Advances in the pathophysiology and clinical behavior of NF-1 associated optic pathway gliomas (OPG) made over the past 10 years are examined, and evidence-based recommendations for diagnosis and management are proposed by researchers from Children's Memorial Hospital, Chicago; St Thomas's Hospital, London; Children's Hospital of Philadelphia; University of Pennsylvania School of Medicine, Philadelphia; and Washington University School of Medicine, St Louis, MO, The initial diagnostic and management guidelines proposed by a task force in 1997 [1] are extended, and unanswered questions are addressed. OPG may arise de novo or progress later in childhood or adulthood. The prevalence rate of OPG with NF-1 is estimated at 15% (between 5 and 25%). Children 6 years and younger are at greatest risk, but older children and adults with NF-1 are susceptible. Visual signs are present at the time of diagnosis in 59% of patients with OPG, including decreased visual acuity, proptosis, and nystagmus. Precocious puberty, manifested initially by accelerated growth, occurred in patients older than 6 years at diagnosis, and in 12-40% of those with chiasmal OPG. Progressive disease leading to treatment occurs in 35-52% cases, but risk factors for progression are not clearly defined. Late presentation at 10 years or older may correlate with progressive disease requiring treatment.

A synopsis of recommendations for diagnosis and management of NF-1 and OPG:

  1. Annual complete eye exam for children with NF-1 younger than 8 years.
  2. Eye exam every 2 years until 18 years of age, for children >8 years. No role for VEP.
  3. Yearly height and weight in all NF-1 children, to detect sign of precocious puberty.
  4. MRI of brain and orbits, and repeated eye exams, once abnormal eye exam recorded and OPG diagnosed, and at varying intervals (3 months or longer) thereafter.
  5. Treatment should be deferred until clear evidence of progression. Chemotherapy is firstline therapy. Radiation is not recommended. Surgery is considered with excessive proptosis and blindness. [2]

COMMENT. In a prospective, longitudinal study at Children's Memorial Hospital, Chicago, OPGs were found in 19% of 176 children with NF-1 who had CT or MRI at a median age of 4.1 years [3]. OPG had not developed at follow-up in those not receiving an MRI. Eye lesions such as proptosis or glaucoma were most common in younger children (median age 1.9 years). OPG was asymptomatic at time of diagnosis in 76%, and eye findings were normal in 64%. At followup of 0.2-8 years, only 3 (9%) showed progressive tumor growth on MRI or deteriorating vision after diagnosis. Patients with symptomatic OPG were all diagnosed before age 6 years. Tumor growth after 6 years is unusual. Progressive abnormalities and precocious puberty occurred only with chiasmatic OPG. In accord with the present recommendations, serial eye exams in young children with NF-1 but not MRI were advocated in this earlier report.