Videos

NF1-Related Ophthalmologic Risks and Imaging Practices in Early Childhood

ByP. Leia Nghiemphu, MD,Christopher Moertel, MD

In this segment, the physicians discuss the broader spectrum of ophthalmologic issues seen in patients with NF1, particularly during early childhood. One physician explains that the first five to six years of life represent the highest-risk period for developing optic pathway gliomas, tumors driven by the same RAS–MEK pathway that contributes to plexiform neurofibroma formation. He emphasizes that careful ophthalmologic evaluation, especially visual acuity testing, remains the most effective method for detecting symptomatic optic gliomas. If visual concerns arise, MRI imaging is pursued to confirm or rule out these tumors. The physicians also address evolving perspectives on preventive imaging. They note that routine baseline brain MRIs are generally discouraged in very young children due to the need for sedation and the associated stress and risks for families. Instead, imaging is recommended only when clear clinical indicators exist. One physician describes his practice of obtaining a screening MRI around age 18 to support patients transitioning into adulthood, though this approach is not yet a formal standard.

Interpreting MEK Inhibitor Clinical Trial Data and Assessing Treatment Response in NF1-PN

ByP. Leia Nghiemphu, MD,Christopher Moertel, MD

In this segment, the physicians examine how clinical trial data for MEK inhibitors translate into everyday practice. They discuss findings from key studies—including the ReNeu (mirdametinib), SPRINT and KOMET (selumetinib) trials—which reported variable volumetric response rates in both children and adults. One physician notes that these studies relied on 3D volumetric MRI measurements, a technique that is rarely available in routine clinical settings, making direct replication of trial results challenging. He explains that this limitation contributes to wide variability in reported response rates, even including unexpected placebo “shrinkage” observed in KOMET. Because volumetrics cannot be consistently applied, the physicians emphasize that clinicians must prioritize symptoms, functional impact, and quality-of-life improvements—especially changes in pain—when judging treatment benefit. They caution against interpreting one MEK inhibitor as superior to another based solely on trial data, concluding instead that both selumetinib and mirdametinib offer meaningful responses and should be selected based on tolerability and patient needs.

Setting Expectations When Considering MEK Inhibitors for Treatment of NF1-PN

ByP. Leia Nghiemphu, MD,Christopher Moertel, MD

In this segment, the physicians discuss how they introduce medical therapy for plexiform neurofibromas (PN) when treatment is first considered for a child with NF1. One physician explains that these conversations begin early—often at the moment of tumor detection—because young children may experience faster tumor growth and require close monitoring. He emphasizes how early discussion helps families understand that effective treatments now exist, alleviating the anxiety rooted in decades of limited options. The segment highlights the importance of new, child-friendly formulations such as the selumetinib SPRINKLE preparation, which allows dosing in infants and toddlers, and notes that mirdametinib was also developed with a soluble form suitable for very young patients. The physicians then shift to treatment expectations. They describe pain relief as the earliest and most meaningful sign of clinical improvement, while radiographic responses—when visible—typically emerge only after several months. Because confirmed tumor shrinkage can take a year or longer, families are counseled that therapy requires long-term commitment.