Key concepts

•Toxocariasis is typically found in children, with the average age at diagnosis estimated to be 7.5 years.

•ELISA is the most reliable and readily available test for the evaluation of antibodies directed against this organism.

•If medical therapy is considered, anthelmintic drugs such as thiabendazole or diethylcarbamazine are frequently used, and prednisone can be used to reduce the secondary inflammatory response.

Nematode infections of the eye have been noted for some time; Calhoun,1 in 1937, observed a larva in the anterior chamber of an 8-year-old boy that ultimately was resorbed. By its description it was thought to be an ascarid. In 1950, Wilder2 reported on 24 patients in whom eyes enucleated for suspected retinoblastoma were found to have nematodes. Four of these lesions were later determined by Nichols3 to be caused by Toxocara canis. Over the years, this entity has been recognized to cause a disorder with potentially serious consequences for vision.

T. canis is an ascarid (i.e., a member of the Ascariditae family) that can only complete its lifecycle in the dog. An adult dog can acquire the infection by ingesting eggs with stage I encapsulated larvae that are found in the soil; by ingesting second stage larvae from infected meat (mice, rabbits, etc.); or by ingesting advanced-stage larvae from the feces of prenatally infected pups.4 In some parts of the United States toxocariasis is found in 100% of puppies less than 6 months of age.5 Eggs in the intestine will ultimately hatch, and the larvae will migrate out of the intestine to all parts of the body. Most will encyst as stage II larvae and not develop further. However, pregnancy will reactivate some of these dormant larvae, allowing them to re-enter the bloodstream and pass through the placenta to infest the growing pups. At birth, the larvae will migrate to the lungs and become stage III. These can be coughed up and then swallowed, whereupon these larvae develop into stage IV and ultimately into the adult worm. These adult worms will lay massive numbers of eggs that pass out of the host in the feces. Humans enter the pathway when they ingest soil, food, or other materials contaminated with the eggs. A survey of sandpits in parks in Japan found Toxocara eggs in 12 of 13 surveyed. The eggs were present both on the surface and in the depths of the sand.6 Once in the human intestine the stage II larva will enter the bloodstream, migrating

Toxocara canis

Robert B. Nussenblatt

throughout the body until the vascular lumen becomes small enough to block its progress. At this point the larva bores into the tissue and encysts. In addition to the eye, such cysts are frequently found in the brain, liver, and lungs. Because the larvae cannot migrate out of the human lungs, the life cycle ends at the stage II larval state, and Toxocara eggs will not be found in the feces of infected persons.

The encysted larvae may stay dormant without causing any clinically overt symptoms, although they are present in large numbers. However, one encysted larva in the eye can lead to serious visual disturbance. An acute systemic disease (visceral larval migrans [VLM]) is due to the migration of the stage II larva of T. canis.

T. canis infestation is associated with fever, pulmonary symptoms such as a dry, hacking cough or asthma-like attacks, splenomegaly and hepatomegaly, skin lesions, neurologic symptoms such as convulsions, and a meningitic picture.

T. canis is an ubiquitous parasite found worldwide. The incidence of infected puppies has been estimated to vary from 33% in London to 98% in Columbus, Ohio, to 100% in Brisbane, Australia.7 In one case–control study comparing 24 ageand sex-matched patients with VLM with control subjects, 23 of the patients with VLM had had dogs in their homes some time before their illness, and an association with puppies in households of patients with VLM within 1 year of onset was statistically significant.8

The disease is thought to be fairly uncommon in the devleoped world. At the Francis I. Proctor Foundation at the University of California, San Francisco, over a 20-year period, there were 22 cases out of 22 185 seen (Table 16-1), In an article9 estimating the prevalence of T. canis in Ireland, 120 00 participants were surveyed, and a prevalence of 6.6 cases/100 000 was calculated (Table 16-2). This rose to 9.7/100 000 if the cases thought to be highly suspect plus those diagnosed were included. The highest rate of seropositivity to Toxocara in adults seems to be on the island of Réunion, with a rate of 92.8%.10 It should be mentioned here that another member of the Ascariditae family, Toxocara cati, also needs to be considered in the differential diagnosis.11

Ocular manifestations

Toxocariasis is typically found in children; the average age of diagnosis is estimated to be 7.5 years, with a range from 2 to 31 years,12 and 80% of patients are under 16.13 It is still a diagnosis that should be considered in adults, such as the case reported in a 36-year-old woman.14 Yokoi and

Part 4 • Infectious Uveitic Conditions

Chapter 16 Toxocara canis

Table 16-1  Demographics and other information on Toxocara patients seen at the Proctor Foundation, UCSF. (From Stewart JM, et al. Prevalence, clinical features, and causes of vision loss among patients with ocular toxocariasis. Retina 2005; 25: 1005–13, with permission.)

colleagues15 reported this entity in 34 adults. Although exceptions have certainly been reported, this tends to be a uniocular disorder. The real prevalence of this disease may be underestimated because most reports dealing with blinding disorders chose patients with 6/60 or worse visual acuity in the best eye, and this disorder is typically unilateral.16 However, Benitez del Castillo and associates17 reported a bilateral occurrence of T. canis infestation in a patient who had a positive Witmer quotient for the parasite in both eyes.

Several ‘typical’ ocular presentations have been recognized. Probably the most common is a granuloma either in the posterior pole or in the periphery. This is presumed to arise after a stage II larva has been lodged in the choroid and becomes encysted.18 The lesion itself will be raised and whitish in color, with a width of 0.75 to 2 or 3 disc diameters (Fig. 16-1). In the report19 reviewing the 22 cases seen at the

Proctor Foundation mentioned earlier, 50% presented with a peripheral retinal granuloma and 25% as macular lesions. This diagnosis must also be considered in the differential diagnosis of leukokoria because the lesion may become very large, encompassing a large portion of the vitreal cavity, and look suspiciously like a retinoblastoma. The disorder is frequently associated with a massive vitritis, probably the result of the release of highly immunogenic antigens from a dead worm.

Live larvae have been observed in the retinal vessels.20 Another recognized presentation of this entity is a peripheral retinitis, which is thought to be the result of a larva lodging in the peripheral retinal vasculature.

A hypopyon uveitis can be seen with any of these posterior pole manifestations. Fuchs’ heterochromia has been reported associated with this entity, just as has been noted in cases of ocular toxoplasmosis21 (Fig. 16-2).

A less common presentation of T. canis infestation in the eye is optic nerve disease;22,23 Brown and Tasman24 reported an 11-year-old child with a presumed toxocaral neuroretinitis associated with a branch retinal artery obstruction. Karel and colleagues25 reported a patient in whom the Toxocara larva observed in a choroidal granuloma migrated into the lens through the posterior capsule.

Figure 16-2.  Right eye with heterochromia in a 20-year-old woman. The right eye fundus had a peripheral lesion compatible with Toxocara.

(Reproduced with permission from Teyssot, Cassoux, Lehoang, Bodaghi, Fuchs, Heterochromic Cyclitis and Ocular Toxocariasis. Am J Ophthalmol 2005;139:915–916.)

Ocular manifestations

Five cases of ocular toxocariasis in adults were reported by Steahly and Mader,26 all with presentations similar to those seen in children. A recent report described a Toxocara lesion presenting as a vasoproliferative tumor in a 64-year-old man.27

As mentioned earlier, the most important alternative diagnosis to consider is retinoblastoma.28 Shields29 has written that T. canis endophthalmitis is the most common entity confused with retinoblastoma. Further, presumed ocular toxocariasis accounted for 26% of the pseudoretinoblastomas seen at the Oncology Service of the Wills Eye Hospital, Philadelphia. Children with retinoblastoma usually are younger than those with ocular toxocariasis, the vitreous is usually clear, and there may be a familial history of the disorder. Ultrasound,30 radiographs, or other imaging methods will usually help distinguish this entity from retinoblastoma because calcification is found frequently in retinoblastoma, although it has also been reported in some patients with toxocariasis.31 Using a standardized echographic approach, Wan and colleagues32 studied the eyes of 11 patients with toxocariasis. In 10 of them the following characteristics were found: a solid highly reflective mass; vitreous bands or membranes that extended from the mass to the posterior pole; and a traction retinal detachment or fold from the mass to the posterior pole (Fig. 16-3). The migration of the Toxocara larva in the retina has been tracked by the use of OCT and fluorescein angiography.33 OCT demonstrated larva to produce a highly reflective signature, moving in the nerve fiber layer (Fig. 16-4). Angiograms performed during this study showed severe inflammatory disease even before the presumed death of the organism.

The aqueous to serum lactate dehydrogenase ratio is >1 in patients with retinoblastoma, and the phosphoglucose to isomerase ratio should be >2 in eyes with retinoblastoma. Other diagnoses to consider include toxoplasmosis; primary hyperplastic primary vitreous; Coats’ disease; focal choroiditis from another cause, such as sarcoid; and retrolental fibroplasia.