Fungal keratitis

Can be Useful as Short Notes!!!

1. FUNGAL KERATITIS

2. 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

3. Filamentous Septate Fungi (Non Pigmented): Fusarium , Aspergillus Filamentous Septate Fungi(Pigmented): Alternaria , Curvularia Filamentous Non Septate : Mucor Yeasts: Candida Diagnostic/Laboratory Groups

4. 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%) Epidemiology

5. 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. Pathogenesis

6. 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 Risk Factors

7. 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 ) Clinical Features

8. Stains: Gram Stain Giemsa Stain Grocott’s Methamine Silver PAS Stain lectins Fluoroscent Microscopy Acridine Orange Calcoflour white Smear: Potassium Hydroxide Wet Mount (10-20%) Laboratory Diagnosis

9. 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.

10. 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

11. 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

12. 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 Management

13. 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

14. 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 1 st choice) Severe deep keratitis Scleritis Endophthalmitis Prophylactic t/t after Penetrating Keratoplasty for Fungal Keratitis Virulent Fungus

15. 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

16. Synergism: Amphotericin B & flucytosine Natamycin & Ketoconazole Antagonism: Amphotericin B & Imidazoles Antibiotics with Antifungal Property: Chloramphenicol - fusarium , Aspergillus Moxifloxacin & tobramycin - Fusarium Chlorhexidine Povidone Iodine.

17. Debridement Therapeutic Penetrating Keratoplasty Conjunctival Flap Flap + Keratectomy Flap + Penetrating Graft Lamellar Graft Cryotherapy ( In Keratoscleritis ) Surgical management

18. Debridemen t: 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

19. 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.

20. 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

21. Factors associated with Treatment Failure: Large ulcer size (greater than 14mm square) Presence of Hypopyon Aspergillus as causative organism Prognosis

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