Optic Nerve

Optic Nerve

Developmental anomalies of the optic nerve include optic nerve aplasia and hypoplasia, optic pits, optic nerve colobomas, and the morning glory disc anomaly (MGDA). Bilateral hypoplasia is often associated with congenital syndromes such as de Morsier syndrome of septo-optic dysplasia, which includes bilateral hypoplastic nerves, pituitary dysfunction, and midline abnormalities of the brain, including absence of the corpus callosum and septum pellucidum and Aicardi syndrome. Aicardi syndrome includes peripapillary chorioretinal lacunae, ectopic RPE, agenesis of the corpus callosum, infantile spasms, and mental retardation. It is an X-linked dominant disorder caused by mutations in the AIC gene on Xp22.

Colobomas of the optic nerve (Fig. 15-1) are caused by incomplete closure of the posterior portion of the fetal fissure. Eyes with extensive optic nerve colobomas may be microophthalmic and have a cystic outpouching of the posterior sclera (microphthalmos with cyst) (Fig. 2-2). The cyst typically is lined by dysplastic neuroectodermal tissue, which communicates with the retina via the coloboma. Optic nerve colobomas occasionally are associated with choristomatous malformations that contain smooth muscle and heterotopic fat.

Optic pits are small crater-like holes that usually occur unilaterally at the temporal margin of the optic disc. Pathogenesis probably is related to anomalous closure of the superior margin of the embryonic fissure. Optic pits frequently are complicated by serous macular detachment and retinoschisis. Studies suggest that the vitreous probably is the source of the subretinal and intraretinal fluid.

The MGDA or morning glory syndrome is a congenital optic nerve anomaly characterized by a funnel-shaped excavation in the optic nerve head that appears to contain a central tuft of glial tissue believed to be residual Bergmeister papilla. Cilioretinal vessels radiate from the margin of the disc, which is surrounded by an elevated annulus of disturbed chorioretinal pigment and may lack a central retinal artery. About one half of cases of MGDA have cerebrovascular disease including bilateral carotid stenosis and moyamoya disease that predispose to stroke. Patients with MGDA should have neuroimaging to detect vascular and structural brain anomalies.

FIG. 15-1. A, B. Optic nerve coloboma. Optic nerve colobomas are caused by incomplete closure of the fetal fissure. (B. H&E ×10.)

Optic disc drusen are globular aggregates of concentrically laminated, calcified material, probably calcium phosphate, that are located in the prelaminar optic nerve head within the scleral ring (Fig. 15-2). Optic disc drusen appear ophthalmoscopically as tan, yellow, or straw-colored glistening or refractile spheric structures. They typically are found in a small, crowded optic disc that has a small or absent cup. Optic disc drusen are unrelated to drusen of the RPE or the heavily calcified epipapillary astrocytomas called giant drusen of the optic disc that occur in some patients with tuberous sclerosis complex. Optic disc drusen are important clinically because they may be misdiagnosed as papilledema and prompt an unnecessary neurological evaluation. The pathogenesis of optic disc drusen may be related to blockage of axoplasmic flow in ganglion cell axons within a narrow crowded scleral canal. Tso suggested that calcified mitochondria dispersed from prelaminar corpora amylacea may provide a nidus for further calcium deposition. Optic disc drusen occur sporadically or may be inherited as an irregular autosomal dominant trait. Disc drusen also occur in some patients with retinitis pigmentosa or pseudoxanthoma elasticum with angioid streaks.

FIG. 15-2. Optic disc drusen. A. Anterior substance of optic disc contains yellow spherical refractile bodies. Optic disc drusen may be misdiagnosed clinically as papilledema. B. A conglomeration of calcareous deposits is present in the optic nerve anterior to the lamina cribrosa. The drusen have fractured during sectioning. They were unsuspected, and the specimen was not decalcified. (A. Photo courtesy of Dr. Peter Savino, B. H&E ×25).


Although optic disc edema (papilledema) classically is associated with elevated intracranial pressure and spaceoccupying intracranial lesions, swollen optic discs also occur in eyes with acute glaucoma, ocular hypotony, central retinal vein occlusion, juxtapapillary tumors, and severe hypertensive retinopathy. Optic disc edema does not result from an accumulation of fluid in the extracellular spaces of the disc. Rather, the increase in the volume of the nerve head reflects the intracytoplasmic swelling and distension of ganglion cell axons caused by blockage of axoplasmic flow in the distorted lamina cribrosa (Fig. 15-3D). The pores of the lamina cribrosa are distorted by a pressure gradient between the intraocular pressure and pressure in the retrolaminar optic nerve. A pressure gradient can form if the intracranial pressure is elevated (classic papilledema), the intraocular pressure is low (hypotony), or the intraocular pressure is acutely elevated (acute glaucoma) (Fig. 15-3). Histopathologically, the nerve head is swollen and the physiological cup is narrowed (Fig. 15-3). The increase in the volume of nerve head tissue displaces the photoreceptors laterally from the margin of the disc (Fig. 15-3C). This lateral displacement of photoreceptors and an accompanying shallow peripapillary collection of serous subretinal fluid are responsible for enlargement of the blind spot on visual field testing. Paton folds are also found in the outer retinal layers. Extensive gliosis and axonal loss occur in chronic papilledema.


Optic nerve atrophy is characterized pathologically by shrinkage of the parenchyma of the optic nerve caused by loss of ganglion cell axons (Fig. 15-4). The subarachnoid space around the shrunken nerve becomes widened, and the dura appears redundant and folded. Light microscopy discloses loss of axons and thickening of the pia mater and pial septa. Gliosis may or may not become prominent depending on the cause of the atrophy.

By convention, the terms primary or descending optic atrophy are applied to atrophy of the nerve caused by lesions in the central nervous system or orbit. Primary optic atrophy generally is not associated with an ophthalmoscopically visible glial or mesenchymal reaction. Causes of primary optic atrophy include optic nerve trauma, compression by neoplasms or enlarged extraocular muscles in thyroid ophthalmopathy, neurosyphilis, demyelinating diseases including multiple sclerosis, heritable leukodystrophies, and toxic and nutritional optic neuropathies.

Inflammatory, neoplastic, or vascular lesions located in the retina or the vicinity of the optic disc cause secondary or ascending optic atrophy, which is often marked by pronounced alterations in the glial and mesenchymal tissues of the nerve head. Common retinal causes of optic atrophy include chorioretinitis, retinitis pigmentosa, and trauma.

Leber hereditary optic neuropathy (LHON) is caused by mutations in mitochondrial DNA. Three-point mutations in the ND4, ND1, and ND6 subunit genes of complex I that code for the NADH dehydrogenase protein in the mitochondrial oxidative phosphorylation chain are responsible for most cases, and 70% of Northern European and 90% of Asian cases harbor the ND4 G11778A “Wallace mutation.” The retinal ganglion cells, especially those in the maculopapillary bundle, are primarily affected and undergo apoptosis and degeneration.

LHON is maternally inherited because the mother’s egg cells are the developing embryo’s sole source of mitochondria and mitochondrial DNA. LHON usually presents with subacute progressive bilateral central visual loss in males between ages 18 and 30 years. Some patients have optic disc swelling and telangiectatic peripapillary vessels. Although retinal ganglion cells and axons are lost in both primary and glaucomatous optic atrophies, cupping of the disc generally occurs in glaucomatous optic atrophy and is not prominent in primary optic atrophy.

FIG. 15-3. Optic disc edema. A. The optic nerve is massively swollen and injected and has blurred margins. Concentric folds and exudates are present in the adjacent retina. B. Optic disc edema, secondary to juxtapapillary melanoma. Small choroidal tumor has invaded the optic nerve sheath, severely compressing the nerve and blocking axoplasmic flow. The nerve head is massively swollen and the photoreceptors are displaced laterally. C. The photoreceptors of the swollen optic nerve are displaced laterally. Paton’s folds and exudates are noted in the outer retina. D. Dilated axonal profiles in prelaminar optic nerve are filled with blocked axoplasm. (B. H&E ×25, C. H&E ×100, D. H&E ×400.)

FIG. 15-4. Optic atrophy. A. The optic nerve is atrophic and the subarachnoid space is widened. The severity of the optic atrophy makes the meninges appear redundant. B. The pia and pial septa are markedly thickened, and the substance of the nerve is severely atrophic. C. Transverse section shows that most of the parenchyma of the severely atrophic optic nerve has been replaced by blue-staining collagenous connective tissue. The pia and pial septa are markedly widened. (B. H&E ×10, C. Masson trichrome ×25.)

Schnabel cavernous optic atrophy is a relatively rare type of optic atrophy characterized by the presence of large spaces filled with hyaluronic acid in the retrolaminar part of the nerve (Fig. 15-5).

Schnabel cavernous optic atrophy classically was associated with an acute elevation of intraocular pressure, but a large postmortem study found many cases in elderly women who had systemic vascular disease and no evidence of glaucoma. Hypothetical sources of the mucopolysaccharide include the vitreous in glaucomatous eyes or in situ production within areas of optic nerve infarction. No gliosis or histiocytic reaction typically is seen. Intraocular silicone oil instilled during vitreoretinal surgery occasionally infiltrates the optic nerve in glaucomatous eyes producing pseudo-Schnabel cavernous atrophy (Fig. 15-6). In rare instances, the silicone oil can migrate to the brain.

FIG. 15-5. Schnabel cavernous optic atrophy. A. Diameter of transversely sectioned optic nerve is markedly widening. Small cystoid spaces replace myelinated parenchyma. B. Retrolaminar optic nerve contains pools of clear mucoid material. C. Clear spaces in retrolaminar optic nerve stain intensely for acid mucopolysaccharide. D. Positive staining is abolished by pretreatment with hyaluronidase indicating that the substance is hyaluronic acid. (B. H&E ×10, C. colloidal iron for AMP ×10, D. colloidal iron after hyaluronidase digestion ×10.)

FIG. 15-6. Pseudo-Schnabel cavernous atrophy. A. Vacuoles of silicone oil are present in retrolaminar part of deeply cupped optic nerve. Clumps of macrophages that have ingested emulsified oil are present on the inner surface of the retina and glaucoma cup. B. Large silicone oil vacuoles in transversely sectioned nerve. (A. H&E ×10, B. H&E ×50.)


The term optic neuritis refers to involvement of any part of the optic nerve by an inflammatory disease process. The process is called retrobulbar neuritis clinically when the inflammation involves the retrobulbar part of the optic nerve, and ophthalmoscopy initially reveals no abnormalities. Multiple sclerosis is a relatively common cause of retrobulbar neuritis. The term papillitis is used when the optic disc is affected, and the process is called neuroretinitis if the peripapillary retina is involved by edema, hemorrhage, and inflammation. Optic neuritis is classified topographically as perineuritis, periaxial neuritis, axial neuritis, and transverse neuritis. It can be caused by bacterial, mycobacterial, viral, mycotic, and parasitic infection as well as by granulomatous disorders such as sarcoidosis
and granulomatosis with polyangiitis (Wegener) (Fig. 15-7). Large granulomas occur on the surface of the optic disc in some patients with sarcoidosis.

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Oct 28, 2018 | Posted by in GENERAL | Comments Off on Optic Nerve

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