and lack of prominent inflammatory reaction in the vitreous and anterior chambers [47, 48, 50].

Acute retinal necrosis is a clinical syndrome consisting of peripheral necrotizing retinitis, occlusive retinal vasculitis, and notable anterior chamber and vitreous inflammation resulting from infection of the retina by certain members of the Herpesviridae family [50–53]. CMV retinitis is a well-recognized complication of immunodeficiency. It has been described as an early, small, opaque lesion with a white granular area of retinal necrosis that spreads in a centrifugal, brushfire-like manner, with vascular sheathing and intraretinal hemorrhages [51, 54, 55].

28.4.3 Fungal

The fungal infections most likely to have systemic manifestations involving the eye are presented here.

28.4.3.1 Candida Species

Candidiasis occurs worldwide. Candida species are normal commensals of humans and are commonly found in the oropharynx, the gastrointestinal tract, and the vagina and on the skin [12, 14]. Predisposition to candidiasis has become more common with the advent of antibiotics, which destroy the normal inhibitory bacterial flora and inhibit neutrophil phagocytosis, and with the use of cytotoxic chemotherapy; immunosuppressive agents, such as corticosteroids; and implantation of prosthetic devices, such as catheters, cardiac valves, and artificial hearts [12, 14, 16, 56].

Most cases of disseminated candidiasis are due to Candida albicans or Candida tropicalis. Patients typically present with fever and toxic effects but few localizing findings. When Candida disseminates, multiple organs are usually affected; renal, cerebral, cardiac, and ocular involvements are the most common, followed by hepatic and splenic involvement and, less frequent, pulmonary, gastrointestinal, cutaneous, bone, and endocrine involvements [12, 16].

Some patients with disseminated candidiasis have Candida endophthalmitis with single or multiple raised, white, fluffy, cotton-ball-like chorioretinal lesions in the presence or absence of overlying vitreous haze [12, 57, 58]. Lesions are usually in the macular area and may extend rapidly into the vitreous humor. Less common findings include hemorrhages, Roth spots, hypopyon, anterior chamber inflammation, and iritis [58]. Patients may complain of orbital pain, blurred vision, floating scotomas, or opacities in the visual fields. The presence of endophthalmitis serves as a major clue to the diagnosis of hematogenously disseminated candidiasis and is a potential cause of permanent blindness [58].

28.4.3.2 Aspergillus Species

Aspergillus species are often nonpathogenic residents of normal body flora as well as common contaminants in bacteriology laboratories and in unfiltered outside air.

Aspergillus species are ubiquitous in the environments of most countries of the world [12, 14]. The fungus grows well on a variety of substrates, including stored hay or grain, compost piles, dead leaves, soil, and dung [12, 14]. Aspergillosis is usually acquired by inhalation of airborne spores (conidia) that reach alveoli or paranasal sinuses. Among immunosuppressed patients, aspergillosis is second only to candidiasis as an opportunistic mycosis [12, 14, 16].

In severely immunosuppressed patients, skin or corneal trauma may be a nidus for Aspergillus infection [14]. The most common cause of aspergillosis is A. fumigatus. A. flavus is the second most common cause and assumes importance in immunosuppressed patients and in patients with nasal or paranasal sinus disease [14, 16, 17]. Host defense against aspergillosis relies primarily on cell-mediated immunity (neutrophils, monocytes, and macrophages) and not on antibodies or lymphocytes [16, 17]. Macrophages are responsible for killing conidia, whereas neutrophils attack mycelia. The complement cascade facilitates neutrophil damage to hyphae and monocyte killing of conidia and also provides a source of chemotactic factor [14–17].

Aspergillus species can infect and invade multiple organ systems, including the ear, sinuses, eye, lung, central nervous system, heart, gastrointestinal tract, skin, and bone [12]. A hyphal ball may form in a chronically obstructed paranasal sinus without tissue invasion. Fibrosing granulomatous inflammation with scanty Aspergillus hyphae within tissue may begin in the sinus and slowly invade the orbit and brain [58]. Clinically, patients with Aspergillus sinusitis may develop head or sinus pain, proptosis, or monocular blindness. In severely neutropenic patients, mucosal invasion beginning in the nose or sinus can spread rapidly to contiguous structures, causing vascular invasion and necrosis. A. flavus is particularly common in isolates from invasive aspergillosis of the nose and the paranasal sinuses. Invasive pulmonary aspergillosis occurs most commonly in patients who have a hematologic or lymphoreticular malignancy and patients who have undergone organ transplantation and are receiving high doses of corticosteroids, cytotoxic agents, or both [12, 14]. de O Machado et al. [59] reported a case of bilateral Aspergillus endophthalmitis in a patient with chronic lymphocytic leukemia.

Aspergillus endophthalmitis is a relatively rare condition that has a devastating course, with blindness as its usual outcome [58, 59]. Manifestations include cloudy vision, redness of the conjunctivae, and pain. Hypopyon with severe exudation into the anterior and posterior chambers may develop. Aspergillus keratitis may be caused by minor trauma to the eye, allowing deep stromal invasion by the fungus [12, 58]. Finally, Aspergillus infection may be a source of orbital cellulitis.

28.4.3.3 Other Fungal Species

Mucormycosis is the common name given to infection by any of several different fungi of the order Mucorales. Mucormycosis is best known for its ability to rapidly invade arterial vessels and for its rapid, destructive, and often fatal course

[12]. Members of the order Mucorales are ubiquitous worldwide and are common inhabitants of the soil and decaying organic debris [14, 16]. Inhalation of conidia must be fairly common, yet colonization and infection are infrequent, attesting to their low virulence and the importance of normal host defenses [12]. Mucormycosis tends to be limited to patients with immunosuppression, trauma, or diabetes mellitus, in whom mucormycosis is particularly common in patients with ketoacidosis [2, 12].

The fungus typically gains entrance to the body through the respiratory tract. The spores deposit on the mucous membranes of the nasal turbinates, where they germinate and then may be inhaled into the pulmonary alveoli [12, 60, 61]. To cause disease, spores must overcome the host’s natural immunity and specific humoral and cell-mediated immune mechanisms [2, 14]. Once the fungus begins to grow, the hyphae invade tissue, cause suppuration with little granulomatous response, and have a special affinity for blood vessels [60, 61]. Direct penetration and growth through the blood vessel walls explain the propensity for thrombosis, embolization, infarction, and tissue necrosis. Disease spreads by both direct and hematogenous extensions [2, 14, 60, 61].

In patients with neutropenia and leukemia, burns, or open wounds, mucormycosis leads to rhinocerebral, pulmonary, or disseminated disease [2, 12, 14, 60, 61]. These patients with rhinocerebral mucormycosis may have facial pain, headache, or both. Other manifestations include nasal stuffiness, blood-tinged nasal discharge, and facial swelling [60, 61]. An examination of the nasal mucosa reveals necrotic turbinates. Fever, facial cellulitis, palatal or nasal septal perforation, and signs of sinusitis may be present. Spread of infection to the orbit results in orbital cellulitis, loss of extraocular muscle function, and proptosis with failing vision [60, 61]. Ultimately, there is a full-blown orbital apex syndrome with destruction of cranial nerves III, IV, and VI; the ophthalmic branch of V; and blood vessels traversing the optic foramen and superior orbital fissure [60, 61]. Mucorales organisms may also invade the cavernous sinus and internal carotid artery, causing thrombosis; cerebral infarction as a result of vascular compromise is common [60, 61].

Alternaria species are ubiquitous fungi known to be soil saprobes and plant pathogens. Ocular manifestations include keratitis and cutaneous involvement [12]. Pseudallescheria boydii, a fungus frequently isolated from soil, can cause a wide range of fungal diseases, including corneal ulcers and endophthalmitis [12].

Cases of Fusarium keratitis and endophthalmitis have been reported [57, 58, 62]. Scedosporium apiospermum is an opportunistic fungus usually found in soil. Orbital involvement by this organism is very rare [63]. In immunocompromised hosts, aggressive spread is common [64]. In 1977, Gluckman et al. [65] reported orbital extension of pansinusitis due to S. apiospermum in a diabetic patient. In 1984, Anderson et al. [66] described successful treatment of an orbitocranial infection due to this organism. And in 1999, Jones et al. [67] described a case of subperiosteal abscess in a leukemic patient. S. apiospermum was also found in a case of osteomyelitis of the orbit in an immunocompromised patient [63].