Ocular = Toxoplasmosis:

Ocular=20 Toxoplasmosis

Dr Dipankar = Das

Associate = Consultant,

Department of uvea and ocular=20 pathology

Sri Sankardeva=20 Nethralaya,

Guwahati, Assam, = India

Ocular=20 Toxoplasmosis is the most common cause of

Posterior=20 uveitis, the=20 lesions develop in deep

retina,=20 in which case few to no Vitreous cell may

be=20 present.

Critical sign include white yellow = retinal=20 lesion associated with hazy Vitreous as a result of presence of Vitreous = cells=20 (Head light in fog). Old=20 Choroiretinal scar can be seen often adjacent to new white yellow lesion = but it=20 is not always present. Sometime Disc edema may be present. Choroiretinal = scar=20 are occasionally found in uninvolved eyes. =20 Associated CME or CNVM is seen on rare occasion or as late=20 sequelae.

Work Up:

F Ocular toxoplasmosis can = frequently be diagnosed clinically on the basis of its characteristic=20 chorioretinal scar and inflammation. =20 Serologic testing confirms the clinical diagnosis of = Toxoplasmosis.

* =20 History of taking raw = meat or=20 exposed

to cats (source of acquired = infection). =20

Most common presentation of = acquired=20

Toxoplasmosis is lymphedenopathy, = fever,=20 headaches, malaise, pharangitis, fatigue, night sweat etc. In case of congenital=20

Toxoplasmosis enquire about previous=20

maternal abortion, birth history, h/o=20

Seizures etc.

* =20 Complete ocular = examination=20 included

dilated fundus evaluation.=20

* =20 Serum antitoxoplasma antibody=20 titers: =

Should have a positive titer = from current or = previous=20 infection (IgG the dilution is unimportant), but a negative titer on any = dilution does not exclude the diagnosis. =20 Immunoglobulin M (IgM) is found approximately 2 to 6 months of = initial=20 infection, after which only IgG remains. Ask the laboratory to do a 1:1=20 dilution, as only a positive result is necessary in the setting of = classic=20 fundus findings.

Value=20 of Serological Tests for Toxoplasmosis

IgG:=20

No=20 previous infection: < 1:16

Prevalent=20 in general population: 1:16-1:256

Suggests=20 recent infection: > 1:256

Suggests=20 active infection: > 1:1024

IgM:

In=20 children: any titer = is=20 significant

In=20 adults: > 1:64 indicates active infection

* These values are not = absolute,=20 laboratory variation may be there. =20

F =20 As is true for several laboratory

tests, a=20 negative result for antibodies to Toxoplasmosis is sometimes more = informative=20 than a positive result. = All=20 patients with ocular toxoplasmosis should have some evidence for an = immune=20 response to toxoplasma. = Thus the=20 absence of antibodies to Toxoplasmosis may exclude the diagnosis of=20 Toxoplasmosis. There are 3 caveats to this = dictum:=20 - An absent antibody response could represent a laboratory = error, An=20 Immunocompromised patient could have a minimal immune response, Because = the=20 infection may be confined to the eye, the systemic expression of the = immune=20 response could be meager. =20

A=20 primary infection with Toxoplasmosis is suggested = by: - Flu like symptoms, a positive = IgM antibody=20 titer to toxoplasma and A fall in IgM or a marked decrease of IgG titer = several=20 months after the onset of ocular inflammation.

* =20 Consider an HIV test in = atypical=20 cases

or when the patient is a high-risk=20

Candidate for = AIDS.

* Anterior chamber paracentasis for =

= Toxoplasmosis=20 (Wherever available):

This is useful in the diagnosis = of = atypical=20 toxoplasmosis cases including = determination of=20 local antibody =20 production in aqueous humour. =20 To =20 demonstrate intraocular anti-T.gondii = antibody=20 production, total IgG amount and specific anti-T.gondii IgG titer are = determined=20 within each serum and aqueous humor sample. Total IgG concentrations are = measured by=20 nephelometry and specific anti-T.gondii IgG = titers are=20 nephelometry and specific anti- T. gondii IgG titers are assessed by a = high=20 sensitivitiy- agglutination test. =20 The Goldman-Witmer coefficient (C) is calculated by the following = formula: C=3DC1/C2, where C1 =3D anti-T. Gondi IgG titer/total IgG = concentration=20 within ocular fluid and C2 represents the same ratio within serum. A Goldman-Witmer coefficient = of 3.0 or=20 greater is considered proof or antibody production within the ocular = tissue=20 (local antibody production), thus reflecting ocular toxoplasmosis.

* =20 Polymerase Chain Reaction (PCR) = For=20

Toxoplasmosis =96 Recently PCR amplification of = r-RNA gene of=20 T. gondii from aqueous samples found to be important tool for the = diagnosis of=20 toxoplasmosis. =20

Treatment:

* =20 The disease is self-limited in an immunocompetent patient. Mild peripheral = retinochoriditis may not=20 require treatment. Some congenital cases with bilateral macular healed=20 toxoplasma scar require squint clinic opinion & low vision aid and = regular=20 follow up. If there is = headache or=20 neurological problem, skull X-Ray or CT scan brain is advised to note = any=20 intracranial calcification and required neurologist consultation and = follow=20 up. =20

* =20 If anterior = chamber reaction=20 is present, a topical Cycloplegic with or without topical steroid can be = given. The drops are = tapered as=20 anterior chamber reaction resolves.

* Treatment should be considered = if =96 * A lesion affecting or near = the optic=20 nerve (within 2 disc diameter), * a=20 lesion within the temporal arcade, *=20 a lesion that threatens a large retinal vessel, * a lesion that has induced a = substantial hemorrhage, * = a lesion=20 with intense inflammatory reaction, Extensive chronic exudative lesions=20 regardless of location, * = Severe=20 vitreous haze, * loss of = more than=20 two lines in visual acuity, = *=20 persistence of inflammation for more than a month, * congenital Toxoplasma=20 retino-choroiditis in the first year of life, * a newborn diagnosed with = congenital=20 toxoplasmosis regardless of the presence of ocular lesions, * and any lesion in an=20 immunocompromised host.

Dosing of nonpregnant adult is = listed=20 below-

* =20 Pyrimethamine, = adult 100 mg,=20 per orally(p.o.) load and = then=20 25mg, p.o., b.i.d, for 30 to 60 days. =20 Children 4mg per/kg-loading dose followed by 1 mg/kg/day divided = in 2=20 doses. Newborn should be = treated=20 daily for first 6 months and the 3 times per week for their first year = of life.=20 Follow weekly with CBC. If the platelet count decreases below 1 lakh = then reduce=20 the dosage of Pyrimethamine and increase the folinic acid.

* =20 Folinic acid, 10mg, p.o., = twice weekly=20 (to minimize bone marrow toxicity of = Pyrimethamine).

* =20 Sulfadiazine, 2g, p.o. load = and then 1=20 g, p.o., q.i.d., for 30 =96 60 days.

* =20 Clindamycin, 300 mg, children = 16 to 20=20 mg/kg/day divided every 6 hours, p.o., q.i.d, for 30 =96 40 days. may be = used with=20 Pyrimethamine as alternative therapy (if the patient is sulfa allergic) = or as an=20 adjunct to previously discussed therapy. Pseudomembranous colitis can = develop in=20 0.01% to 10% of patients requiring immediate interruption of therapy and = administration of vancomycin (Cap. Vancocin- 500mg daily for = 10-14days or=20 metronidazole (drug of = choice)=20 200-400mg 8 hrly for 7-10 days.

* =20 Prednisolone may be = added,=20 after initiation of antibiotic therapy, at a dose of 40 to 100 mg per = day for=20 adult (Children 1-2mg/kg/day). =20 Start at the same time or delayed by 12 to 48 hours to = achieve=20 therapeutic level of antimicrobial drugs and = ideally tapered=20 off about 2 weeks before discontinuing the anti-Toxoplasma therapy. = Other=20 alternative therapies are Azithromycin=20 (Tab. Azithral)- 500-1000mg/day for 3 weeks, Atovaquone (e.g., Mepron) not available in India =96 = 750mg every 6=20 hours for 4-6 weeks. Tetracycline (Cap/Dragees = Hostacycline)=20 =96 500mg every 6 hrs loading dose, followed by 250mg every 6 hours for=20 30-40days. Trimethoprim=20 sulfamethoxazole (Tab. Bactrin = DS) =96=20 160/800 mg (one tab. Every 12 hrs. for 30-40 days. Spiramycin (Tab. ROVAMYCIN FORTE, = 3miu)=20 (drug of choice during = pregnancy) -=20 Pregnancy 500mg every 6 hr for 3 weeks, regimen may be repeated after 25 = days. Children- = 16-20mg/kg/day=20 divided every 6 hrs,

Treatment of Ocular=20 toxoplasmosis:

(AJO, 111:601,=20 1991)

Regimen=20 1:

=20 Pyrimethamine

+=20 Sulfadiazine

+=20 Folinic acid

Regimen=20 2:

=20 Pyrimethamine

+=20 Sulfadiazine

+=20 Clindamycin

+=20 folinic acid

Regimen=20 3:

=20 Sulfadiazine

+=20 Clindamycin

Regimen=20 4:

=20 Clindamycin

Regimen=20 5:

=20 Trimethoprim

+=20 Sulfamethoxazole

* Prednisolone (40-60 = mg/day) may be=20 added to any of the regimens.

* Presently newer drugs with less = side effects=20 are tried in ocular toxoplasmosis and their long-term results are to be=20 evaluated.=20

* =20 Laser = photocoagulation,=20 cryotherapy and vitrectomy have been used as adjunctive treatment=20 modalities.

* =20 Maintenance therapy (if patient is immunosuppressed) ; = Pyrimethamine, 25=20 to 50 mg, p.o., q.i.d.; =20 Sulfadiazine, 500 to 1,000 mg, p.o., q.i.d. ; Folinic acid, 10mg, = p.o.,=20 q.i.d. ; if sulfa = allergic, may use=20 Clindamycin, 300 mg, p.o., q.i.d..

F =20 Systemic steroids = should never be=20 used without antimicrobial treatment and rarely used in = immunocompromised=20 patients. =20

F =20 Topical corticosteroids are used for anterior uveitis but periocular injections are=20 contraindicated to avoid local immunosuppression and = uncontrollable=20 disease.

F =20 If a patient cannot use or must discontinue Clindamycin, = tetracycline, 2g=20 load, p.o., followed by 250 mg, p.o., q.i.d., is used = alternatively. Do=20 not give tetracycline to children or pregnant or breast-feeding=20 women.

F =20 Pyrimethamine should not be given = to=20 pregnant or breast-feeding women.

F =20 Only women who develop toxoplasmosis during pregnancy can = transmit it to=20 their fetuses. A woman = cannot=20 transmit congenital toxoplasmosis.

F =20 Indocyanine green angiography has demonstrated that toxoplasma=20 retinochoriditis is more widespread than can be appreciated clinically = and can=20 be used to assess the extent of the disease.

Follow-up: =20

In 3 to 7 days for blood tests or = ocular=20 assessment or both, and then every 1 to 2 weeks on therapy.=20

Prevention:

Measures for the prevention of = toxoplasmosis=20 are primarily directed towards prevention of primary infection-

* Meat should be = cooked to=20 60^oC (140^o F) for at least 15 minutes or frozen to = temperatures below =9620^o C for at least 24 hours to destroy = the=20 cysts.

* =20 Any contact with cat feces should be = avoided.

* =20 Hands should be = washed after=20 touching uncooked meat and after contact with cats or soil that could be = contaminated with cat feces.

* Consumption of raw = eggs and=20 nonpasteurized milk, particularly goat=92s milk, should be avoided.=20

* Fruits and = vegetables should=20 be adequately washed before ingestion.

* =20 Daily cleaning of cat = litter box=20 removes the oocysts before they become infectious, because they need 1 = to 3 days=20 after excretion to undergo sporulation. Only=20 a non-pregnant individual should perform this duty.=20

* =20 Blood transfusions and organ = transplants=20 from seropositive donors should be avoided if the recipient is=20 seronegative.