Purpose
To investigate clinical characteristics and treatment outcomes of proven ocular toxocariasis (OT) in adult patients.
Design
Retrospective, consecutive, interventional case series.
Methods
setting : Institutional. study population : Consecutive OT patients with positive serum serology and positive western blot (WB) on ocular sample. observation procedures : Clinical features, optical coherence tomography (OCT), and treatment outcomes. main outcome measures : Best-corrected visual acuity (BCVA) and OCT central foveal thickness (CFT).
Results
Fourteen patients were included between 2011 and 2013. Mean age at diagnosis was 45.6 years. Mean duration between the first symptoms and diagnosis was 15.1 months. Uveitis was unilateral in all cases and all patients displayed vitreous inflammation. The main baseline findings were presence of ≥1 peripheral granulomas (57.1%), vasculitis (57.1%), vitreoretinal traction (57.1%), and chronic macular edema (ME) (71.4%). Delayed diagnosis (>8 months) seemed to be associated with higher rate of ME. All patients received albendazole. Systemic (n = 5) and/or local corticosteroids (CS) (n = 7) were administered in case of ME and/or posterior segment inflammation. Vitrectomy was performed when vitreous inflammation was severe and persistent despite CS or in case of threatening traction or visually significant epimacular membrane (28.6%). Overall, this regimen allowed significant decrease of CFT ( P = .01). In the vitrectomy subgroup, mean BCVA increased ( P = .01) and CFT decreased ( P = .017).
Conclusion
While some features such as granuloma are typical signs of OT, atypical features can delay the diagnosis. In doubtful situations, WB on ocular samples seems to be more specific than serum antibodies alone. ME seems to be a common complication of longstanding OT in the adult.
Ocular toxocariasis (OT) is a parasitic infection of the eye that occurs after ingestion of food soiled by dog or cat feces containing the larvae of Toxocara canis and, more rarely, Toxocara cati . In children, presentation is with an acutely red eye usually associated with significant visual loss. In adults only a few cases of OT have been described, and their clinical presentation can be atypical and quite different from their juvenile counterparts. Indeed, granuloma is usually peripheral and might involve significant vitreoretinal traction, which may result in retinal detachment. Retinal fluorescein angiography (FA) can objectivize either active or atrophic retinal lesions with progressive staining and late leakage of dye. Ultrasound examination can show a solid mass that usually matches a granuloma associated with echogenic traction, adjacent choroidal thickening, or localized retinal detachment. However, there are a few situations in which atypical features (eg, isolated peripheral retinochoroiditis, endophthalmitis, subacute neuroretinitis, keratitis, conjunctivitis) can misguide the practitioner and delay the diagnosis, emphasizing the importance of ancillary confirmatory methods, especially in the adult.
Serum, aqueous humor, and vitreous screening for antibodies using enzyme-linked immunosorbent assay (ELISA) is probably the most commonly used method. However, this technique shows a non-negligible rate of cross-reactivity with other helminths. On the other hand, Western blot (WB) allows qualitative diagnosis on aqueous humor or vitreous and seems to be more specific than ELISA, which makes it useful especially in atypical cases. In addition, diagnosis on ocular samples seems to be more sensitive and specific than on serum samples alone.
There is no specific treatment protocol for OT. Previous studies showed the effectiveness of albendazole in combination with steroids. In case of retinal complications (including presence of vitreoretinal traction, retinal detachment, or epiretinal membrane), pars plana vitrectomy can be performed.
We describe a series of consecutive adult atypical cases of OT whose diagnosis was prospectively confirmed by WB analysis on ocular samples and serum serology, and investigate their clinical features and treatment outcomes.
Methods
Institutional review board approvals for retrospective chart reviews were obtained commensurate with the respective institutional requirements prior to the beginning of the study. Described research was approved by the Ethics Committee of the French Society of Ophthalmology and adhered to the tenets of the Declaration of Helsinki. Fully informed consent was obtained for all patients.
This was a hospital-based retrospective, interventional case series that reviewed the files of all consecutive patients with chronic uveitis that was clinically consistent with OT, and for whom diagnosis was confirmed by serum antibodies and WB analysis on aqueous and/or vitreous humor at a single tertiary center (Pitié Salpétrière Hospital, Paris) between June 1, 2011 and November 4, 2013. Data were recorded prospectively and analyzed retrospectively. For all patients, exhaustive investigations (including infectious serologies [eg, Human Immunodeficiency virus, Treponema pallidum particle agglutination assay, Venereal disease research laboratory, Herpes simplex virus 1 and 2, Varicella-zoster virus, Cytomegalovirus], pulmonary function tests, salivary glandular biopsy, targeted ancillary tests, and clinical examination by an internal medicine specialist) ruled out the main differential diagnoses (eg, ocular sarcoidosis, hypersensitivity to Mycobacterium tuberculosis , Behçet disease).
For each patient, demographic data including age, sex, ethnicity, and medical history were recorded. Clinical assessment including Snellen best-corrected visual acuity (BCVA), intraocular pressure (IOP), presence of anterior or posterior segment inflammation, optical coherence tomography (OCT) data including central foveal thickness (CFT), and FA and infracyanine green angiography (ICG-A) data were collected at baseline and final visit. All patients were clinically examined by the same uveitis specialist (C.F.). Anterior segment inflammation was objectively quantified using a Laser Cell Flare Meter analyzer (Kowa FC 1000; Kowa, Tokyo, Japan). Vitreous inflammatory reaction was clinically determined based on the SUN criteria. OCT analyses were performed using a Cirrus device (Carl Zeiss, Jena, Germany). FA and ICG-A were performed on a Topcon camera coupled to IMAGENet picture digitizing system (Topcon, Tokyo, Japan).
All patients underwent analysis of Toxocara antibodies on serum (ELISA) and aqueous humor material (WB on anterior chamber paracentesis) and for those who underwent vitrectomy, WB was additionally performed on vitreous samples (Toxocara Western Blot IgG; LDBIO Diagnostics, Lyon, France). The principle of WB for OT diagnosis was described in detail elsewhere. Briefly, Toxocara antigens are first obtained after in vitro culture and then separated by electrophoresis on a polyacrylamide gel, which allows obtaining multiple bands of various protein weights. Those are then electro-transferred on nitrocellulose and incubated with patients’ aqueous humor or vitreous samples. When the samples are immunized against Toxocara antigens, antigen-antibody reaction occurs at the level of the corresponding antigenic band. Secondary revelation is then made with secondary antibodies (anti-IgG). Up to 5 bands in the 24–35 kDa zone are specific to toxocariasis and OT’s diagnosis is considered to be positive in the presence of at least 2 bands in that zone. Ocular samples on anterior chamber fluid after paracentesis were also tested against toxoplasmosis and herpes (HSV1, HSV2, VZV, CMV) and were negative for all patients.
All patients received the same systemic antihelminthic regimen consisting of albendazole, 200 mg twice daily for 15 days. Additionally, when macular edema (ME) and/or posterior inflammatory reaction was present, they also received corticosteroid (CS) therapy: local CS (sub-Tenon or intravitreal injection of trimacinolone) and/or systemic CS treatment (methylprednisolone, 1 mg/kg with progressive tapering over 4–6 months). Similarly, vitrectomy was performed when posterior inflammation was chronically ≥2+ despite CS, or in the case of visually significant epiretinal membrane, threatening traction, or retinal detachment. In case of mild posterior inflammatory reaction (<1+) with no ME and preserved visual acuity, no anti-inflammatory treatment was administered.
Epidemiologic, clinical, OCT, and angiographic features at baseline and after treatment were described. Correlation between final visual outcome, baseline characteristics, and administered treatments was investigated.
Statistical analyses were performed using R 3.0.2 (2013; R Development Core Team, Vienna, Austria). Correlations were performed using Mann-Whitney and Fisher exact tests. P values < .05 were considered statistically significant.
Results
Demographic and Clinical Characteristics
Fourteen patients were included during the study period. Patients’ demographic and clinical characteristics are detailed in Table 1 .
| Mean ± SD; or N | Percentage | |
|---|---|---|
| Patient age (y) | 45.6 ± 14.8 | – |
| Sex ratio (female/male) | 0.75 | – |
| Mean disease duration at diagnosis (mo) | 15.1 ± 16.8 | – |
| Follow-up duration (mo) | 21.4 ± 13.3 | – |
| Clinical features at baseline | ||
| Intraocular inflammation | 14 | 100% |
| Panuveitis | 11 | 78.6% |
| Anterior uveitis | ||
| Anterior chamber inflammation | 7 | 50% |
| Hypopyon | 1 | 7.1% |
| Retrodescemetic precipitates | 10 | 71.4% |
| Granulomatous/nongranulomatous | 6/4 | 42.9%/28.6% |
| Iridolenticular synechiae | 2 | 14.3% |
| High IOP | 3 | 21.4% |
| Pupillary seclusion | 1 | 7.1% |
| Retinal granuloma (≥1) | 11 | 78.6% |
| Peripheral | 8 | 57.1% |
| Posterior pole | 3 | 21.4% |
| Vitreoretinal comorbidities | ||
| Retinal hemorrhage | 5 | 35.7% |
| Vasculitis | 8 | 57.1% |
| Vitreoretinal tractions | 8 | 57.1% |
| Retinal detachment | 1 | 7.1% |
| Macular edema | 10 | 71.4% |
| Cystoid/noncystoid | 7/3 | 50%/21.4% |
| Mean CFT (μm) | 402 ± 98.9 | |
| Epimacular membrane | 5 | 35.7% |
| FA and ICG-A features | ||
| Veinous vasculitis | 8 | 57.1% |
| Optic nerve swelling | 4 | 28.6% |
| Diagnostic markers | ||
| Positive WB a | 14 | 100% |
| Aqueous humor | 13 (of 14) | 92.9% |
| Vitreous | 5 (of 5) | 100% |
a WB was considered positive in the presence of ≥2 toxocariasis-specific bands.
Ocular Toxocariasis Diagnosis
For all patients, serum antibodies were positive for toxocariasis and ocular involvement was confirmed by WB analysis on ocular samples. WB analysis was performed in all cases on aqueous humor and came back positive for 13 of 14 patients (92.9%) and negative for 1 patient. For this patient, WB confirmed the diagnosis on vitreous material. When vitrectomy was performed, WB analysis was systematically performed and was positive in all cases (n = 5).
Ocular Findings at Baseline
Ocular findings at baseline are detailed in Tables 1 and 2 . All patients experienced a unilateral course and presented initially with acute symptoms. In addition, disease evolution was chronic for all participants. On FA, 8 patients displayed late macular leakage consistent with macular edema, with (n = 5) or without (n = 3) foveal cysts. Blood tests showed elevated eosinophil counts (mean 860 ± 70.3 eosinophils/mL, >500 in 5 cases).
| Baseline Value | Baseline Range | Value at 1-Year Follow-up | 1-Year Follow-up Range | P Value | |
|---|---|---|---|---|---|
| Best-corrected visual acuity, Snellen | 20/100 | 20/800 to 20/25 | 20/63 | 20/400 to 20/20 | .18 |
| Anterior chamber inflammation | |||||
| Flare (photons/ms) | 41.1 ± 60.94 | 2–223 | 14.4 ± 14.1 | 2–59.4 | .06 |
| Posterior chamber inflammation a | 1.7 ± 0.4 | 1–3 | 0.37 ± 0.4 | 0–1 | 7.4E-6 ∗ |
| Macular edema | 10 (71.4) | 1 (7.1) | .0004 ∗ | ||
| CFT (μm) | 402 ± 98.9 | 190–496 | 249.3 ± 36.4 | [187–310] | .01 ∗ |
| Active granuloma | 11 (78.6) | 0 (0) | 2E-5 ∗ | ||
| Epiretinal membrane | 5 (35.7) | 3 (21.4) | .4 | ||
| Vitreoretinal traction | 8 (57.1) | 3 (21.4) | .05 ∗ | ||
Ocular Findings and Clinical Course at 1-Year Follow-up
At 1-year follow-up, mean BCVA improved to an average of 20/63 (range, 20/400 to 20/20). Mean CFT was overall thinner than initially and mean anterior chamber and vitreous inflammation were lower than initially. Funduscopy revealed no remnant of active focal retinal lesions, hemorrhages, or vasculitis. Three patients had epiretinal membrane and/or nonthreatening vitreoretinal traction. On FA, there were no persistent signs of macular, optic nerve, or perivascular swelling. Patients’ clinical findings before and at the end of follow-up are detailed in Table 2 .
Table 3 shows treatment outcomes. All patients received the same antiparasitic medical treatment previous to any anti-inflammatory regimen (albendazole, as described previously). Only 4 patients with mild posterior inflammatory reaction and no macular edema did not receive CS. In this group, patients displayed good BCVA values at baseline that remained stable after albendazole therapy (BCVA 20/25 before and after albendazole treatment). On the other hand, all patients with initial macular edema and severe posterior inflammation (n = 10, 71.4%) received CS treatments: oral CS (1 mg/kg with progressive tapering over 4–6 months, n = 5) and/or single injection of local CS (n = 7) (sub-Tenon injection [delayed triamcinolone 40 mg, n = 6] or intravitreal injection [2 mg triamcinolone, n = 1]). The use of CS significantly decreased the degree of inflammation. In fact, in this group, mean anterior chamber inflammation was initially low (18.1 ± 23.18 photons/ms) and remained stable 1 year after treatment ( P = .34). Mean vitreous inflammatory reaction was overall lower than initially (mean values <0.5+ after treatment) ( P = 3.5E-5). Despite the resolution of inflammation, there was no statistically significant BCVA improvement in either subgroup with CS. However, visual improvement seemed to be overall better in the group with local CS vs systemic CS only. Besides, there seemed to be a significant decrease of CFT after local CS ( P = .01) vs systemic CS ( P = .25). Importantly, intravitreal corticosteroid injection (IVI) was complicated by elevated IOP in the only patient who received IVI. High IOP eventually stabilized after nonperforating sclerectomy. Five patients underwent pars plana vitrectomy for diagnostic reasons (n = 1) or as a result of visually significant epiretinal membrane and/or significant and persistent vitreous inflammation despite medical treatment (vitreous haze ≥2+ after at least 3 months of systemic ± local CS treatment) (n = 3), and/or when there was threatening vitreoretinal traction or as a result of a retinal detachment (n = 1). In the group undergoing vitrectomy for chronic recurrent inflammation (n = 4), mean BCVA was significantly increased from 20/100 to 20/32 ( P = .01). Besides, there was a significant decrease in CFT from 286 ± 24.2 μm before vitrectomy to 245 ± 12.3 μm after surgery ( P = .017). Additionally, no recurrence was detected after vitrectomy after a mean follow-up of 21.4 months.
