Bacterial Uveitis - Dr. Prabhat Devkota.pptx

Dr. Prabhat Devkota
MBBS(TU), MD(NAMS)
Ophthalmology
Uveitis
Eye

1. BACTERIAL UVEITIS DR. PRABHAT DEVKOTA MBBS(TU), MD(NAMS) 1

2. Layout Ocular Tuberculosis Syphilis Leprosy Lyme disease Leptospirosis Ocular Nocardiosis Cat scratch disease Whipple disease 2

3. Ocular tuberculosis Chornic infection caused by Mycobacterium tuberculosis, characterized by formation of necrotizing granuloma Tuberculosis primarily involves lung (80%) Extrapulmonary TB (20%) 3

4. E pidemology 1.25 million people die from tuberculosis (TB) in 2023 (including 161,000 people with HIV) 10.8 million people fell ill with TB worldwide including 6.0 million men and 3.6 million women and 1.3 million children Global effort to combat TB have saved an estimated 79 million lives since the year 2000 Ending the TB epidemic by 2030 is among the health targets of the United Nations Sustainable Developent Goals (SDGs). 4

5. Increased prevalance of TB among Asians, African, Americans and Hispanics when compared to non- Hispanics white Risk factors : Diabetes mellitus Coinfection with HIV Malnutrition Substance abuse Residence in crowded settings 5

6. Epidemology - Nepal Tuberculosis prevalance survey (TBPS) 2018-19 , jointly carried out by the National TB programme , Government of Nepal, with support from World Health Organization (WHO) Around 117,000 people are living in Nepal with TB Everyday in Nepal, around 15 people lose their lives to TB and over 180 people fall ill 6

7. TB and HIV TB is the most common opportunistic infection in HIV – positive patient in many developing countries Coinfection rate ( the prevalence of HIV infection among TB patient) in Nepal is 2.4% Overall prevalence in Nepal is estimated at 0.30% in adult population 7

8. Caused by three species of mycobacteria M. tuberculosis M. africanum M. bovis 8

9. Mycobacterium tuberculosis Aerobic Non spore forming Non motile Curved intracellular rods 0.2- 0.5 um by 2-4 um Acid fast bacilli 9

10. Transmission Airborne transmission Transmitted from a person with infectious pulmonary TB by droplet nuclei -> aerosolized by coughing, sneezing or speaking The tiny droplets remain suspended in the air for several hours and may reach the terminal air passages when inhaled 3000 infectious nuclei per cough 10

11. Pathogenesis 11

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13. Ocular tuberculosis Ocular TB is defined as an infection by MTB in the eye, around the eye or on its surface Ocular TB may not be associated with clinical evidence of pulmonary TB Ocular TB may be an initial presentation of extra-pulmonary dissemination of infection Posterior uveitis is the most common presentation of intraocular TB 13

14. Types of Ocular TB Primary If the eye is initial port of entry Conjunctival, corneal and scleral disease Secondary Organisms spread to eye hematogenously Uveal tract, retinal, optic nerve Not same as systemic primary and secondary TB 14

15. Ocular manifestation of TB Adenexal manifestation Anterior segment manifestation Posterior segment manifestation Neuro-ophthalmic manifestation Drug- related ocular toxicity in TB infected patient 15

16. Adenexal manifestation Lupus Vulgaris Eyelid tuberculosis Granuloma 16

17. Anterior segment involvement Tuberculous conjunctivitis Conjunctival granuloma Phlyctenular keratoconjunctivitis 17

18. Tuberculous episcleritis and scleritis Interstitial keratitis 18

19. Anterior uveitis Usually is granulomatous and is characterized by Mutton fat keratic precipitates Koeppe and Busacca nodues Iris or angle granuloma Broad base posterior synechia Hypopyon can occur 19

20. Intermediate uveitis Chronic, low grade, vitritis with snowball opacities, snow banking, peripheral vascular sheathening and peripheral granuloma 20

21. Posterior segment manifestations The ocular changes can be divided into four groups Choroidal tubercles Choroidal tuberculoma Serpinginous like choroiditis Subretinal abscess 21

22. Choroidal tubercles Most common manifestation of intra-ocular tuberculosis and result from hematogenous spread 5 to several hundreds in number Each lesion 0.5 to 3mm in diameter Unilateral or bilateral, yellowish lesion with indistinct borders are located mostly in posterior pole 22

23. Fundus fluorescein angiography (FFA) 23

24. Choroidal Tuberculoma Choroidal tubercle continues to grow and forms a solitary mass measuring 4 to 14mm ( tuberculoma ) Presents as a solitary, yellowish, subretinal mass with surrounding exudative retinal detachment, mimicking a choridal tumor May be located anywhere 24

25. Serpinginous like choroiditis Bilateral, chronic, progressive and recurrent inflammation Either solitary or multifocal Solitary are diffuse and plaque like Multifocal are discrete and initially non- contigious 25

26. SERPIGINOUS LIKE CHOROIDITIS SERPIGINOUS CHOROIDOPATHY Unilateral Bilateral Vitritis +, AC reaction + Vitritis absent, AC reaction absent Posterior pole origin Peripapillary origin Multifocal or placoid Not multifocal but large placoid lesion Pigment clumping at centre of healed lesion Pigment clumping at border of healed lesion Infective Immunological 26

27. FAF (Fundus Auto Fluorescence) 27

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30. Subretinal abscess Multiplication of bacilli in caseous material of granulomas can lead to liquefaction necrosis and abscess formation and form yellowish subretinal mass lesions accompanied by exudative retinal detachment Rarely, these lesions can rupture into vitreous cavity and may lead to endophthalmitis or panophthalmitis 30

31. Retinal vasculitis Veins are involved commonly or rarely arteries Characteristic features include bilateral , vitreous infiltrates ( vitritis ), perivascular cuffing, infiltrates, retinal hemorrhages, perivascular choroiditis scars, neovascularization and neuro-retinitis 31

32. Eales’ disease: 32 Unilateral , idiopathic retinal vasculitis, O cclusive, peripheral periphlebitis and neovascularization. Recurrent attacks of diminution of vision in young males (20-40yrs) - recurrent vitreous hemorrhage . Mild uveitis is common

33. Neuro –ophthalmic manifestation Optic neuropathy develops either from direct infection induced by mycobacteria or from a hypersensitivity to infectious agents Involvement may manifest as an optic nerve tubercle, papillitis , papilledema, optic neuritis, retrobulbar neuritis, neuroretinitis 33

34. Drug- related ocular toxicity in TB infected patient Ethambutol Ocular toxic effects include optic neuritis, colour vision abnormalities and visual field defects Toxicity typically occurs within 3-6 months of starting treatment 2) Rifampicin – orange- red discoloration of tears 3) Isoniazid : peripheral neuritis, Steven Johnson syndrome involving lids and conjunctiva 4) Rifabutin used for treatment of pulmonary tuberculosis may in itself cause anterior uveitis 34

35. Diagnosis Clinical signs Ocular investigations Systemic investigations Exclusion of other uveitis entities Therapeutic test New diagnostic assay 35

36. Clinical Signs Presence of any one of following: Uveitis, cyclitis , choriditis , retinitis, retinal vasculitis, neuroretinitis , optic neuropathy, endophthalmitis and panophthalmitis An intractable disease course with multiple recurrence on non specific treatment (corticosteroids) is a clue suggesting a possible tubercular etiology 36

37. Ocular investigations: Demonstration of AFB by microscope or culture of M.tuberculosis from intraocular fluid/tissue- media Positive polymerase chain reaction from intraocular fluids Fluorescein angiography : to establish heather choroiditis is active, as well as confirming pre-retinal neovascularization, demonstrating ischemia 37

38. 4) Indocyanin green angiography : In acute phase choroidal lesions show hypofluorescence during initial and transit period Progressing to a hypofluorescent center with surrounding hyperfluorescent edges during the late phase of the angiogram 5) FAF : allows activity staging, lesions become progressively hypoautofluorescent with healing 6) OCT : for macular evaluation 7) USG B-scan 38

39. Systemic investigation : Positive Mantoux reaction Evidence of healed or active tubercular lesion on radiography of chest Evidence of confirmed active extrapulmonary tuberculosis (either by microscopic examination or by culture of affected tissue for M. tuberculosis) 39

40. Mantoux interpretation 40

41. Chest X-ray Ghon complex/ cavities Mediastinal / hilar lymphadenitis Calcified lymph nodes HRCT chest 41

42. Exclusion of other uveitic inclusions : Various laboratory investigations including serology for syphilis, toxoplasmosis, sarcoidosis and others Therapeutic test A positive response to 4-drug ATT (isoniazid, rifampicin, ethambutol and pyrazinamide ) over a period of 4 to 6 weeks can be diagnostic 42

43. New diagnostic test Interferon- gamma release assay (IGRA) It based on the in-vitro assays that measure interferon- gamma released by sensitized T cells after stimulation by mycobacterium tuberculosis antiens Two kits are available commercially TSPOT. TB test QuantiFERON – TB GOLD 43

44. Gene Xpert : CBNAAT ( Catridge based nucleic acid amplification test) Detection of mycobacterium tuberculosis in early stage where direct smear is negative) Early detection of Rifampicin resistance PCR 44

45. Definitive diagnosis Clinical feature + microbiological confirmation of MTB Presumptive diagnosis: Clinical feature + mantoux / C- xray / quantiferon TB-gold / HRCT 45

46. Treatment Complex, high levels of patient adherence are required Inappropriate management can result in life-threatening consequences as well as drug resistance Multiple drug regimen is recommended to avoid resistance 46

47. For uncomplicated pulmonary and extrapulmonary TB : HRZE first 2 months, HR for 4 months In disseminated TB , TB meningitis and TB in AIDS : 9 months The World Health Organization is recommending “directly observed treatment, short course” (DOTS) to cure 95% of all TB 47

48. 1 st line oral anti tubercular drugs: Drugs Dosage Isoniazide 4-6mg/kg ( upto 300mg) Rifampicin 8-12 mg/kg Ethambutol 15-20 mg/kg Pyrazinamide 20-25 mg/ kg 48

49. Fluroquinolones : (group 2) Ofloxacin : 15 mg/kg Levofloxacin : 15mg/kg Moxifloxacin 7.5-10 mg/kg 49

50. Injectable drug (group 3) Capreomycin : 15mg/kg Kanamycin : 15mg/kg Amikacin : 15mg/kg Streptomycin : 15mg/kg 50

51. Group 4 drugs Ethinamide / prothionamide : 15mg/kg Cycloserine / terizidone 15mg/ kg P- aminosalicyclic acid : 150mg/kg 51

52. Group 5 Clofazimine : 100 mg Amoxicillin with clavulanate Linezolide : 600mg Imipenem : 500-1000 mg 8 hourly Clarithromycin 500mg/12 hour Thioacetazone : 150mg 52

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54. Corticosteroids in treatment Systemic corticosteroids also may be needed to preserve vision in which severe intraocular inflammation for 4-6 weeks together with ATT : limit damage by delayed HSVR Dose of corticosteroid should be as low as possible to avoid immnuosupression and infection flare-up Topical corticosteroids can be used safely for anterior uveitis, interstitial keratitis and phlyctenulosis 54

55. Complications of ocular TB Corneal scarring Cataract Glaucoma Vitreous hemorrhage Subretinal fibrosis CNV Cystoid macular edema Retinal Detachment 55

56. SYPHILIS 56

57. Organism Syphilis is caused by a spirochete Treponema pallidum Responsible for <2% of all oveitis cases In last two decades incidence rate of syphilis has been rising with two fold rise in incidence of congenital syphilis in USA (from 9.4 to 15.7 per 100,000 births) 57

58. Transmission Sexually transmitted disease Trans placental : mainly after 10 th week of pregnancy Rarely by saliva, blood transfusion or percutaneous injury 58

59. Classification Congenital syphilis Acquired Syphilis Primary syphilis Secondary syphilis Tertiary syphilis 59

60. Congenital syphilis Early congenital syphilis Age 2 years or younger Systemic findings : hepatosplenomegaly, abdominal distension, desquamative skin rash, low birth weiht , pneumonia and severe anemia Late congenital syphilis Age 3 years or older Hutchinson teeth, mulberry molars, abnormal facoes , cranial nerve, VIII deafness, bony changes such as saber shins and perforation of the hard palate, cutaneous lesions such as rhagades and neurosyphilis 60

61. Congenital syphilis : ocular manifestation Uveitis, interstitial keratits , optic neuritis, glaucoma, and congental cataract Multifocal chorioretinits and retinal vasculitis are the most frequent uveitic manifestation (early phase) results in a bilateral salt and pepper fundus Non ulcerative stromal interstitial keratitis with anterior uveitis (untreated late congenital syphilis) occurring in up to 50% of cases, most commonly in girls The constellation of interstitial keratitis, cranial nerve, VIII deafness and Hutchinson teeth : Hutchinson triad 61

62. Primary syphilis Follows an incubation period of approximately 3 weeks Characterized by a chancre Neurologic findings often absent 62

63. Secondary syphilis Occurs 6-8 weeks later A generalized maculopapular rash and lymphadenopathy, that may be prominent on the palms and soles Uveitis occurs in approximately 10% of cases This phase is followed by a latent period ranging from 1 year (early latency) to decdes (late latency) 63

64. Tertiary syphilis One third of untreated patients develop tertiary syphilis Subcategorized as : Benign tertiary syphilis : Gumma Cardiovascular syphilis and Neurosyphilis Uveitis may occur in up to 5% of patient 64

65. Ocular manifestation Patients present with pain, redness, photophobia, blurred vision and floaters Intraocular inflammation may be granulomatous or non granulomatous, unilateral or bilateral and it may affect the anterior or posterior segment Anterior segment findings: Iris roseola Iris papuloosa Iris nodosa Gummata Interstitial keratitis Posterior synechia , lens dislocation , iris atrophy 65

66. Posterior segment findings: Vitritis Chorioretinitis Focal/ multifocal retinitis Necrotizing retinochoroiditis Retinal vasculitis Exudative retinal detachment Isolated papilitis and neuroretinits 66

67. Syphilitic posterior placoid chorioretinitis Pathognomic of secondary syphilis Solitary or multifocal, macular or papillary, placoid , yellowish gray lesions at the level of the RPE, often with accompanying vitritis Fluorescein angiography: display corresponding early hypofluorescence and late staining, along with retinal perivenous staining Indocyanine green (ICG) angiography: shows hypofluorescent spots corresponding to the lesion Optical coherence tomography (OCT) : irregularities at the level of RPE, with corresponding disorganization of outer retinal layers 67

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69. Neuro- ophthalmic manifestations: Optic neuritis Neuroretinitis Argyll Robertson pupil Ocular motor nerve palsies Retrobulbar optic neuritis 69

70. Diagnosis The diagnosis of syphilitic uveitis is supported by history and clinical presentation It is confirmed by serologic testing Primary syphilis may occasionaly be diagnosed by direct visualization of spirochetes with dark field microscopy and by direct fluorescent antibody tests of lesion exudates or tissue 70

71. Serodiagnosis : Non treponemal (non specific ) test: detect non specific antibody VDRL RPR Treponemal test : Detect specific antibody Fluorescent treponemal antibody absorbed test (FTA-ABS) Treponema pallidum hemagglutination test (TPHA) Treponemal antigen based enzyme immune assay for IgG and IgM 71

72. Enzyme – linked immunosorbent assay (ELISA) PCR 72

73. Treatment Parenteral penicillin G is the preferred treatment for all stages of syphilis , Patients with syphilitic uveitis should be managed as though they have neurosyphilis , Congenital syphilis: i.v aqueous crystalline penicillin G: 100,000- 150,000 units/kg/day, everly 12 hourly during first 7 days and 8 hourly thereafter for total of 10 days. Alternative: procaine penicillin G 50,000 u/kg/dose i.m , single dose for 10 days. 73

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75. Topical, periocular, and/or systemic corticosteroids , under appropriate antibiotic cover, may be useful adjuncts for treating the anterior and posterior segment inflammation associated with syphilitic uveitis. Sexual contacts of the patient must be identified and treated. 75

76. Leprosy Mycobacterium leprae , Spreads by nasal secretions , Highest incidence of ocular complication among all systemic bacterial infection, 70-75 % of patients with leprosy develop ocular complication . Infection is thought to lead to chronic immune response that leads to peripheral neuropathy : primary pathogenetic mechanism. 76

77. Systemtic features Tuberculoid : one or more hypopigmented macules and anaesthetic skin patches, Borderline: similar to tuberculoid but more numerous and extensive , Lepromatous : leonine facial apperarance , peripheral plaques or nodules, upper respiratory tract involvement, peripheral nerve lesions facilitating trauma resulting shortening and loss of digits. 77

78. Ocular manifestation: Adenexal Madarosis Ectropion Entropion Trichiasis Decreased blinking Paralytic lagophthalmos 78

79. 2) Ocular surface: Corneal hypoesthesia Corneal nerve beading Dry eye Exposure keratitis Secondary infectious keratits Corneal scarring 79

80. 3) Intraocular Chornic granulomatous iridocyclitis Diffuse iris atrophy Iris pearls Miotic pupils Complicated cataract 80

81. Diagnosis Hypopigmented or reddish skin lesion Definite sensory loss, with or without thickened peripheral nerves Acid fast bacilli identified on skin smears or biopsy samples 81

82. Treatment 82

83. Clinical features Stage I: Annular skin lesion (erythema chronicum migrans ) at the site of bite, Along with constitution symptoms: fever, malaise, fatigue, myalgia, arthralgia , Stage II: cranial nerve palsies, meningitis, cardiac arrhythmias, Stage III: chronic arthritis of large joints, polyneuropathy, encephalopathy 83

84. Ocular manifestation Ocular findings are generally not prominent in Lyme disease, Uveitis: Intermediate (most common), Anterior: granulomatous or non granulomatous, Posterior: multifocal choroiditis, vasculitis and neruoretinits , Other: transient conjunctivitis, bilateral stromal keratitis, episcleritis , scleritis , orbital myositis, optic neuritis, papilledema, ocular motor and facial nerve palsy 84

85. Treatment Oral doxycycline, amoxicillin, erythromycin , If ocular involvement, neurological involvement: intravenous penicillin G, ceftriaxone , Keratitis and uveitis: may require topical/ systemic steroids , Personal protections : clothing, insect repellants to be adopted 85

86. Ocular Nocardiosis Nocardia asteroides is a gram- positive rod, partially acid- fast beaded branching filaments: a bacterium that acts like a fungus. Organism: commonly found in soil, initial infection occurs by ingestion or inhalation, Immunocompromised individuals are more likely to be affected, Ocular involvement rare, Systemic disease characterized by pneumonia and disseminated abscesses. 86

87. Ocular involvement Presentation may vary from the mild pain and redness of anterior uveitis to the severe pain and decreased vision of panophthalmitis . Can affect essentially any ocular structure, including periorbital tissue and the adnexae . Findings: keratitis, necrotizing scleritis , Choroidal or subretinal mass (abscess) with minimal vitritis to panuveitis with anterior chamber cell and flare. 87

88. Diagnosis Gram stain, Culture. Treatment: Systemic sulfonamides (trimethoprim-sulfamethoxazole) 88

89. Whipple disease Rare multisystem disease caused by Tropheryma whipplei bacterium Middle aged white men, Migratory arthritis, GI symptoms, cardiomyopathy, CNS symptoms 89

90. Ocular manifestation Neuro-ophthalmic signs: CN palsies, nystagmus,ophthalmoplegia Anterior uveitis with vitritis , Panuveitis Retinal vasculitis Retinal vascular occlusion Retinal hemorrhages Optic disc edema Optic atrophy 90

91. Diagnosis Duodenal biopsy PCR Treatment: Oral trimethoprim-sulfamethoxazole If allergic: ceftriaxone, tetracycline, or chloramphenicol 91

92. Reference American academy of ophthalmology, intraocular inflammation and uveitis, 2022-2023 Kanski’s Clinical Ophthalmology-9 th edition, Myron yanoff - Duker ophthalmology-5 th edition 92