Description of the condition
Ocular toxoplasmosis (OT) is the most common cause of posterior uveitis, and is the result of an acquired or congenital infection by the parasite Toxoplasma gondii (T. gondii). Congenitally acquired OT results from vertical transmission from mother to child, and may become apparent at birth or later, depending on the severity and location of the retinochoroidal lesions and if there is CNS compromise. Postnatally acquired OT becomes apparent when symptoms associated with an active retinochoroidal lesion are present. The sources of infection are food and water contaminated with oocysts from feline stool, or meat contaminated by tisular cysts. Clinical manifestations associated with the two etiologies are frequently indistinguishable. Positive IgG and IgM antibodies are found in patients with postnatally acquired OT if the infection is recent.
The most common manifestation of ocular toxoplasmosis is toxoplasmic retinochoroiditis (TR) which is typically a unilateral, unifocal, retinochoroidal lesion, usually associated with vitritis [
1]. Even though the ocular signs of TR are highly suggestive of this disease, they may be mimicked by other infections [
2]. Furthermore, in some cases, the symptoms may be atypical [
3,
4], prompting the need to strengthen the evaluation by including biological diagnostic confirmation of OT [
5]. Granulomatous anterior chamber inflammation is frequent, and retinal vasculitis (usually arteriolitis) is present in about a third of patients [
1]. Visual acuity loss during acute TR results from vitritis or from involvement of the macula and the optic nerve. Visual loss may be permanent due to formation of a macular scar or optic atrophy. The scarring resulting from TR can be associated with severe visual field loss when it occurs in the macula or close to the optic disc [
1].
The prevalence of TR follows the same pattern as general toxoplasmosis—varying greatly between regions of a country—and an estimated 25–30% of the world population is infected [
6]. Low prevalences have been reported in southeastern Asia, North America, Northern Europe, and Sahelian countries of Africa (10–30%) [
3,
4]. Moderate prevalences (30–50%) have been reported in Central and Southern Europe, and higher prevalences have been reported in Latin America and tropical African countries [
7,
8].
OT in Europe and South America presents differently with respect to epidemiology, clinical manifestations, and immunology. Concerning epidemiology, OT is more common in South America, Central America, the Caribbean, and some parts of tropical Africa compared with Europe and North America, and it is very unusual in China. Ocular infection in South America is more severe than in other continents due to the existence of particularly virulent genotypes of the parasite [
9‐
12] and the characteristics of the disease also differ in diverse areas of the world [
13]. This variability yields significant consequences for therapeutic approaches [
14] (higher macular involvement, vitreous and anterior chamber inflammation, bilateral involvement, strabismus, and synechiae) [
5,
13].
Evaluation of cohorts of congenitally infected children showed that congenital toxoplasmosis was more frequently symptomatic in South America than in Europe (50–65% of the children developed ocular lesions) [
15,
16]. In Colombia, a South American country, the lethality rate in congenitally infected children with lack of prenatal therapy can be as high as 25% [
17].
Traditionally, antibiotics and corticosteroids have been the mainstay of pharmacologic therapy against
T.
gondii. Treatment is given to reduce the risk of permanent visual impairment (aiming to reduce the size of the retinochoroidal scar), the risk of recurrence, and the severity and duration of acute symptoms. Antibiotics are usually given for 6 to 8 weeks. Steroids are also sometimes used to decrease the severity of intraocular inflammation symptoms [
18]. The aim of the treatment of gestational toxoplasmosis is to prevent fetal infection [
19].
Antibiotics used for the treatment of TR have included trimethoprim-sulfamethoxazole, pyrimethamine, sulfadoxine, sulfadiazine, clindamycin, tetracyclines, clarithromycin, azithromycin, atovaquone, minocycline, spiramycin, rifabutin, trimetrexate, lincomycin, dapsone, sulfafurazole, ciprofloxacin, doxycycline, miokamycin, erythromycin, macrolide, sulfonamide, sulfamerazine, nifurtimox, methotrexate, alone or in combination [
18,
20‐
23].
Several drugs are used in the treatment of toxoplasmosis. They act primarily against tachyzoites, and do not affect encysted forms. The synergistic action of pyrimethamine and sulfonamides has been demonstrated to interfere with parasitic replication by means of inhibiting its folate pathway. Spyramicin, a macrolide, can be used for the treatment of pregnant women because it has not been shown to be teratogenic [
19]. However, in case of an established fetal infection (through ultrasonography amniocentesis), pyrimethamine and sulfadiazine plus folinic acid should be used after 18 weeks of gestation since pyrimethamine is potentially teratogenic [
24]. Other macrolides, notably azithromycin, are also effective. Clindamycin, a Lincomycin, inhibits
T.
gondii by an unknown mechanism that involves the parasite organelle apicoplast. Other drugs against
T.
gondii include Dapsone, Azithromycin, Minocycline, and Rifabutin. Combinations of drugs are thought to be more effective [
6,
19].
A key challenge is the development of a drug able to eliminate the cyst stage of the parasite, allowing it to effectively surpass host immuno-surveillance and drug pharmacodynamics. The ideal agent should be concentrated in the eye and should be able to effectively eliminate bradyzoites and tachyzoites as well as to penetrate cyst walls. It should also be well tolerated, causing no adverse effects [
6].