Toxoplasmosis

Toxoplasmosis is caused by Toxoplasma gondii, an obligate intracellular protozoan parasite capable of infecting essentially any warm-blooded animal, with domestic and wild cats as its only definitive host — the only species in which the parasite completes sexual reproduction and sheds environmentally resistant oocysts in feces.^[1] Three transmission routes account for the great majority of human infection: eating undercooked or cured meat containing tissue cysts (pork, lamb, and venison/wild game carry meaningfully higher risk than beef or poultry); ingesting oocyst-contaminated soil, unwashed produce, or untreated water; and direct or indirect contact with a cat's litter box or contaminated garden soil.^[1][2] A pharmacist's exposure-history questions — recent undercooked meat, gardening without gloves, a new or outdoor cat, an unchanged litter box — are frequently what actually points toward the diagnosis, since routine serologic screening is deliberately not universal in Canada (see Assessment & Diagnosis).

In an immunocompetent host, primary infection is asymptomatic in the large majority of cases and, when symptomatic, is typically a mild, self-limited illness that does not require antiparasitic treatment — a genuinely important, easily over-treated point covered fully in Choose Initial Treatment. This chapter is organized around four clinically distinct pictures that share one parasite and one diagnostic toolkit: the ordinary immunocompetent primary infection (usually no treatment needed); primary infection acquired during pregnancy, where the entire clinical significance shifts to the risk of congenital transmission and which is this chapter's counseling centerpiece; reactivation disease in an immunocompromised host, most classically toxoplasmic encephalitis in advanced HIV/AIDS; and ocular toxoplasmosis (chorioretinitis), a distinct presentation that can occur congenitally or be reactivated later in life. One more cross-cutting point worth flagging up front: acute toxoplasmosis can produce a clinical picture resembling infectious mononucleosis and is a recognized cause of a false-positive heterophile (monospot) screening test — see this platform's Infectious Mononucleosis chapter for that test's other limitations; a compatible exposure history in a mono-like presentation should prompt toxoplasma-specific serology rather than accepting a positive monospot at face value.

Four clinical pictures, one parasite

Parasite biology in brief — why reactivation and delayed ocular disease both happen

T. gondii exists in three forms relevant to this chapter: tachyzoites, the rapidly dividing form responsible for acute, active infection and tissue invasion; bradyzoites, a slow-dividing form contained within tissue cysts that establish a lifelong latent reservoir, preferentially in brain, retina, and skeletal/cardiac muscle; and sporozoites, contained within the oocysts shed only by cats. After primary infection, the initial tachyzoite phase is normally controlled by an intact cell-mediated immune response, and the parasite persists indefinitely as encysted bradyzoites rather than being fully eradicated. This single fact explains two of this chapter's four clinical pictures at once: reactivation encephalitis occurs when severe immunosuppression allows dormant brain cysts to reactivate into destructive tachyzoites, and a meaningful proportion of ocular disease represents local reactivation of a dormant retinal cyst — sometimes years to decades after an entirely unnoticed primary infection — rather than a new exposure.^[4][5]

Congenital toxoplasmosis — the clinical spectrum in the newborn

The classic teaching triad of congenital toxoplasmosis — chorioretinitis, hydrocephalus, and intracranial calcifications — is the exception, not the rule: the great majority of congenitally infected infants are subclinically infected and appear entirely normal at birth, with no obvious sign to prompt suspicion without deliberate testing.^[4] When present, clinical findings span a wide spectrum: chorioretinitis (the single most common manifestation, and one that can appear for the first time well into childhood or young adulthood even when the newborn exam was normal), hydrocephalus, intracranial calcifications, microcephaly, seizures, sensorineural hearing loss, hepatosplenomegaly, jaundice, thrombocytopenia, and, in the most severely affected infants infected very early in gestation, a combination approaching the full classic triad.^[4] This subclinical-at-birth pattern is the central reason confirmed or highly probable congenital infection is treated for an extended course regardless of how well the newborn looks (see Choose Initial Treatment and Special Populations), and why lifelong ophthalmologic follow-up matters even after an apparently uneventful neonatal course (see Monitoring & Follow-Up).

• Eating undercooked, rare, or cured/smoked meat — pork, lamb, and venison/other wild game carry meaningfully higher tissue-cyst risk than beef or poultry; tasting meat before it is fully cooked is a specific, common exposure worth asking about directly.^[1]
• Unwashed or unpeeled fruits and vegetables, and untreated or unfiltered water, that may be contaminated with oocyst-bearing soil.^[1]
• Gardening or handling soil/sand without gloves — outdoor soil and children's sandboxes can harbor oocysts from cat defecation.^[2]
• Cat litter box exposure, particularly changing litter without gloves and without prompt hand hygiene, and particularly for a cat that hunts or is fed raw/undercooked meat (see Non-Pharmacologic Treatment for the specific, reassuring detail about how briefly cats actually shed infectious oocysts).
• Unpasteurized dairy, particularly unpasteurized goat's milk.
• Immunocompromise — advanced HIV/AIDS (particularly CD4 <100 cells/mm³), solid organ or hematopoietic stem cell transplantation, and other significant iatrogenic immunosuppression are risk factors for reactivation disease rather than for acquiring new infection (see Special Populations).^[5]
• Solid organ transplantation with a seropositive donor into a seronegative recipient — a specific, well-recognized transmission route distinct from reactivation of the recipient's own latent infection, classically relevant for heart transplantation given tissue cysts in donor myocardium (see Special Populations).
• Occupational exposure — veterinary staff, abattoir/meat-processing workers, and laboratory personnel handling the organism.
• Blood transfusion and needlestick/laboratory accidents are recognized but uncommon transmission routes.

Serology — the diagnostic mainstay, with real interpretive limitations

Diagnosis in a non-pregnant, immunocompetent adult is rarely pursued at all, since treatment is usually not needed regardless of the result (see Choose Initial Treatment). When testing is indicated, IgG and IgM serology are the initial tests: IgG indicates past or current exposure and, once positive, generally remains positive for life; IgM appears early but has a well-documented, clinically important limitation — it can remain detectable for months to years after the acute infection has resolved, so a positive IgM alone does not reliably confirm a recent infection.^[2] This is the same limitation-of-a-single-test-in-isolation pattern this platform's Infectious Mononucleosis chapter describes for the heterophile test — a positive result needs interpretation in clinical context, not automatic acceptance.

IgG avidity testing is the specific tool used to resolve this ambiguity: antibody avidity (binding strength) starts low early after infection and matures to high avidity over roughly 3-5 months. A high-avidity result reliably excludes infection acquired in the preceding 3-5 months — genuinely useful for timing a pregnancy-relevant infection relative to conception or a specific trimester. A low-avidity result is less definitive: it is consistent with recent infection but does not prove it, since avidity maturation is variable and can remain low for longer than 5 months in a minority of patients — low avidity therefore requires correlation with the clinical picture and repeat testing rather than being treated as confirmatory on its own.

Canada's screening policy — deliberately not universal

Unlike some countries that perform routine monthly serologic screening throughout pregnancy, SOGC does not recommend routine universal toxoplasma screening for pregnant patients at low risk in Canada. Screening should be offered specifically to pregnant patients considered at risk for primary infection (a compatible exposure history, or symptoms suggestive of acute infection) and to patients who are immunosuppressed or HIV-positive, given their risk of reactivation disease.^[3] This is a genuinely important, easily assumed-otherwise point for pharmacist counseling: a pregnant patient without a specific risk factor should not automatically be offered — or expect — a toxoplasma screening test at every prenatal visit.

If acute infection is suspected (a compatible exposure history, symptoms, or an initial equivocal result), repeat serologic testing in 2-3 weeks, and consider starting spiramycin immediately rather than waiting for the repeat result if clinical suspicion is genuinely high — the treatment's purpose is to reduce placental transmission risk while the diagnosis is being confirmed, not only after it is certain (see Choose Initial Treatment).^[3]

Amniocentesis and fetal diagnosis

Amniocentesis for amniotic fluid PCR testing should be offered when maternal primary infection is diagnosed, when serologic testing cannot confirm or exclude acute infection, or in the presence of abnormal ultrasound findings suggestive of congenital infection (ventriculomegaly, intracranial calcifications, hepatosplenomegaly, ascites, or growth restriction).^[3] Timing matters specifically: amniocentesis should not be performed before 18 weeks' gestation, and should be performed no less than 4 weeks after the suspected acute maternal infection — both rules exist specifically to reduce the occurrence of false-negative results from testing too early in the window before fetal infection (if present) becomes PCR-detectable.^[3]

Ultrasound surveillance

Serial obstetric ultrasound is used to monitor for findings suggestive of congenital infection throughout a pregnancy with confirmed or suspected maternal infection, and factors into the amniocentesis decision above.^[3]

Newborn diagnosis

Maternal IgG crosses the placenta, so a positive IgG in a newborn reflects maternal antibody and is not diagnostic on its own; congenital infection is confirmed instead through IgM or IgA serology in the infant (which does not cross the placenta), PCR testing of placental tissue, cord blood, or cerebrospinal fluid, and a full evaluation — ophthalmologic exam and neuroimaging — of every exposed infant regardless of whether the newborn appears clinically well.^[4]

Immunocompromised host with neurologic symptoms

For suspected toxoplasmic encephalitis, contrast-enhanced brain MRI is preferred over CT for its greater sensitivity, classically showing multiple ring-enhancing lesions, often at the basal ganglia or corticomedullary junction, together with a positive toxoplasma IgG (reactivation disease in a seronegative patient is rare enough that a negative IgG should prompt reconsideration of the diagnosis).^[5] The key differential is primary CNS lymphoma, which can look similar radiographically; a genuinely useful diagnostic approach in a patient with a compatible presentation and imaging is a 10-14 day empiric treatment trial, with clinical and radiographic improvement supporting the toxoplasmosis diagnosis and reserving brain biopsy for patients who do not improve (see Treatment Failure/Next Step).^[5]

Ocular disease

Diagnosis of ocular toxoplasmosis is primarily clinical, made by dilated fundoscopic examination showing a focal necrotizing retinochoroiditis, often adjacent to an old pigmented chorioretinal scar from a prior episode, with overlying vitreous inflammation. Serology is supportive, not diagnostic on its own — a positive IgG is common in the general population and does not, by itself, confirm that a given retinal lesion is actively caused by toxoplasmosis; a false sense of diagnostic confirmation from serology alone is a genuine pitfall here (see Common Errors to Avoid).^[4]

• Avoid unnecessary antiparasitic treatment of an ordinary, self-limited primary infection in an immunocompetent, non-pregnant adult, where treatment adds risk without meaningful benefit.
• Reduce placental transmission risk in confirmed maternal infection during pregnancy through correctly timed spiramycin, switched to pyrimethamine-sulfadiazine-folinic acid once fetal infection is confirmed or highly likely.
• Deliver genuine, specific, actionable prevention counseling to pregnant and at-risk patients on food safety, produce handling, and cat litter box precautions — the highest-yield pharmacist contribution in this condition.
• Recognize and treat reactivation disease (toxoplasmic encephalitis) promptly in an immunocompromised host, and maintain appropriate primary and secondary prophylaxis in patients at ongoing risk.
• Preserve vision in ocular toxoplasmosis by identifying vision-threatening lesions early and combining antiparasitic therapy with adjunctive corticosteroids only when genuinely indicated and only after antiparasitic treatment has started.
• Use folinic acid (leucovorin), never plain folic acid, alongside every pyrimethamine-containing regimen.
• Ensure every congenitally exposed infant receives full diagnostic testing, extended treatment when infection is confirmed, and long-term ophthalmologic follow-up regardless of how the newborn appears clinically.

Prevention counseling — the highest-yield pharmacist contribution in this condition

• Cook meat thoroughly — to a safe internal temperature throughout (whole cuts of beef, veal, and lamb to at least 63°C/145°F with a 3-minute rest; ground meat to at least 71°C/160°F; poultry to at least 74°C/165°F) — and do not taste meat before it is fully cooked.^[1]
• Freezing meat reduces but does not reliably eliminate tissue-cyst risk — it is a useful adjunct, not a substitute for thorough cooking.^[1]
• Wash and, where practical, peel all fruits and vegetables before eating, cutting, or peeling, and wash hands, cutting boards, and utensils that contacted raw meat before they touch other food.^[1]
• Avoid unpasteurized dairy, particularly unpasteurized goat's milk.
• Cat litter box precautions — ideally, someone other than the pregnant or immunocompromised patient changes the litter box during pregnancy or significant immunosuppression. If that is not possible, wear disposable gloves, change the litter daily, and wash hands thoroughly immediately afterward. The daily-change detail is not arbitrary: oocysts shed in cat feces take roughly 1-5 days after being shed to sporulate and become infectious, so litter removed before that window has passed is not yet capable of transmitting infection.^[2]
• Wear gloves when gardening or handling outdoor soil or sand (including children's sandboxes), and wash hands afterward — outdoor soil can be contaminated with oocysts from any cat that has defecated in the area, not only an owned cat.^[2]
• Reassurance worth giving explicitly: a pregnant or immunocompromised patient does not need to give away or avoid petting a household cat — direct contact with the animal itself does not transmit infection; it is contact with feces (litter box, contaminated soil) that matters, and this distinction genuinely changes how counseling lands with an anxious, cat-owning patient.^[2]
• Cats shed infectious oocysts for only a relatively brief period — typically 1-3 weeks — following their own first exposure to the parasite, most often early in life; most adult cats, especially those kept exclusively indoors and not fed raw meat, are not actively shedding oocysts at any given time. Keeping cats indoors and feeding only commercial cat food (not raw or undercooked meat) reduces the cat's own infection risk and, by extension, the household's exposure risk.
• Avoid adopting or handling unfamiliar stray or new outdoor cats during pregnancy or significant immunosuppression, since a newly acquired cat is more likely to be in — or approaching — its own primary-infection shedding window.

Pregnancy — the counseling centerpiece of this chapter

Transmission risk rises with gestational age at maternal infection, while the severity of fetal disease when transmission does occur falls — a genuinely important, non-intuitive pattern that shapes everything else in this section. A peer-reviewed meta-analysis found vertical transmission rates of roughly 5% (first trimester), 13% (second trimester), and 32% (third trimester) of confirmed maternal infections, with an overall transmission rate around 20%.^[7] At the same time, when transmission does occur, disease is more severe with earlier gestational age at infection — first-trimester transmission, though the least likely to occur, carries the highest risk of severe congenital disease, while third-trimester transmission, though the most likely to occur, is more often subclinical or mild at birth.^[7][4] Confirmed maternal infection is also associated with meaningfully increased risk of miscarriage, fetal anomaly, and stillbirth compared with an uninfected pregnancy, independent of congenital transmission specifically.^[7]

Screening in Canada is risk-based, not universal — offered to patients with a specific exposure history or compatible symptoms, and to immunosuppressed or HIV-positive patients (see Assessment & Diagnosis).^[3] Prevention counseling (food safety, produce handling, cat litter box precautions — see Non-Pharmacologic Treatment) is therefore the single most broadly applicable intervention, since it reaches every pregnant patient rather than only those already flagged for screening.

Treatment follows a gestational-age- and fetal-infection-status-driven switch: spiramycin when maternal infection is confirmed before roughly 18 weeks and fetal infection is not yet confirmed, switching to pyrimethamine-sulfadiazine-folinic acid once fetal infection is confirmed or highly likely, or when maternal infection itself is acquired later in pregnancy (see Choose Initial Treatment). Delivery planning should involve maternal-fetal medicine and pediatrics jointly, particularly given the sulfadiazine-near-term bilirubin consideration noted in Choose Initial Treatment.

Reactivation disease in HIV/AIDS

Toxoplasma-seropositive patients with CD4 counts below 100 cells/mm³ are at meaningful risk of reactivation toxoplasmic encephalitis and should receive primary prophylaxis (see Choose Initial Treatment).^[5] Following successful acute treatment of confirmed encephalitis, secondary prophylaxis (maintenance therapy) at reduced doses is continued until sustained immune reconstitution — current guidance supports discontinuation once the patient has completed initial therapy, remains asymptomatic, and has maintained a CD4 count above 200 cells/mm³ for more than 6 months in response to antiretroviral therapy; restart if the CD4 count subsequently falls back below that threshold.^[5]

Solid organ and hematopoietic stem cell transplantation

A seropositive donor organ transplanted into a seronegative recipient is a specific, well-recognized transmission route distinct from reactivation of the recipient's own latent infection — classically relevant for heart transplantation, given tissue cysts that can be present in donor myocardium. Transplant centres typically use post-transplant prophylaxis (commonly sulfamethoxazole/trimethoprim) in this serologic-mismatch scenario per institutional protocol; hematopoietic stem cell transplant recipients with pre-transplant seropositivity are separately at risk of reactivation from their own latent infection during the period of post-transplant immunosuppression.

Congenital infection and long-term pediatric follow-up

Every infant with confirmed or strongly suspected congenital infection needs the extended treatment course described in Choose Initial Treatment and long-term ophthalmologic follow-up, since chorioretinitis from congenital infection can present for the first time years after an entirely normal newborn eye exam — this is not a one-time evaluation that can be considered complete after the neonatal period (see Monitoring & Follow-Up).^[4]

Renal and hepatic impairment

Ensure adequate hydration with sulfadiazine given its crystalluria risk, which is compounded by renal impairment or volume depletion; consult product-specific and institutional dosing guidance for pyrimethamine, sulfadiazine, clindamycin, and sulfamethoxazole/trimethoprim in significant renal or hepatic impairment rather than using standard doses unmodified.

Breastfeeding

Management decisions in a breastfeeding parent should involve obstetrics/infectious diseases given the specialized nature of these regimens; this is not a routine community-pharmacy breastfeeding-compatibility question to answer in isolation.

• Pregnancy: serial ultrasound surveillance through the remainder of pregnancy in confirmed or suspected maternal infection, coordinated with maternal-fetal medicine; reassess the treatment regimen (spiramycin vs. pyrimethamine-sulfadiazine-folinic acid) whenever new amniocentesis or ultrasound information becomes available (see Choose Initial Treatment).^[3]
• Every pyrimethamine-containing regimen: monitor CBC (looking specifically for megaloblastic anemia, leukopenia, and thrombocytopenia) at baseline and periodically through treatment, and increase folinic acid dosing (per specialist direction) if cytopenias develop rather than stopping folinic acid.
• Every sulfadiazine-containing regimen: encourage generous fluid intake and monitor for signs of crystalluria; watch for early signs of a sulfonamide hypersensitivity reaction (rash, fever, mucosal involvement).
• Toxoplasmic encephalitis: reassess clinically and radiographically at 10-14 days of acute treatment — improvement supports the diagnosis and continuation to complete a minimum 6-week acute course before transitioning to secondary prophylaxis (see Treatment Failure/Next Step for the alternative).^[5]
• Ocular disease: ophthalmology follow-up through and after treatment to confirm lesion inactivation/scarring and to monitor visual acuity and intraocular pressure (relevant with corticosteroid use).
• Congenitally infected infants: long-term, scheduled ophthalmologic follow-up well beyond the neonatal period and the treatment course itself, given the recognized risk of chorioretinitis presenting for the first time later in childhood or young adulthood; coordinate audiology and neurodevelopmental follow-up per pediatric infectious diseases direction.^[4]
• HIV: track CD4 count trend to guide both primary-prophylaxis initiation/discontinuation and secondary-prophylaxis discontinuation decisions (see Special Populations).^[5]

1. No clinical or radiographic improvement in suspected toxoplasmic encephalitis after 10-14 days of empiric treatment: reconsider the diagnosis rather than simply extending the same regimen — proceed to brain biopsy to evaluate for primary CNS lymphoma or another process, since the empiric-treatment-trial approach specifically depends on a genuine 10-14 day response check (see Assessment & Diagnosis).^[5]
2. Continued or progressive ocular inflammation/lesion growth on a standard oral regimen: escalate to ophthalmology for consideration of intravitreal clindamycin/dexamethasone or an alternate systemic regimen rather than simply prolonging an apparently ineffective course.^[6]
3. Persistent cytopenias despite folinic acid supplementation on a pyrimethamine-containing regimen: increase the folinic acid dose per specialist direction; hold pyrimethamine temporarily for severe cytopenia, with hematology input, rather than continuing unmodified.
4. New or worsening sulfonamide intolerance/allergy during pregnancy, congenital, or CNS treatment: switch to a clindamycin-based alternative regimen (with pyrimethamine and folinic acid retained) rather than continuing a poorly tolerated sulfa-based course (see Choose Initial Treatment).
5. Amniotic fluid PCR result pending or equivocal in a patient already started on spiramycin: continue spiramycin and reassess with repeat testing/ultrasound rather than switching to pyrimethamine-sulfadiazine-folinic acid prematurely on an unconfirmed result, or withholding treatment entirely while awaiting confirmation.
6. A newborn initially appears well but a parent/family later reports new visual symptoms in childhood or young adulthood, with a known or possible history of congenital exposure: refer for ophthalmologic evaluation for reactivation chorioretinitis rather than assuming a normal newborn exam ruled this out permanently (see Monitoring & Follow-Up).

• Prescribing plain folic acid instead of folinic acid (leucovorin) alongside a pyrimethamine-containing regimen — folic acid lacks the selective human-cell-only rescue effect and risks interfering with the regimen's antiparasitic activity (see the central teaching point in Choose Initial Treatment).
• Continuing spiramycin after fetal infection has been confirmed by amniotic fluid PCR or strongly suggested by abnormal ultrasound findings, instead of switching to pyrimethamine-sulfadiazine-folinic acid — spiramycin reduces placental transmission risk but does not reliably treat an already-infected fetus.
• Ordering (or expecting) universal toxoplasma serologic screening on every pregnant patient in Canada — SOGC specifically recommends a risk-based approach, not universal screening, for patients at low risk.^[3]
• Advising a pregnant or immunocompromised patient to give away or avoid a household cat — unnecessary; direct animal contact does not transmit infection, and litter box hygiene/food safety precautions are what actually matter (see Non-Pharmacologic Treatment).
• Treating a single positive IgM result as proof of recent, acute infection without avidity testing or a repeat titer — IgM can remain detectable for months to years after the acute infection has resolved.
• Missing toxoplasmic encephalitis in a patient with advanced HIV and new neurologic symptoms by not considering the diagnosis or not obtaining contrast-enhanced brain imaging promptly.
• Starting an oral corticosteroid for vision-threatening ocular chorioretinitis before, or at the same time as, antiparasitic therapy — this risks unchecked organism proliferation; the corticosteroid follows the antiparasitic regimen by roughly 3 days.^[6]
• Assuming an infant who appears normal at birth does not have congenital toxoplasmosis — the great majority of congenitally infected infants are subclinical at birth, which is exactly why confirmed/suspected congenital infection is treated for an extended course regardless of the newborn's appearance.^[4]
• Treating a positive toxoplasma IgG as proof that a specific retinal lesion currently being evaluated is actively caused by toxoplasmosis — IgG seropositivity is common in the general population and is supportive, not diagnostic, on its own.
• Discontinuing long-term ophthalmologic follow-up in a congenitally infected child after an apparently successful treatment course and a normal eye exam — reactivation chorioretinitis can present for the first time years later.

How to use this table: Doses are adult doses and require patient-specific confirmation (renal/hepatic function, weight, allergy history). Pediatric dosing is weight-based per the current product monograph unless stated. Drug pricing is intentionally omitted. Select any drug name to open its complete Pharmasist Drug Database page.

Immunocompetent Host — Supportive Care Only

Antiparasitic treatment is not usually needed for a self-limited primary infection in an immunocompetent, non-pregnant adult.

Pregnancy — Maternal Infection Confirmed, Fetal Infection Not Yet Confirmed

Started as soon as acute maternal infection is confirmed or strongly suspected, without waiting for a repeat serology result if suspicion is high.

Confirmed/Suspected Fetal Infection in Pregnancy, and Confirmed Congenital Infection in the Newborn

Replaces spiramycin once fetal infection is confirmed or highly likely, or when maternal infection itself was acquired at or after ~18 weeks' gestation; continued for an extended course (commonly 12 months) in a newborn with confirmed congenital infection, under pediatric infectious diseases direction.

Toxoplasmic Encephalitis — Advanced HIV/AIDS or Other Severe Immunosuppression

A minimum 6-week acute course, then transition to a lower-dose secondary prophylaxis (maintenance) regimen continued until sustained immune reconstitution.

Sulfa-Allergic or Intolerant Alternative — CNS or Ocular Disease

Substituted for sulfadiazine when a genuine sulfonamide allergy or intolerance is present; pyrimethamine and folinic acid are retained.

HIV — Primary Prophylaxis (Toxoplasma IgG-Positive, CD4 <100 cells/mm³)

Discontinue once CD4 count rises and is sustained above the threshold used for secondary-prophylaxis discontinuation, in coordination with the patient's HIV care team.

Ocular Chorioretinitis — Vision-Threatening Lesion

Classic triple therapy for a lesion involving or threatening the macula, optic nerve, or major retinal vessels, or with significant vitritis; a small peripheral lesion in an immunocompetent host with no vision threat may reasonably be observed instead.