Ocular Toxocariasis

Toxocariasis is a zoonotic infection of global importance.^1,2 Transmission is typically fecal-oral and results from accidental exposure to food, water, or soil contaminated by either dog or, less commonly, cat roundworms – the helminths Toxocara canis and Toxocara cati, respectively. Infection is common and affects approximately 20% of the world’s population, with seroprevalence rates surpassing 80% in some tropical and subtropical regions in Africa³ and Asia.⁴

While many Toxocara infections are asymptomatic, moderate to severe systemic, neurologic, and/or ocular infections can occur. These are referred to respectively as visceral (VLM), neurologic (NVM), and ocular larva migrans (OLM; also known as ocular toxocariasis OT).^1,2 Three classic patterns or OT have been described, including posterior granuloma – typically submacular or peripapillary and with pronounced retinal striae or folds; peripheral granuloma, often with a vitreoretinal traction band extending toward the posterior pole; and severe, unilateral intermediate or panuveitis referred to as nematode or Toxocara endophthalmitis. Atypical presentations of OT also exist.^5–8 One metanalysis,⁹ three original articles,¹⁰⁻¹² and one letter¹⁰ in this issue of Ocular Immunology & Inflammation (OII) address aspects of the prevalence, presentation, treatment and outcome of OT.

Badri et al.⁹ performed a meta-analysis of five English language database listings (PubMed, Scopus, Science Direct, Web of Science, and Google Scholar) from January 1966 to December 2019 to explore the prevalence of OT in six recognized World Health Organization (WHO)-epidemiological regions. A total of 101 studies with 331,602 cases from 35 countries met the inclusion criteria. Overall, studies that utilized immunologic methods, such as serology for nematode-specific antibodies, showed a higher pooled prevalence than those where the diagnosis was based on ophthalmological examination (9%, 95% CI 6–12% vs 1%, 95% CI 1–2%), male subjects were identified slightly more often than female subjects (OR 1.44, 95% CI 0.94–2.20, nominal p < .01), and the diagnosis of OT was made most often in the second decade of life (7%, 95% CI 1–18%, nominal p < .01) vs roughly half that prevalence for other age groups, and regions of lower-middle class income (6%, 95% CI 2–12%, nominal p < .01). The pooled prevalence of OT in the African WHO-epidemiological region was highest at 10% (95% CI 7–13%), followed by the European region at 8% (95% CI 4–12%), the region of the Americas at 6% (95% CI 2–10%), the Eastern Mediterranean and Western Pacific regions at 3% each (95% CI 0–10% and 1–5%, respectively), and the South-East Asia Region at 1% (95% CI 0–3%). It should be noted, however, that only one study was available from Africa – specifically Sierra Leone (10%, 95% CI 7–13%). Other countries of high prevalence included Peru (39%, 95% CI0-99%) and Slovenia (39%, 95% CI17-36%). Pooled prevalences of near zero were identified in Ireland, Germany, Spain and Nepal, and slightly higher at about 1% in Turkey, Myanmar, and the Czech Republic. Identified risk factors for a higher pooled prevalence of OT included ownership of dogs or cats (18%, 95% CI 0–96%), contact with dogs (17%, 95% CI3-39%), consumption of raw or undercooked meat (12%, 95% CI 0–53%), and exposure to soil (6%, 95% CI 0–27%). The anatomic location of inflammation was described most often as intermediate (6%, 95% CI 1–15%), followed by anterior (3%, 95% CI 0–10%), posterior (2%, 95% CI 1–4%), and panuveitis (1%, 95% CI 0–1%). Granulomas, when described, were most often central (5%, 95% CI 3–7%), followed by peripheral (4%, 95% CI1-8%). The authors concluded that their findings were generally in agreement with those of global epidemiologic studies based on the analyses of anti-Toxocara seroprevalence. They also emphasized the importance of considering OT in endemic areas, and of good hygiene, limiting pet exposure to public places, such as playgrounds and parks, and of monitoring and treating dogs and cats for helminthic infections.

Martinez et al¹¹ retrospectively reviewed the epidemiologic and clinical characteristics, as well as treatment and outcome of 157 patients less than 13 years of age with OT seen in a tertiary referral center in Costa Rica between January 1998 and December 2018. All patients had unilateral disease, the mean age was 6.7 ± 2.8 years, 97 (61.8%) were male, 145 (92.4%) had positive serology for T. canis, and 79 (50.3%) had eosinophilia. The most common reasons for consultation included decreased vision (29.9%), strabismus (26.7%), leukocoria (19.7%) and red eye (17.8%). The vast majority of patients presented with vision between 20/200 and no light perception (NLP, 89.2%). Associated ocular complications included cataract (17.5%), posterior synechiae formation (9.7%), band keratopathy (3.9%), and hypopyon formation (1.3%). The posterior segment could not be visualized in 12.7% of affected eyes. In the remaining eyes, a peripheral granuloma was identified in 57 (54.2%), a posterior granuloma in 27 (25.8%), and no granuloma in 21 (20.0%). Eighty-eight (56.1%) had a retinal detachment (RD). Treatments were tailored to findings and included no therapy in 64 eyes (40.8%), use of prednisone in 32 eyes (20.4%), pars plana vitrectomy (PPV) alone in 23 eyes (14.6%), prednisone plus thiabendazole in 16 eyes (10.2%), cataract surgery in 9 eyes (5.7%), 5 eyes (3.2%) treated with thiabendazole alone, and 3 eyes (1.9%) treated with regional corticosteroids alone. Most eyes with RD failed to show functional improvement despite treatment. The authors concluded that OT is an important cause of moderate-to-severe vision loss in Costa Rica, and that RD, in particular, is a predictor of poor visual outcome.

Wang and Tao¹² retrospectively reviewed the clinical characteristics, pattern of inflammatory cytokines, ocular complications and predictors of recurrence of inflammation within 6 months of presentation and treatment in a cohort of 38 subjects with OT seen at a tertiary referral center in Beijing, China, between January 2016 and December 2018. All patients had unilateral disease. Twenty-eight patients with age-related cataract served as controls. Identified risk factors included exposure to dogs or cats (65.8%), exposure to soil (36.8%), and eating raw or undercooked meat (34.2%). Twenty-three (60.5%) subjects were male, 26 (68.4%) were less than 10 years of age (range 5–48 years; mean 14.3 ± 13.7 years). Thirty-five affected eyes (92.1%) had vision loss at presentation (range NLP to 0.5 [Snellen 20/40]), with 22 (57.9%) having severe vision loss (≤0.1 [Snellen 20/200]). Active intraocular inflammation was observed in 36 eyes (94.7%), and was most often intermediate in location (68.4%). Ocular complications included cataract (50.0%), RD (10.5%), epiretinal membrane formation (5.3%), and macular hole formation (2.6%). In eyes with OT, 24/32 (75.0%) tested had anti-T. canis IgG antibodies in the aqueous humor, 23/26 (88.5%) had anti-T. canis IgG antibodies in the vitreous, and elevated levels of vascular endothelial growth factor (VEGF, nominal p = .012), and of IL-6, IL-8, and IL-10 (nominal p < .001). Treatment was tailored to the findings in each patient, but could include albendazole, topical and/or regional corticosteroids, and/or PPV for eyes with RD or severe vitreous opacity. Both anterior chamber inflammation (nominal p = .036) and best-corrected visual acuity (nominal p = .003) improved after treatment. Inflammation recurred within six months in 14 eyes (36.8%). Multivariate logistic region found that both severity of anterior chamber inflammation at presentation (p = .008) and duration of inflammation (p = .025) were associated with increased likelihood of recurrent inflammation, whereas regional triamcinolone acetonide (TA) injection at the time of PPV was associated with decreased risk of recurrence (p = .031). The authors recommended prompt and aggressive management of OT in eyes with moderate to severe, active inflammation, including consideration of albendazole, corticosteroids, and PPV as indicated. When PPV is employed, they recommended regional TA unless otherwise contraindicated.

Hernanz et al¹³ described five eyes of five patients seen at a tertiary referral clinic in Barcelona, Spain, in whom ultrawide-field (UWF) pseudocolor and fundus autofluorescence (FAF) imaging and spectral domain-optical coherence tomography (SD-OCT) aided in the diagnosis of OT. Three of the five patients were male with a median age of 32.6 years (range 16–56 years). No active inflammation was observed in four of the five eyes. Two patients had positive serum anti-Toxocara antibodies, and one of these had mild eosinophilia. Two of the three patients without serologic evidence of toxocariasis had a characteristic peripheral granuloma. A third peripheral granuloma was noted in one of the two patients with positive anti-T. canis antibodies. The authors identified a vitelliform spot at the fovea clinically, localized it to the vitreoretinal interface on SD-OCT in two eyes and suggested that such spots might represent the sight were a Toxocara nematode might pass through the retina as it enters the vitreous. The authors suggested that UWF pseudocolor and FAF imaging together with SD-OCT might aid in diagnosis of OT, particularly when suggestive findings are identified in the absence of serologic support.

Or et al.¹⁰ reported a case of unilateral exotropia in a 5-week-old infant who was found to have dense vitritis, a posterior granuloma, retinal striae, and serum anti-T. canis antibodies – all supportive of congenital OT. The authors concluded that vertical transmission of Toxocara from the mother to the fetus can occur rarely and cited both animal studies¹⁴ and a previous case report¹⁵ in support of their assertion.

Together, these studies highlight the continued importance of OT, particularly in regions of high seroprevalence. Children, teenagers and young adults are most often affected, with both ocular complications and permanent, vision loss occurring in a high proportion of patients. The diagnosis of OT is usually suggested by characteristic clinical changes, including identification of the posterior or peripheral granuloma, or acute onset of a moderate to severe, unilateral, intermediate or panuveitis. Laboratory support can come from the identification of anti-Toxocara antibodies and/or eosinophilia in the serum or ocular fluids, although false negative rates for both are high. Treatment needs to be tailored to the individual patient and presentation, but can include systemic and regional corticosteroids, anti-helminthic agents such as abendazole or thiobendazole, and PPV as indicated.

Acknowledgments

The authors have no relevant financial conflicts.