Multimodality Imaging of Optic Neuropathies

Jason M. Johnson, MD; Adam B. Cohen, MD; Gul Moonis, MD; Christopher G. Filippi, MD

Imaging of Optic Neuropathies

Purpose To review the anatomy and embryologic development of the retina and optic nerve. To illustrate the various modalities used to analyze optic nerve pathology. To review the multimodality findings in pathologies affecting the optic nerve. To discuss the list of differential diagnosis when examining abnormalities of the optic nerve.
2

Imaging of Optic Neuropathies: Contents

Anatomy & Embryology Imaging Techniques Optic Neuropathies
Congenital / Developmental Infectious / Inflammatory Ischemic Degenerative Neoplastic

Summary
3

Normal Anatomy of the Optic Nerve

Normal Retina
Retinal vein

Normal Optic Disc

Optic cup

Fovea Retinal artery Neuroretinal rim

Anatomy & Embryology / Imaging Techniques / Optic Neuropathies / Summary

Anatomy of Optical Coherence Tomography

The most anterior section of the anterior optic nerve is the optic disc. The optic disc has two parts: a neuroretinal rim and an optic cup The posterior optic nerve is posterior to the lamina cribrosa.
Normal

Anatomy & Embryology / Imaging Techniques / Optic Neuropathies / Summary

Cross Sectional Anatomy of the Orbital Nerve

Globe Optic Disc Lateral Rectus Medial Rectus Optic nerve / sheath complex

Anatomy & Embryology / Imaging Techniques / Optic Neuropathies / Summary

Optic Nerve and Radiation Fiber Tracking

Diffusion tensor imaging (DTI) utilizes the anisotropic diffusivity of water along organized nerve fiber tracts such at the optic nerve. The fractional anisotrophy of nerve fiber tracts decreases with pathologies of the optic nerve in a non-specific fashion.
Normal 9 month old child optic nerve tractography.
Becker, M., Masterson, K., Delavelle, J., Viallon, M., Vargas, M.-I., & Becker, C. D. (2010). Imaging of the optic nerve. European journal of radiology, 74(2), 299313. doi:10.1016/j.ejrad. 2009.09.029

Anatomy & Embryology / Imaging Techniques / Optic Neuropathies / Summary

Embryology of the Optic Nerve

3.5 Weeks
The optic vesicles appear set at 180 degrees to each other.

4 Weeks
The optic cups involute and the lens placodes/pits form.

5 Weeks
The lens vesicles separate from the overlying ectoderm; the choroidal fissures appear in the optic cups and stalks; the vitreous appears.

6 Weeks
The retina is differentiated into neural and pigment layers; the lens thickens; the eyes rotate to 160 degrees.

Images from 20th U.S. edition of Gray's Anatomy of the Human Body, public domain.

Anatomy & Embryology / Imaging Techniques / Optic Neuropathies / Summary

Embryology of the Optic Nerve

7 Weeks The choroidal fissures close; the lens cavities are obliterated; the lids begin to form; axons enter the optic stalks. 10 Weeks The eyelids fuse; the ciliary body and iris are forming. 12 Weeks The layers of the retina are organizing. 21 Weeks The retinal layering is complete and responsive to light; the eyelids open.

Images from 20th U.S. edition of Gray's Anatomy of the Human Body, public domain.

Anatomy & Embryology / Imaging Techniques / Optic Neuropathies / Summary

Optic Neuropathies: Imaging Techniques

Fundoscopic Examination Availability Relative Cost Ionizing Radiation Anatomic Assessment Nerve Integrity Assessment
10

OCT
+ +++ None
Limited to Retinal Nerve Fiber Layer

CT
++ ++ xx
Globe, Orbit, Brain

MRI
++ ++++ None
Globe, Orbit, Brain

DTI
+ w/ MRI None
Limited to organized fiber tracts

+++ + None Intraocular x

Anatomy & Embryology / Imaging Techniques / Optic Neuropathies / Summary

Optic Neuropathy: Common Fundoscopic Findings

Edema
Optic disc edema can be caused by multiple etiologies

(ischemic, infectious, demyelinating, high ICP).

Papilledema specifically refers to (typically bilateral) optic disc
Edema

edema from high ICP.

Unilateral papilledema can be seen with the Foster Kennedy

syndrome in which a frontal lobe tumor compresses and destroys the optic nerve on one side before causing increased intracranial pressure.

Atrophy
Can results from any type of optic neuropathy after about 2-4

weeks. Manifests as pallor of the optic disc related to loss of the fine optic disc capillary network, gliosis, and perhaps, actual loss or atrophy of nerve fibers.

Atrophy

11

Anatomy & Embryology / Imaging Techniques / Optic Neuropathies / Summary

Papilledema

T2 MR shows dilated CSF spaces around the tortuous optic nerve (green arrow) and protrusion of the optic nerve papilla into the posterior globes (red arrows). OCT also shows the optic nerve papilla protrusion. Prominent CSF space in the suprasellar cistern represents a partially empty sella (yellow arrow). Fundoscopic exam shows severe papilledema evidenced by hemorrhages and optic disc swelling with disc margin blurring (black arrow).
Anatomy & Embryology / Imaging Techniques / Optic Neuropathies / Summary

Atrophy

Regardless of the cause, atrophy results from any type of prolonged neuropathy after about 2-4 weeks. Optic atrophy manifests as pallor of the optic disc from loss of the fine optic disc capillary network, gliosis, and loss or atrophy of nerve fibers. At right, a case of nerve atrophy secondary to a large pituitary mass with compression of the optic chiasm (arrow) is seen.

Anatomy & Embryology / Imaging Techniques / Optic Neuropathies / Summary

Optic Neuropathies: Cases

Congenital / Developmental Infectious / Inflammatory

Anopthalmia

SOD

Optic Neuritis

Lupus

Ischemic

Degenerative

Neoplastic

Trauma

Infarction

Meningioma

Retinoblastoma

14

Anatomy & Embryology / Imaging Techniques / Optic Neuropathies / Summary

Congenital / Developmental Optic Neuropathies

*Illustrated in this presentation

Degenerative optic neuropathy Anopthalmia* Micropthalmia* Coloboma* Septo-Optic Dysplasia* Persistent hyperplastic primary vitreous Holoprosencephaly

Anatomy & Embryology / Imaging Techniques / Optic Neuropathies / Summary

Anopthalmia / Micropthalmia
A B C

Anophthalmia

Orbital cyst

Bilateral micropthalmia and colobomas (arrows) in CHARGE syndrome

(A & B) Complete absence of globe in presence of ocular adnexa.

Microphthalmia (C) Axial length < 2 SD below mean for age; < 19 mm in 1 year old or < 21 mm in
adult.

Nanophthalmos
Simple microphthalmia with microcornea and bilateral axial length < 18 mm.
Schneider, A., Bardakjian, T., Reis, L. M., Tyler, R. C., & Semina, E. V. (2009). Novel SOX2 mutations and genotype -phenotype correlation in anophthalmia and microphthalmia. AJMG, 149A(12), 27062715.

Anatomy & Embryology / Imaging Techniques / Optic Neuropathies / Summary

Septo-optic dysplasia (AKA: De Morsier syndrome)

SOD is a heterogeneous ventral forebrain patterning syndrome characterized by hypoplasia of optic nerves/tract/chiasm, absent septum pellucidum, and (variable) hypothalamic-pituitary dysfunction. Frequently associated with other cerebral anomalies including: schizencephaly, polymicrogyria, midline malformations, ocular anomalies, and olfactory tract/bulb hypoplasia. SOD with hypoplastic right orbital nerve (white arrow). Left orbital nerve tract was unable to be established.
Salmela, M., Cauley, K., Nickerson, J., & Koski, C. (2010). Magnetic resonance diffusion tensor imaging (MRDTI) and tractography in children with septo-optic dysplasia. Pediatric radiology.

Anatomy & Embryology / Imaging Techniques / Optic Neuropathies / Summary

Colobomas

Coloboma = gap or defect of ocular tissue. Important causes of childhood visual impairment and blindness. Can be isolated or as part of a syndrome. SHH and PAX6 are associated with many implicated pathways.

Journal of Medical Genetics, 41(12), 881891. doi:10.1136/jmg.2004.025494

Anatomy & Embryology / Imaging Techniques / Optic Neuropathies / Summary

Infectious / Inflammatory Optic Neuropathies

Neuromyelitis Optica Multiple Sclerosis* Sarcoidosis* Idiopathic perineuritis (pseudotumor) Systemic Lupus Erythematosus* Infectious optic neuropathy*
*Illustrated in this presentation

Anatomy & Embryology / Imaging Techniques / Optic Neuropathies / Summary

Optic Neuritis
Optic Neuritis inflammation + demyelination with pain & loss of visual acuity. Most typically associated with MS (A & B) where the disc shows mild swelling and the corresponding MRI shows diffuse enlargement and enhancement ON can also be seen secondary to infectious (C) and inflammatory disorders (D).
A B

Anatomy & Embryology / Imaging Techniques / Optic Neuropathies / Summary

Granulomatous Optic Neuritis

Granulomatous diseases are often
multisystem in their involvement. Sarcoidosis is the most common of these in USA. In sarcoidosis, ocular involvement occurs in up to 25% such as in the case right which can present with mass-like lacrimal, uveal, and muscle infiltration, optic nerve thickening and enhancement. In the case (right) the chest findings of upper lobe reticulonodular findings and LAD (not shown) were characteristic of sarcoid.
Mouedden, El, J., Duray, M. C., Hernalsteen, D., & Cosnard, G. (2011). Extensive neurosarcoidosis and optic nerve complications. (KBVR), 94(2), 6667.

Anatomy & Embryology / Imaging Techniques / Optic Neuropathies / Summary

Systemic Lupus Erythematosus-related optic neuropathy

SLE may affect the visual system in up to 1/3 of patients. Patient may present with acute onset of vision loss (optic neuritis-like presentation). Fundoscopic examination and MRI findings are non-specific and include disc swelling, nerve enhancement and enlargement. Differentiating tests are history of SLE and antiphospholipid Abs.
Frigui, M., Frikha, F., Sellemi, D., Chouayakh, F., Feki, J., & Bahloul, Z. (2011). Optic neuropathy as a presenting feature of systemic lupus erythematosus: two case reports and literature review Lupus, 20(11), 12141218.

Anatomy & Embryology / Imaging Techniques / Optic Neuropathies / Summary

Ischemic Optic Neuropathies

*Illustrated in this presentation

Trauma* Ischemia* Nonarteritic anterior ischemic optic neuropathy Anterior optic neuropathy Posterior optic neuropathy

Intracranial hypertension (chronic)*

Traumatic Optic Neuropathy

Fundoscopic image shows hemorrhage and swelling at disc boundary. CE CT of the orbit shows pre- and post-septal contusion and fat stranding along with posterior optic nerve edema. Traumatic ON can be separated into direct (as in this case) and indirect which can be due to extrinsic masses or masslike effects on the ON.

Awan, A. (2007). Traumatic Optic Neuropathy. Pak J Ophthalmol.

Anatomy & Embryology / Imaging Techniques / Optic Neuropathies / Summary

Ischemic optic neuropathy (ION)

Ischemia of optic nerve usually leads to permanent visual deficit. Ischemic optic neuropathy divided into anterior and posterior on the basis of fundoscopic findings and mechanism. Anterior ION is usually idiopathic or from giant cell arteritis in elderly (fundus shown with disc swelling and hemorrhage) Posterior ION usually in setting of hemorrhagic blood loss, severe hypovolemia, fungal infection. In the case (right) there is proximal optic nerve enlargement along with restricted diffusion. This patient presented with acute vision loss a week after pituitary surgery.
Becker, M., Masterson, K., Delavelle, J., Viallon, M., Vargas, M.-I., & Becker, C. D. (2010). Imaging of the optic nerve. European journal of radiology, 74(2), 299313.

Anatomy & Embryology / Imaging Techniques / Optic Neuropathies / Summary

Degenerative Optic Neuropathies

Diabetic papillopathy Drusen* Metabolic Radiation-induced

Drusen
Hyaline calcific deposits which typically have a characteristic appearance on fundoscopic examination (A) which are common in the elderly and seen in 0.3% of patients. On CT they present as punctate calcifications (B) typically at the optic nerve head or macula, but they can occur anywhere along the retina. Typically occult on MR, but may be seen on Gradient Echo, Susceptibility-weighted (C) and B0 images. No soft tissue mass but may be associated with retinal detachment.
Becker, M., Masterson, K., Delavelle, J., Viallon, M., Vargas, M.-I., & Becker, C. D. (2010). Imaging of the optic nerve. European journal of radiology, 74(2), 299313.

Anatomy & Embryology / Imaging Techniques / Optic Neuropathies / Summary

Neoplastic Optic Neuropathies

Optic Glioma* Retinoblastoma* Meningioma* Leukemia Lymphoma Metastasis Retinal Angiomatosis

Anatomy & Embryology / Imaging Techniques / Optic Neuropathies / Summary

Bilateral Optic Pathway Gliomas

These typically present with fusiform ON mass (C) with variable posterior pathway (A) involvement as either asymptomatic lesions or with decreased vision. They can be seen as benign childhood tumors NF1 or as adult tumors that are typically malignant. Lesions range from no enhancement to intense homogeneous enhancement (C). Ca++ is rare unlike in optic nerve sheath meningiomas. 30-40% of patients with OPG have NF1; 15% of patients with NF1 have OPG. Fundoscopic examination is non-specific showing a spectrum from papilledema (B) to atrophy.
Kreusel, K.-M. (2005). Ophthalmological manifestations in VHL and NF 1: pathological and diagnostic implications. Familial Cancer, 4(1), 4347.

Retinoblastoma
RB is the most common primary intraocular malignancy of childhood. Tumors appear as amelanotic endophytic or exophytic calcified masses. Associated with mutations in the RB1 gene which codes for the pRB tumor suppressor protein. Diagnosis is made based on the clinical appearance of the lesion. Management is based on the age of child, unilateral vs. bilateral disease, and extent. Unilateral retinoblastoma accounts for approximately 60% of the disease and is diagnosed at a mean age of 25 months. Perineural spread of RB can mimic inflammatory disease in the diffuse form (Arrows).
Wilson, M. W., Rodriguez-Galindo, C., Billups, C., Haik, B. G., Laningham, F., & Patay, Z. (2009). Lack of Correlation between the Histologic and Magnetic Resonance Imaging Results of Optic Nerve Involvement in Eyes Primarily Enucleated for Retinoblastoma. Ophthalmology, 116(8), 15581563.

Optic Neuropathies / Summary

Optic nerve meningioma

Relatively common tumor with mean age of presentation at 40.3 and representing ~10% of orbital tumors & ~42% of optic nerve tumors. Fundoscopic and OCT exam typically non-specific. Most commonly presenting as a solid, homogeneously enhancing well-defined mass surrounding the intraorbital optic nerve with variable calcification. "Tram-tracking" appearance = tumor enhancement or calcification on either side of optic nerve
Ophthalmology 2003;110:20192030

Anatomy & Embryology / Imaging Techniques / Optic Neuropathies / Summary

Imaging of Pathologies of the Optic Nerve

Summary
This exhibit reviews the normal anatomy and embryology of the optic nerve and correlates it with the spectrum of pathologies involving this organ. After reviewing this exhibit, the reader will be familiar with the anatomy, embryology and pathologies of the optic nerve. The imaging features of a broad spectrum of pathologies and appropriate differential diagnoses will be discussed.

32

Anatomy & Embryology / Imaging Techniques / Optic Neuropathies / Summary