The vast majority of acquired toxoplasma infections in immunocompetent hosts are subclinical and asymptomatic [4]. In some cases, lymphadenopathy may be the only presenting symptom [5]. However, ocular toxoplasmosis may be seen even in immunocompetent hosts and is caused by reactivation of the parasite after an initial self-resolving infection of the retina [6]. This is characterized by a chorioretinitis with a predilection for the posterior pole and presents with blurry vision and eye pain that may progress to blindness if involving the macula or region near the optic nerve. Importantly, ocular toxoplasmosis can be due to reactivation of a congenitally acquired infection as well as an acute acquired infection as an adult [7]. There is a documented lag time of several years from initial infection to ocular manifestation [8]. Presentation is typically unilateral when the infection is acquired as an adult, but can be bilateral if the infection was acquired congenitally or in early childhood.

When the host is immunocompromised, reactivation of the latent parasite or acute infection is more systemic and severe. In patients with HIV, toxoplasmosis becomes a real concern when the CD4 count drops below 100 cells/microliter [9]. Cases of ocular toxoplasmosis have also been reported in organ or bone marrow transplantation patients on chronic immunosuppressive regimens [10–12]. The symptoms and signs of ocular toxoplasmosis in immunosuppressed patients include decreased vision and eye pain. However, the eye disease may be more severe, especially in elderly patients [13]. While bilateral disease is overall rare, there have been multiple reports of bilateral involvement in immunocompromised patients [10–12].

Cerebral involvement characterized by brain abscesses is the most common manifestation of toxoplasmosis in the immunocompromised patient and induces symptoms including headache, confusion, fever, focal neurological deficits, and seizures [9]. In one study, 50 % of patients with cerebral toxoplasmosis also had ocular toxoplasmosis, and 63 % of patients with ocular toxoplasmosis also had cerebral lesions [14]. Pneumonitis also occurs commonly presenting with nonproductive cough and dyspnea [15]. Toxoplasma may also affect other organs, including the liver, heart, musculoskeletal system, and the gastrointestinal tract. Widely disseminated toxoplasmosis has also been reported to lead to septic shock [14].

Congenital toxoplasmosis occurs when the mother becomes infected with the parasite during pregnancy, and the infection is passed to the fetus via the placenta. The mother can be either asymptomatic or can develop a “mononucleosis like” syndrome. Transmission by breastfeeding has not been demonstrated. Fetal infection in the first trimester has been associated with increased severity of disease [16], and can lead to still birth or result in central nervous system involvement, such as intracranial calcification and hydrocephalous. Most cases of congenital toxoplasmosis are actually subclinical, but even in this subset, retinal scars are often present, and recurrent reactivation of the parasite may occur later in life [17]. When infection is symptomatic, disease usually occurs in the neonatal period and first few months of life. The eye is involved in approximately 85 % of cases [18], with bilateral disease occurring in a majority of cases with ocular involvement, with reports ranging from 65 to 85 % [19–21]. In addition to chorioretinitis, other findings such as retinal detachment, nystagmus, microphthalmia, strabismus, and cataract have been reported [20].

Extraocular manifestations of congenital toxoplasmosis include hydrocephalus, intracranial calcifications, seizures, jaundice, lymphadenopathy, hepatosplenomegaly, pneumonitis, and fever. However, the classic triad of chorioretinitis, hydrocephalus, and intracranial calcifications occurs in fewer than 10 % of clinically apparent infections [22].

The typical presentation of an acute episode of ocular toxoplasmosis in immunocompetent patients is unilateral chorioretinitis characterized by a focal necrotizing fluffy whitish lesion in the retina with surrounding edema (Figs. 14.2 and 14.6). The degree of vitritis can be severe enough to be described as a “headlight in the fog” via indirect ophthalmoscopy. The retina is the primary site of inflammation which may spread to the choroid and sclera. Over the course of 2–4 months in immunocompetent patients, this lesion results in scar formation. These scars are often variably pigmented with an area of central atrophy where the sclera is often visible (Fig. 14.3).

Often, the disease recurs at the outer regions of old retinal scars, known as “satellite” lesions (Fig. 14.4). These active lesions are frequently adjacent to old scars, suggesting previous infection, either acquired or congenital infection. Vitreous inflammation may be present as well, and can be either localized or diffuse. In severe cases, the view of the underlying retina may be obscured, and the inflammation can even spread to the anterior segment. In as many as 30 % of cases, the intraocular pressure may be elevated [23]. Other conditions can have similar ocular manifestations to toxoplasmosis and should be considered [24] (see Table 14.1).

Immunocompromised patients (especially HIV-positive patients with CD4 count below 100 cells/microliter, patients on chronic immunosuppression or corticosteroids, and elderly patients) can have more severe presentations of ocular toxoplasmosis. The areas of retinal necrosis are often more extensive, multifocal, and present bilaterally. In some cases, the presentation can appear similar to acute retinal necrosis. In immunocompromised patients, the disease is more aggressive, and complications including retinal detachment, endophthalmitis, and even orbital cellulitis may occur without prompt treatment [25].

In less typical cases, ocular toxoplasmosis presents as punctate outer retinal lesions. These are characterized by multiple gray-white lesions that are associated with little to no vitreous inflammation [26]. This is because the inflammation involves deeper layers of the retina and the retinal pigment epithelium as has been demonstrated by optical coherence tomography (OCT) [27], although early one the inner retina is affected (Fig. 14.6).

Other atypical presentations of ocular toxoplasmosis include neuroretinitis characterized by optic nerve edema and a macular stellate exudate, typically presenting with rapid loss of vision. Retinal vasculitis is a common finding (see Figs. 14.5 and 14.6), typically affecting vessels in the same quadrant as the chorioretinitis, manifesting as sheathing of the vessels. Rarely, this can lead to vascular occlusion and subsequent infarction of the retina [28]. Retinal and subretinal neovascularization have also been observed as a result of retinal vasculitis in ocular toxoplasmosis. Retinal detachment, usually rhegmatogenous or tractional, may occur in approximately 5 % of cases [29]. Scleritis has been described as a manifestation of ocular toxoplasmosis but is quite rare [30].

The typical whitish retinal lesions seen in adults are also seen in children with congenital toxoplasmosis. However, the more typical finding on fundoscopy is a wagon wheel-shaped scar in the retina [20]. It is comprised of a central area of variable pigmentation surrounded by a ring of pigment. These lesions commonly involve the macula. Other ocular manifestations of congenital toxoplasmosis include cataract, nystagmus, strabismus, and microphthalmia [20]. In a recent largest observational series of infected newborns from France showed that of 2361 suspected consecutive pregnancies, 485 live-born children were infected and 30 % of them developed ocular manifestation over the follow-up time (median 10.5 years of follow-up). Seventy percent of the children had only one eye affected and 80 % of those lesions caused no vision loss. The initial lesion was detected during the first 2 weeks of life in only 5 % and overall detection of first lesion occurred at a median age of 4.2 years (range: 35 days to 20.7 years). Incidence of retinochoroiditis increased steadily over time with a cumulative estimated probability at 18 years of close to 50 % [31]. There are other potential infectious conditions that can mimic congenital toxoplasmosis which should also be excluded (see Table 14.2).

The diagnosis of ocular toxoplasmosis is most often made by clinical findings based on the characteristic focal necrotizing chorioretinitis with or without accompanying retinal scars and other sequelae such as vitritis, neuroretinitis, retinal vasculitis, and anterior segment inflammation [24].

Serology can be supportive in making the diagnosis but as seropositivity rates in the general population are high (approximately 25 % of the patients in the United States are seropositive [32]), the presence of positive IgG antibody testing may not necessarily be diagnostic. Conversely, the absence of IgG antibodies can effectively exclude the disease even in immunocompromised patients [33]. In addition, low IgG avidity suggests primary infection while high IgG avidity suggests reactivation [34]. Seropositivity for immunoglobulin M (IgM) supports primary infection [35].

In atypical or uncertain cases, additional tests on ocular fluids may be performed to further support the diagnosis. In these cases, sampling of the aqueous humor can be helpful. The presence of anti-toxoplasma IgG antibodies in the aqueous humor supports active infection. Furthermore, the Goldmann-Witmer (GW) coefficient can be used to increase both sensitivity and specificity [36]. This metric is the ratio of intraocular anti-toxoplasma IgG to total intraocular IgG and serum anti-toxoplasma IgG to total serum IgG. A high coefficient of 3 or greater suggests active ocular infection [37, 38].

More recently, polymerase chain reaction (PCR) analysis of either the aqueous humor or vitreous humor can aid in the diagnosis, particularly in immunosuppressed patients where serology may be less sensitive. In addition, PCR has the advantage of requiring a smaller volume of fluid. PCR is highly specific and sensitivities vary from 15 to 100 % depending on the study [39]. Sampling from the vitreous humor as opposed to aqueous humor may increase sensitivity [39, 40]. If the diagnosis remains uncertain, a diagnostic para plans vitrectomy (PPV) with or without chorioretinal biopsy may be performed to obtain tissue for analysis [39].