See the discussion of endophthalmitis in Chapter 10 in this volume and in BCSC Section 9, Uveitis and Ocular Inflammation.
Multiple viruses may cause retinal infections, including rubella virus, measles virus, human immunodeficiency virus (HIV), herpes simplex virus (HSV), varicella-zoster virus (VZV), and cytomegalovirus (CMV). Two of the most frequent clinical presentations of retinal viral infection, acute retinal necrosis (ARN) and CMV retinitis, are discussed here.
Acute retinal necrosis is a rapidly progressive, necrotizing retinitis caused by infection with HSV types 1 and 2, VZV, or in rare instances, CMV. ARN can occur in healthy or immunocompromised individuals. Histologic findings include robust inflammation in the vitreous and anterior chamber with prominent obliterative retinal vasculitis and retinal necrosis (Fig 11-7). Inflammatory cells include neutrophils, lymphocytes, plasma cells, and epithelioid histiocytes. Electron microscopy has shown viral inclusions in retinal cells. Polymerase chain reaction analysis of aqueous or vitreous samples is the most sensitive and most rapid method for identifying the presence of virus, reducing the need for viral culture, intraocular antibody analysis, immunohistochemistry, or other diagnostic techniques.
CMV retinitis is an opportunistic infection that occurs in immunosuppressed patients (Fig 11-8). Histologically, it is characterized by retinal necrosis that heals with a thin fibroglial scar. Acute lesions show enlarged neurons (20–30 µm) that contain large eosinophilic intranuclear and/or intracytoplasmic inclusion bodies (see Fig 11-8C, D). At the cellular level, CMV may infect vascular endothelial cells, retinal neurons, the RPE, and histiocytes. Because of the immunocompromised status of the infected host, a prominent inflammatory infiltrate is typically not present.
Figure 11-7 Acute retinal necrosis (ARN). A, Wide-field fundus photograph reveals areas of retinal necrosis manifesting as white areas and hemorrhage (arrow) in the periphery. The hazy appearance is due to vitritis. B, Photomicrograph from a different patient reveals full-thickness necrosis of the retina (black bracket), identified by remaining photoreceptor outer segments (asterisk) and RPE cells (arrowhead). Acute and chronic granulomatous inflammation is present below Bruch membrane (red bracket). Neutrophils, epithelioid histiocytes, lymphocytes, and plasma cells are present with a zonal arrangement from top to bottom.
(Part A courtesy of Benjamin J. Kim, MD; part B courtesy of Vivian Lee, MD.)
Figure 11-8 Cytomegalovirus (CMV) retinitis. A, Retinal hemorrhages and areas of opaque retina are present. Note the white vascular sheathing along the superotemporal arcade and hard exudates in the macular region. B, Histologically, full-thickness retinal necrosis is present. Note the loss of the normal lamellar architecture of the retina, including disruption of the RPE (arrows).C, Large syncytial cells infected with virus (arrowheads) are present in areas of necrosis, characteristic of CMV retinitis. D, Intranuclear “owl’s eye” inclusions (arrows) and intracytoplasmic inclusion bodies (arrowhead) are present in CMV-infected cells.
(Courtesy of Robert H. Rosa Jr, MD.)
Fungal infections of the retina are uncommon, occurring most often in immunosuppressed patients and in patients with fungemia (eg, from parenteral nutrition or intravenous drug use). These infections usually begin as single or multiple small foci in the choroid or retina (Fig 11-9). The most common causative fungi are Candida species, particularly C albicans. Less common agents include Aspergillus species and Cryptococcus neoformans.
Histologically, fungal infections are characterized by necrotizing granulomatous inflammation. A central zone of necrosis is typically surrounded by the granulomatous inflammation with an outer layer of lymphocytes. Although histologic examination may reveal the causative agent, a culture and/or molecular studies are required for definitive identification of the organism. With treatment, these lesions heal with a fibroglial scar.
Toxoplasmic retinochoroiditis (also called toxoplasmic chorioretinitis, ocular toxoplasmosis) is the most common infectious retinitis. It may be due to reactivation of a congenitally acquired infection or to an acquired Toxoplasma infection in healthy or immunocompromised individuals. In patients with reactivated disease, toxoplasmic retinochoroiditis typically presents as a posterior uveitis or panuveitis with marked vitritis and focal retinochoroiditis adjacent to a pigmented chorioretinal scar. The absence of a preexisting chorioretinal scar suggests newly acquired disease.
Figure 11-9 Fungal chorioretinitis. A, Clinical appearance of vitreous, retinal, and choroidal infiltrates in a patient with fungal chorioretinitis. The vitreous cells give the photograph a hazy appearance. B, Granulomatous infiltration surrounding a central area of necrosis (asterisk). Frequent multinucleated giant cells are present (arrows).C, Grocott-Gomori methenamine–silver nitrate stain of the section parallel to that shown in part B demonstrating numerous fungal hyphae, which stain black (arrows).
(Courtesy of David J. Wilson, MD.)
Figure 11-10 Toxoplasmic retinochoroiditis. A, Fundus photograph showing chorioretinal scars rimmed with pigment (double arrow), typical of prior infection with Toxoplasma species. Active retinitis (arrowhead) and perivascular sheathing (arrow) are present. B, Cysts (arrow) and extracellular organisms (tachyzoites, arrowhead) in active toxoplasmic retinochoroiditis.
(Courtesy of Hans E. Grossniklaus, MD.)
Microscopic examination of active toxoplasmic retinochoroiditis reveals necrosis of the retina, a prominent infiltrate of neutrophils and lymphocytes, and Toxoplasma organisms in the form of tissue cysts and tachyzoites (Fig 11-10). There is generally a prominent lymphocytic infiltrate in the vitreous and the anterior segment and granulomatous inflammation in the inner choroid. Healing brings resolution of the inflammatory cell infiltrate with encystment of the organisms in the retina adjacent to the atrophic chorioretinal scar. See also BCSC Section 9, Uveitis and Ocular Inflammation, and Section 12, Retina and Vitreous.
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.