====== Ocular Toxoplasmosis ======

===== Toxoplasma gondii =====
  * Obligate intracellular protozoan
  * 500 million have antibodies worldwide
  * 50% of adult population in US have asymptomatic infection
  * 28-55% of all cases of posterior uveitis
  * First isolated from the brain of a "gondii" (North African Rodent)
  * Cat family is definitive host, can infect other mammals and birds
  * Oocysts found in intestinal tracts of cats
  * Cysts ingested (most likely)
  * Poor hygiene, infected pork, chicken but probably not beef
  * Can survive outside host for up to 1 year
  * Two forms in humans: cysts or tachyzoites.
  * Propensity for cardiac and skeletal muscle and neural tissue (brain & eye)

===== Clinical Manifestations =====
==== Acquired vs. Congenital ====
  * Most cases are presumed reactivation of congenital infection
  * 2 to 6/1000 women acquire infection while pregnant, 40% risk of transmission to fetus.
  * Of infected infants: 70% chorioretinal scars, 5% will die or severe disability, 1-2% severe visual impairment
  * Northern Brazil has high rate of acquired disease

==== Systemic ====
  * 90% lympadenopathy
  * fever, malaise, occasional sore throat
  * immunocompromised- fulminant CNS disease

==== Ocular ====
  * Keratic Precipitates, anterior chamber cell and flare, posterior synechia, cataract
  * Retinochoroiditis
  * Vitritis- concentrated over lesion, scaffolding of vitreous strands
  * Macular edema
  * Retinal vasculitis
  * VF defect in area of scar
  * FFA of active lesion- early blockage and subsequent leakage

==== Atypical Presentations ====
  * In early infection: gray-white fine punctate lesions in deep retina and RPE, progress to more classic lesions
  * Papillitis, vitreal inflammation, nerve fiber bundle defects
  * Bullous like inflammatory lesions in mid-periphery
  * Wide ring-like lesion near extreme periphery resembling pars planitis
  * Scleritis
==== Reasons for Vision Loss ====
  * Vitreal inflammation causing clouding
  * Lesion in posterior pole with edema affecting fovea
  * Lesion in fovea
  * Subsequent CNVM

===== Diagnosis =====
  * Typical lesions
  * Toxoplasmosis titers are supportive
    * IgM titers- can be missed
    * IgG titers- high rate of false positives
  * Immunoflourescence, ELISA
  * Western blot for Toxo antigens
  * PCR and Southern Blot for Toxo DNA
  * Angiography: flourescein tagged Ab (successful in rabbit studies)

===== Therapy =====
  * Should you treat it at all?
    * Lesion within temporal arcade
    * Lesion next to optic nerve or large vessel
    * Lesion has induced large degree of hemorrhage
    * Vision drop of > two lines
    * Multiple recurrences with vitreal contraction
  * No truly randomized, controlled clinical trials to compare efficacy
  * Generally 4-6 weeks, multi-drug regimens

===== Medications =====
  * Sulfadiazine 1g PO QID
  * Pyrimethamine 75-100mg load and 25-50mg PO BID (bone marrow suppression, nausea)
    * Use concurrently: Folinic Acid 3-5mg PO 3 times/week (Baseline CBC, follow q week)
  * Clindamycin 150-300mg PO TID-QID (?reduces recurrence, risk of pseudomembranous colitis)
  * Trimethoprim-sulfamethoxazole (DS) I PO BID
  * Atovaquone (Mepron) 750mg PO BID (kills cysts in vitro)
  * Tetracycline 2g load and 250mg PO QID (to replace clindamycin)
  * Prednisone 20-60 mg/day not used alone

===== Rothova et.al. (The Netherlands) Am J Ophth, 115:515-523. April, 1993 =====
==== Treatment Regimen #1 ====
  * Pyrimethamine, Sulfadiazine, Folinic Acid, Prednisone
  * Best at reducing size of lesions (49%), 
  * more medication side effects (26%), 
  * recurrence rate at 3 years (42%)

==== Treatment Regimen #2 ====
  * Clindamycin, Sulfadiazine, Prednisone
  * Reducing size of lesions >1/2 DD (28%) 
  * med side effects (17%)
  * recurrence rate at 3 years (67%)
==== Treatment Regimen #3 ====
  * Co-trimoxazole, Prednisone
  * Reducing size of lesions >1/2 DD (11%)
  * med side effec!ts (4%)
  * recurrence rate at 3 years (40%)

==== Treatment Regimen #4 ====
  * No treatment (peripheral lesions)
  * Reducing size of lesions >1/2 DD (20%)
  * no med side effects
  * recurrence rate at 3 years (53%)

==== Comments ====
  * Recurrence rates not statistically significant
  * Size of retinal lesion correlated with duration of inflammation
  * All side-effects were reversible
  * Delay in starting medication (even up to 1 week) did not alter duration of inflammation
  * Sub-tenon's steroid- risk of increasing activity of organism
  * Vitrectomy- for vitreal haze reducing vision, perioperative antibiotics advocated
  * Cryotherapy and Laser photocoagulation generally not successful