Noninfectious Optic Neuritis
Noninfectious inflammatory disorders of the optic nerve include classic optic neuritis in the setting of multiple sclerosis, giant cell arteritis (GCA), and sarcoidosis. Multiple sclerosis is a common inflammatory demyelinating disease of the CNS that causes optic neuritis. The histologic findings of optic neuritis from multiple sclerosis are similar to those of ADEM, with loss of myelin in the retrolaminar optic nerve and sectoral atrophy of the ganglion cells in more advanced cases (Fig 15-5). Further discussion on optic neuritis can be found in BCSC Section 5, Neuro-Ophthalmology.
Although GCA does not cause direct inflammation of the optic nerve, it is included here because it is a systemic inflammatory disorder that can cause optic nerve ischemia resulting in profound vision loss. GCA is characterized by inflammation that affects medium to large arteries. The gold standard for histologic diagnosis of GCA is a superficial temporal artery biopsy (Fig 15-6). It is critical to obtain a specimen of adequate length, approximately 2 cm, because areas of involvement can be patchy (ie, skip lesions). As such, a careful histologic examination requires stepped sections that sample the entire paraffin block; at minimum, 4 levels are evaluated.
Histologically, a chronic inflammatory infiltrate is seen in the vessel wall, often centered on the internal elastic lamina, resulting in its destruction. The inflammation is granulomatous with the presence of epithelioid histiocytes and sometimes multinucleated giant cells as well as lymphocytes. The intima is usually thickened and fibrotic, with broad disruption of the internal elastic lamina; the lumen may be thrombosed and subsequently recanalized. These same inflammatory features can affect the posterior ciliary arteries, resulting in their occlusion and liquefactive necrosis of the optic nerve. When the inflammation subsides, it can result in a scar in the vessel wall, primarily in the intima with focal loss of the muscularis layer (transmural scarring). This can be the primary finding in a biopsy specimen rather than active inflammation. Despite the name of the disease, the presence of giant cells is not required for diagnosis.
Figure 15-5 Demyelination of the optic nerve. A, Luxol fast blue stain for myelin. The bluestaining area indicates normal myelin. Note the sectoral absence of myelin in the lower left corner of the optic nerve (asterisk), corresponding to a focal area of demyelination. B, Higher magnification. The blue material (myelin) is engulfed by histiocytes (macrophages).
Figure 15-6 Temporal artery biopsy in giant cell arteritis. A, Vascular lumen (arrow) is markedly narrowed by intimal edema and inflammation. A prominent transmural inflammatory infiltrate with numerous multinucleated giant cells (arrowheads) is observed. B, Elastic stain highlights the diffuse loss of the internal elastic lamina. A short segment of the wavy internal elastic lamina remains (arrow). Giant cells (arrowheads) are noted at the level of the internal elastic lamina. A = adventitia; I = intima; M = media.
(Courtesy of Tatyana Milman, MD.)
Corticosteroid therapy is the mainstay of treatment and should be initiated immediately when GCA is suspected. Temporal artery biopsy should be performed within 10–14 days because corticosteroid treatment can alter histologic findings, mainly diminishing the inflammation. Therefore, it is important to inform the pathologist of any corticosteroid treatment so that the findings can be interpreted appropriately. Bilateral temporal artery biopsies are rarely useful, increasing the yield at most by 2%–5%. Typically, contralateral biopsies are employed when findings on the initial temporal artery biopsy are negative or atypical and there is high clinical suspicion for GCA. In the event of an unexpected biopsy result, a second opinion from a pathologist experienced in the interpretation of these biopsies may be helpful. Further discussion can be found in BCSC Section 5, Neuro-Ophthalmology.
Figure 15-7 Sarcoidosis of the optic nerve. A, Low-magnification photomicrograph shows a cross section of the optic nerve with discrete noncaseating granulomas (arrows).B, Higher magnification shows multinucleated giant cells (arrows) in the granulomas.
(Courtesy of Hans E. Grossniklaus, MD.)
Sarcoidosis, another systemic disorder that can involve the optic nerve, is often associated with retinal, vitreal, and uveal lesions (Fig 15-7; see also Chapter 12, Fig 12-10). Unlike the characteristic noncaseating granulomas in the eye, optic nerve lesions may show necrosis. Refer to BCSC Section 5, Neuro-Ophthalmology, and Section 9, Uveitis and Ocular Inflammation, for further discussion.
Excerpted from BCSC 2020-2021 series: Section 4 - Ophthalmic Pathology and Intraocular Tumors. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.