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.

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.

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.