FUNGAL CORNEAL ULCER
• Chairman : Dr. Md. Abdul Quader
Professor of Cornea , NIO&H
• Moderator : Dr. Tania Hussain Sharmee
Jr. Consultant. of Cornea , NIO&H
• Presenter : Dr. Mahamud Adnan
DO Resident, NIO&H
Introduction
EPIDEMIOLOGY :
• Worldwide, fungal keratitis is a significant cause of
ocular morbidity and unilateral blindness.
• Fungal corneal ulcers accounts 36% in Bangladesh.
• Following ocular trauma from vegetable matter;
thus, agricultural workers are at greater risk.
• Rural > Urban
• More common in tropical regions.
• More common in males than in females
• Ulcer :
“ Is a local defect ,or excavation, of the surface of
an organ or tissue that is produced by the sloughing
(shedding) of inflamed necrotic tissue “ (Ref. Robins
pathology )
• Corneal ulcer :
Refers to tissue excavation associated with an
epithelial defect , usually with infiltration and
necrosis.
• Corneal keratitis :
Presence of tissue inflammation with or
without epithelial defect.
Etiological classification of corneal
Ulcer
• Bacterial
• Fungal
• Viral
• Protozoal
• Helminthic
Infective :
Fungi Causing keratitis
1. Filamentous -
a. Septated :
Nonpigmented hyphae (hyaline)
• Fusarium species
• Aspergillus
• Trichophyton
Pigmented hyphae(dimorphic)
• Alternaria
• Curvularia
• Histoplasma
b.Nonseptated :
• Mucor species
• Rhizopous species
Fungi Causing keratitis (cont)
2. Yeast :
Candida species
• Trichosporon
• Cryptococcus
Release of matrix metalloproteinase & corneal necrosis
Recruitment of inflammatory cell from tear & limbal
vessel
Invade & proliferate in corneal stroma release cytokines &
chemokine
Pathogens adhere to cornea
Micro trauma and breach in the integrity of the corneal
epithelium
Pathogenesis
Risk Factors
• Trauma
• Chronic ocular surface disease
• Topical medications (long term use of
corticosteroid)
• Contact lens wear
• Immunosupression & diabetes
• Corneal surgery ( penetrating keratoplasty ,
LASIK, radial keratotomy )
History
• Recent ocular trauma
• Contact lens wear
• Use of ocular medications
• Recent ocular surgery
• Previous ocular disease
• Systemic illness : Diabetes
Immunosuppression
Clinical Features
Symptoms :
• Gradual onset of pain
• Grittiness
• Photophobia
• Blurred vision
• Watery or muco-purulent discharge
Signs :
• Gray or Yellow – white stromal infiltration
• Progressive Infiltration
• Satellite lesions
• Feathery branch or Ring shaped infiltration
• Elevated edges
• Progressive necrosis and thinning
Figure : showing (B) filamentous keratitis with fluffy
edges , epithelial defect and folds in Descemet membrane
(C)showing satellite lesions
Figure : Showing ring infiltration, with satellite
lesions
Signs (cont) :
• Anterior uveitis
• Hypopyon
• Endothelial plaque
• Raised IOP
• Scleritis
• Sterile or infective endophthalmitis
Differential diagnosis
• Bacterial corneal ulcer
• Viral (herpetic) keratitis
• Acanthamoeba keratitis
Investigations (Microbiological)
1. Corneal scraping
Staining
Culture
2. Corneal biopsy
Corneal smear for staining
Culture
Histopathology
Corneal Scraping & Staining
• KOH wet mount preparation
• Gram stain
• Giemsa stain
• Periodic acid-Schiff stain
• Calcofluor white stain
• Methenamine silver stain
Scraping Procedure
• Informed consent
• Topical anesthesia
• Instrument: no. 15 blade, bent 21 G needle or
Kimura spatula
• Site: floor and margin of ulcer
• Under slit lamp or operating microscope.
KOH preparation technique
• After obtaining specimen:
1. Place specimen on a clean slide.
2. Add a drop of 10% KOH to the specimen.
3. Cover the specimen with a cover slip, being
careful to avoid air bubbles.
KOH preparation technique(cont)
4. Incubate for 5-10 minutes at room temperature.
5. Examine saline wet mount with 10x and 40x
objective to identify any budding yeast,
pseudohyphae, organisms, or cells.
6. Examine KOH mount with 10x for yeast
pseudohyphae and fungal hyphal filaments.
Culture Media
• Sabouraud dextrose agar media
- White mycelium , black spore
- Growth with cream colonies
• Blood agar media
• Brain–heart infusion media
Corneal Biopsy
Indication :
• Absence of clinical improvement after 3-4 days
• Failure to identify organism
Repeated smear examination
Repeated culture of corneal scraping
• Deeply seated keratitis
• Intrastromal abscess
Smear examination
Culture
Histopathology
Newer Diagnostic Modalities
• Polymerase chain reaction
- Rapid and highly sensitive
• Anterior chamber tap
- In resistant cases
• Confocal microscopy
- Permits identification of organism in vivo
Treatment
1. General measures:
Hospitalization for –
- Aggressive disease.
- If involving an only eye.
- If patient unable to self administer treatment.
2. Medical Therapy
3. Surgical Therapy
Antifungal agents
Four group of antifungal drugs -
1. Polyenes
• Amphotericin B 0.15%
• Natamycin 5%
2. Azoles
• Econazole 2%
• Miconazole 1%
• Ketoconazole
• Fluconazole 0.2%
• Itraconazole 1%
• Voriconazole 1%
3. Pyrimidine
• 5-Fluorocytosine
4. Echinocandins
• Caspofungin 0.5%
• Micafungin 0.1%
Medical Therapy
1.Topical antifungals:
• Clinically initial drug of choice is natamycin 5%
suspension particularly for filamentous keratitis and
for yeast keratitis.
• Amphitericin-B 0.15% for yeast keratitis, also for
filamentous keratitis caused by Aspergillus species.
• Topical voriconazole 1% for non responding
traditional treatment.
Medical Therapy(cont)
Dose:
• Initially one hourly round the clock until signs of
healing/regression then tapered and if responding
continue treatment
• Length of treatment: Until healing of ulcer (at
least 12 weeks)
2. Systemic Antifungals :
• Indicated in severe keratitis, scleritis, lesions near
limbus or suspected endophthalmitis
Medical therapy(cont)
• Options include
• Oral ketoconazole 200 mg twice daily for severe
filamentous and yeast keratitis
• Oral fluconazole 200 mg twice daily for severe yeast
keratitis
• Oral itraconazole 200 mg once daily for aspergillus
species
• Oral voriconazole 400 mg twice daily for broad
spectrum coverage
Medical Therapy(cont)
3. Broad spectrum antibiotics: if bacterial co-
infection present
4. Cycloplegia: to reduce pain and to prevent
formation of posterior synechia
5. IOP should be monitored by Non-contact or digital
tonometry or tonopen
6. Subconjunctival fluconazole (In severe cases )
7. Tetaracycline (Doxycycline, in significant corneal
thinning due to its anticollagenase effect )
Surgical Therapy
1. Therapeutic scraping/Debulking (superficial
keratectomy):
Done everyday or every alternate day to
reduce number of organisms , necrotic material &
to enhance penetration of topical antifungal drugs.
2. Conjunctival Flap
Surgical Therapy(cont.)
3. N-butyl cyanoacrylate tissue adhesive and
bandage contact lens to prevent or need for
corneal transplant in severe thinning &
perforation(<2 mm)
4. Anterior chamber washout with intracameral
antifungal injection in unresponsive case for
stable corneal infiltrate but enlarging endothelial
exudation
Surgical Therapy(cont.)
5. Therapeutic keratoplasty
(penetrating/deep anterior lamellar) :
when medical therapy ineffective or
following perforation or recurrence.
Sequel & Complication
• Corneal Scaring (opacification)
• Descemetocele
• Secondary glaucoma
• Perforation
• Pseudo cornea
• Anterior staphyloma
• Endophthalmitis
Prognosis
• Depends on size and depth of lesion and causative
organism
• Small superficial lesion respond to topical therapy
• Deep stromal infection , concomitant scleritis and
intraocular involvement are difficult to eradicate
Prognosis (cont.)
• Three factors associated with treatment failure:
large ulcer size(8-12 mm),
presence of hypopeon and
aspergillus organism
• Surgical therapy successful when medical
treatment fails.
Take Home Message
• Diagnosis & treatment of fungal keratitis is
challenging.
• Lab. Diagnosis helps to correct the diagnosis.
• Early diagnosis and proper management plan can
save valuable vision of the patient.
Fungal corneal-ulcer-final

Fungal corneal-ulcer-final

  • 1.
  • 2.
    • Chairman :Dr. Md. Abdul Quader Professor of Cornea , NIO&H • Moderator : Dr. Tania Hussain Sharmee Jr. Consultant. of Cornea , NIO&H • Presenter : Dr. Mahamud Adnan DO Resident, NIO&H
  • 3.
    Introduction EPIDEMIOLOGY : • Worldwide,fungal keratitis is a significant cause of ocular morbidity and unilateral blindness. • Fungal corneal ulcers accounts 36% in Bangladesh. • Following ocular trauma from vegetable matter; thus, agricultural workers are at greater risk. • Rural > Urban • More common in tropical regions. • More common in males than in females
  • 4.
    • Ulcer : “Is a local defect ,or excavation, of the surface of an organ or tissue that is produced by the sloughing (shedding) of inflamed necrotic tissue “ (Ref. Robins pathology ) • Corneal ulcer : Refers to tissue excavation associated with an epithelial defect , usually with infiltration and necrosis. • Corneal keratitis : Presence of tissue inflammation with or without epithelial defect.
  • 5.
    Etiological classification ofcorneal Ulcer • Bacterial • Fungal • Viral • Protozoal • Helminthic Infective :
  • 6.
    Fungi Causing keratitis 1.Filamentous - a. Septated : Nonpigmented hyphae (hyaline) • Fusarium species • Aspergillus • Trichophyton Pigmented hyphae(dimorphic) • Alternaria • Curvularia • Histoplasma b.Nonseptated : • Mucor species • Rhizopous species
  • 7.
    Fungi Causing keratitis(cont) 2. Yeast : Candida species • Trichosporon • Cryptococcus
  • 8.
    Release of matrixmetalloproteinase & corneal necrosis Recruitment of inflammatory cell from tear & limbal vessel Invade & proliferate in corneal stroma release cytokines & chemokine Pathogens adhere to cornea Micro trauma and breach in the integrity of the corneal epithelium Pathogenesis
  • 9.
    Risk Factors • Trauma •Chronic ocular surface disease • Topical medications (long term use of corticosteroid) • Contact lens wear • Immunosupression & diabetes • Corneal surgery ( penetrating keratoplasty , LASIK, radial keratotomy )
  • 10.
    History • Recent oculartrauma • Contact lens wear • Use of ocular medications • Recent ocular surgery • Previous ocular disease • Systemic illness : Diabetes Immunosuppression
  • 11.
    Clinical Features Symptoms : •Gradual onset of pain • Grittiness • Photophobia • Blurred vision • Watery or muco-purulent discharge
  • 12.
    Signs : • Grayor Yellow – white stromal infiltration • Progressive Infiltration • Satellite lesions • Feathery branch or Ring shaped infiltration • Elevated edges • Progressive necrosis and thinning
  • 13.
    Figure : showing(B) filamentous keratitis with fluffy edges , epithelial defect and folds in Descemet membrane (C)showing satellite lesions
  • 14.
    Figure : Showingring infiltration, with satellite lesions
  • 15.
    Signs (cont) : •Anterior uveitis • Hypopyon • Endothelial plaque • Raised IOP • Scleritis • Sterile or infective endophthalmitis
  • 16.
    Differential diagnosis • Bacterialcorneal ulcer • Viral (herpetic) keratitis • Acanthamoeba keratitis
  • 17.
    Investigations (Microbiological) 1. Cornealscraping Staining Culture 2. Corneal biopsy Corneal smear for staining Culture Histopathology
  • 18.
    Corneal Scraping &Staining • KOH wet mount preparation • Gram stain • Giemsa stain • Periodic acid-Schiff stain • Calcofluor white stain • Methenamine silver stain
  • 19.
    Scraping Procedure • Informedconsent • Topical anesthesia • Instrument: no. 15 blade, bent 21 G needle or Kimura spatula • Site: floor and margin of ulcer • Under slit lamp or operating microscope.
  • 21.
    KOH preparation technique •After obtaining specimen: 1. Place specimen on a clean slide. 2. Add a drop of 10% KOH to the specimen. 3. Cover the specimen with a cover slip, being careful to avoid air bubbles.
  • 22.
    KOH preparation technique(cont) 4.Incubate for 5-10 minutes at room temperature. 5. Examine saline wet mount with 10x and 40x objective to identify any budding yeast, pseudohyphae, organisms, or cells. 6. Examine KOH mount with 10x for yeast pseudohyphae and fungal hyphal filaments.
  • 23.
    Culture Media • Sabourauddextrose agar media - White mycelium , black spore - Growth with cream colonies • Blood agar media • Brain–heart infusion media
  • 24.
    Corneal Biopsy Indication : •Absence of clinical improvement after 3-4 days • Failure to identify organism Repeated smear examination Repeated culture of corneal scraping • Deeply seated keratitis • Intrastromal abscess Smear examination Culture Histopathology
  • 25.
    Newer Diagnostic Modalities •Polymerase chain reaction - Rapid and highly sensitive • Anterior chamber tap - In resistant cases • Confocal microscopy - Permits identification of organism in vivo
  • 26.
    Treatment 1. General measures: Hospitalizationfor – - Aggressive disease. - If involving an only eye. - If patient unable to self administer treatment. 2. Medical Therapy 3. Surgical Therapy
  • 27.
    Antifungal agents Four groupof antifungal drugs - 1. Polyenes • Amphotericin B 0.15% • Natamycin 5% 2. Azoles • Econazole 2% • Miconazole 1% • Ketoconazole • Fluconazole 0.2% • Itraconazole 1% • Voriconazole 1% 3. Pyrimidine • 5-Fluorocytosine 4. Echinocandins • Caspofungin 0.5% • Micafungin 0.1%
  • 28.
    Medical Therapy 1.Topical antifungals: •Clinically initial drug of choice is natamycin 5% suspension particularly for filamentous keratitis and for yeast keratitis. • Amphitericin-B 0.15% for yeast keratitis, also for filamentous keratitis caused by Aspergillus species. • Topical voriconazole 1% for non responding traditional treatment.
  • 29.
    Medical Therapy(cont) Dose: • Initiallyone hourly round the clock until signs of healing/regression then tapered and if responding continue treatment • Length of treatment: Until healing of ulcer (at least 12 weeks) 2. Systemic Antifungals : • Indicated in severe keratitis, scleritis, lesions near limbus or suspected endophthalmitis
  • 30.
    Medical therapy(cont) • Optionsinclude • Oral ketoconazole 200 mg twice daily for severe filamentous and yeast keratitis • Oral fluconazole 200 mg twice daily for severe yeast keratitis • Oral itraconazole 200 mg once daily for aspergillus species • Oral voriconazole 400 mg twice daily for broad spectrum coverage
  • 31.
    Medical Therapy(cont) 3. Broadspectrum antibiotics: if bacterial co- infection present 4. Cycloplegia: to reduce pain and to prevent formation of posterior synechia 5. IOP should be monitored by Non-contact or digital tonometry or tonopen 6. Subconjunctival fluconazole (In severe cases ) 7. Tetaracycline (Doxycycline, in significant corneal thinning due to its anticollagenase effect )
  • 32.
    Surgical Therapy 1. Therapeuticscraping/Debulking (superficial keratectomy): Done everyday or every alternate day to reduce number of organisms , necrotic material & to enhance penetration of topical antifungal drugs. 2. Conjunctival Flap
  • 33.
    Surgical Therapy(cont.) 3. N-butylcyanoacrylate tissue adhesive and bandage contact lens to prevent or need for corneal transplant in severe thinning & perforation(<2 mm) 4. Anterior chamber washout with intracameral antifungal injection in unresponsive case for stable corneal infiltrate but enlarging endothelial exudation
  • 34.
    Surgical Therapy(cont.) 5. Therapeutickeratoplasty (penetrating/deep anterior lamellar) : when medical therapy ineffective or following perforation or recurrence.
  • 35.
    Sequel & Complication •Corneal Scaring (opacification) • Descemetocele • Secondary glaucoma • Perforation • Pseudo cornea • Anterior staphyloma • Endophthalmitis
  • 36.
    Prognosis • Depends onsize and depth of lesion and causative organism • Small superficial lesion respond to topical therapy • Deep stromal infection , concomitant scleritis and intraocular involvement are difficult to eradicate
  • 37.
    Prognosis (cont.) • Threefactors associated with treatment failure: large ulcer size(8-12 mm), presence of hypopeon and aspergillus organism • Surgical therapy successful when medical treatment fails.
  • 38.
    Take Home Message •Diagnosis & treatment of fungal keratitis is challenging. • Lab. Diagnosis helps to correct the diagnosis. • Early diagnosis and proper management plan can save valuable vision of the patient.