Noninfectious uveitis can be divided into nonspecific and specific forms. Most uveitides are nonspecific with no etiologic causes found and likely represent localized autoimmune disease. Several types of specific uveitis are discussed in the following sections.
Sympathetic ophthalmia is a rare bilateral granulomatous panuveitis that occurs after accidental or surgical injury to one eye (the exciting, or inciting, eye), followed by a latent period of weeks to years before development of uveitis in the uninjured globe (the sympathizing eye).
Sympathetic ophthalmia is a clinical diagnosis. The histologic findings are not pathognomonic. Furthermore, immunomodulatory therapy may modify these findings. Histologically, a diffuse granulomatous inflammatory reaction occurs within the uveal tract and is composed of lymphocytes and epithelioid histiocytes containing phagocytosed melanin (Figs 12-8, 12-9). Plasma cells are usually scant, suggesting a cell-mediated response. Classically, in the early stages of the disease, the choriocapillaris is spared. Varying degrees of inflammation may be present in the anterior chamber, such as clusters of histiocytes deposited on the corneal endothelium (mutton-fat keratic precipitates). Dalen-Fuchs nodules, which are accumulations of epithelioid histiocytes and lymphocytes between the RPE and Bruch membrane, may be seen in some cases (see Fig 12-9). As these nodules may also be present in other diseases, such as Vogt-Koyanagi-Harada syndrome, they are not pathognomonic of sympathetic ophthalmia.
See BCSC Section 7, Oculofacial Plastic and Orbital Surgery, for additional discussion.
Figure 12-8 Sympathetic ophthalmia. A, Diffuse infiltration of the uveal tract by chronic inflammatory cells, seen as a purple layer beneath the retina (arrows).B, Higher magnification of the RPE (asterisk) and choroid shows a multinucleated giant cell (arrowhead), epithelioid histiocytes (black arrows), and lymphocytes (red arrows). Note the relative sparing of the choriocapillaris, beneath the RPE.
(Part A courtesy of Hans E. Grossniklaus, MD; part B courtesy of Michele Bloomer, MD.)
Figure 12-9 Dalen-Fuchs nodules in sympathetic ophthalmia. A, Focal aggregates of inflammatory cells are present between the RPE and Bruch membrane (arrows). B, Higher magnification demonstrates epithelioid histiocytes containing cytoplasmic pigment (arrows) within the nodules (H&E stain).
(Courtesy of Hans E. Grossniklaus, MD.)
Vogt-Koyanagi-Harada (VKH) syndrome is a rare cause of posterior or diffuse uveitis and may have both ocular and systemic manifestations. The syndrome occurs more commonly in patients with Asian or Native American ancestry and usually affects individuals between 30 and 50 years of age.
The chronic, diffuse granulomatous uveitis of VKH resembles the uveitis seen in sympathetic ophthalmia. However, in VKH, the entire choroid, including the choriocapillaris, is typically involved by the inflammatory reaction. The granulomatous inflammation may extend into the retina. Because the disease is one of exacerbation and remission, chorioretinal scarring and RPE hyperplasia and/or atrophy may also occur.
Sarcoidosis is an inflammatory disorder (or group of disorders) that can affect nearly all systems of the body. The disease is characterized by granulomatous inflammation, specifically, the formation of granulomas, in various organs and tissues. The uveal tract is the most common site of ocular involvement. Anteriorly, inflammatory nodules of the iris may develop, either at the pupillary margin (Koeppe nodules) or elsewhere in the iris stroma (Busacca nodules). In the posterior segment, chorioretinitis (Fig 12-10A, B), periphlebitis, and chorioretinal nodules may be present. Periphlebitis may appear clinically as inflammatory lesions, referred to as candlewax drippings (perivenous exudates). Inflammatory cell infiltration may cause the optic nerve head to become swollen.
Histologically, the classic sarcoid nodule is a nonnecrotizing (noncaseating) granuloma. These granulomas are collections of epithelioid histiocytes, sometimes accompanied by multinucleated giant cells, surrounded by a cuff of lymphocytes (Fig 12-10C). In the uveal tract, the inflammatory infiltrate may show a more diffuse distribution of lymphocytes and epithelioid histiocytes (granulomatous inflammation). Multinucleated giant cells may contain asteroid bodies (star-shaped, acidophilic inclusion bodies) and/or Schaumann bodies (spherical, basophilic, calcified inclusion bodies) in their cytoplasm (Fig 12-10D). Neither asteroid nor Schaumann bodies are pathognomonic for sarcoidosis.
Figure 12-10 Sarcoidosis. A, Chorioretinitis in the fundus. B, Optical coherence tomography of the unaffected eye (top) and the eye with chorioretinitis (bottom) demonstrating thickening of the choroid in the eye with inflammation. C, Biopsy of a sarcoid nodule showing epithelioid histiocytes and lymphocytes (chronic granulomatous inflammation) arranged as a nonnecrotizing granuloma (circle).D, High-magnification photomicrograph of a sarcoid nodule demonstrating an asteroid body (arrow) within a multinucleated giant cell.
(Parts A and B courtesy of H. Josefine Fuchs, MD; parts C and D courtesy of Nasreen A. Syed, MD.)
Behçet disease is an occlusive systemic vasculitis that can cause nongranulomatous, necrotizing inflammation in the uveal tract. See BCSC Section 9, Uveitis and Ocular Inflammation, for further discussion of this disease.
Juvenile xanthogranuloma is an uncommon inflammatory condition that occurs in children. The skin and uvea are commonly affected. In the uveal tract, lesions may present as a solid mass, mimicking a neoplastic process. The characteristic histologic features of the lesions include lipid-laden histiocytes, Touton giant cells, lymphocytes, and occasional eosinophils (Fig 12-11). The lesions are often vascularized, and the blood vessels tend to be fragile, resulting in intralesional hemorrhage. Iris lesions in juvenile xanthogranuloma may cause a spontaneous hyphema.
Figure 12-11 Juvenile xanthogranuloma. Touton giant cells (arrow) with a ring of nuclei, inner eosinophilic cytoplasm, and outer vacuolated or foamy cytoplasm; foamy histiocytes (arrowhead); and lymphocytes are admixed.
(Courtesy of Nasreen A. Syed, MD.)
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.