Blurred vision and floaters. May have redness and photophobia. Pain depends on the severity of associated iridocyclitis.

(See Figure 12.9.1.)

Figure 12.9.1: Area of active toxoplasmosis retinochoroiditis adjacent to a pigmented scar.

Critical

New, unilateral “fluffy” white retinal lesion often associated with an old pigmented chorioretinal scar. There is a moderate to severe focal vitreous inflammatory reaction directly over the lesion, which may obscure the active lesion on dilated fundus examination, resulting in the “headlight-in-fog” sign. Scar may be absent in cases of newly acquired toxoplasmosis or in immunocompromised patients.

Other

• Anterior: Mild AC spillover may be present, with increased IOP in 10% to 20%.

• Posterior: Vitreous debris, optic disc swelling due to peripapillary lesions often with edema extending into the retina, neuroretinitis with/without macular star, optic neuritis with significant vitritis, retinal vasculitis, rarely retinal artery or vein occlusion in the area of the inflammation. Kyrieleis plaques are periarterial exudates, which may occur near the retinitis or elsewhere in the retina; IVFA typically does  not show vascular occlusion. Chorioretinal scars are occasionally found in the uninvolved eye. CME, retinal neovascularization and retinal detachment may also be present.

NOTE Toxoplasmosis can also develop in the deep retina (punctate outer retinal toxoplasmosis) with few to no vitreous cells present. More common in HIV-infected patients. See SPECIAL CONSIDERATION IN IMMUNOCOMPROMISED PATIENTS at the end of this section.

See 12.3, Posterior Uveitis, for a complete list. The following rarely may closely simulate toxoplasmosis.

• Syphilis (see 12.10, Syphilis) and TB.

• Toxocariasis: Usually affects children. Chorioretinal scars are not typically seen. See 12.4, Panuveitis and 8.1, Leukocoria.

• ARN. See 12.13, Acute Retinal Necrosis(see Table 12.12.1).

• PORN. See 12.13, Acute Retinal Necrosis(see Table 12.12.1).

NOTE Toxoplasmosis is the most common cause of posterior uveitis and accounts for approximately 90% of focal necrotizing retinitis. Infection can be congenital or acquired.

See 12.4, Panuveitis, for workup recommendations when the diagnosis is in doubt.

1. History: risk factors include handling or eating raw meat (e.g., venison), exposure to cats or especially kittens (sources of acquired infection), and hunters who dress their own game. Inquire about risk factors for HIV in atypical cases (e.g., multifocal retinitis). Water- and air-borne outbreaks of toxoplasmosis have been reported.

2. Complete ocular examination, including an IOP check and a dilated fundus examination.

3. Focused serologic testing based on history and examination:

   • Serum anti-Toxoplasma antibody titer to indicate remote (IgG) or recent (IgM) infection (usually not necessary). IgM is found approximately 2 weeks to 6 months after initial infection, after which only IgG remains positive.

     NOTE A negative toxoplasmosis serum antibody titer (IgG and IgM) makes the diagnosis of toxoplasmosis highly unlikely.

   • Treponemal test (syphilis EIA, FTA-ABS, TP-PA), followed by confirmatory nontreponemal test (RPR, VDRL). See 12.10, Syphilis.

   • Interferon gamma releasing assay (IGRA, QuantiFERON Gold) and/or PPD. Consider chest imaging (CXR or CT chest) to assess for signs of active or prior pulmonary disease.

     • In those at risk for TB (e.g., immigrants from high-risk areas such as India, HIV-positive patients), homeless patients, or prisoners.

     • If considering immunosuppressive therapy (especially biologics).

   • ACE, lysozyme, and chest imaging (CXR or CT chest).

4. PCR testing from aqueous or vitreous specimens for Toxoplasma gondii is more specific than serologic testing.

5. Ocular fluid for PCR testing for Toxoplasma DNA may be acquired through AC or vitreous taps or via diagnostic vitrectomy in equivocal cases. 

6. Consider HIV testing in atypical cases or high-risk patients. See below.

1. Treat elevated IOP with aqueous suppressants and treat intraocular inflammation with topical steroid (e.g., prednisolone acetate 1% q2h) with or without a topical cycloplegic (e.g., cyclopentolate 1% to 2% t.i.d.).

2. Mild peripheral retinochoroiditis.

   • Self-limited in immunocompetent patients, usually resolving in 4 to 8 weeks. May consider observation only for peripheral lesions.

3. Vision-threatening lesions (within the macula, 2 to 3 mm of the disc, or threatening a large retinal vessel) or lesions that are associated with severe vitritis causing decreased vision, or disease in an immunocompromised patient.

   • Classic first-line triple therapy (for 4 to 6 weeks):

     • Pyrimethamine, 200 mg p.o. load (or two 100 mg doses p.o. 12 hours apart), and then 25 to 50 mg p.o. daily. Do not give pyrimethamine to pregnant or breastfeeding women (use spiramycin 1 g p.o. t.i.d. for women who seroconvert in pregnancy).

     • Folinic acid 10 mg p.o. every other day (to minimize bone marrow toxicity of pyrimethamine).

     • Sulfadiazine 2 g p.o. load and then 1 g p.o. q.i.d. Expensive and difficult to obtain; trimethoprim/sulfamethoxazole 160 mg/800 mg twice daily may be substituted.

     • Prednisone may be added 20 to 60 mg p.o. daily beginning at least 24 hours after initiating antimicrobial therapy and tapered 10 days before stopping antibiotics. Periocular steroids should be avoided.

     NOTE Due to potential bone marrow suppression, a CBC must be obtained once per week while a patient is taking pyrimethamine. If the platelet count decreases below 100,000, then reduce the dosage of pyrimethamine and increase the folinic acid. Patients taking pyrimethamine should not take vitamins that contain folic acid. The medication should be given with meals to reduce anorexia.

   • Alternate regimens:

     • Clindamycin 150 to 450 mg p.o. t.i.d. to q.i.d. (maximum 1.8 g/d) may be used alone, with pyrimethamine as the alternative therapy (if the patient is sulfa allergic), or as an adjunct (quadruple therapy). Patients on clindamycin should be warned about pseudomembranous colitis, and the medication should be stopped if diarrhea develops.

     • Intravitreal injection of clindamycin (0.1 mg/0.1 mL) and dexamethasone (0.4 mg/0.1 mL) can be effective for macular-threatening cases, or when the patient is intolerant to systemic medication.

     • Atovaquone 750 mg p.o. q.i.d.

     • Trimethoprim/sulfamethoxazole (160 mg/800 mg) one tablet p.o. b.i.d.

     • Azithromycin loading dose 1 g (day 1) and then 250 to 500 mg daily. May be used alone or in combination with pyrimethamine (50 mg daily).

     • Spiramycin 400 mg p.o. t.i.d. may be considered in cases of pregnancy but must be obtained from the Centers for Disease Control and Prevention.

   NOTE Systemic steroids should only rarely be used in immunocompromised patients. Before systemic steroid use, evaluation of fasting blood sugar/hemoglobin A1c and studies to rule out TB are prudent.

4. Vitrectomy has been used for nonclearing dense vitritis or other vitreoretinal complications (e.g., retinal detachment).

5. Maintenance therapy (if the patient is immunosuppressed, e.g., HIV with CD4 count <100): Trimethoprim/sulfamethoxazole 160 mg/800 mg one tablet daily.

6. Prophylaxis: Trimethoprim/sulfamethoxazole 160 mg/800 mg every Monday, Wednesday, and Friday for 1 year has been shown to greatly reduce the risk of reactivation over a 6-year follow-up period.

Initially, every 3 to 7 days to ensure improvement, then every 1 to 4 weeks while on therapy. 

SPECIAL CONSIDERATION IN IMMUNOCOMPROMISED PATIENTS

Vitritis is usually much less prominent. Adjacent retinochoroidal scars may not be present. The lesions may be single or multifocal, discrete or diffuse, and unilateral or bilateral. CNS imaging is essential because of high association with CNS disease (e.g., toxoplasmic encephalitis in HIV patients). Diagnostic vitrectomy may be necessary because of the multiple simulating entities and the variability of laboratory diagnostic tests. Systemic steroids for ocular toxoplasmosis should be used very cautiously in patients with AIDS.