Infectious uveitic conditions may be caused by bacteria, viruses, fungi, or parasites and must be treated with appropriate anti-infective agents. Differentiating infectious from inflammatory causes of uveitis may be difficult and require clinical or laboratory testing.
Herpes simplex virus, HSV, and varicella-zoster virus (VZV) belong to Herpesviridae family of double stranded DNA viruses and are an important cause of ocular infection. HSV type 1 and type 2 are related antigenically and may coinfect the same nerve ganglia. HSV-1 more commonly causes infection above the waist (oro-facial, ocular infection), and HSV-2 below the waist (genital infection). 40-80% of adults have positive serology for HSV-1 antibodies.
Transmission is by direct contact with infected lesions, but most commonly occurs as a result of exposure to virus shed asymptomatically. Varicella-zoster virus causes a primary infection (varicella or chickenpox) and subsequent latency, occasionally followed later by recurrent disease (zoster or shingles). Zoster affects more frequent patients in their 6th to 9th decades, and the majority are healthy, with no predisposing factors. However, Zoster is more common in patients on immunosuppressive therapy, in those with a systemic malignancy, or HIV infection. The most commonly affected dermatomes are on the thorax and those supplied by the 5th cranial nerve (CN V). Ocular involvement occurs in more than 70% of patients with zoster in the first division of CN V. The ocular findings of herpes simplex and herpes zoster infection are indistinguishable for the most part, and may affect the anterior segment or posterior segment of the eye. Anterior segment findings include blepharoconjuntivitis, cutaneous vesicles, epithelial keratitis, stromal keratitis, and endothelial (disciform) keratitis. It may also cause iridocyclitis or affect the posterior segment with viral retinitis or vasculitis. Acute retinal necrosis (ARN) may affect immunocompromised or immunocompetent patients. Treatment includes oral or intraocular antiviral therapy, cycloplegics, and corticosteroids in cases not affecting the corneal epithelium. Posterior involvement can be complicated by macular edema and retinal detachment.
Cat Scratch Disease (Bartonella henselae)
Cat Scratch Disease (CSD) is a systemic infection which in unusual cases can involve a diffuse uveitis with neuroretinitis. CSD uveitis is recognizable as a unilateral swelling of the optic disc with macular exudates in a star-shaped configuration. There may be inner white retinal lesions in all location of the fundus with predilection for major arteries and less common retinal veins. There is a moderate cellular inflammation of the vitreous and anterior chamber. Vision loss is substantial until treatment is complete, which involves several weeks of antibiotic therapy.
The cytomegalovirus is in the herpes family of the viruses. It is commonly associated with opportunitistic infection in HIV AIDS and immuno-compromised patients. Up to 40% of AIDS patients can present with CMV retinitis. Untreated, CMV can destroy the retina within 3 - 6 months. Diagnosis is generally clinical, as serologic tests and viral culture are of limited value as majority of population show evidence of previous exposure. Roughly one fifth of patients develop retinal detachment, especially with large areas of anterior retinal necrosis. In patients with small peripheral lesions, it can often mimic cotton-wool spots seen in HIV retinopathy. These patients can often be followed clinically with routine fundus photos to document progression in a CMV infection. Treatment includes intravitreal injections along with oral administration of antiviral agents.
Syphilis is a multisystemic, chronic bacterial infection caused by the spirochete Treponema pallidum and is associated with multiple ocular manifestations that occur both with congenital and acquired forms. Transmission occurs most often during sexual contact and transplacental infection of the fetus. Incidence of syphilis is 2.5 cases per 100.000 population and 11.1 per 100.000 live births for congenital form. Although not a common cause of uveitis, syphilis is a notorious masquerader, and should always be considered in the differential diagnosis of any case of intraocular inflammatory disease. Syphilitic uveitis can take any form. One should be especially concerned about this infection if a patient has both scleritis and uveitis concomitantly or if a patient believes himself or herself to be at high risk for the disease. This diagnosis should also be considered if corticosteroids have effected incomplete resolution of the disease or if the retina is involved in the inflammatory process. Treatment of syphilis is typical performed by infectious disease specialists with intravenous penicillin. Comcomitant topical or periocular corticosteroids are used to control inflammation for the duration of antibacterial treatment.
Brucella abortus and Brucella suis live in the genitourinary tract of cattles and pigs. Infection is transmitted to humans from animals as a consequence of occupational exposure (slaughterhouse workers, vets) or ingestion of contaminated milk, unpasturized products.
Clinical findings include lymphadenopathy, fever, and chills/sweats. Ocular findings include anterior uveitis, nodular choroiditis, nummular keratitis, or optic neuritis. Treatment includes antibiotics with a prolonged treatment course.
The pathogenic agent Mycobacterium leprae has an affinity for skin, peripheral nerves and anterior segment of the eye. Leprosy was the first documented infection in humans and, has the highest incidence of ocular complications of any systemic infection. Although rare in developed countries, is it not uncommon in subspecialty uveitis clinics, and most uveitis specialists see the occasional case. Mycobacterium leprae is a gram positive intracellular bacillus with tropism in parts of body with low temperature. Leprosy may be tuberculoid or lepromatous; the later group of patients suffers from uveitis. Clinical findings include hypopigmented skin macules, facial skin thickening, saddle nose deformity, and swollen peripheral nerves. Ocular Findings include decreased corneal sensation, prominent corneal nerves, conjunctivitis, scleral nodules, and a chronic granulomatous uveitis, attributable to direct invasion of the iris and ciliary body by the organism, with granuloma formation.
Treatment includes dapsone, rifampin, and clofazimine.
Diffuse Unilateral Subacute Neuroretinits (DUSN)
DUSN is a rare infectious retinochoroiditis associated with subretinal nematode, T canis and Baylisascaris procyonis. This clinical entity was first described by Gass and Scelfo in 1978. The smaller worm T Canis, a common hookworm of parasites of dogs is 400 to 1000 microns in size. The larger worm Baylisascaris procyonis, is an intestinal round worm of raccoons and squirrels, 1500 to 2000 microns in length. The worm propels itself by a series of slow coiling and uncoiling movements. It is likely that a variety of nematodes with localized enzymes and metabolic waste products stimulate a localized inflammatory response. Early in the disease, patients notice floaters, mild visual loss and occasionally migratory paracentral or central scotoma. An afferent papillary defect is usually present. If untreated for extended period of time, late manifestations include a dense central scotoma and eventually severe vision loss. Stool samples for ova and parasites are unrevealing, and serum eosinophilia is not found. The live nematodes can live up to four years or longer in the subretinal space. Laser treatment is used to kill the nematode with adjunctive oral antibiotics.
The causative organism Toxoplasma gondii is an obligate intracellular protozoan and the most frequent cause of infectious posterior uveitis in healthy individuals. It is estimated that over 500 million individual have been infected worldwide. The toxplasma life cycle involves 3 forms. The tachyzoite is the form that actually travels in the body and causes infection in many tissues, including the eyes. Humans can acquire tachyzoites 3 ways: 1) directly, by infusing or ingesting tachyzoite-infected bodily fluids; 2) by ingesting undercooked meat containing toxoplasma tissue cysts, or bradyzoites, that then mature into tachyzoites in the human intestinal tract; 3) by ingesting oocysts that contain sporozoites, a toxoplasma life cycle form found in cat feces. Sporozoites will also transform into tachyzoites in the intestinal mucosa; 4) transplacentally, if a woman acquires toxoplamosis during pregnancy (before the third trimester) and the infecting tachyzoites cross the placenta. Tachyzoites travel in the body and take up residence in tissues including the retina and central nervous system, where they then transform into tissue cysts (bradyzoites) that can remain dormant for years. Active toxoplasmosis infection results from the rupture of these tissue cysts with release of tachyzoites, which are highly immunogenic and cause marked inflammation. This is the basis for toxoplasma retinitis. Treatment is not always necessary. Most practitioners treat if visual acuity has decreased > 2 lines due to vitreous cells, if there is macular involvement or threat to the optic nerve (within 800 microns), or if patients are immune-compromised. Antimicrobial therapy classically includes pyrimethamine (Daraprim) together with sulfadiazine, although clindamycin or trimethoprim/sulfamethoxazole are reasonable alternatives. Oral treatment may be combinted with intravitreal clindamycin with serial injections. Corticosteroid therapy is essential but should be used with carefully, since corticosteroids without concomitant antimicrobial treatment will worsen the infection.
Ocular Toxocariasis was first recognized in eyes enucleated for presumed retinoblastoma and Coats’ disease. The organism Toxocara canis is found in dogs, and adult worms shed over 200,000 eggs per day in dog feces. Humans acquire the infection by ingesting eggs in the soil or via contaminated food. The encapsulated larvae will mature in the intestine and bore through the intestine wall to migrate to the brain, lungs and liver. Ocular toxocariasis is a rare uniocular disease most commonly presenting with leukocoria, strabismus and vitreitis. Patients with ocular toxocariasis do not generally have eosinophilia. The average age at presentation is approximately 8 years. Injury to ocular structures can be caused by migration of T. canis larvae, and toxic injury resulting from produced by worm excretions. There is often a delay of at least a year between ocular symptoms and diagnosis. Systemic treatment of toxocariasis is indicated as well as control of the ocular inflammation.
Uveitis due to Lyme is generally chronic, bilateral and may be granulomatous. If patients give a history of a rash or joint pain within months prior to presentation, we order Lyme serologies. Treatment for Lyme disease may be prolonged.
Uveitis due to TB is rare as a cause of uveitis in developed countries, and would most commonly be chronic, unilateral and may be granulomatous. We suspect TB in patients who have immigrated from areas where TB is endemic, or who live in contact with persons who have the disease, and we test for it with a purified protein derivative (PPD) test or with a quantiferon gold assay.