Ocular Toxoplasmosis Dr. Prabhat Devkota.pptx

Dr. Prabhat Devkota
MBBS(TU), MD(NAMS)

1. Ocular Toxoplasmosis DR. PRABHAT DEVKOTA MBBS(TU), MD(NAMS)

2. Layout Introduction Causative organism Epidemiology Risk factors Systemic syndrome Ocular Toxoplasmosis Signs and symptoms Management

3. Introduction Causative organism Toxoplasma gondii Toxoplasmosis is a parasitic disease caused by Toxoplasma gondii

4. History 4 1908 1960 1923

5. Genotypes 3 genotypes: Type I, II and III 5 Type I Type II Type III Very virulent Post natal acquired infection Associated with strong pro-inflammatory response and severe tissue damage Least virulent Encyst in tissue under immune response Responsible for chronic infection Congenital infection and encephalitis Less virulent

6. Lifecycle

7. Epidemiology In Nepal Toxoplasma infection in selected patients in Kathmandu, Nepal 272 patients with: Ocular diseases(uveitis, retinochoroiditis) Malignancy(including leukemia) Women with bad obstetric history(BOH) and Others( patients with fever, lymphadenitis and encephalitis) 8 Rai SK, Upadhyay MP, Shrestha HG. Toxoplasma infection in selected patients in Kathmandu, Nepal. Nepal Medical College journal: NMCJ. 2003 Dec;5(2):89-91

8. Contd … Toxoplasma antibodies were detected by microlatex agglutination and IgM ELISA techniques Overall, 50.7%(132) had Toxoplasma antibodies, out of which 5.7%(8) had IgM antibodies Patient with malignancy had highest positive rate(68%) Women with BOH had highest Toxoplasma IgM positive rate(25%) 9 Rai SK, Upadhyay MP, Shrestha HG. Toxoplasma infection in selected patients in Kathmandu, Nepal. Nepal Medical College journal: NMCJ. 2003 Dec;5(2):89-91

9. Patterns of Uveitis among Nepalese Population Presenting at a Tertiary Referral Eye Care Centre in Nepal Study period: 2012-2017 Total patient attending BPKLCOS: 5,34,292 Total patient diagnosed with uveitis: 4359 [0.82%] Patients diagnosed with toxoplasmosis : 272 [6.24%] Kharel R, Khatri A, et al. Patterns of uveitis among Nepalese population presenting at a tertiary referral eye care centre in Nepal. DOI: 10.15761/NFO.1000238

10. Modes Of Transmission 11 Incubation period: 10 to 23 days after ingesting contaminated meat 5 to 20 days after exposure to infected cats

11. Risk factors Exposure to environments where the infectious organism is found, especially those frequented by felines. Increased risk of infection in males, if you own more than 3 kittens, and eating raw or undercooked meat (lamb, ground beef, shell fish, game).

12. Pathogenesis Depends on a delicate balance between host immunity and parasite virulence Adaptive immune response is medicated by CD4+ T lymphocytes and macrophages synthesis of various proinflammatory cytokines  IL-12,IFN γ and TNF α act synergistically to contain parasite replication Th 2 response counterbalances proinflammatory Th 1 pathway 13

13. Ocular T oxoplasmosis

14. Clinical Manifestation 15

15. Immunocompetent Patients Generally asymptomatic 10-20% will develop cervical lymphadenopathy and or flu like illness Benign clinical course Early retinitis may occur in about 20% Symptoms usually resolve without treatment within weeks to months, although some cases may take upto year 16

16. Immunocompromised Patients May be acquired or result from reactivation of pre-existing disease Often severe Neurologic disease is most common sign, particularly in reactivated infection May develop encephalitis, chorioretinitis, myocarditis and pneumonitis Can cause multiple abscesses in nervous tissue with symptoms of mass lesion 17

17. Congenital Toxoplasmosis Results from acute primary infection acquired by mother 40% of primary maternal infection can cause congenital infection Transplacental transmission is highest during 3 rd trimester, but severity is inversely proportional to gestational age Fetal death occurs in 10% of all congenital toxoplasmosis Neurological and visceral involvement may be subclinical 18

18. Congenital Toxoplasmosis Results from acute primary infection acquired by mother 40% of primary maternal infection can cause congenital infection Transplacental transmission is highest during 3 rd trimester, but severity is inversely proportional to gestational age Fetal death occurs in 10% of all congenital toxoplasmosis Neurological and visceral involvement may be subclinical 19

19. Congenital T oxoplasmosis

20. Contd … Retinochoroiditis occur in over 75% leaving scars that are commonly a later incidental finding Early infection: spontaneous abortion, still birth, severe congenital disease Late infection: asymptomatic, normal appearing infant with latent infection 21

21. Contd.. 22 Retinochoroiditis Hydrocephalus or microcephaly Intracranial calcifications Sabin’s tetrad Cognitive impairment

22. Contd.. Generalized disease Exanthematous rash Petechiae Ecchymosis Icterus Fever or hypothermia Anemia Lymphadenopathy Hepatosplenomegaly Pneumonitis Vomiting and diarrhea 23

23. Contd … Ocular sequalae 25% of these become blind in one or both eyes Retinochoroidal scars Cataracts Microphthalmia Phthisis bulbi Strabismus Nystagmus Optic atrophy Macular membrane 24

24. Postnatal Childhood Acquisition Accounts for 50% cases of childhood toxoplasmosis Ocular lesions are common but may not develop for years after initial infection 25

25. Ocular Toxoplasmosis 20-60% of all posterior uveitis 80-90% congenital Classic lesion: Focal necrotizing retinochoroiditis with vitreous inflammation can be accompanied by granulomatous anterior uveitis Retina: primary site of parasite multiplication Choroid and sclera: site of contiguous inflammation 26

26. Cont … Lesions in macular area: 76% macular involvement Established as result of entrapment of freely swimming organisms or parasite containing macrophages in terminal capillaries of perifoveal retina 27

27. Symptoms Blurred vision Floaters Eye pain Redness Metamorphopsia Photophobia 28

28. Signs Anterior uveitis Elevated IOP - 20% cases May develop Mutton fat KPs Posterior synechiae Fibrin deposition Koeppe and Bussaca nodules 29 Prompt therapy to avoid complication like pupillary seclusions, rubeosis iridis , secondary glaucoma

29. Signs Vitritis severe Retino -choroiditis with vitritis 30 Headlight in fog appearance Complication: PVD, Vitreous Contraction, RD

30. 31 Single fluffy white lesion associated with pigmented scar(satellite lesion adjacent to old scar) De novo foci: not associated with old scar/multiple lesions Inflammatory focus

31. Vascular Involvement Either in vicinity of active lesion or in distance retina Diffuse or segmental vasculitis Ag-Ab complex deposition in vessel wall Primarily involves vein 32 Complications: Retinal hemorrhage, vascular obstruction, shunting, neovascularization

32. Contd … 33 Periarterial lipid exudate Kyerieleis Arteriolitis

33. Subretinal Neovascularization 34 Retinal ischemia associated with severe retinal vasculitis Inflammatory reactions Neovascularization of retina

34. Optic Nerve Involvement Optic neuritis or papillitis associated with edema Direct extension of cerebral infection through sheath of optic nerve Patient with toxoplasma papillitis may present without evidence of focus of retinitis 35

35. Atypical Toxoplasmosis Multifocal retinochoroiditis Low-grade or absent vitreal infiltration Absence of retinochoroidal scar Bilaterality Optic disc involvement Choroiditis without retinitis 36

36. 37 Forms of atypical retinitis: Punctate outer retinal toxoplasmosis Neuroretinitis (aggressively involving ON) Neuritis Multiple pseudoretinitis Punctate outer retinal toxoplamosis (PORT) S mall, multifocal gray white lesion Minimal vitreous involvement and punctate infiltrates in outer retina with serous RD

37. Neuroretinitis Active lesions localized to juxtrapapillary region, aggressively involving retina and optic nerve Initially presents as severe papillitis with disc hemorrhages, venous engorgement and overlying vitritis 38

38. Multiple pseudoretinitis Simultaneous presence of retinal lesions, which appears to be active However, close observation reveals just a single active lesion accompanied by noncontiguous areas of retinal edema Once true active lesion heals, pseudo lesions completely disappear without scarring 39

39. Healing Spontaneously 6-8weeks Associated with decrease in retinal edema and flattening of lesion with evidence of scar formation surrounded by variable amounts of pigment 40

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42. Recurrent Toxoplasmic Retinitis Retinochoroiditis scar may harbor toxoplasmic cyst Immunological suppression recurrence Frequently appears as satellite or occurs adjacent to previous scar Lesion tends to involve posterior pole 43

43. Toxoplasmosis Immunocompetent Immunocompromised Isolated often unilateral lesion Multifocal and bilateral White fluffy focus of necrotizing retinitis with associated retinal edema, retinal vasculitis and vitritis Less vitritis and lesions may simulate appearance of viral retinitis such as ARN or CMV retinitis Secondary non granulomatous inflammation of adjacent choroid and sclera 44

44. Variants 1 st variant: Lesions larger than 1DD dense and elevated Largely destructive lesion with significant vitritis and AC reaction Prompt therapy is necessary 2 nd variant: Punctate lesions of inner retina Inflammation is mild No therapy necessary unless lesion is close to macula and vision threatening 3 rd variant: Punctate lesions in outer retina and mild vitritis Lesion slowly resolves spontaneously 45

45. Complications 46 Permanent vision loss Macular inflammatory lesion and edema Optic nerve involvement Vascular occlusion Serous, rhegmatogenous and tractional RD Late secondary choroidal neovascularization

46. Complications Secondary glaucoma Cataract Vitreous hemorrhage Proliferative vitreoretinopathy Retinal detachment Macular dragging Epiretinal membrane Cystoid macular edema Macular hole Retinovascular occlusion Vascular shunts Choroidal neovascular membrane Optic atrophy Phthis 47

47. Diagnosis Serological tests: IgG, IgM, Sabin-Feldman dye test Polymerase chain reaction (PCR) for intraocular fluid Diagnostic pars plana vitrectomy with or without choroidal biopsy Imaging modalities B-scan: to exclude RD if severe vitritis present OCT Fluorescein angiography 48

48. Serology IgG antibody Usually appears within 1-2 weeks of infection, peak within 1-2 months, fall at variable rates and usually persist for life Titer doesn’t correlate with severity of illness Crosses placenta IgM antibody Determine acute phase of infection or in distant past Persist for month to more than year Do not cross placenta Presence of IgM in newborns confirm congenital infection 49

49. Ocular Fluid Antibody Assessment Goldman-Witmer coefficient Ratio of specific IgG in aqueous humor to that in serum as measured by ELISA or radioimmunoassay GW ratio: <2 in immunocompetent patient- no active ocular toxoplasmosis Between 2 and 4- active ocular disease >4 is diagnostic of active ocular toxoplasmosis 50

50. Polymerase Chain Reaction Used to detect T.gondii DNA in body fluids and tissues Used to diagnose congenital, ocular, cerebral and disseminated toxoplasmosis PCR performed on amniotic fluid diagnosis of fetal T.gondii infection 51

51. Imaging OCT: hyperreflectivity of retinal layers with thickening of posterior hyaloid 52

52. Differential Diagnosis Infectious Cytomegalovirus Syphilis Herpes simplex Tuberculosis Toxocariasis Non-infectious Retinal and choroidal coloboma Retinoblastoma Retinopathy of prematurity Retinal vascular membrane Serpiginous choroidopathy 53

53. Differential Diagnosis(Atypical Presentation) Acute posterior multifocal placoid pigment epitheliopathy Punctate inner choroidopathy Multifocal choroiditis Diffuse unilateral subacute neuroretinitis 54

54. 55 Toxoplasma ARN of Viral etiology CMV Retinitis Chorioretinitis of Tubercular etiology Endogenous Endohthalmitis History Prior relapses +-/Acute onset, Contact with cats/dogs, contaminated food Generally, no prior relapses e Acute onset Acute onset Prior relapses Insidious onset History of fever, systemic infections, acute onset Complaint Blur vision, pain or watering Blur vision /pain +/- Blur vision, No pain Blur vision, mild pain/ redness+/ Blur vison, with Pain and redness Anterior Segment Granulomatous > Nongranulomatous KPs +/-, No hypopyon Decrease in corneal sensation +/-, Diffuse pigmented KPs, i ris atrophy+/ Diffuse KPs+/-, No hypopyon Iris nodules/ granuloma +/- granulomatous KPs, Broad based synechia Hypopyon +/-, Fibrinous reaction+/-, generally nongranulomatous KPs +/

55. 56 Toxoplasmosis ARN of viral etiology CMV retinitis Chorioretinitis of tubercular etiology Endogenous ophthalmitis Posterior segment Moderate – severe vitritis , generally single retinitis lesion, occasionally associated chorio -retinal scars , frequently associated exudative vasculitis Circumferential progression , arteriorlar vasculitis, Hemorrhages +/-, No dense scarring after resolution Larger lesions, few hemorrhages, pizza pie appearance , no scarring after resolution choroidal or outer retinal lesions, Occlusive vasculitis +/ Generally larger lesions arising from choroid and involving outer retina first , vasculitis component is not clear OCT Thick ERM, Full thickness retinal involvement, choroidal elevation +/- Full thickness involvement, No choroidal elevation Ellipsoid zone disruption, choroidal involvement Choroidal elevation, outer retinal involvement first

56. Treatment Aim: To reduce risk of permanent visual loss To reduce recurrent retinochoroiditis To reduce severity and duration of acute symptoms 57

57. Indications Lesions threatening optic nerve or fovea Decreased visual acuity Lesions associated with moderate to severe vitreous inflammation Lesions greater than 1 disc diameter in size Persistence of disease for more than 1 month Presence of multiple active lesions 58

58. Indications Immunocompromise patient Congenital toxoplasmosis regardless of presence of ocular lesion Pregnant women with recently acquired disease 59

59. Medical Therapy Classic regimen 4-8 weeks Folinic acid 5-10mg/day is added to prevent myelosuppression 60 Pyrimethamine Loading dose 50-100mg/day Maintenance dose 25-50mg/day Sulfadiazine Loading dose 2-4g Maintenance dose 1g, 4times daily

60. Pyrimethamine Folic acid antagonist Mechanism of action Inhibits dihydrofolate reductase enzyme Preventing conversion of folic acid to folinic Adverse effects Leukopenia Thrombocytopenia Megaloblastic anemia 61

61. Complete blood count- 2weekly Contraindicated in 1 st trimester of pregnancy 62

62. Sulfonamides Mechanism of action: Structural analogues and competitive antagonists of paraaminobenzoic acid (PABA) Prevent normal utilization of PABA for synthesis of folic acid by parasites Adverse effects Crystalluria , hematuria, and renal damage Acute hemolytic anemia Agranulocytosis Hypersensitivity reactions 63

63. Contraindications Glucose 6-phosphate dehydrogenase deficiency Third trimester of gestation Doses: Adults: 2gm loading dose followed by 1gm every 6hourly for 30-60days Children: 100mg/kg/day divided every 6hourly Newborns: 100mg/kg/day divided into 2 doses 64

64. Clindamycin Mechanism of action: Inhibits ribosomal protein synthesis Adverse effects : Pseudomembranous colitis Skin rashes Diarrhea Dose: Adult: 300mg every 6hours for 30-40 days Children: 16-20mg/kg/day divided every 6hourly 65

65. Intravitreal Therapy Advantages: Increased patient convenience Improved systemic side effect profile Greater drug availability 66 1mg of Clindamycin 0.4mg of Dexamethasone

66. Co-trimoxazole Mechanism of action: Trimethoprim prevents reduction from dihydrofolate to tetrahydrofolate Sulfamethoxazole inhibits incorporation of PABA in synthesis of folic acid Dose: 160/800mg(one tablet) every 12 hours for 30-40days Combination with prednisolone(1mg/kg) 67

67. Azithromycin Mechanism of action : Inhibits ribosomal protein synthesis Effective against encysted forms of parasite (bradyzoites) in vitro Dose: 500- 1000mg/ day for 3 weeks Reduce rate of recurrence of retinochoroiditis 70

68. Atovaquone Mechanism of action Interferes mitochondrial electrical transport chain Potent action against tachyzoites Theoretically attacks encysted bradyzoites but does not seem to prevent recurrence in vivo Dose 750mg every 6hourly for 4-6weeks No serous adverse effects 71

69. Spiramycin Macrolide antibiotic and antiparasitic Protein synthesis inhibitor Reduces rate of tachyzoite transmission to fetus Drug of choice in pregnancy Dose: 500mg every 6hourly for 3 weeks, regimen may be repeated after 21 days Adults: 500-750 mg every 6hourly for 30-40 days Children: 100 mg/kg/day divided every 6hour 72

70. Treatment Updates Triple drug therapy Pyrimethamine + Sulfadiazine + Prednisolone Quadruple therapy Pyrimethamine + Sulfadiazine + Prednisolone + Clindamycin 73

71. Laser Photocoagulation For extramacular chronically exudative lesion in individuals nonresponsive to or not tolerating systemic therapy 74

72. Pars Plana Vitrectomy For removal of persistent vitreous opacity or to relieve vitreoretinal traction that may lead to retinal detachment Also removes antigenic proteins with inflammatory cells from vitreous 75

73. Course And Prognosis Recurrent disease Around 2/3 rd of patients develop reactivations later in life More common in congenital>postnatally acquired toxoplasmosis Occur especially in first year after previous episode Some patients, however, sustain long-lasting disease remission 76

74. Prevention Meat should be cooked to 600C for at least 15minutes or frozen to temperature below -200C for at least 24hours to destroy cysts Any contact with cat feces should be avoided Hands should be washed after touching uncooked meat and after contact with cats or soil that could be contaminated with cat feces Consumption of raw eggs and unpasteurized milk, particularly goat’s milk should be avoided 77

75. Bibliography Uvea, American Academy of Ophthalmology, 2022-2023 Kanski’s Clinical Ophthalmology, 9 th Edition Myron Yanoff and Jay S. Duker , Ophthalmology, 5 th Edition Uveitis, A Practical Guide to the Diagnosis and Treatment of Intraocular Inflammation 78