 7 patients (21.9%), minor response in 7 (21.9%), stable disease in 15 (46.9%), and progressive disease in 3 (9.3%). Progression-free survival at 18 and 36 months after the start of BVZ reduced from 70.9% to 38.0%. Toxicity (≥grade 3 CTCAE) during treatment was observed in five patients (15.2%). Conclusion: Treatment of BVZ in pediatric patients with OPG revealed stabilisation in the majority of patients, but was followed by progression at a later time point in more than 60% of patients. This profile seems relatively acceptable given the benefits of visual field improvement in more than 70% of analysed eyes and visual acuity improvement in more than 20% of eyes at the cessation of BVZ.

Pediatric optic pathway glioma (OPG) can seriously decrease visual function in the case of progression. Systemic anticancer therapy (SAT) is considered the treatment of first choice for unresectable OPG. New SAT modalities for the treatment of progressive OPG have been introduced in the last decade, including VEGF and MAPK pathway inhibition. This systematic review evaluated the effect of SAT on change in visual acuity and visual field in OPG. A systematic review was performed on SAT for OPG (January 1990 to August 2020). MEDLINE and EMBASE (Ovid) were searched for studies reporting on change in visual acuity and visual field after treatment with SAT for OPG. Overall, 11 series, including 358 patients, fulfilled the eligibility criteria. After follow-up of median 3.7 years (range: cessation of SAT– 8.2 years), improvement in binocular VA was found in 0–45% of studies, stability in 18–77% and a decrease in 0–82%. Two studies reported on change in visual field (improvement in 19% and 71% of patients), although either the change was not defined or the testing strategy was lacking. Considerable heterogeneity was present among the included studies, such as variety in the combinations of SAT administered, status of neurofibromatosis type 1, definition regarding change in visual acuity, 1- or 2-eye analysis, diversity in anatomic location, and extent of follow-up, all of which made meta-analysis inappropriate. This systematic review suggests that the impact of SAT in OPG on visual function is still unclear. The wide ranges reported on the efficacy of SAT and the observed heterogeneity highlight the need for prospective studies with uniform definitions of outcome parameters.

Background: Progressive isolated optic nerve glioma (ONG) in children is a rare disease, treated with various modalities. A global treatment consensus is not available. Methods: We conducted a national retrospective multicenter cohort study (1995–2020) to investigate how different treatment strategies impact outcome for ONG in children, by assessing treatment responses to systemic anticancer therapy (SAT), surgery, and radiotherapy for ONG. The primary endpoints included changes in best‐corrected visual acuity (BCVA) and tumor volume (TV) on MRI, both evaluated at the start and end of therapy and at long‐term follow up. Results: A total of 21 ONGs (20 patients) received SAT ( n = 14 (66.7%)), surgery ( n = 4 (19.0%)), and radiotherapy ( n = 3 (14.3%)). After SAT BCVA stabilized or improved in 66.6% ( n = 4) and the TV decreased by a median of 45.1% (range: −88.6% to +31.5%) ( n = 13). Before resection two eyes were already blind. After resection BCVA decreased to blindness in one eye. In total all four eyes were blind after resection. After first‐line RT BCVA decreased in 66.7% of ONG to counting fingers or less, TV increased <3 months after RT by a median of 47.3% (range: −42.8% to +245.1%) ( n = 3), followed by a long‐term decrease of 94.4 and 13.8% ( n = 2), respectively. Conclusion: SAT appears to be the preferred modality for progressive ONG in case of potential rescue of visual functions. Complete resection of ONG appears effective to reduce proptosis in case of preexisting blindness. The use of radiotherapy requires careful consideration due to the risk of severe visual impairment and secondary disease.

Objective To prospectively determine the value of optical coherence tomography (OCT) as a surrogate outcome measure for the progression of myelopathy in males with adrenoleukodystrophy. Methods Retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness were measured at baseline, 1‐ and 2‐year follow‐up in patients and age‐matched controls. We assessed the severity of myelopathy with clinical parameters: Expanded Disability Status Scale (EDSS), Severity Scoring system for Progressive Myelopathy (SSPROM), and timed up‐and‐go. Linear mixed model analysis was used to compare changes in retinal layer thickness of patients to controls. In addition, we correlated changes in retinal layer thickness with changes in clinical parameters. Results Longitudinal data were available for 28 patients and 29 controls. Peripapillary RNFL (pRNFL) thickness decreased significantly in patients compared to controls (−1.75µm, p = 0.001), whereas change in macular GCL and RNFL was not different between groups. Analysis of the symptomatic subgroup showed that, apart from a similar decrease in pRNFL thickness, GCL thickness decreased significantly (−0.55 µm, p = 0.014). There were moderately strong correlations between changes in retinal layer thickness and changes in clinical parameters of severity of myelopathy. Interpretation This prospective study demonstrates the potential of OCT‐measured retinal neurodegeneration as a surrogate outcome measure for the progression of myelopathy in adrenoleukodystrophy. As differences were small, our findings need to be confirmed with longer follow‐up and/or in a larger patient sample.

Background: The current standard therapy for pediatric optic pathway/hypothalamic glioma (OPHG) is systemic anticancer therapy (SAT) over surgery and radiotherapy. Nevertheless, recurrent radiological or clinical tumor progression after SAT forms a considerable challenge. Sporadic OPHGs are considered to have a higher tendency toward progression after first-line systemic anticancer therapy (SAT) compared to neurofibromatosis type-1-associated (NF1) OPHGs. Methods: The objective of this study was to conduct a national retrospective cohort analysis of children who received various treatments for a progressive OPHG, involving the hypothalamus and/or chiasm and/or optic radiations. The study aimed to examine the differences in clinical course and the range of treatment modalities applied to both sporadic and NF1-associated OPHGs between 1995 and 2020. Additionally, we sought to identify risk factors for 3- and 5-year progression following first- and second-order SAT. Results: In total, 136 children received treatment, of whom 49 of 136 (36.0%) had NF1. Within a median of 7.5 years (range: 0.1–23.8 years) of follow-up, sporadic OPHGs received more treatments compared to NF1-associated OPHGs (median of 2 (range: 1–8) vs. median of 1 (range: 1–7) (p < 0.01)). Nine children with sporadic OPHGs (6.6%) died. Of 112 children (82.4%) receiving SAT, 92% received combined first-line vincristine and carboplatin. These children had a 3- and 5-year progression-free survival of 61.8% (95% CI: 51.0–72.6%) and 48.4% (95% CI: 38.0–58.8%), respectively. Sporadic OPHGs had a higher rate of second progression (p < 0.01). Starting first-line vincristine and carboplatin at an age below one year was the only independent risk factor for progression. Conclusions: In this national historic cohort of pediatric OPHGs, four out of five children received SAT. Sporadic OPHGs received a higher number of various SATs compared to NF1-associated OPHGs, but the sporadic appearance of OPHGs was not an independent risk factor for progression after combined vincristine and carboplatin, as ‘age below one year at the start’ was the only factor.