prevent further progression of ocular lesions and shorten the course of active disease, but it does not prevent late recurrences [94].

Complications of ocular toxoplasmosis include cataract formation, CME, serous or traction retinal detachment, optic atrophy, and choroidal neovascularization.

19.5.2  Toxocariasis

19.5.2.1  Historical Context/Pathophysiology

Ocular toxocariasis results from infection by the sec- ond-stage larvae of the dog roundworm Toxocara canis, or much less commonly the cat roundworm Toxocara cati. Nematodes were first recognized histopathologically as ocular pathogens of the posterior segment by Wilder in 1950, although at the time she did not realize the specimens represented Toxocara species larvae [95].

Toxocara species larvae are a common intestinal parasite of dogs and cats. T canis has been found in 80% of puppies 2–6 mo old and 10–30% of soil samples from public parks and playgrounds [96]. The adult T canis female worm can excrete as many as 200,000 eggs per day into the environment, which under optimal environmental conditions develop into infective embryonated eggs that can survive for years. Human infection results from ingesting ova from contaminated dirt, or from improperly cleaned foods. Once in the small intestine of a human host, the eggs decorticate and release the larvae. The organism grows in the small intestine, and subsequently penetrates the bowel wall and enters portal circulation.Itdisseminatesthroughoutthebodyhematogenously and lymphatically to reside in target tissues including the liver, lung, muscle, brain, and eye. Maturation of the worm does not occur in humans, and thus ova are not shed in the alimentary tract. For this reason, stool analysis for larvae in humans is unproductive [97].

Systemic infection can result in a mild, subclinical, febrile illness, or visceral larval migrans (VLM), which is most common in children from 6 months to 3 years old. Systemic symptoms include fever, cough, malaise, and anorexia. Ocular toxocariasis results from migration of the larva into the posterior segment of the eye, and is most common in older children and adults. Interestingly, VLM and ocular toxocariasis rarely present within the same individual [98].

Tissue damage and disease severity is thought to depend largely on the degree of allergic reaction in the host. The pathologic manifestations result from an infl­ ammatory response directed against secreted larval antigens that are liberated from the outer epicuticle coat when bound by specific antibodies. The antigens induce a Th2-type CD4+ cellular immune response characterized by the production of interleukin 4 that promotes B-cells to produce immunoglobulin E (IgE) and interleukin 5, resulting in eosinophil differentiation and vascular adhesion [96, 99]. The inflammatory reaction causes epithelioid cells to surround each larva, and, subsequently, a dense fibrous capsule invests each granuloma.

Histopathologically, nematode larva or residual hyaline capsules can be demonstrated. Enucleated eyes demonstrate a varying degree of intraocular disorganization, retinal detachment, and vitreous membrane formation. Focal inflammatory masses, consisting of granuloma formation with eosinophilic abscesses, may be incorporated into the retina and overlying vitreous. The foci are surrounded by epithelioid and giant cells, lymphocytes, plasma cells, and fibroblasts. The underlying retinal pigment epithelium can be atrophic or demonstrate hyperplasia [96].

19.5.2.2  Clinical Findings/Natural History

Patients often present with unilateral decreased vision, and they may have pain, photophobia, floaters, strabismus, or leukocoria. Bilateral disease is exceedingly rare. The anterior segment is usually white and quiet, however nongranulomatous inflammation can be present. There are three common posterior segment manifestations. Most commonly there is formation of a peripheral granuloma (50% of presentations), which appears clinically as a local mass of whitish tissue involving the retina and peripheral vitreous. Inflammatory vitreous membranes frequently radiate out from the mass circumferentially, and contraction of the membranes can result in localized tractional elevation and formation of characteristic radial retinal folds (Fig. 19.7). These often lead from the peripheral mass to the optic nerve-head. The second posterior manifestation is moderate to severe vitreous inflammation (Fig. 19.8b), which can result in leukocoria and mimic endophthalmitis (25% of presentations), although such eyes are typically white and have no pain. Lastly, ocular toxocariasis commonly presents as a localized macular granuloma (25% of presentations), typically

whitish or grayish-white in color, centered anywhere in posterior pole (Fig. 19.8c). Other uncommon variants include unilateral pars planitis with diffuse peripheral inflammatory exudates, and granulomas of optic nerve head [100].

Genetics

There does not appear to be any genetic influence that alters human susceptibility to ocular toxocariasis.

Diagnosis/Treatment/Complications

The diagnosis of ocular toxocariasis is essentially clinical, based on lesion morphology, supportive laboratory data, and imaging studies. Serum ELISA is performed for antibodies to toxocara, and any positive titer is considered significant in the appropriate clinical

context. Titers of > or = 1:8 have a sensitivity and specificity of greater than 90% for prior exposure to the organism, [101] however absence of serum antibodies does not rule out ocular toxocariasis. ELISA of the aqueous or vitreous can be performed for specific T canis antibodies, and a positive Goldmann–Witmer coefficient provides additional evidence for ocular involvement. B-scan and CT are useful in the setting of media opacities such as vitreous membranes and tractional retinal detachment, and can confirm the absence of calcium that is characteristic of retinoblastoma.

There is no uniformly satisfactory treatment for ocular toxocariasis. In the absence of a severe inflammatory response, peripheral lesions may be amenable to observation. Periocular and systemic corticosteroids are used for posterior lesions and endophthalmitis, to reduce the inflammatory response and prevent structural complications. Topical corticosteroids are inadequate. The utility of antihelminthic therapy for ocular toxocariasis has not been established [96, 102]. Laser