Table 16-3  Sensitivity and specificity of ELISA for diagnosis of ocular toxocariasis. (From Hagler WS, Pollard ZF, Jarrett WH, et al. Results of surgery for ocular Toxocara canis. Ophthalmology 1981; 88: 1081–6, with permission)

Sharkey and McKay50 reported a patient who had repeatedly negative ELISA test results. In a review of 383 Japanese patients with uveitis,51 55 had serum antibodies to T. canis, whereas 11 of 22 vitreous samples tested from these patients showed positive results. Interestingly, samples from eight patients had antibodies to T. canis in both serum and vitreous, but three had antibodies only in the vitreous. In another patient reported by Schneider and colleagues,52 results from serum were negative but results from the polymerase chain reaction (PCR) performed on the aqueous were positive. A possible confounding factor is a crossreactivity with T. cati. Sakai53 and coauthors reported the case of a patient presumed to have T. canis infestation but observed that the titer for the ELISA directed against the second larval stage of T. canis was minimal. An ELISA using antigens from adult canis and cati showed very high antibody levels to T. cati.

Magnaval and colleagues54 tested the value of Western blotting techniques against that of the standard ELISA. Using the same excretory/secretory antigens for both, results with the Western blotting technique correlated well with those for the ELISA technique. One advantage of the Western blotting technique was that banding patterns were such that problems of cross-reactivity with sera infected with other helminths were avoided.

A study of the aqueous or vitreous for local production of specific antibody or its cellular components has been done. Felberg and colleagues55 found higher anti-Toxocara titers in the aqueous of patients with ocular toxocariasis than in those for serum, which suggests that local production of the antibody was taking place. Cytologic examination of the aspirate in ocular toxocariasis should demonstrate eosinophils and not lymphocytes as in other types of uveitides. Further, one may see tumor cells in the aspirate from an eye with retinoblastoma.

Treatment

Several treatment approaches have been suggested for this disorder, which suggests perhaps that the results for each therapy remain unclear or unsatisfactory. The medical

Treatment

therapy for T. canis infestation centers on two very different approaches. The first is treatment with anthelmintic drugs such as thiabendazole or diethylcarbamazine, and the second is treatment with prednisone to reduce the secondary inflammatory response. Rubin and colleagues20 reported the use of systemic prednisone (40 mg/day) with thiabendazole (2 g daily for 5 days) which produced disappearance of the active larva 24 hours after the initiation of therapy but no change in the preand posttreatment visual acuity. Wilkinson and Welch56 reported that thiabendazole and prednisone given to different patients were not successful in treating the disorder.

It has been always believed that the live larva may not induce a significant inflammatory response, but that on death the inflammation may be considerable, with serious sequelae to the eye. If that is the case, it would not be clear how helpful the addition of anthelmintics is. In most published studies successful treatment included the use of corticosteroids simultaneously with the anthelmintic. The use of corticosteroids seems justified when dealing with a severe intraocular infection, whereas the treatment of patients with an anthelmintic drug (thiabendazole), if used, should be accompanied by steroids, and the patients need to be followed up by either a pediatrician or an internist. Evidence reported by Suzuki33 would suggest that mere movement of the larva through the retina induces an inflammatory response and justifies giving the anthelmintic. Dinning and colleagues57 proposed a threestep approach for the ocular manifestations of toxocariasis. Initially, local, periocular, and systemic steroids combined with surgery, if appropriate, is suggested. If this approach is not successful, thiabendazole (50 mg/kg/day) should be considered. Finally, if the eye disease is associated with VLM or a high antibody titer, local and systemic steroid therapy combined with thiabendazole or albendazole (800 mg twice daily for adults or 400 mg twice daily for children, for 10 days to 2 weeks)58 can be considered. In one study, Vermazol 300 mg was given for 1 week.59 One concern we had was with a young patient with ocular toxcariasis who had a very high serum titer. Would systemic therapy induce a general immune response, similar to what is seen in onchocercisis (Mazzoti reaction) or in some cases of syphilis (Herxheimer reaction)? Upon discussion with infectious disease experts the feeling was that such a reaction would not occur, and it did not when we treated the child.

Vitreous surgery has also been suggested as an effective method by which the secondary effects of toxocariasis can be managed. Indeed, there is one report of the organism being recovered by vitrectomy.59 Hagler and colleagues60 operated on 17 patients with retinal complications of this disorder; three of them had active infection at the time of surgery. The authors were able to reattach the retina in 12 of these patients, and in 15 a stabilization or improvement of visual acuity was obtained. Belmont and colleagues61also reported a favorable outcome in patients with ocular toxocariasis who underwent pars plana vitrectomy. Gonvers and colleagues62 reported the case of a 30-year-old patient with a traction detachment as a result of an inflammatory granuloma (see Fig. 16-5). The granuloma was removed in toto and showed a typical toxocariasis lesion. Results of the ELISA performed on the vitreous sample were strongly positive (see

223

Fig. 16-2). Maguire and colleagues63 performed a vitrectomy for vitreopapillary traction and extracted an intact T. canis organism. If the larva is visible and is at least 3 mm from the foveola, photocoagulation can be attempted to kill it.24 This may induce inflammation that will require prednisone therapy. Amin and associates64 reported an improvement in visual acuity in five of 10 eyes with Toxocara lesions having a traction retinal detachment needing repair, membrane removal, scleral buckle and fluid–gas exchange or silicone oil. Monshizadeh and colleagues65 reported a choroidal neovascular membrane as a complication of an inactive Toxocara lesion in a 17-year-old woman. The lesion was treated with a laser, and vision went from 20/40 to 20/20. Cryopexy was used to treat the patient with a vasoproliferative tumor secondary to the organism.27

Case 16-1

A 5-year-old boy was referred for examination after having failed a routine eye-screening examination in his

pediatrician’s office. According to his parents, he had no visual complaints and his behavior, physical examination performed by the pediatrician and a complete blood cell count with a differential were normal. Although the family had no pets, several neighbors owned dogs. The

visual acuity was 20/400 in the left eye, 20/20 in the right eye. There was a small-angle exotropia. The anterior segment was quiet. The intraocular pressure was normal. The lens was clear. The vitreous in the right eye had 1+ cells with trace haze. The vitreous of the left eye was quiet. In the macula of the right eye there was a gray-white subretinal granulomatous macular lesion, with preretinal gliosis

extending from the disk to the macula associated with retinal wrinkling. The left eye was normal. Results of the ELISA for

T. canis were positive, with a titer of 1 : 64, and the diagnosis of ocular toxocariasis was made. A course of systemic corticosteroids was started, but there was no improvement of visual acuity in the left eye, and the therapy was stopped. The posterior segment has remained unchanged for more than 3 years.

1.Calhoun FP. Intraocular lesion by the larva of ascaris. Arch Ophthalmol 1937;

18:963–970.

2.Wilder HC. Nematode endophthalmitis. Trans Am Acad Ophthalmol Otolaryngol 1950; 55: 99–109.

3.Nichols RL. The etiology of visceral larva migrans. I. Diagnostic morphology of infective second stage Toxocara larvae. J Parasitol 1956; 42: 349–362.

4.Molk R. Ocular toxocariasis: a review of the literature. Ann Ophthalmol 1983; 15: 216–231.

5.Kazacos KR. Visceral and ocular larva migrans. Semin Vet Med Surg (small animal) 1991; 6: 227–235.

6.Uga S. Prevalence of Toxocara eggs and number of faecal deposits from dogs and cats in sandpits of public parks in Japan. J Helminthol 1993; 67: 78–82.

7.Mok CH. Visceral larva migrans. Clin Pediatr 1968; 7: 565–573.

8.Schantz PM, Weis PE, Pollard ZF, et al. Risk factors for toxocaral ocular larva migrans: a case-control study. Am J Public Health 1980; 12: 1269–1272.

9.Good B, Holland CV, Taylor MR, et al. Ocular toxocariasis in schoolchildren. Clin Infect Dis 2004; 39(2): 173– 178.

10.Magnaval JF, Michault A, Calon N, et al. Epidemiology of human toxocariasis in La Reunion. Trans Roy

Soc Trop Med Hyg 1994; 88: 531–533.

11.Sakai R, Kawashima H, Shibui H, et al. Toxocaria cati-induced ocular toxocariasis. Arch Ophthalmol 1998;

116:1686–1687.

12.Brown DH. Ocular Toxocara canis. II. clinical review. J Pediatr Ophthalmol 1970; 7: 182–191.

13.Diallo JS, ed. Syndromes de larva migrans. Manifestations ophtalmologiques des parasitoses. 1985, Masson: Paris. 155–161.

14.Beerlandt N, Dralands L, Vanginderdeuren R, et al. Ocular toxocariasis in a 36 year old patient: a case report. Bull Soc Belge Ophtalmol 1995; 259: 177–181.

15.Yokoi K, Goto H, Sakai J, et al. Clinical features of ocular toxocariasis in Japan. Ocul Immunol Inflamm 2003; 11(4):

269–275.

16.Taylor MR. The epidemiology of ocular toxocariasis. J Helminthol 2001; 75: 109–118.

17.Benitez del Castillo JM, Herreros G, Guillen JL, et al. Bilateral ocular toxocariasis demonstrated by aqueous humor enzyme-linked immunosorbent assay. Am J Ophthalmol 1995; 119: 514–516.

18.Upadhyay M, Rai NC. Toxocara granuloma of the retina. Jpn J Ophthalmol 1980; 24: 278–281.

19.Stewart JM, Cubillan LD, Cunningham ET Jr. Prevalence, clinical features, and causes of vision loss among patients with ocular toxocariasis. Retina 2005; 25(8): 1005–1013.

20.Rubin ML, Kaufman HE, Tierney JP, et al. An intraretinal nematode. Trans Am Acad Ophthalmol Otolaryngol 1968; 72: 855–866.

21.Teyssot N, Cassoux N, Lehoang P, et al. Fuchs heterochromic cyclitis and ocular toxocariasis. Am J Ophthalmol 2005; 139(5): 915–916.

22.Bird AC, Smith JL, Curtin VT, Nematode optic neuritis. Am J Ophthalmol 1964; 69: 72–77.

23.Cox TA, Haskins GE, Gangitano JL, et al. Bilateral toxocara optic

neuropathy. J Clin Neuro Ophthalmol 1983; 3: 267–274.

24.Brown GC, Tasman WS. Retinal arterial obstruction in association with presumed Toxocara canis neuroretinitis. Ann Ophthalmol 1981; 13: 1385– 1387.

25.Karel I, Peleska M, Uhlíková M, et al. Larval migrans lentis. Ophthalmologia 1977; 174: 14–19.

26.Steahly LP, Mader T, Acute ocular toxocariasis in adults. J Ocul Ther Surg 1985; 4: 93–99.

27.Mori K, Ohta K, Murata T, Vasoproliferative tumors of the retina secondary to ocular toxocariasis. Can J Ophthalmol 2007; 42(5): 758–759.

28.Shields CL, Honavar S, Shields JA, et al. Vitrectomy in eyes with unsuspected retinoblastoma.

Ophthalmology 2000; 107: 2250–2255.

29.Shields JA. Ocular toxocariasis: a review. Surv Ophthalmol 1984; 28: 361–381.

30.Kennedy JJ, Defeo E. Ocular toxocariasis demonstrated by ultrasound. Ann Ophthalmol 1981; 13: 1357–1358.

31.Howard GM, Ellsworth RM. Differential diagnosis of retinoblastoma. Am J Ophthalmol 1965; 60: 610–616.

32.Wan WL, Cano MR, Pince KJ, et al. Echographic characteristics of ocular toxocariasis. Ophthalmology 1991; 98: 28–31.

33.Suzuki T, Joko T, Akao N, et al. Following the migration of a Toxocara larva in the retina by optical coherence tomography and fluorescein angiography. Jpn J Ophthalmol 2005; 49(2): 159–161.

34.Del Prete GF, De Carli M, Mastromauro C, et al. Purified protein derivative of

Mycobacterium tuberculosis and excretory-secretory antigen(s) of Toxocara canis expand in vitro human T cells with stable and opposite (type 1 T helper or type 2 T helper) profile of cytokine production. J Clin Invest 1991; 88: 346–350.

35.Werner JC, Ross RD, Green WR, et al. Pars plan vitrectomy and subretinal surgery for ocular toxocariasis. Arch Ophthalmol 1999; 117: 532–534.

36.Rockey JH, Donnelly JJ, Stromberg BE, et al. Immunopathology of Toxocara canis and Ascaris suum infections of the eye: the role of the eosinophil. Invest Ophthalmol Vis Sci 1979; 18: 1172–1184.

37.Rockey JH, John T, Donnelly JJ, et al. In vitro interaction of eosinophils from ascarid-infected eyes with Ascaris suum and Toxocara canis larvae. Invest Ophthalmol Vis Sci 1983; 24: 1346–1357.

38.Kayes SG. Human toxocariasis and the visceral larva migrans syndrome: correlative immunopathology. Chem Immunol 1997; 66: 99–124.

39.Carter KC. The use of 35S-labelled Toxocara canis to determine larval numbers in tissues. J Helminthol 1992;

66:279–287.

40.Cuellar C, Fenoy S, Aguila C, et al. Evaluation of chemotherapy in experimental toxocariasis by determination of specific immune complexes. J Helminthol 1990; 64: 279–289.

41.Fenoy S, Ollero MD, Guillén JL, et al. Animal models in ocular toxocariasis. J Helminthol 2001; 75: 119–124.

42.Ollero MD, Fenoy S, Cuéllar C, et al. Experimental toxocariosis in BALB/c mice: effect of the inoculation dose on brain and eye involvement. Acta Trop 2008; 105(2): 124–130.

43.el-Ganayni GA, Handousa AE. The effect of cyclosporin A (CSA) on murine visceral toxocariasis canis.

J Egypt Soc Parasitol 1992; 22: 487–494.

44.Glickman LT, Grieve RB, Lauria SS, et al. Serodiagnosis of ocular toxocariasis: a comparison of two antigens. J Clin Pathol 1985; 38: 103–107.

45.Gillespie SH, Bidwell D, Voller A, et al. Diagnosis of human toxocariasis by antigen capture enzyme linked immunosorbent assay. J Clin Pathol 1993; 46: 551–554.

46.Jacquier P, Gottstein B, Stingelin Y,

et al. Immunodiagnosis of toxocariasis in humans: evaluation of a new enzyme-linked immunosorbent assay kit. J Clin Microbiol 1991; 29: 1831–1835.

47.de Visser L, Rothova A, de Boer JH, et al. Diagnosis of ocular toxocariasis by establishing intraocular antibody production. Am J Ophthalmol 2008; 145(2): 369–374.

48.Albert DM, Marcus L. Ocular toxocariasis presenting as leukocoria in a patient with low ELISA titer to Toxocara canis. Ophthalmology 1981;

88:1302–1306.

49.Kieler RA. Toxocara canis endophthalmitis with low ELISA titer. Ann Ophthalmol 1983; 15: 447–449.

50.Sharkey JA, McKay PS. Ocular toxocariasis in a patient with repeatedly negative ELISA titre to Toxocara canis. Br J Ophthalmol 1993; 77: 253–

254.

51.Yoshida M, Shirao Y, Asai H, et al. A retrospective study of ocular toxocariasis in Japan: correlation with antibody prevalence and

ophthalmological findings of patients

225

61.Belmont JB, Irvine A, Benson W, et al. Vitrectomy in ocular toxocariasis. Arch Ophthalmol 1982; 100: 1912–1915.

62.Gonvers M, Mermoud A, Uffer S, et al. Ocular Toxocara canis in a 30-year-old adult. Klin Monatsbl Augenheilkd 1992; 200: 522–524.

63.Maguire AM, Green WR, Michels RG, et al. Recovery of intraocular Toxocara canis by pars plana vitrectomy.

Ophthalmology 1990; 97: 675–680.

64.Amin HI, McDonald HR, Han DP, et al. Vitrectomy update for macular traction in ocular toxocariasis. Retina 2000; 20: 80–85.

65.Monshizadeh R, Ashrafzadeh MT, Rumelt S. Choroidal neovascular membrane: A late complication of inactive Toxocara chorioretinitis. Retina 2000; 20: 219–220.