Fig. 4.6 Posterior pole granuloma superior to the optic disk with secondary fibrocellular membranes extending into the optic nerve, vitreous, and surrounding retina in a

10-year-old boy with Toxocara canis. (a) Color photograph. (b) Fluorescein angiogram

also may lead to retinal breaks in atrophic retina, creating a combined tractional-rhegmatogenous detachment [19]. An optic papillitis also can occur, usually because of an invasion of the nerve by the nematode or as an inflammatory response to the organism in another site of the eye [1].

Epidemiology

Uveitis is a common cause of vision loss, accounting for 5–20% of all cases of blindness worldwide [17]. Toxoplasmosis is the most common etiology of infectious posterior uveitis and having OT as one of the less frequent cause [20]. However, the study of the epidemiology of human toxocariasis remains problematic for a number of reasons. First, much of the epidemiology of human toxocariasis is based on serodiagnosis, which has inherent problems, and our understanding of the relationship between exposure and disease remains poor. Second, the lack of standardization of both clinical signs and symptoms and serological testing can introduce variation between studies and make comparisons difficult. Third, randomly selected data at the population level is scarce, and therefore, it is difficult to assess the public health significance of disease in different countries [4].

The prevalence of infection of dogs with adult Toxocara worms was reported to be about 25% in Western countries [3, 21], while the

rate in cats in France was 30–60% [3]. The prevalence of infection tends to decrease with increasing age of the animal and is lower in well-cared-for pet dogs than in stray or pound dogs. This high prevalence, together with the high fecundity of Toxocara and the increasing number of pet animals in Western countries, explains the high level of soil contamination with Toxocara eggs in parks, playgrounds, and other public places [3].

Recent studies have demonstrated that soil samples taken from gardens of homes where a clinical case of toxocariasis is found are likely to be contaminated. Toxocara eggs have been recovered from salads and other raw vegetables taken from such gardens [3]. Geophagia or soil eating is a specific type of pica that increases the risk of toxocariasis, especially in children living in homes with puppies that have not been dewormed. Poor personal hygiene as well as consumption of raw vegetables grown in contaminated kitchen gardens may result in chronic low-dose infections [3].

Toxocara seroprevalences range from 4% to 46% in adults and can be as high as 77.6% in school children [22], and the disease affects females and males with approximately equal frequency [17]. In the United States, the overall prevalence was found to vary between 4.6% and 7.3%, but ranged as high as 10% in the American South and over 30% for socioeconomically disadvantaged African American children. Higher

seroprevalence was also linked to markers of low socioeconomic status, including poverty and crowding and lower educational level for head of household [23, 24]. In 2008, the Centers for Disease Control and Prevention (CDC) in the United States reported on Toxocara seroprevalence from the Third National Health and Nutrition Examination Survey (NHANES III), a cross-sectional survey conducted between 1988 and 1994. The survey sampled at higher rates specific minority groups (e.g., non-Hispanic Blacks and Mexican Americans) and age groups (young children and the elderly). Based on a representative sample of just over 20,000 in individuals over the age of 6, the overall seroprevalence was 13.9% [23, 25], suggesting that ten million Americans are infected with Toxocara. However, the seroprevalence was found to be considerably higher among non-Hispanic Blacks and people living in poverty.

Based on the number of African Americans living in poverty in the United States, it has been calculated that as many as 2.8 million have toxocariasis, making this disease one of the most common infections among any underrepresented minority groups [23]. In a separate study conducted in the 1990s, high rates of toxocariasis were also found among inner-city Hispanic populations in Bridgeport and New Haven, Connecticut, especially among Puerto Rican immigrants [23, 26]. On the other hand, unlike previous reports in other countries, most patients reported with ocular toxocariasis in Japan are adult, and this prevalence may be due to the changing dietary habit in that country [14].

Diagnosis

The diagnosis of OT is difficult and, in the majority of cases, remains only presumptive. Standard diagnostic methods for ocular Toxocara are fundoscopy, imaging, and serologic testing [13].

Most patients with visceral larva migrans will manifest a leukocytosis and hypereosinophilia. On the other hand, eosinophilia is usually absent in OT. Tissue biopsy can show the presence of larvae, but because the larvae rarely are able to

finish their life cycle in human beings, stool analysis will not detect Toxocara [1]. In the absence of parasitological evidence of infection, diagnosis of toxocariasis has relied mainly on immunological methods [10, 27]. Thus, the Toxocara excreted-secreted antigens (TES) have been applied to different immunological assays. The TES-based enzyme-linked immunosorbent assay (ELISA) for detection of IgG-specific antibodies, in particular, is widely preferred for diagnostic purposes and also for seroepidemiologic surveys [10].

Toxocara is a parasite with the ability to evade the immune system, which could explain the chronicity and persistence of the infection [10]. The ELISA has made immunodiagnosis the main serologic method for detecting visceral larva migrans and for confirming the clinical suspicion of OT [1]. Moreover, measurement of avidity (functional affinity) of specific IgG antibodies seems to be useful to discriminate between chronic and early phases of the infection, as in the case for other infectious diseases. In other words, high avidity IgG antibodies are associated with the chronic phase low avidity (functional affinity) of specific IgG antibodies that are associated with the chronic phase and low avidity IgG with freshly acquired toxocariasis. There are few follow-up studies of toxocariasis patients after chemotherapy, but it has been reported that specific IgG antibody levels remain elevated for many years [10]. In toxocariasis, specific IgM antibodies were reported to occur in both acute and chronic phases, differing from most unrelated infections in which they are transient [10]. Lately, IgA and IgE have been found to be useful for diagnosis and follow-up of toxocariasis.

For VLM and some forms of covert toxocariasis, the sensitivity and specificity of the Toxocara ELISA are estimated at 78% and 92%, respectively, at a titer of 1:32 [23]. The sensitivity of the ELISA for OLM, however, is considerably less. The larvae may remain alive within the host for months, and host antibody levels may remain strongly positive for 2 or 3 years or more [23, 25]. Therefore, in the CDC, the presence of antibody titers greater than 1:32 may be considered reflective of active infection [23].

The presence of any level of antibodies in the serum is therefore likely to support the diagnosis of Toxocara uveitis if the clinical picture raises this possibility. However, most ophthalmologists consider a serum titer of ³1:8 to be positive for OT if the patient has clinical features consistent with the diagnosis [7, 28]. On the other hand, the absence of serum antibodies does not rule out the diagnosis [17].

The possibility that T. cati might play a part in causing ocular lesions has been raised by Petithory et al., who reported positive ELISA test for T. cati in the vitreous of six out of nine patients with OLM, all nine of whom also had positive vitreous T. canis ELISA tests [29]. Therefore, testing intraocular fluid for antibodies has also been shown to be helpful in diagnosing toxocariasis. These samples often contain higher levels of antibody than the serum [17, 30]. Taking into account that establishing the diagnosis of OT based on clinical features and serologic results is unreliable, we suggest the addition of T. canis and T. cati Goldmann-Witmer coefficient (GWC) determination to the diagnostic repertoire in patients with unexplained focal chorioretinitis or vitritis [22]. Cytology of the aqueous or vitreous may play a role in the differentiation between retinoblastoma and Toxocara posterior pole granuloma in children. The presence of eosinophils in aqueous or vitreous biopsy specimens also suggests the diagnosis to toxocariasis [31].

Imaging studies, particularly ultrasound examination and computed tomography (CT), are useful. Three ecographic patterns in 11 patients with OT were reported [31, 32]: (1) a solid, highly reflective peripheral mass (located in the temporal periphery in 91%) of patients, (2) a vitreous membrane extending between the posterior pole and the mass, and (3) traction retinal detachment or fold from the posterior pole of the mass (Fig. 4.7). Also described was pseudocystic transformation of the peripheral vitreous on ultrasound biomicroscopy. Intraocular calcification is not uniformly present, but may be seen in eyes with ocular toxocariasis with significant ocular disruption or phthisis [31].

Recently, it was demonstrated that optical coherence tomography (OCT) is useful for the

differential diagnosis between Toxocara granuloma that have subretinal extension and idiopathic choroidal neovascularization in the active stage. In general, OCT examination demonstrates a Toxocara granuloma as a highly reflective mass, protruding above the retinal pigment epithelium, and sometimes surrounded by subretinal fluid (see Fig. 4.4b) [13, 33, 34].

Differential Diagnosis

Patients with OT will often seek treatment because of leukocoria. The differential diagnosis of OT varies with the clinical presentation of the disease. It includes retinoblastoma (RB), retinopathy of prematurity (ROP), congenital cataracts, persistent fetal vasculature, infectious endophthalmitis, various forms of trauma, and the general groups of severe exudative and hemorrhagic retinopathies, which may present a similar clinical picture [1].

As RB is the most common malignant intraocular neoplasm of childhood, it is critically important to distinguish it, particularly the sporadic, unilateral variant, from OT. Factors that may be helpful in making this distinction include the following: (1) mean age at presentation for OT, 7.5– 8.9 years, versus for RB, 22–23 months; (2) paucity of inflammatory stigmata in RB; and (3) continuous growth of RB lesions. Furthermore, normal levels of aqueous humor lactate dehydrogenase and phosphoglucose isomerase, the demonstration of eosinophils in vitreous or aqueous aspirates, and absence of malignant cells favor a diagnosis of OT [31].

Infectious endophthalmitis is distinguished by the history of recent trauma or ocular surgery. Acute signs of external inflammation typical for bacterial endophthalmitis are uncharacteristic in toxocariasis. However, a delayed onset with less virulent bacterial or fungal organisms needs to be differentiated. Vitreous or aqueous sampling for microscopic examination and microbiologic studies should provide a definitive diagnosis in these cases. Endogenous endophthalmitis usually occurs in the setting of immunodeficiency and positive blood cultures [8].

Fig. 4.7 Two different cases demonstrating the ultrasound characteristics of advanced ocular toxocariasis. (a) A solid, highly reflective peripheral mass and a vitreous membrane extending between the posterior pole and

the mass. (b) A tractional retinal detachment at the posterior pole from the mass (Courtesy of Guillermo Talevi, M.D., and Carina Tallano, M.D.)

Differentiation between active toxoplasmic retinochoroiditis and toxocariasis may be difficult, particularly when severe vitritis is present. Serologic studies for toxoplasmosis should provide the diagnosis information [8].

Other pediatric conditions such as ROP, familial exudative vitreoretinopathy (FEVR), persis-

tent fetal vasculature, and Coats’ disease usually present neonatally or in early infancy and lack the signs of inflammation of the posterior segment. Retinopathy of prematurity is bilateral, encountered in infants with a history of prematurity and low birth weight, and characterized by proliferative changes and membrane formation.