28.4 Ocular and Orbital Manifestations of Infection

28.4.1 Bacterial

Most systemic bacterial infections that affect the eye do so through bacteremia via hematogenous seeding. Ocular manifestations of bacteremia may be suppurative or nonsuppurative. Suppurative findings include endophthalmitis, subretinal abscess, and preseptal and orbital cellulitis, while nonsuppurative findings include nonspecific retinal lesions (e.g., cotton-wool spots) and uveitis [20, 21]. Conventional methods of culture of blood or vitreous are usually successful in diagnosing suppurative ocular complications of acute systemic infections, while molecular diagnostic techniques are proving useful in diagnosing nonsuppurative ocular complications of indolent systemic infections [20].

The ocular manifestation of an acute systemic bacterial infection, such as endocarditis or liver abscess, is usually acute endophthalmitis, while the ocular manifestation of a chronic systemic infection, such as tuberculosis or syphilis, is often a subacute uveitis [22–24]. Intraocular findings in patients with acute bacteremia include cotton-wool spots, superficial retinal hemorrhages, white-centered retinal hemorrhages (Roth spots), and endogenous endophthalmitis [20–23].

Orbital infections in the immunocompromised host are most commonly caused by bacteria, and a wide spectrum of bacteria are associated with orbital disease [23]. Infection reaches the orbit by one of three methods: implantation, local extension, or hematogenous spread. Specific anatomic features of the midface place the orbit at risk of infection. Implantation, which may occur in patients with an orbital foreign body, results from trauma to the periorbital area or sinuses. Local extension most often occurs as spread from a contiguous sinus, and hematogenous spread may occur from a multiplicity of distant sites in immunocompromised patients. Coagulasenegative staphylococci, S. aureus, viridans streptococci, and enterococci are now the major gram-positive pathogens. E. coli, Klebsiella species, and P. aeruginosa are the most common gram-negative pathogens causing initial fever [20–22].

Systemic immunosuppression may predispose patients to the development of infectious crystalline keratopathy, a distinct clinical entity characterized by intrastromal noninflammatory bacterial colonization seen morphologically as graywhite, needle-like branching opacities occurring commonly in the anterior or midcorneal stroma in an otherwise relatively quiet eye [25]. Alpha-hemolytic streptococci are the common causative organism, though other bacteria and even fungi have also been reported to cause infectious crystalline keratopathy. An immunocompromised state is a common predisposing factor. Infectious crystalline keratopathy is typically seen in a patient with an epithelial defect with or without a history of penetrating keratoplasty who is using topical steroids [25].

Concurrent orbital cellulitis and panophthalmitis have been reported by Jain and Garg [26], Tabbara et al. [27], Hornblass et al. [28], and Li et al. [29]. Additionally, a case of concurrent orbital cellulitis and suppurative panophthalmitis with associated ecthyma gangrenosum in an immunocompromised patient with Pseudomonas septicemia was described by Maccheron et al. [30].

Infections involving Nocardia organisms represent an increasingly recognized problem among patients with immunosuppression. It is estimated that at least 1000 new cases occur every year in the United States [2, 31]. Nocardia organisms are aerobic, soil-dwelling actinomycetes involved in the decay of organic matter. Nocardiosis is a multisystem disease that has high mortality and ocular morbidity rates. The choroid seems to be the site in the eye most commonly affected, followed by the cornea and sclera [31]. Lakosha et al. [31] have reported choroidal abscess development in a patient with chronic myeloid leukemia due to Nocardia farcinica.

Bartonella henselae is a gram-negative bacilli that causes the majority of cases of cat-scratch disease. The vast majority of cases of cat-scratch disease occur in children who present with local infection at the inoculation site followed by tender regional lymphadenopathy. In contrast, cat-scratch disease in immunosuppressed patients and those who have undergone organ transplantation can disseminate from the lymph nodes and cause neuroretinitis and chorioretinitis. Bartonella organisms responsible for cutaneous bacillary angiomatosis of the anterior orbit, eyelid, and conjunctiva have been described [32]. Patel et al. [33] reported an atypical presentation of B. henselae infection: bilateral chorioretinitis in an immunocompromised patient.

A rarely described bacterium, gram-negative Providencia rettgeri, has been responsible for dacryocystitis, conjunctivitis, keratitis, and endophthalmitis in patients with an immunocompromised state [34].

Disseminated toxoplasmosis is a well-known complication of immunodeficiency, including immunodeficiency induced by cancer, steroid therapy, cytotoxic drug therapy, and AIDS. When ocular toxoplasmosis occurs in an immunodeficient host or when immunosuppressive therapy is administered to a patient with active toxoplasmosis, widespread tissue destruction by proliferating organisms may result [20]. Ocular toxoplasmosis in an immunocompromised host presents difficult problems in diagnosis and management. There may be a variety of clinical lesions, including single foci of retinochoroiditis in one or both eyes, multifocal lesions, or diffuse areas of retinal necrosis [20, 35]. The majority of lesions do not arise from the borders of preexisting scars, which suggest that they result from acquired infection or dissemination of organisms from nonocular sites of disease [20]. In immunocompromised patients, Toxoplasma gondii may infect the iris, choroids, and vitreous tissues, which are not usually infected in immunocompetent hosts [35]. In patients with disseminated toxoplasmosis, ocular lesions appear to respond to standard antiparasitic drug therapies, but in the most immunocompromised patients, continued treatment is probably necessary to prevent reactivation of disease [20].

Mycobacterium haemophilum is an increasingly recognized pathogen in immunocompromised patients [36–39]. This nontuberculous mycobacterium has been isolated from specimens of skin, synovial fluid, bone, lung tissue, sputum, bronchoalveolar lavage fluid, lymph nodes, blood, and bone marrow [36]. Cutaneous and subcutaneous manifestations are the most frequently reported presentation of M. haemophilum infection. M. haemophilum infection presenting as filamentary keratopathy can occur in immunocompromised patients [37]. Chronic granulomatous iridocyclitis progressing to endophthalmitis has been reported [38].

Mycobacterium fortuitum infection masquerading as an orbital mass causing diplopia was reported by Ali et al. [39].

28.4.2 Viral

Despite significant advances in our ability to diagnose and treat viral infections, viruses continue to be a significant cause of both systemic and ocular illnesses.

Primary infection with HSV results from direct contact with infected secretions, typically from the mucosal surface of an infected person. The incubation period ranges from 2 to 12 days [11, 40]. Primary gingivostomatitis, which is most common in children but also occurs in adults, presents with a prodrome of fever, malaise, and pharyngitis, followed by the onset of small intraoral vesicles that coalesce to form painful ulcers [11, 41]. These lesions frequently involve the pharyngeal and buccal mucosa, soft palate, and gums and may extend to the posterior pharynx, tonsils, or lips [41]. Occasionally, spread to other cutaneous sites such as the face and eyelids is observed. Primary ocular involvement results in follicular conjunctivitis, which is typically unilateral with regional adenopathy, vesicular blepharitis, and epithelial keratitis [41]. Dacryoadenitis associated with HSV conjunctivitis can also result [42].

In severely immunocompromised patients, herpes zoster can present with unusual manifestations and can cause potentially life-threatening complications such as atypical generalized herpes zoster or abdominal herpes zoster. Ocular manifestations of varicella zoster virus infections are protean and include dermatitis, episcleritis, keratitis with neurotrophic ulceration and stromal scarring, uveitis, iris atrophy, retinitis, and optic nerve involvement [43]. Patients who are immunocompromised are particularly susceptible to these complications, which frequently occur without typical cutaneous dermatomal eruptions [41–43]. Simultaneous involvement of the retina and optic nerve by varicella zoster virus in acute retinal necrosis syndrome is well documented [43]. Greven et al. [44] reported a case of simultaneous involvement of the retina, optic nerve, and optic chiasm with varicella zoster virus. Optic disc edema with associated optic neuropathy and retrobulbar optic neuritis due to varicella zoster virus has been described in immunocompromised patients [45, 46].

Herpetic necrotizing retinitis is caused by the herpesvirus group of viruses: HSV, varicella zoster virus, CMV, and Epstein–Barr virus [20, 23, 47]. Progressive outer retinal necrosis is described as a distinct form of varicella zoster virus necrotizing chorioretinitis and is found almost exclusively in patients with AIDS. However, a few cases in non-AIDS patients have been reported. These patients were immunocompromised owing to therapy for idiopathic thrombocytopenic purpura, cutaneous non-Hodgkin’s lymphoma, rheumatoid arthritis, renal transplantation, or allogeneic stem cell transplantation [47–49]. Typical features of progressive outer retinal necrosis include retinal lesions that are multifocal, coalescing, and beginning in the peripheral retina; rapid progression of these lesions; lack of response to treatment;