pragya rai rohilkhand medical college

1. OCULAR TOXOPLASMOSIS
PRAGYA RAI PG-2

2. • Definition: Ocular toxoplasmosis is a recurrent
retinochoroiditis.
• Caused by the organism Toxoplasma gondii,
and represents the most common cause
infectious posterior uveitis worldwide.

3. • Toxoplasmosis Represents the main cause of
infectious posterior uveitis worldwide and
may lead to visual threatening complications
including severe retinochoroidal scarring,
vitreous opacities, cataracts, glaucoma and
choroidal neovascularization.

4. ORGANISM AND LIFE CYCLE
• Intracellular parasites, capable of infecting
virtually any warm-blooded animal and
establishing life-long chronic infection.
• Domestic cat represents the archetypical definite
host for T. Gondii.
• Three forms
• Sporozoites
• Trachyzoite
• Bradyzoit (tissue cyst)

5. • Sporozoites contained within an oocyst and result from
sexual reproduction of the organisms with the intestinal
mucosa of cat.
• Bradyzoites are relatively inactive and are contained within
tissue cyst , commonly develop in brain , eye, heart ,
skeletal muscles and lymph nodes.
• The tachyzoite is the active proliferating form, present in
intermediate and definite hosts during acute infection.
• It is able to penetrate any nucleated cell and
circulate all over the body, leading to cell lysis, direct tissue
damage.

6. • Tachyzoites differentiate into bradyzoites,
forming tissue cysts.
• The definite host becomes infected by either
ingesting meat containing tissue
cysts/tachyzoites from intermediated hosts, or
by ingesting sporulated oocysts, present in the
soil and shed in the feces of another feline
host.

7. • These maturate in the soil into sporulated
oocysts, becoming infective after 1–21 days,
and persisting in the environment for up to 18
months.
• Transplacental transmission in recently
infected hosts, and more rarely laboratory
accidents and organ transplantation, are other
possible modes of infection.

8. Transmission
• Beef
• Undercooked lamb , pork, chicken
• Environment contaminated by feces of
infected cats family
• Organ transplantation
• Blood transfusion
• Water

9. EPIDEMIOLOGY
• United States antibodies to T. gondii are found
in nearly 20% of the human population.
• France, as well as in South America this rate
reaches up to 80%
• first trimester of pregnancy, rates of
transplacental infection are around 10–25%,
and progressively increase to reach 60–80% in
the third trimester.

10. • Congenital toxoplasmosis used to be blamed
for most cases of ocular toxoplasmosis.

11. pathology
• Histopathologically , active ocular toxoplasmosis
is manifest as a focal retinochoroiditis with
necrotizing granulomatous inflamation of the
retina ,choroid viterous and ant. uveal tract.
• Mononuclear inflamatory infiltrates are present.
• Disruption / migration of RPE is observed.
• Inflammatory process can extend to underlying
sclera.

13. Pathogenesis
• Depend upon a delicate balance b/w
hostimmunity and parasite virulence.
• Immunoimmaturity associated with congenital
toxoplasmosis clearly asst. with systemic and
ocular lesions .
• Some are related to disruption of
embryogenesis and fetogenesis.

14. • In immunocompetent patients with postnatal
infection , a small number of these individuals
develop ocular disease soon after
seroconversion.
• The local innate immune response driven by a
variety of cells including polymorphonuclear
leukocytes , macrophages , B/T lymphocytes
and NK cells.

15. • Other such as dendritic cells , also help to
trigger the adaptive immune response.
• The adaptive immune response is mainly
coordinated by CD4+T lymphocytes and
macrophages.
• CD8+t lymphocytes are also cytotoxic to
infected cells.

16. • Parasite virulence is also an important
determination of pathogenesis
• Type 1 are highly virulent
• Type 2 are the lest virulent
• Type 3 are also lest virulent

17. In Immunosuppressed
• Have both tachyzoites and tissue cysts in
areas of retinal necrosis and within retinal
pigment epithelial cells.
• Parasites can occasionally be found in the iris,
choroid, vitreous, and optic nerve

18. CLINICAL MANIFESTATIONS
• Systemic disease-Immunocompetent individuals with postnatally
acquired toxoplasmosis are frequently asymptomatic.
• Some develop fever, malaise and variable lymphadenopathy.
• Only a small number evolve to severe systemic disease, including
pneumonitis, hepatitis, myocarditis and even encephalitis.
• Immunocompromised individuals, especially those with AIDS , are
susceptible to life threatening disease .(neurotoxoplasmosis)

19. • Congenital toxoplasmosis is associated with a
large spectrum of systemic manifestations,
ranging from intrauterine death/severe
malformations to a neonatal infectious
syndrome including
anemia,thrombocytopenia, cutaneous rash,
hepatitis, pneumonitis, myocarditis and even
encephalitis.

20. Ocular presentation
Symptoms
• Floaters
• Reduced central vision
• Metamorphopsia
• photophobia
Sign (The hallmarks)
• Vitreous inflammation
• Anterior uveitis
• Retinal vasculitis is also
present (occationally)
• These active lesions
associated with more
severe vitreous haze can
typically display a
‘headlight-in-the-fog’
• Intraocular pressure is
elevated in 10–30% of these
cases.

21. necrotizing retinochoroiditis
Satellite lesion adjacent to old
hyperpigmented scars
The typical wagon-wheel scar in the
macula

22. Lipidic exudates (kyrieles
arteriolitis) Herpetic retinitis

23. • New or Acute lesion
– Intensely white
– Focal lesion overlying vitreous inflammatory haze
(head light in the fog)
– Acute anterior uveitis
• Healed lesion
– Border become more defined
– Hyperpigmented after several months
– Large scar will have atrophic center (devoid of all
choroidal retinal elements)

25. Investigation
• Serological test-presence of IgG antibodies
specific to T. gondii and denoting previous
exposure to it. Absence of specific IgG and
IgM virtually excludes the possibility of
toxoplasmosis.
• Congenital toxoplasmosis, specific IgM and/or
IgA antibodies and/or persistently high levels
of specific IgG antibodies to T. gondii after 12
months of life seal the diagnosis.

26. • (PCR) of ocular fluids-The former is possible
through calculation of the Goldman-Witmer or
Witmer-Desmonts coefficient, based on the
correlation between titers of specific antibodies
to T. gondii in aqueous humor/serum, versus the
globulin titers in the same fluids.
• A high coefficient indicates intraocular synthesis
of anti-T. gondii antibodies, and a low coefficient
has an opposite interpretation, although this may
also occur in the setting of severe disruption of
the blood-ocular barrier.

27. • Sabin-Feldman dye test <1:16 or 1:32 is negative
• Western blot analysis (identify membrane and cytoplasmic antigen)
• ELISA
• Indirect fluorescein antibody test.(IFA)
• Hemagglutination test.
• Indirect hemagglutination test
• Imaging modalities including echography, fluorescein or
indocyanine green angiography, as well as optical coherence
tomography are seldom decisive to the diagnosis.
• X-ray skull
• CT and MRI

28. DIFFERENTIAL DIAGNOSIS OF PRIMARY
OR RECURRENTTOXOPLASMIC
RETINOCHOROIDITIS
• Infectious
• Bacterial
• Syphilis
• Tuberculosis
• Bartonellosis (neuroretinitis, focal retinitis, and
angiomatous lesions)
• Lyme disease
• Endogenous endophthalmitis
• Others

29. • Viral
• Acute retinal necrosis/necrotizing herpetic retinopathy
• CMV retinitis
• Progressive outer retinal necrosis
• Others
• Fungal
• Candidiasis (particularly endogenous endophthamitis)
• Aspergillosis
• Others
• Parasitic
• DUSN
• Toxocariasis
• Others

30. • Noninfectious
• Associated with systemic disease
• Behçet’s disease
• Sarcoidosis
• Others
• Primarily not associated with systemic disease
• Serpiginous/ampiginous choroiditis and others
• Multifocal choroiditis and panuveitis
• Punctate inner choroidopathy
• Multiple evanescent white dots syndrome
• Unilateral acute idiopathic maculopathy
• Others
• Neoplastic
• Primary vitreoretinal lymphoma

31. Complication
Nearly 25 % of eyes develop visual loss as a result of the following-
Common –
• Direct involvement of the macula .
• Secondary ON head involvement due to a juxtapapillary lesion
Uncommon-
Primary ON head involvement
Occlusion of a major blood vessel
Choroidal neovascularization
Serous RD
Tractional RD
Macular oedema.

32. Treatment and Prevention
• Available drugs do not eliminate tissue cysts
and cannot prevent chronic infection
• No treatment has proven to be superior or
even more effective than no treatment
• Antitoxoplasmic agents and systemic steroids
have never been studied in large clinical trials

33. Drug and dosage Precautions and observations
Sulfadiazine
1 g QID in adults
50-100 mg/kg/day in children
Caution and dose correction for hepatic renal
failure.
Contraindicated in G6PDH deficiency.
Hydration and alcalinization of urine may prevent
crystalluria.
Avoid at the end of gestation (risk of kernicterus).
Hypersensitivity and allergies demand suspension.
Stevens-Johnson syndrome possible but rare.
Bone marrow suppression in < 0.1%.
Pyrimethamine
Loading dose of 100 mg, followed
by 25–50 mg/day
1 mg/kg/day in children
Caution in hepatic or renal failure.
Contraindicated in first trimester (teratogenic).
Common gastrointestinal disturbances.
Risk of bone marrow depression demands
concomitant use of folinic acid (5–7.5 mg/day
or 15 mg 3×/week) and periodic CBC
monitoring

34. Clindamycin
300 mg qid
10–25 mg/kg/day in children
Caution in hepatic or renal failure.
Common gastrointestinal disturbances. Risk of
pseudomembranous colitis (suspend if bloody
diarrhea
Azithromycin
250–500 mg/day
5 mg/kg/day in children
Food decreases oral absorption.
Gastrointestinal disturbances in less than 10%.
May be used in pregnancy.

35. Sulfamethoxazole/
trimethoprim
800 mg/160 mg bid
40–50 mg/8–10 mg/kg/day
in
children
Better tolerated than classic therapy, but probably
less effective.
Caution and dose correction in case of hepatic/
renal failure. Contraindicated in G6PDH
deficiency.
Avoid during gestation (risk of teratogeny and
kernicterus).
Risk of sulfa hypersensitivity.
Bone marrow suppression uncommon.
Spiramycin
1.5 million IU (500 mg) qid
Atovaquone
750 mg qid
30 mg/kg/day in children
High levels in placenta.
Safest antiparasitic drug in pregnancy.
Limited intraocular penetration.
Gastrointestinal disturbances and hypersensitivity.
Caution with liver failure.
Food increases drug absorption.
Maculopapular rash in up to 20%.
No safety studies concerning gestation / lactation.

36. MAIN FACTORS INFLUENCING
TREATMENTDECISION ON ACTIVE
TOXOPLASMIC RETINOCHOROIDITIS
• Immune status of the individual
• Location and size of the active lesion
• Presence of macular and/or optic disc edema
• Degree of vitritis and of decreased vision
• Clinical course
• Special situations (newborns, pregnant women, drug
allergy)
• Adverse effects of antiparasitic drugs and
corticosteroids

37. Primary prophylactic measures are essential in
seronegative women right before and during pregnancy
and in immunosuppressed patients.
These measures include:
• Avoiding ingestion of raw/undercooked meat (freezing at
−20°C/−4°F
• overnight also destroys tissue cysts);
• Drinking only well-filtered or boiled water;
• Carefully washing vegetables/fruits before consumption;
• Using gloves and washing hands/kitchen utensils after manipulating
• meat/soil;
• Avoiding contact with felines and their feces (even in soil or litter
• boxes).
• Monthly serologic screening of susceptible women during
pregnancy is also highly recommended.

38. COURSE AND PROGNOSIS
• Toxoplasmic retinochoroiditis is a recurrent
disease, with up to two thirds of patients
developing reactivations later in life. These are
more common in congenital than in
postnatally acquired toxoplasmosis, and occur
especially in the first year after the previous
episode.
• Some patients, however, sustain long-lasting
disease remission

39. • Prognosis depends on the immune status and
age of the patient, as well as on the size and
location of the lesions
• Local complications such as persistent
vitreous opacities, macular edema, epiretinal
membranes, extensive retinochoroidal
scarring, choroidal neovascularization, optic
atrophy and even retinal detachment may be
associated with significantly decrease.

40. THANK YOU