Case 3 : A Case of Ocular Toxoplasmosis

1. Case 3 : A Case of Ocular Toxoplasmosis Dr Johnson Tan Medical Officer Tan Tock Seng Hospital

2. 17/Chinese/male c/o: RE floaters x 5 days No trauma O/E : VA 6/7.5 OU No RAPD Colour 15/15 OU Decreased red desaturation RE Confrontational fields full Anterior segment NAD RTL cells 1 + Mr SCHA

3. On examination of RE,

4. What were the findings? • Rt superior optic disc swelling superiorly • Superior-temporal peripapillary white lesion with indistinct edges • Adjacent vasculitis • What would be the next step? • Take a full history

5. Further questioning… • No headache / neck stiffness / tinnitus • No joint pains • No mouth ulcers • No dysuria • No travel history • No chronic cough / fever / constitutional symptoms • No contact history with TB

6. Investigations • ESR / CRP • ANA, dsDNA • ANCA • CXR / Mantoux • VDRL/TPHA • Toxoplasma IgG : 18.7 IU/ml (positive) • Aqueous tap for CMV/HSV/VZV/Toxoplasma /TB PCR: not detected NORMAL

7. Ocular Toxoplasmosis • Obligate, intracellular parasite • Commonest cause of retinochoroiditis and posterior uveitis • Manifest between the 2nd & 4th decades of life • Risk factors • Immunodeficiency states • Exposure to cats • Eating raw or partially cooked meat • Symptoms • Blurred vision • Floaters • Pain • Red eye • Metamorphopsia • Photophobia

8. Ocular Presentations • Iridocyclitis • Unifocal superficial necrotizing retinochoroiditis • Classical presentation involving inner retina • Surrounded by oedema with contiguous inflammation of choroid and sclera • May be a/w dense vitritis "headlight in the fog" • May be a/w adjacent focal vasculitis kyrieleis arteriolitis • Jensen’s papillitis • Involvement of optic nerve from adjacent juxtapapillary retinitis • Optic nerve sheath may serve as a conduit for the direct spread of Toxoplasma into the optic nerve from an adjacent cerebral infection  optic neuritis/papillitis • Punctate outer retinitis -rare • Deep retinitis - rare

9. Uncommon Ocular findings • Ocular inflammation without necrotizing retinochoroiditis • Retinal and optic nerve neovascularization, usually regresses with resolution of inflammation. • Exact aetiology not well understood • Retinal ischemia associated with severe retinal vasculitis • Inflammatory reaction

10. Optic neuritis vs disc swelling from contiguous spread?

11. Ocular Toxoplasmosis Immunocompetent adults: • Unilateral, painless. unifocal • Vision good if macula not involved Neonates: • Congenital toxoplasmosis • Bilateral, severe • 70% retinochorioditis • ⅔ macula involved a/w severe visual loss • Micorophthalmia, vitritis, glaucoma, ocular palsies Immunocompromised: • Bilateral, multifocal, severe • May be a/w SOL of CNS  Ocular palsies, nystagmus, VF defects

12. Follow-up • Bactrim 11/11 bid x 1/12 • Prednisolone 1mg/kg (50mg od) tapered over 2 weeks

13. Typical Presentation & Course

14. Serological diagnosis IgG: • IgG seroconversion 2-4 weeks after systemic infection, peak titres 4-6 weeks after infection • Titres maintained at high levels for many months or years. • Recent infection : 4x rise in antibody titres over a 2-4 week period • Clinical signs may develop before seroconversion occurs, or after peak titres have developed. • A single antibody titre is difficult to interpret and is rarely of any value Negative IgG excludes ocular toxoplasmosis

15. Serological diagnosis IgM • Less value than IgG • A negative IgM test excludes recent infection • A positive IgM test is difficult to interpret because Toxoplasma-specific IgM antibodies may be detected up to 18 months after acute acquired infection Goldmann-Witmer coefficient Ratio of Toxoplasma IgG [eye] : [serum] > 3 is generally accepted as being consistent with active ocular infection • But invasive procedure! Aqueous humor and serum immunoblotting for immunoglobulin types G, A, M, and E in cases of human ocular toxoplasmosis. J Clin Microbiol. 2004 Oct;42(10):4593-8.

16. PCR • Presence of T. gondii in ocular fluids is detected on PCR considered to be confirmation of active eye disease • A negative finding does not exclude ocular toxoplasmosis • Real-time PCR (Light-cycler, LC-PCR) more sensitive than nested PCR (n-PCR). Evaluation of a Real-time PCR-based assay using the lightcycler system for detection of Toxoplasma gondii bradyzoite genes in blood specimens from patients with toxoplasmic retinochoroiditis. Int J Parasitol. 2005 Mar;35(3):275-83. Epub 2005 Jan

17. Treatment: Updates • Triple drug therapy :pyrimethamine, sulfadiazine, prednisolone • Quadruple therapy : pyrimethamine, sulfadiazine, clindamycin, prednisolone. • Bactrim (2 tabs bid) is as effective as pyrimethamine/sulfadiazine for lesions outside fovea. • 61% in classic triple therapy grp vs 59% in Bactrim grp Soheilian et al. Prospective randomised trial of Trimethoprim/sulfamethoxazole vs pyrimethamine & sulfadiazine in the treatment of ocular toxoplasmosis. Ophthalmology. 2005 Nov;112(11):1876-82 • At least 6 weeks treatment • Others: Azithromycin + pyrimethamine (AJO 2002;134:34-40) Spiramycin (Klin Montasbl Augenheildk 1998;212:84-7) Atovaquone (hydroxynaphthoquinone) (Ophthalmology 1999;106:148-53) Allopurinol (Adam et al. Berlin 2000) • Corticosteroids • Topical : depending on AC reaction. • Depot absolutely contraindicated • Risk of rampant necrosis and blind, phthisical globe • Systemic adjunct to minimize collateral damage from the inflammatory response • Usually from Day 3 @ 1mg/kg, tapered over 2 weeks

18. Thank you A presentation by The Eye Institute @ Tan Tock Seng Hospital