Toxoplasmosis: Ocular disease

INTRODUCTION — Toxoplasmosis, an infection with a worldwide distribution, is caused by the intracellular protozoan parasite, Toxoplasma gondii. Immunocompetent persons with primary infection are usually asymptomatic. However, in some immunocompetent individuals, T. gondii infection can present as an acute systemic infection. Toxoplasmosis can also present as ocular disease (eg, posterior uveitis), presenting either in the context of recently acquired infection or reactivated disease. In some patients, posterior uveitis may be the only symptom of an acute T. gondii infection.

This topic will review the pathogenesis, clinical manifestations, diagnosis, and treatment of ocular toxoplasmosis. Discussions of acute systemic infection, as well as toxoplasmosis in special populations (individuals with HIV infection, pregnant women, neonates), are presented elsewhere. (See "Toxoplasmosis: Acute systemic disease" and "Toxoplasmosis in patients with HIV" and "Toxoplasmosis and pregnancy" and "Congenital toxoplasmosis: Clinical features and diagnosis".)

IMPORTANCE OF GENOTYPES — It is well established that T. gondii can be divided into different genotypes, which are prevalent in different geographic areas. The different genotypes differ in pathogenicity and can therefore impact the clinical presentation and clinical course of T. gondii infection [1].

The three main T. gondii genotypes are types I, II, and III. In Europe and the United States, where genotype II is prevalent, 80 to 90 percent of individuals who become infected are asymptomatic. This is in contrast to South and Central America, where genotype I and atypical strains predominate, resulting in a substantially increased severity of clinical disease. As an example, T. gondii infection in South and Central America is associated with much higher rates of posterior uveitis compared with other geographic areas. In Brazil, the seroprevalence of T. gondii has been reported to be as high as 80 percent; the prevalence of ocular toxoplasmosis ranges from 6 to almost 18 percent in immunocompetent individuals with T. gondii infection (depending upon the geographic area) and is seen in approximately 80 percent of children with congenital infection [2-10]. By contrast, ocular toxoplasmosis occurs in less than 2 percent of individuals infected with T. gondii in the United States [11].

CLINICAL MANIFESTATIONS

Scarring without evidence of active disease — Most patients with ocular disease due to toxoplasmosis in Europe and North America are asymptomatic. Such patients typically have scarring noted on routine examination without any history or evidence of active retinochoroiditis (picture 1). (See 'Inactive disease' below.)

Posterior uveitis — Patients with active ocular disease typically present with posterior uveitis. T. gondii is the most common pathogen to cause posterior uveitis in immunocompetent hosts. (See "Uveitis: Etiology, clinical manifestations, and diagnosis".)

In patients with posterior uveitis, the retina and choroid are the primary sites of inflammation, although secondary vitreal inflammation is typically the symptomatic finding that leads to consultation with an ophthalmologist.

Signs and symptoms — Posterior uveitis due to T. gondii typically begins within the retina and spreads into the choroid. Satellites may frequently be found in the area of an active lesion within the neuroretina, which is typical for ocular toxoplasmosis and helpful when differentiating toxoplasmosis from other causes of posterior uveitis. (See "Uveitis: Etiology, clinical manifestations, and diagnosis" and 'Differential diagnosis' below.)

Immunocompetent adults with ocular toxoplasmosis typically present with floaters and visual loss, which may be permanent if the lesion affects the macula. Floaters alone are often the presenting sign if the retinochoroidal lesion is not located within the central retina.

The severity of vitreous inflammation correlates with the parasite strain, parasite load, and the host immune response. Consequently, immunocompetent individuals with acquired disease typically develop more severe vitreal infiltration, whereas elderly and immunocompromised patients develop larger lesions with a less severe vitreal infiltration. These lesions are frequently atypical in their presentation, which leads to a higher risk of early misdiagnosis. (See 'Exam findings' below.)

Acute versus reactivated disease — Ocular toxoplasmosis can present either in the context of recently acquired infection or reactivated disease.

●Acute ocular disease – Acute ocular disease can be seen in all age groups. In some patients, posterior uveitis may be the only symptom of acute T. gondii infection. (See "Toxoplasmosis: Acute systemic disease".)

It is estimated that up to 2 percent of Toxoplasma-infected people in the United States develop retinochoroiditis associated with primary infection; however, in some patients, ocular findings may not be recognized in the acute phase but detected later as a retinal scar [12]. The risk of developing ocular disease is greater in patients from South and Central America. (See 'Importance of genotypes' above.)

In children with congenital toxoplasmosis, retinochoroiditis is the most common late manifestation, and patients can develop complications such as visual impairment, retinal detachment, choroidal neovascularization, and optic nerve head involvement [13]. A more detailed discussion of congenital toxoplasmosis is found elsewhere. (See "Congenital toxoplasmosis: Clinical features and diagnosis".)

●Reactivated disease – Patients with reactivated ocular disease (presence of old scars and an active lesion) typically have acquired their infection either in utero or postnatally. Immunocompetent patients with reactivation of their disease can present with bilateral involvement, unlike those with recent infection, who typically present with unilateral ocular disease [14].

Patients can present with reactivated disease at any age. Those who present with ocular toxoplasmosis when they are older than 40 years of age are at higher risk of recurrence than younger patients, and a relapsing and remitting course can develop after a prolonged disease-free interval [15].

In immunocompetent hosts, reactivation of toxoplasmosis almost always presents as retinochoroiditis. This is in contrast to immunocompromised hosts, who often present with central nervous system manifestations. (See "Toxoplasmosis in patients with HIV".)

Other manifestations — Isolated anterior uveitis has rarely been observed, whereas an anterior segment involvement with granulomatous corneal precipitates and a rise in intraocular pressure may be seen. Optic nerve head involvement and lesions close to the optic disc (Jensen disease) may be clinically less prominent, but result in substantial visual field defects. Similar to posterior uveitis, these manifestations can present during primary or reactivated disease.

DIAGNOSIS

Inactive disease — In typical cases of inactive ocular toxoplasmosis, the diagnosis is based upon characteristic clinical findings in combination with anti-Toxoplasma immunoglobulin G (IgG) antibodies. (See "Diagnostic testing for toxoplasmosis infection", section on 'Serologic testing'.)

The most frequent clinical finding is an inactive scar. Discrete neuroretinal satellites may also be seen, the presence of which supports the diagnosis. (See 'Scarring without evidence of active disease' above.)

If disease activity is absent, laboratory evaluation other than serologic testing to confirm past infection (if requested) is not needed. This is in contrast to active disease, in which combined analysis of blood and ocular fluid (aqueous humor) may be required to confirm the diagnosis. (See 'Serologic testing' below and 'Aqueous humor analysis' below.)

Active disease

When to suspect toxoplasmosis — Ocular toxoplasmosis should be suspected in a patient who presents with visual loss or vitreal floaters along with an inflammatory retinal or chorioretinal lesion. The diagnosis of ocular disease is typically suggested by findings on ophthalmologic examination and supported by serologic testing and/or aqueous humor analysis, as described below.

Exam findings — Findings on ophthalmologic examination usually include mild iritis and marked vitreous inflammation (white blood cells in the vitreous), accompanied by whitish retinal lesions representing retinochoroiditis (picture 2). However, retinochoroiditis may be masked by the dense vitreous inflammation.

Fluorescein angiography may be helpful for diagnosis in some cases with optic nerve head involvement or prominent vasculitis (picture 3), as well as for detection of a presumed secondary choroidal neovascularization.

Serologic testing — Testing for IgM and IgG antibodies using an enzyme-linked immunosorbent assay (ELISA) should be performed to support the diagnosis of ocular toxoplasmosis. In acute systemic infection, Toxoplasma-specific IgM antibodies usually appear within 7 to 10 days and can persist for a variable duration. Toxoplasma-specific IgG antibodies develop within approximately two weeks of primary infection, peak within approximately eight weeks, and generally persist for life. (See "Diagnostic testing for toxoplasmosis infection", section on 'Serologic testing'.)

●Acute infection – In patients who present with ocular disease in the setting of acute infection, IgG is almost always present. IgM may also be present; however, a negative IgM does not exclude the diagnosis, since ocular manifestations usually develop several months after the initial infection and IgM may no longer be present at that time.

●Reactivated disease – In patients with ocular lesions due to reactivation of a previous infection, IgM antibodies are usually not present, and IgG may range from detectable to increased. However, in immunocompromised patients, serology can be more difficult to interpret. Although a negative Toxoplasma-specific IgG makes the diagnosis of reactivated disease unlikely, rare cases of seronegative ocular disease have been reported, as illustrated in a patient with chronic lymphocytic leukemia who had polymerase chain reaction (PCR)-confirmed ocular toxoplasmosis despite repeatedly negative Toxoplasma IgG [16].

Although a positive IgG antibody test supports the diagnosis of ocular toxoplasmosis, it does not confirm the diagnosis, since IgG alone cannot distinguish active from past infection and posterior uveitis due to other causes can be seen in patients with a previous T. gondii infection. Thus, if the clinical exam findings are unclear, additional testing may be needed to establish the diagnosis. These tests include antibody testing of paired serum and aqueous humor samples to test for local antibody production, PCR testing of aqueous humor for T. gondii DNA, and, rarely, cytopathology from vitreal specimen. (See 'Aqueous humor analysis' below.)

Aqueous humor analysis — In patients with an atypical presentation and in those with disease involving the macula, aqueous humor analysis may be reasonable in conjunction with serum antibody testing. Aqueous humor analysis should include both multiplex and quantitative PCR, as well as antibody testing. Testing should be performed by laboratories with specific experience in the work-up of small volumes of aqueous humor and serum in parallel. The sensitivity and specificity of intraocular antibody detection have been reported to be 63 and 89 percent, respectively [17,18]. The sensitivity of PCR positivity ranges from 15 to 65 percent and depends in part upon the quality of ocular sampling [19,20].

Once testing is obtained, some laboratories calculate the Goldmann-Witmer coefficient, which can be used as a tool to compare the local versus systemic Toxoplasma-specific IgG. This index compares the relative proportion of Toxoplasma-specific IgG to total IgG in the aqueous humor and in the serum. A value of 2 or above is considered evidence of the intraocular synthesis of Toxoplasma-specific IgG in response to ongoing active disease.

The use of aqueous humor analysis was supported in a study that included 18 patients with suspected ocular toxoplasmosis, in which ocular toxoplasmosis was confirmed in 15 (83 percent) patients when serum antibody testing was combined with aqueous humor analysis (PCR and antibody testing determining the T. gondii-specific IgG ration between blood and aqueous humor) [17]. In another study that evaluated the use of aqueous humor analysis in 137 immunocompetent patients with posterior uveitis resulting from a suspected infectious etiology, 37 patients had positive results, and of those, 75 percent had evidence of Toxoplasma infection [21]. Most immunocompetent cases were diagnosed using measurements of intraocular antibody production. (See "Diagnostic testing for toxoplasmosis infection", section on 'Serologic testing'.)

Differential diagnosis — The differential diagnosis depends on the clinical picture and includes all diseases that can present as chorioretinitis or retinal necrosis. (See "Retinal vasculitis associated with systemic disorders and infections".)

This includes:

●Tuberculosis (see "Tuberculosis and the eye")

●Sarcoidosis (see "Overview of extrapulmonary manifestations of sarcoidosis", section on 'Ocular')

●Lyme disease (see "Clinical manifestations of Lyme disease in adults", section on 'Ocular manifestations')

●Syphilis (see "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in patients without HIV", section on 'Neurologic findings')

●Viral retinal necrosis (see "Epidemiology, clinical manifestations, and diagnosis of herpes zoster", section on 'Acute retinal necrosis' and "Epidemiology, clinical manifestations, and diagnosis of herpes simplex virus type 1 infection", section on 'Ocular manifestations' and "Epidemiology, clinical manifestations, and treatment of cytomegalovirus infection in immunocompetent adults", section on 'Ocular manifestations')

●Fungal chorioretinitis or endophthalmitis (see "Epidemiology, clinical manifestations, and diagnosis of fungal endophthalmitis")

●Autoimmune retinal disease (Behçet, lupus) (see "Clinical manifestations and diagnosis of Behçet syndrome", section on 'Ocular disease' and "Clinical manifestations and diagnosis of systemic lupus erythematosus in adults", section on 'Ophthalmologic involvement')

If diagnostic testing is not revealing, the diagnosis is sometimes made based upon the clinical response to treatment. (See 'Follow-up' below.)

TREATMENT — This section will focus on treatment of ocular toxoplasmosis in nonpregnant adults. Patients should be managed by an ophthalmologist experienced in the diagnosis and treatment of retinochoroiditis and uveitis. Special considerations in the management of pregnant women and children are discussed elsewhere. (See "Toxoplasmosis and pregnancy" and "Congenital toxoplasmosis: Treatment, outcome, and prevention".)

Antimicrobial therapy for ocular disease — Ocular toxoplasmosis is generally treated with oral therapy (eg, trimethoprim-sulfamethoxazole [TMP-SMX] or pyrimethamine plus sulfadiazine). The duration of therapy is typically six weeks but may be extended based upon the specific regimen and the clinical response. (See 'Treatment regimens' below and 'Follow-up' below and 'Duration of treatment' below.)

For certain patients (eg, those with severe vitreal infiltration, optic nerve head involvement, or retinal vasculitis), there may be a role for glucocorticoids in combination with antimicrobial therapy [22]. (See 'Adjunctive glucocorticoids' below.)

Indications — The decision to treat ocular toxoplasmosis is typically based upon the clinical presentation (eg, the severity of vision loss, the size and proximity of the lesion to the central retina, the host immune status).

●Most patients with inactive ocular toxoplasmosis, even if newly detected, do not require treatment or regular follow-up as long as they are asymptomatic. However, there are special considerations in children with congenital toxoplasmosis, which are presented in a separate topic review. (See "Congenital toxoplasmosis: Treatment, outcome, and prevention", section on 'Whom to treat'.)

In addition, some adults with scars who require immunosuppressive therapy may not warrant treatment but would benefit from prophylactic therapy to prevent recurrence. This should be determined on a case-by-case basis. Additional information on the use of prophylactic therapy is found below. (See 'Duration of treatment' below.)

●In patients with active ocular toxoplasmosis, we suggest antimicrobial therapy for those with ocular findings or conditions that put them at risk for developing site-threatening disease [23-25]. This includes:

•Lesions threatening the optic nerve or fovea (eg, a central lesion within the vessel arcades or close to the optic disc).

•Decreased visual acuity with or without suspected optic nerve involvement.

•Lesions associated with moderate to severe vitreous inflammation or retinal vasculitis.

•Atypical lesions and lesions greater than one disc diameter in size.

•A progressive or prolonged clinical course (persistence of disease for more than one month).

•The presence of multiple active lesions.

•Immunocompromised patients (eg, patients with HIV/AIDS; those receiving cancer chemotherapy, high-dose systemic corticosteroids, and/or other immunomodulatory therapy).

Treatment is also indicated for pregnant women with acquired disease. In such patients, the goal of treatment is also to prevent adverse outcomes in the fetus. (See "Toxoplasmosis and pregnancy", section on 'Approach to maternal treatment for reduction of congenital toxoplasmosis'.)

Although most cases of active ocular toxoplasmosis resolve spontaneously over the course of four to eight weeks, limited data suggest that systemic antimicrobial therapy (with or without glucocorticoids) may be associated with a reduction of the lesion size in active retinochoroiditis and faster visual recovery [26-31]. As an example, in a prospective multicenter study of 149 patients with ocular toxoplasmosis, patients with central lesions were treated with one of three different antimicrobial regimens in combination with glucocorticoids, whereas those with peripheral lesions did not receive systemic therapy [27]. Approximately half of the 35 patients treated with a pyrimethamine-containing regimen had a reduction in the size of the retinal inflammatory lesion compared with 20 percent (8 of 41) who did not receive systemic therapy.

The use of antimicrobial therapy may also be associated with a reduced risk of recurrent disease [29,32,33]. In a meta-analysis that included data from three randomized trials with a total of 227 patients, antimicrobial therapy reduced the risk of recurrent retinochoroiditis compared with placebo by approximately 75 percent (risk ratio 0.26, 95% CI 0.11-0.63) [29]. However, the absolute risk varied with the geographic setting; in countries where the risk of ocular disease was low (eg, the United States and Europe), the risk of recurrence decreased from 110 to 26 cases per 1000; by contrast, in areas where the risk of ocular disease was high (eg, Brazil), the risk of recurrence decreased from 250 to 65 cases per 1000.

Indications for the use of adjunctive glucocorticoids are discussed below. (See 'Adjunctive glucocorticoids' below.)

Treatment regimens — Ocular toxoplasmosis is generally treated with oral therapy.

●Preferred regimens in nonpregnant adults – For nonpregnant adults who require treatment for ocular toxoplasmosis, we administer TMP-SMX (160 mg TMP/800 mg SMX twice daily in patients with normal renal function). Treatment should be administered for a minimum of six weeks. (See 'Duration of treatment' below.)

Another reasonable option is pyrimethamine plus sulfadiazine plus leucovorin (pyrimethamine [100 mg] plus sulfadiazine [3 g] given as a single loading dose on the first day of treatment; followed by pyrimethamine [25 mg daily] plus sulfadiazine [1 g three times daily] plus leucovorin [10 mg daily]).

Pyrimethamine plus sulfadiazine has traditionally been considered the treatment of choice for ocular toxoplasmosis since there is the most experience with this combination. However, experts are increasingly using TMP-SMX, as limited evidence suggests these regimens have comparable efficacy and there appear to be fewer side effects with TMP-SMX [34,35]. In addition, in some countries pyrimethamine can be expensive and difficult to obtain.

●Alternative regimens in nonpregnant adults – If a patient is intolerant to first-line regimens (eg, patients with a sulfonamide allergy), atovaquone (750 mg four times a day) in combination with pyrimethamine (100 mg loading dose followed by 25 mg daily) plus leucovorin (10 mg per day) for a minimum of six weeks can be used. Atovaquone can be given alone if pyrimethamine is not tolerated or not available; however, in this setting it is given for at least three months [36]. (See 'Duration of treatment' below.)

Azithromycin 500 mg daily, ideally in combination with pyrimethamine (100 mg loading dose followed by 25 mg daily) plus leucovorin (10 mg per day), is another option. This regimen appears to be effective, but resolution of findings is slower than with the pyrimethamine-sulfadiazine combination [37]. Treatment should be administered for a minimum of six weeks. (See 'Duration of treatment' below.)

Intravitreal clindamycin (1.0 mg/0.1 mL) with one or more injections administered over a period of six weeks can also be used. The number of injections is based upon disease activity on examination. We typically reserve this regimen for those who are intolerant to systemic treatment or as adjunctive treatment to systemic therapy if the lesion approaches the macula. This regimen may be associated with an increased risk of ocular complications (eg, retinal toxicity due to dosing or dilution errors, endophthalmitis) compared with systemic treatment, and it must be applied by a retina specialist [38-40]. In addition, toxoplasmosis is a systemic disease, and intravitreal therapy provides no benefit outside of the eye. Oral clindamycin is not routinely recommended to treat ocular infection because it does not readily pass the blood-ocular barrier and may thus not achieve sufficient intraocular drug concentrations.

If leucovorin (folinic acid) is included as a component of the regimen, it should not be replaced by folic acid. Folic acid counteracts the effect of pyrimethamine and can result in prolonged disease activity due to incomplete control of parasite proliferation.

Special considerations regarding antimicrobial therapy for pregnant women and children are discussed separately. (See "Toxoplasmosis and pregnancy" and "Congenital toxoplasmosis: Treatment, outcome, and prevention".)

Adjunctive glucocorticoids — We suggest glucocorticoids be given to patients with significant vitreous inflammation and retinal vasculitis in addition to antimicrobial therapy. We believe glucocorticoids help preserve vision and enhance visual recovery in this setting; however, there are no definitive data to support the efficacy of glucocorticoids or the best dosing regimen [41].

Our approach is as follows:

●Glucocorticoids should be initiated two to three days after antimicrobial therapy has been started. Glucocorticoid therapy is usually delayed to reduce parasite proliferation and thereby minimize the likelihood that glucocorticoids will exacerbate the infection. This approach has successfully been used in clinical trials evaluating different treatment regimens for ocular disease [34,42].

●The initial dose of prednisone is 40 mg, or approximately 0.5 mg/kg of body weight, once per day. After one week, the daily dose can be tapered depending upon the clearing of inflammatory changes. The dose is generally tapered over a few weeks, but it should be <10 mg per day once the systemic antibiotic regimen is stopped.

In select settings, if an intravitreal injection of clindamycin is used, intravitreal-injected dexamethasone (0.4 mg/0.1 mL) may be added rather than oral prednisone as an adjunctive glucocorticoid. However, the use of this approach must be determined on a case-by-case basis.

Systemic and, more importantly, intravitreal glucocorticoids must never be used without antibiotic coverage, as this may result in significant worsening (including blinding) and may reduce recurrence-free survival time [32]. Intravitreal glucocorticoids maintain immunosuppressive concentrations over at least six to eight weeks [43,44] and thus require an extended period of at least six to eight weeks of antiparasitic therapy in order to prevent retinal necrosis as a consequence of uncontrolled parasite proliferation [45].

Follow-up

●Ophthalmologic exams – Patients require regular ophthalmologic examinations to monitor the response to therapy and to determine the duration of treatment. (See 'Duration of treatment' below.)

The frequency of follow-up depends upon the proximity of the lesion to the central vision and the severity of vitreal infiltration. As an example, patients with central lesions are usually seen at least once weekly.

Untreated patients should be seen four and eight weeks after the diagnosis (unless symptoms worsen), since lesion scarring should be complete by then.

For most patients, regular visits are generally not necessary once a lesion has healed, since the risk of and time to recurrences are not predictable. However, we see those with macular disease every three months during the first year and every six to twelve months in the second year. Children with congenital ocular toxoplasmosis (even those with inactive disease) should also be followed on a regular basis for a period of time. (See "Congenital toxoplasmosis: Treatment, outcome, and prevention", section on 'Disease monitoring'.)

In cases that do not appear to be responding to treatment, the diagnosis should be confirmed (if not previously done) and other diagnoses should be excluded (see 'Diagnosis' above). If the diagnosis is confirmed, systemic therapy can be supplemented by intravitreal clindamycin. (See 'Antimicrobial therapy for ocular disease' above.)

●Monitoring toxicity of therapy – Patients should be monitored closely for toxicity to TMP-SMX- and pyrimethamine-containing regimens. Complete blood count, kidney function, and liver function tests should be obtained at baseline. These tests should be repeated weekly for the first two weeks, and then every two weeks thereafter [46]. Among those with ocular disease who require more prolonged treatment (more than six weeks), these parameters are monitored every four weeks until cessation of therapy.

Common side effects of pyrimethamine include rash, nausea, and bone marrow suppression. Higher doses of leucovorin, up to 50 to 100 mg daily, can be administered to manage hematologic abnormalities [47]. Sulfa-containing agents can lead to rash, fever, leukopenia, hepatitis, nausea, vomiting, diarrhea, crystalluria, and, rarely, more severe reactions such as Stevens-Johnson syndrome. Additional information can be found in the individual drug information topics within UpToDate.

Duration of treatment — Patients with ocular disease are usually treated for six weeks. Ocular findings that support treatment discontinuation include resolution of inflammation and retinitis. Lesion activity and cessation of vasculitis on fluorescein angiography are also useful to help determine if treatment can be stopped.

The ultimate duration also depends upon the specific regimen. Certain agents (eg, atovaquone monotherapy) require a longer course of treatment than others. In addition, in some settings, antimicrobial therapy may need to be extended if glucocorticoids are used. (See 'Treatment regimens' above and 'Adjunctive glucocorticoids' above.)

Some patients may benefit from a prophylactic regimen for a period of time after they complete their initial treatment course to prevent reactivation. This includes patients with:

●Infection with a virulent parasite strain (eg, those from South America) (see 'Importance of genotypes' above)

●A history of frequent recurrences within the last two years

●An increased risk of recurrence (immunocompromised patients, especially those with hematologic malignancies and advanced HIV infection)

Prophylactic therapy with TMP-SMX is administered as (160 mg TMP/800 mg SMX) every other day and is usually continued for a minimum of three months, depending on the medical situation and individual patient factors [26,48]. Prophylactic therapy with TMP-SMX has been found to reduce the risk of recurrent disease, but only as long as it is taken [48,49]; however, long-term prophylaxis is rarely given.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Toxoplasmosis".)

SUMMARY AND RECOMMENDATIONS

●Toxoplasmosis, an infection with a worldwide distribution, is caused by the intracellular protozoan parasite, Toxoplasma gondii. Immunocompetent persons with primary infection are usually asymptomatic. However, in some individuals, T. gondii infection presents as ocular disease. (See 'Introduction' above.)

●Patients with ocular infection can be asymptomatic and have evidence of inactive disease (eg, scarring) found on routine exam, or they can have signs and symptoms of active disease, typically posterior uveitis. Posterior uveitis can develop in the setting of recently acquired infection or reactivated disease. (See 'Clinical manifestations' above.)

●In patients with acute toxoplasmosis, the risk of developing symptomatic disease is related in part to which genotype is causing infection. As an example, in Europe and the United States, where genotype II is prevalent, 80 to 90 percent of individuals who become infected are asymptomatic. This is in contrast to South and Central America, where genotype I and atypical strains predominate and there are higher rates of symptomatic ocular disease. (See 'Importance of genotypes' above.)

●Posterior uveitis due to ocular toxoplasmosis should be suspected in a patient who presents with visual loss or vitreal floaters along with an inflammatory retinal or chorioretinal lesion. The diagnosis of active ocular disease is typically suggested by findings on ophthalmologic examination (eg, marked vitreous inflammation accompanied by whitish retinal lesions representing retinochoroiditis) and supported by serologic testing and/or aqueous humor analysis. (See 'Diagnosis' above.)

●Most patients with inactive ocular toxoplasmosis, even if newly detected, do not require treatment. (See 'Indications' above.)

●In patients with active ocular toxoplasmosis, we suggest antimicrobial therapy (with or without glucocorticoids) in those with ocular findings or conditions that put them at risk for developing site-threatening disease, as described above (Grade 2B). Although most cases of active ocular toxoplasmosis resolve spontaneously over the course of four to eight weeks, antimicrobial therapy may be associated with a reduction of the lesion size in active retinochoroiditis and faster visual recovery, as well as a reduction in the risk of recurrent infection. (See 'Indications' above.)

•For nonpregnant adults who require treatment, we prefer trimethoprim-sulfamethoxazole (TMP-SMX) rather than other regimens. Treatment with pyrimethamine plus sulfadiazine plus leucovorin is also reasonable and has traditionally been considered the treatment of choice for ocular toxoplasmosis. However, experts are increasingly using TMP-SMX, since limited evidence suggests these regimens have comparable efficacy and there appear to be fewer side effects with TMP-SMX. Alternative regimens (eg, for patients with a sulfonamide allergy) include atovaquone or azithromycin, ideally in combination with pyrimethamine and leucovorin, as well as intravitreal clindamycin. (See 'Treatment regimens' above.)

•In patients with significant vitreous inflammation and retinal vasculitis, we suggest adjunctive glucocorticoids two to three days after antimicrobial therapy has been started (Grade 2C). The rationale for using glucocorticoids is to help preserve vision. (See 'Adjunctive glucocorticoids' above.)

•Special considerations regarding treatment of pregnant women and children are discussed separately. (See "Toxoplasmosis and pregnancy" and "Congenital toxoplasmosis: Treatment, outcome, and prevention".)

●Antimicrobial treatment should be continued for a minimum of six weeks. The ultimate duration depends upon the choice of agent and the response to therapy. (See 'Follow-up' above and 'Duration of treatment' above.)

ACKNOWLEDGMENT — The authors and editors would like to recognize Michael Tolentino, MD, who contributed to previous versions of this topic review.