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MICROSPORIDIOSIS
Sujay Chauhan
• 29 years
• Male
• Pondicherry
• Manager, pharmaceutical company
CASEI
• Redness
• Watering
• Blurring of vision
• Photophobia
CHIEF COMPLAINTS
Left eye x 10 days
HISTORY OF PRESENT ILLNESS
Patient was apparently alright 10 days ago when he noticed
redness, watering, blurring of vision and photophobia in left eye on
waking up in the morning
No complaint of ocular discharge, cough, cold or skin vesicles
Consulted Vasan eye care where eye drops moxifloxacin and
carboxymethylcellulose were prescribed - no relief
No history of:
• Ocular trauma or foreign body
• Contact lens wear
• Long term use of any eye drop or other medication
• Diabetes mellitus
• Any other chronic systemic illness
No history of similar episodes in past
PAST HISTORY
GENERAL PHYSICAL EXAMINATION
• Average built and height
• Conscious, cooperative and well oriented
OCULAR EXAMINATION
OD OS
BCVA 6/5, N6 6/12, N10
NCT 9 mm Hg 10 mm Hg
Lids Normal Edematous
ROPLAS Negative Negative
Conjunctiva Normal
Congested
No papillae or follicles
No foreign body
Sclera Normal Normal
Cornea Clear
• Multiple superficial punctate grey-white
epithelial infiltrates <1mm with distinct
margins over central cornea
(fluorescein stain+)
• Few subepithelial infiltrates
• No keratic precipitates
• Sensation normal
10X
10X
25X
Anterior
chamber
Normal depth & quiet Normal depth & quiet
Iris Normal Normal
Pupil
Round,
normal reaction to light
Round,
normal reaction to light
Lens Clear Clear
Fundus
Cup:Disc ratio = 0.3:1
Healthy neuroretinal rim
Macula & blood vessels
normal
Cup:Disc ratio = 0.2:1
Healthy neuroretinal rim
Macula & blood vessels
normal
DIFFERENTIAL DIAGNOSIS
• Adenoviral keratitis
• Herpes simplex/zoster superficial punctate keratitis
• Microsporidial keratoconjunctivitis
• Mycobacterial keratitis
• Thygeson superficial punctate keratitis
INVESTIGATIONS
Gram stain
Corneal scraping
• Few healthy and degenerated epithelial cells
• Few pus cells
• Fibrinous exudates
• No bacterial agent could be made out
Narayana Nethralaya Laboratories, Reference number: N33711
Potassium hydroxide (KOH) + Calcofluor white stain
Many round to oval fluorescent bodies resembling microsporidia (stars
in sky appearance)
Narayana Nethralaya Laboratories, Reference number: N33711
DIAGNOSIS
Left eye microsporidial superficial punctate keratoconjunctivitis
Anterior Segment Optical Coherence
Tomography (AS-OCT)
• Tablet Albendazole 400 mg OD x 7 days
Left eye
• Eye ointment Neosporin® (Neomycin, Bacitracin & Polymyxin B)
QID x 20 days
• Eye drop Flurometholone 0.1% QID x 5 days
TDS x 5 days
BD x 5 days
OD x 5 days
TREATMENT
FOLLOW UP AT 1 WEEK
• Symptomatic improvement
• Decreased conjunctival congestion
• Reduced corneal epithelial and subepithelial infiltrates
10X
• 20 years
• Female
• Anekal, Bangalore
• Student
CASEII
• Redness
• Watering
• Foreign body sensation
CHIEF COMPLAINTS
Right eye x 5 days
No history of:
• Ocular trauma or foreign body
• Long term use of any eye drop
• Contact lens wear
• Diabetes mellitus
• Any chronic illness
Consulted a private practitioner - prescribed eye drop
Ciprofloxacin + Dexamethasone - no improvement
16X
25X
• 44 years
• Male
• Gopalganj, Bihar
• Farmer
CASEIII
• Redness
• Watering
• Burning sensation
• Blurring of vision
• Lower lid swelling
CHIEF COMPLAINTS
Left eye x 15 days
Used some eye drops prescribed by a private practitioner - no relief
16X
25X
FUNGI
DISCUSSION
PROTOZOA
Rx!!! ???
• Protozoa. Recent studies: related to kingdom fungi
• 3.5-5 µ x 2-3 µ
• True nucleus, prokaryotic-like ribosome, lacks mitochondria
• Spore forming
• Obligate intracellular parasite –
vertebrates and invertebrates
• First recognised - 1857
• First reported - 1973, vascularised
corneal scar
Alkatan HM, Al-Zaaidi S, Athmanathan S. Microsporidial keratitis. Saudi J Ophthalmol. 2012
Apr; 26(2): 199–203
• Gastrointestinal tract
• Eye
• Lung
• Kidney
• Sinus
• Immunocompromised
• Increased prevalence of HIV infection - more case reports of
microsporidiosis
1200 species identified. 12 cause human infection.
Family Genera Species
Microsporidia Microsporidium
M. ceylonensis
M. africanum
Encephalitozoonidea Encephalitozoon
E. cuniculi
E. intestinalis
Nosematidea
Nosema
N. ocularum
N. connori
Brachlola
B. algerae
B. vescularum
Enterocytozoonidae Enterocytozoon E. bleneusi
Pleistophoridea Trachipleistophora
T. hominis
T. anthopophthera
anthopophtheraSource: Chaudhari Z, Vananthi M. Postgraduate ophthalmology. 2012; 539.
Recent outbreak in different parts of world:
• Increased awareness
• High level of suspicion
• Precise knowledge of disease
• Better diagnostic methods
Microsporidiosis
outbreak
PREDISPOSING FACTORS
• Trauma
• Contaminated water or soil
• Topical or systemic corticosteroid use
• Contact lens
• Immunosuppression
• Contact with infected person, domestic animals (cats, birds)
LIFE CYCLE
• Transmission of spores through air and water
• Direct inoculation, ingestion or inhalation
Spores
Sporoplasms
Merogony
Merogony
Spore with tubule
Host cell
Sporoblasts
I. Superficial punctate keratoconjunctivitis
– Encephalitozoon
– Immunocompromised
CLINICAL PRESENTATIONS
II. Deep corneal stromal keratitis
– Nosema & Microsporidium
– Immunocompetent
– Chronic refractive infection
– Mimics herpetic keratitis
– Uveitis
– Corneal neovascularisation
– Necrosis
– Perforation
– Poor prognosis
Source: Vemuganti et al. BMC Ophthalmology 2005,5(1):19
Source: Vemuganti et al. BMC Ophthalmology 2005,5(1):19
CLINICAL SUSPICION
• Atypical multifocal epithelial keratitis
• Non-resolving keratitis with conventional anti-microbial
treatment
• Chronic culture-negative stromal keratitis
?
CONFIRMATION
• Isolating the spores
• Difficult due to inadequate samples obtained from corneal
scrapings
• Occasionally conjunctival scraping
Gram’s stain
Mild Gram positive
Source: Vemuganti et al. BMC Ophthalmology 2005,5(1):19
Giemsa stain
Epithelial cells containing cytoplasmic inclusion bodies
Source: Illinois Natural History Survey, 2015
1% acid-fast stain
Bright red with darkly stained band at the tip
Source: Vemuganti et al. BMC Ophthalmology 2005,5(1):19
Modified trichrome stain
Intracellular pink or red spherical bodies
Source: www.studyblue.com
• Immunofluorescence
• Electron microscopy
• PCR
• Confocal microscopy
TREATMENT
TOPICAL
• Fumagillin 70ug/ml (Aspergillus fumigatus, most specific)
• Hexamidine 0.1%
• Propamidine 0.1%
• Fluoroquinolones (moxifloxacin 0.5%, levofloxacin 0.5%,
ciprofloxacin 0.3%)
• Neomycin, Polymyxin B, Bacitracin
• Chlorhexidine 0.02%
ORAL
• Albendazole 400 mg BD
• Itraconazole 400 mg OD
• Benzimidazole 100-5000 mg/day
• HAART for AIDS
• Epithelium debridement (increased risk of stromal infiltration
& secondary infection)
• Penetrating keratoplasty, deep anterior lamellar keratoplasty
(DALK)
Microsporidiosis

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Microsporidiosis

  • 2. • 29 years • Male • Pondicherry • Manager, pharmaceutical company CASEI
  • 3. • Redness • Watering • Blurring of vision • Photophobia CHIEF COMPLAINTS Left eye x 10 days
  • 4. HISTORY OF PRESENT ILLNESS Patient was apparently alright 10 days ago when he noticed redness, watering, blurring of vision and photophobia in left eye on waking up in the morning No complaint of ocular discharge, cough, cold or skin vesicles Consulted Vasan eye care where eye drops moxifloxacin and carboxymethylcellulose were prescribed - no relief
  • 5. No history of: • Ocular trauma or foreign body • Contact lens wear • Long term use of any eye drop or other medication • Diabetes mellitus • Any other chronic systemic illness
  • 6. No history of similar episodes in past PAST HISTORY
  • 7. GENERAL PHYSICAL EXAMINATION • Average built and height • Conscious, cooperative and well oriented
  • 8. OCULAR EXAMINATION OD OS BCVA 6/5, N6 6/12, N10 NCT 9 mm Hg 10 mm Hg Lids Normal Edematous ROPLAS Negative Negative Conjunctiva Normal Congested No papillae or follicles No foreign body Sclera Normal Normal
  • 9. Cornea Clear • Multiple superficial punctate grey-white epithelial infiltrates <1mm with distinct margins over central cornea (fluorescein stain+) • Few subepithelial infiltrates • No keratic precipitates • Sensation normal
  • 10. 10X
  • 11. 10X
  • 12. 25X
  • 13. Anterior chamber Normal depth & quiet Normal depth & quiet Iris Normal Normal Pupil Round, normal reaction to light Round, normal reaction to light Lens Clear Clear Fundus Cup:Disc ratio = 0.3:1 Healthy neuroretinal rim Macula & blood vessels normal Cup:Disc ratio = 0.2:1 Healthy neuroretinal rim Macula & blood vessels normal
  • 14.
  • 15. DIFFERENTIAL DIAGNOSIS • Adenoviral keratitis • Herpes simplex/zoster superficial punctate keratitis • Microsporidial keratoconjunctivitis • Mycobacterial keratitis • Thygeson superficial punctate keratitis
  • 18. • Few healthy and degenerated epithelial cells • Few pus cells • Fibrinous exudates • No bacterial agent could be made out Narayana Nethralaya Laboratories, Reference number: N33711
  • 19. Potassium hydroxide (KOH) + Calcofluor white stain
  • 20.
  • 21. Many round to oval fluorescent bodies resembling microsporidia (stars in sky appearance) Narayana Nethralaya Laboratories, Reference number: N33711
  • 22. DIAGNOSIS Left eye microsporidial superficial punctate keratoconjunctivitis
  • 23. Anterior Segment Optical Coherence Tomography (AS-OCT)
  • 24.
  • 25.
  • 26. • Tablet Albendazole 400 mg OD x 7 days Left eye • Eye ointment Neosporin® (Neomycin, Bacitracin & Polymyxin B) QID x 20 days • Eye drop Flurometholone 0.1% QID x 5 days TDS x 5 days BD x 5 days OD x 5 days TREATMENT
  • 27. FOLLOW UP AT 1 WEEK • Symptomatic improvement • Decreased conjunctival congestion • Reduced corneal epithelial and subepithelial infiltrates
  • 28. 10X
  • 29. • 20 years • Female • Anekal, Bangalore • Student CASEII
  • 30. • Redness • Watering • Foreign body sensation CHIEF COMPLAINTS Right eye x 5 days
  • 31. No history of: • Ocular trauma or foreign body • Long term use of any eye drop • Contact lens wear • Diabetes mellitus • Any chronic illness Consulted a private practitioner - prescribed eye drop Ciprofloxacin + Dexamethasone - no improvement
  • 32. 16X
  • 33. 25X
  • 34. • 44 years • Male • Gopalganj, Bihar • Farmer CASEIII
  • 35. • Redness • Watering • Burning sensation • Blurring of vision • Lower lid swelling CHIEF COMPLAINTS Left eye x 15 days
  • 36. Used some eye drops prescribed by a private practitioner - no relief
  • 37. 16X
  • 38. 25X
  • 40. • Protozoa. Recent studies: related to kingdom fungi • 3.5-5 µ x 2-3 µ • True nucleus, prokaryotic-like ribosome, lacks mitochondria • Spore forming • Obligate intracellular parasite – vertebrates and invertebrates • First recognised - 1857 • First reported - 1973, vascularised corneal scar Alkatan HM, Al-Zaaidi S, Athmanathan S. Microsporidial keratitis. Saudi J Ophthalmol. 2012 Apr; 26(2): 199–203
  • 41. • Gastrointestinal tract • Eye • Lung • Kidney • Sinus • Immunocompromised • Increased prevalence of HIV infection - more case reports of microsporidiosis
  • 42. 1200 species identified. 12 cause human infection. Family Genera Species Microsporidia Microsporidium M. ceylonensis M. africanum Encephalitozoonidea Encephalitozoon E. cuniculi E. intestinalis Nosematidea Nosema N. ocularum N. connori Brachlola B. algerae B. vescularum Enterocytozoonidae Enterocytozoon E. bleneusi Pleistophoridea Trachipleistophora T. hominis T. anthopophthera anthopophtheraSource: Chaudhari Z, Vananthi M. Postgraduate ophthalmology. 2012; 539.
  • 43. Recent outbreak in different parts of world: • Increased awareness • High level of suspicion • Precise knowledge of disease • Better diagnostic methods Microsporidiosis outbreak
  • 45. • Trauma • Contaminated water or soil • Topical or systemic corticosteroid use • Contact lens • Immunosuppression • Contact with infected person, domestic animals (cats, birds)
  • 46. LIFE CYCLE • Transmission of spores through air and water • Direct inoculation, ingestion or inhalation
  • 48. I. Superficial punctate keratoconjunctivitis – Encephalitozoon – Immunocompromised CLINICAL PRESENTATIONS
  • 49. II. Deep corneal stromal keratitis – Nosema & Microsporidium – Immunocompetent – Chronic refractive infection – Mimics herpetic keratitis – Uveitis – Corneal neovascularisation – Necrosis – Perforation – Poor prognosis
  • 50. Source: Vemuganti et al. BMC Ophthalmology 2005,5(1):19
  • 51. Source: Vemuganti et al. BMC Ophthalmology 2005,5(1):19
  • 52. CLINICAL SUSPICION • Atypical multifocal epithelial keratitis • Non-resolving keratitis with conventional anti-microbial treatment • Chronic culture-negative stromal keratitis ?
  • 53. CONFIRMATION • Isolating the spores • Difficult due to inadequate samples obtained from corneal scrapings • Occasionally conjunctival scraping
  • 54. Gram’s stain Mild Gram positive Source: Vemuganti et al. BMC Ophthalmology 2005,5(1):19
  • 55. Giemsa stain Epithelial cells containing cytoplasmic inclusion bodies Source: Illinois Natural History Survey, 2015
  • 56. 1% acid-fast stain Bright red with darkly stained band at the tip Source: Vemuganti et al. BMC Ophthalmology 2005,5(1):19
  • 57. Modified trichrome stain Intracellular pink or red spherical bodies Source: www.studyblue.com
  • 58. • Immunofluorescence • Electron microscopy • PCR • Confocal microscopy
  • 59. TREATMENT TOPICAL • Fumagillin 70ug/ml (Aspergillus fumigatus, most specific) • Hexamidine 0.1% • Propamidine 0.1% • Fluoroquinolones (moxifloxacin 0.5%, levofloxacin 0.5%, ciprofloxacin 0.3%) • Neomycin, Polymyxin B, Bacitracin • Chlorhexidine 0.02%
  • 60. ORAL • Albendazole 400 mg BD • Itraconazole 400 mg OD • Benzimidazole 100-5000 mg/day
  • 61. • HAART for AIDS • Epithelium debridement (increased risk of stromal infiltration & secondary infection) • Penetrating keratoplasty, deep anterior lamellar keratoplasty (DALK)

Editor's Notes

  1. Foreign body, infection (conj, kerat, uv, scler), ac cong glaucoma,
  2. Preauricular lymphadenopathy
  3. Adenoviral: B/L, subepith infiltrates, follicles, HSV: skin lesions, sensation dec, Myco: spoke like margins, Thygeson: epith, idiopathic
  4. HIV test
  5. Hyperreflective lesion at the level of epithelium
  6. Fumagillin – alters DNA content or inhibits RNA synthesis