Neurofibromatosis type 1 (NF1) is a multisystem genetic disorder with hallmark ocular manifestations that can aid early diagnosis and guide clinical management. A recent large-scale pediatric study by Midena and Cosmo offers new insights into the prevalence, incidence, and genotype-phenotype correlations of four key ocular signs: optic pathway glioma (OPG), Lisch nodules (LNs), choroidal abnormalities (CAs), and retinal vascular abnormalities (RVAs).

👁️ Age Matters: When Do Ocular Signs Appear?

The study followed 237 NF1 children (≤16 years) over 12 years, revealing that most ocular signs develop early:

Despite logistic regression curves showing rising probabilities with age (especially for CAs and LNs), the actual onset of new cases after age 8 was rare. This supports the idea that screening is most valuable before age 8, when diagnostic yield is highest.

🧬 Genotype-Phenotype Correlation: Truncating Mutations Hit Harder

Children with truncating mutations (frameshift/nonsense) showed:

• A higher number of ocular signs (1.7 vs 0.9; P = .0019)
• Increased prevalence of CAs (66.4% vs 37.5%; P = .0042)
• More frequent RVAs (14.3% vs 0%; P = .0239)

Interestingly, LNs did not significantly differ between mutation types, suggesting independent developmental pathways.

🔍 Diagnostic Implications

• Revised NF1 criteria now accept ≥2 CAs as an alternative to ≥2 LNs.
• Near-infrared imaging (NIR) is essential for detecting CAs and RVAs.
• OCT of the peripapillary retinal nerve fiber layer (pRNFL) correlates with visual acuity and helps monitor OPG progression.

📌 Clinical Takeaway

This study refines our understanding of NF1 ocular signs and their timing:

• Early screening (before age 8) is critical for diagnosis and risk stratification.
• CAs and LNs should be assessed independently, as they develop separately.
• Genetic testing can inform prognosis, especially in truncating mutation carriers.

Midena E, Cosmo E. Neurofibromatosis Type 1 (NF1)–Related Ocular Signs: New Insights on Their Prevalence, Incidence, and Genotype-Phenotype Correlation in NF1 Children. Am J Ophthalmol. 2025;275:58–73. doi: 10.1016/j.ajo.2025.02.044

Yasunari Nodules: A Diagnostic Criterion for Neurofibromatosis Type 1 (Ophthalmology Retina, 2025):

🔑 Main Points

• Clinical Case:

  • 38-year-old woman with neurofibromatosis type 1 (NF1).
  • Normal visual acuity (20/20) and presence of Lisch nodules.
  • Fundus exam appeared normal.

• Imaging Findings:

  • Infrared reflectance (IR) imaging revealed multiple patchy, highly reflective choroidal nodules.
  • OCT confirmed hyperreflective choroidal nodules corresponding to IR findings.

• Yasunari Nodules:

  • Defined as asymptomatic choroidal lesions detectable on OCT and IR.
  • Considered highly specific for NF1, making them a valuable diagnostic criterion.
  • Can be missed on OCT alone, but are clearly visible on IR, underscoring the importance of reviewing IR images carefully.

• Clinical Relevance:

  • Yasunari nodules provide a non-invasive, imaging-based diagnostic marker for NF1.
  • Their detection improves diagnostic accuracy, especially in patients with otherwise normal fundus exams.

📌 Takeaway:
Yasunari nodules, best detected with infrared reflectance imaging, are a specific and reliable diagnostic sign of NF1. They may not always be obvious on OCT, so IR imaging should be systematically reviewed in suspected cases.