Optic Nerve Hypoplasia and Septo-Optic Dysplasia

Introduction

1. Optic nerve hypoplasia (ONH) is the congenital underdevelopment of the optic nerve. The exact etiology of ONH is presently unclear.
2. The optic nerve, which develops during the first trimester, is a bundle of hundreds of thousands of nerve fibers that sends visual signals from the retina to the brain.
3. In some cases, ONH may be associated with multiple intracranial midline defects including an underdevelopment of the septum pellucidum and/or pituitary gland dysfunction. This association of symptoms is known as septo-optic dysplasia (de Morsier syndrome).

The MRI above depicts a normally sized left optic nerve (LON) compared to an underdeveloped right optic nerve (RON).
Adapted from: Padidela, R. et al. Focal Congenital Hyperinsulinism in a Patient with Septo-Optic Dysplasia. Nat. Rev. Endocrinol. 6, 646-650 (2010).

Epidemiology:

• ONH is the third most prevalent cause of visual impairment in kids under three years of age.
• Most common congenital optic disc abnormality.
• While the estimates of prevalence vary, commonly cited studies from Sweden and more recently in England suggest rates of 7.1 in 100,000 and 10.9 in 100,000, respectively.
• Most often presents bilaterally (75% of cases).
• Among patients with ONH, approximately 10% will present with septo-optic dysplasia. 50% of these patients will have endocrine abnormalities.
• No socio-economic or racial correlations have been established.

Risk Factors:

• Young maternal age (<21 yo)
• Maternal use of anticonvulsants
• Viral infection during pregnancy (e.g. CMV)
• Alcohol use during pregnancy
• Maternal diabetes

Diagnosis

Common Visual Symptoms & Signs:

1. Loss of Visual Acuity
   1. Dependent on degree of hypoplasia
   2. Can range from normal vision to complete loss of light perception
2. Visual Field Defects
   1. Most commonly in nasal or inferior visual fields
   2. Can occur even without loss of visual acuity
3. Strabismus
   1. Occurs in children with unilateral ONH if the affected eye has a loss of light perception
   2. Evaluated with cover/uncover test:

1. Nystagmus (often pendular)

Associated Non-Ophthalmic Findings

1. Developmental delay (as high as 32% of patients)
2. Endocrine abnormalities due to pituitary defects:
   • Dwarfism (decreased growth hormone)
   • Hypothyroidism (central)
   • Neonatal seizures (hypoglycemic)
   • Adrenal insufficiency
   • Diabetes insipidus 

Fundoscopic Findings:

The normal optic disc is doughnut-shaped and comprised of a pink rim with a white central depression. Contrast this image with the optic disc in ONH which has a double-ring sign, the outer demarcates the abnormal yellow ring that encircles the optic disc in ONH.

Management:

1. An MRI must be performed in all children diagnosed with ONH (see figure 4 below) because of the association with endocrine abnormalities and other structural malformations.
   1. A normal MRI does not exclude pituitary abnormalities!
2. Given the association with endocrine abnormalities, referral to an endocrinologist is necessary.
3. Regular follow-up and attention to growth charts is critical because hormonal dysfunction may not present at the time of diagnosis.

Treatment:

1. There is no current curative treatment for optic nerve hypoplasia.
2. Long-term management is focused on:
   • Control of associated endocrine symptoms (including hormone replacement)
   • Occupational/Physical therapy
   • Early Intervention for patients with developmental delays
   • Patching or surgery for strabismus in some patients 

Further Resources:

For health professionals:

University of Iowa EyeRounds ONH Case Reports:

• http://webeye.ophth.uiowa.edu/eyeforum/cases/149-bilateral-optic-nerve-hypoplasia.htm
• http://webeye.ophth.uiowa.edu/eyeforum/cases/138-UnilateralOpticNerveHypoplasia.htm

For families:

Focus Families informational booklet for parents of children with ONH:

• http://www.focusfamilies.org/focus/ONHbooklet/onhbooklet.pdf

Children’s Hospital of Los Angeles informational web portal for parents:

• http://www.chla.org/optic-nerve-hypoplasia

References:

1. Baker MS, Longmuir SQ. 2-month-old with bilateral optic nerve hypoplasia: highlighting the importance of a multi-disciplinary approach. EyeRounds.org. May 18, 2012, Available from: http://EyeRounds.org/cases/149-bilateral-optic-nerve-hypoplasia.htm
2. Blohme, J, Elisabeth BS, Tornqvist, K. Visually impaired Swedish children: Longitudinal comparisons 1980-1999. Acta Ophthalmologica Scandinavica. 2001, 78:416-420.
3. Borchert M, Garcia-Filion P. The syndrome of optic nerve hypoplasia. Current neurology and neuroscience reports. 2008, 8:395-403.
4. Floyd MS, Benson C, Longmuir SQ. Unilateral Optic Nerve Hypoplasia in a patient desiring surgical treatment for his exotropia. EyeRounds.org. August 30, 2011. Available from: http://EyeRounds.org/cases/138-UnilateralOpticNerveHypoplasia.htm.
5. Padidela, R. et al. Focal congenital hyperinsulinism in a patient with septo-optic dysplasia. Nat. Rev. Endocrinol. 2010, 6:646-650.
6. Patel, L., et al. Geographical distribution of optic nerve hypoplasia and septo-optic dysplasia in Northwest England. Journal of Pediatrics. 2006, 148:85-88.