Fungal keratitis

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Fungal keratitis

  1. 1.    Fungal Keratitis is one of the most difficult forms of microbial keratitis to diagnose & to treat successfully. Fungus are eukaryotic heterotrophic organisms & typically forms reproductive spores. Fugus may be a part of normal external ocular flora. ( 3-28% of normal eyes) Most commonly seen are: Aspergillus Rhodotorula Candida Penicillium Cladosporium Alternaria
  2. 2. Filamentous Septate Fungi (Non Pigmented): Fusarium, Aspergillus  Filamentous Septate Fungi(Pigmented): Alternaria, Curvularia  Filamentous Non Septate: Mucor  Yeasts: Candida 
  3. 3. Overall incidence is low- 6-20%  Aspergillus most common organism worldwide.  Incidence varies geographically: Northern US: Candida, Aspergillus Southern US: Fusarium  In India: Aspergillus (27-64%) Fusarium (6-32%) Penicilliun (2-29%) 
  4. 4. Fungi gain entry into stroma through a defect in epithelial barrier.  In stroma, cause tissue necrosis & host inflammatory reaction.  Fungus can penetrate deep into stroma & through intact descemet’s membrane.  Blood borne growth inhibiting factors may not reach avascular structures of eye like cornea so fungi continues to grow & persists i.e. why conjunctival flap help in control of fungal infection. 
  5. 5.       Trauma (M/C) Contact lens use. Cosmetic Lens- filamentous Therapeutic Lens- Yeasts Overall Bacterial infection more common with contact lens users Topical Medications- Corticosteroids Anaesthetic Abuse Broad Spectrum Antibiotics Corneal Sx- Penetrating Keratoplasty, LASIK. Chronic Keratitis- Herpes Simplex, Herpes Zoster,Vernal/allergic keratitis Immunocompromised State- HIV, Leprosy
  6. 6.  Symptoms: Foreign body Sensation Slow onset increasing Pain Clinical signs are more severe than symptoms.  Signs: Nonspecific: Conjunctival injection Epithelial defect Anterior chamber reaction Specific: Infiltrate Feathery Margins Elevated edges Rough Textured Satellite lesions Endothelial Plaque Gray/Brown Pigmentation( s/o Dematiceous Fungi like Curvularia) Hypopyon ( Non Sterile, thick & immobile) Yellow line of demarcation Immune Ring (Wesseley)
  7. 7. Gram Stain Giemsa Stain Grocott’s Methamine Silver PAS Stain lectins  Fluoroscent Microscopy Acridine Orange Calcoflour white  Smear: Potassium Hydroxide Wet Mount (10-20%)  Stains:
  8. 8.  Culture Media: Should include same media for general infectious keratitis work up.  Sheep Blood Agar  Chocolate Agar  Sabouraud’s dextrose Agar  Thioglycollate Broth  Brain Heart Infusion Broth / Solid Media Positive culture expected in 90% cases, within 72 hrs in 83% cases within 1 week in 97% cases Increasing Humidity of medium by placing inoculated agar plates in Plastic bags enhance fungal growth.
  9. 9.  Newer Methods Electron Microscopy Polymerase Chain Reaction SCRAPING Advantage: Provide initial debridement of organisms Improve penetration of drugs Methods:  Surgical Blade  Diamond tipped motorized burr  Diagnostic Superficial Keratectomy/Corneal Biopsy
  10. 10. Done in Minor OT with Topical Anaesthesia 2-3 mm dermatologic trephine on anterior corneal stroma incorporating both clinically infected & adjacent clear cornea.(Avoiding Visual Axis)  Femtosecond Laser  27 guage hypodermic needle  6-0 silk suture  Anterior Chamber Tap: Hypopyon or Endothelial Plaque
  11. 11. ANTIFUNGALS  POLYENES: Amphotericin B, Natamycin Binds to ergosterol in fungal cell membrane & cause the membrane to become leaky.  AZOLES: Ketoconazole, Fluconazole, Voriconazole Inhibits CYP P450 14 a-demethylase enzyme involved in conversion of lanosterol to ergosterol
  12. 12.  PYRIMIDINES: Flucytosine Causes Faulty RNA Synthesis & non competitive inhibitor of Thymidylate Synthesis ALLYLAMINES: Terbinafine Ergosterol Biosynthesis inhibitor   ECHINOCANDINS: Capsofungin, Micafungin Cell wall Synthesis inhibitors, D-glucan synthesis inhibitor
  13. 13. Topical Natamycin 5% is Initial drug of choice.  Topical Amphotericin B 0.15% added in c/o worsening, candida & aspergillus.  Oral or Topical Azole added in c/o Fusarium.   Indication for Systemic antifungals: ( voriconazole 1st choice) Severe deep keratitis Scleritis Endophthalmitis Prophylactic t/t after Penetrating Keratoplasty for Fungal Keratitis Virulent Fungus
  14. 14. Length of treatment is based on clinical response of individual.  If toxicity is suspected and if adequate t/t has been given for 4-6 weeks treatment should be discontinued & patient is observed for reccurence in follow up.  Intrastromal injections: given if infiltrate is recalcitrant to topical t/t & depth of lesion in cornea.  Subconjunctival injections: reserved in cases of scleritis, severe keratitis, endophthalmitis. Miconazole (preferred) as is least toxic 
  15. 15.  Synergism: Amphotericin B & flucytosine Natamycin & Ketoconazole  Antagonism: Amphotericin B & Imidazoles  Antibiotics with Antifungal Property: Chloramphenicol- fusarium, Aspergillus Moxifloxacin & tobramycin- Fusarium Chlorhexidine Povidone Iodine.
  16. 16. 1. 2. 3. 4. 5. 6. 7. Debridement Therapeutic Penetrating Keratoplasty Conjunctival Flap Flap + Keratectomy Flap + Penetrating Graft Lamellar Graft Cryotherapy ( In Keratoscleritis)
  17. 17. Debridement: Done every 24-48 hrs under topical anaesthesia  Debulks necrotic material & organisms  Enhances penetration of topical drugs Penetrating Keratoplasty Indication:  Infectious process progress to limbus or sclera  Failure of medical t/t  Recurrence of infection To delay or prevent the need for corneal transplant with severe thinning or perforation is managed with TISSUE ADHESIVE(N-BUTYL CYANOACRYLATE) BANDAGE CONTACT LENS
  18. 18. Technique for Penetrating Keratoplasty:  Size of trephination should leave 1-1.5 mm clear zone of clinically uninvolved cornea to reduce residual fungus.  Interrupted sutures with slight longer bites Should be used to avoid cheese wiring  Irrigation of Anterior chamber with antifungals  Affected intraocular structures like iris, lens,& vitreous should be excised  Surgical instruments should be changed to sterile ones once infected tissue removed to avoid recontamination.
  19. 19. If endophthalmitis is suspected: Intraocular Antifungal injected at the time of keratoplasty. ( Preferably Amphotericin B)  After PK: Topical antifungals continued to prevent recurrence. If pathology reports are negative for organism at edge of corneal specimen STOP antifungals after 2 weeks and follow up patient for recurrence. If Pathology reports are positive t/t continued for 6-8 weeks.  CICLOSPORIN A: Antifungal that also prevent immune response so can be used in place of steroids 
  20. 20. Factors associated with Treatment Failure:  Large ulcer size (greater than 14mm square)  Presence of Hypopyon  Aspergillus as causative organism

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