FUNGAL KERATITIS

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

Filamentous Septate Fungi (Non Pigmented):

Fusarium, Aspergillus Filamentous Septate

Fungi(Pigmented): Alternaria, Curvularia Filamentous Non Septate: Mucor Yeasts: Candida

Diagnostic/Laboratory Groups

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

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

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

Symptoms: Foreign body Sensation Slow onset increasing PainClinical 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

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

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.

Newer Methods Electron Microscopy Polymerase Chain Reaction

SCRAPING Advantage: Provide initial debridement of organismsImprove penetration of drugs Methods: Surgical Blade Diamond tipped motorized burr Diagnostic Superficial Keratectomy/Corneal

Biopsy

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

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

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

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

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

Synergism: Amphotericin B & flucytosine Natamycin & Ketoconazole

Antagonism: Amphotericin B & Imidazoles

Antibiotics with Antifungal Property: Chloramphenicol- fusarium, Aspergillus Moxifloxacin & tobramycin- Fusarium Chlorhexidine Povidone Iodine.

1. Debridement2. Therapeutic Penetrating Keratoplasty3. Conjunctival Flap4. Flap + Keratectomy5. Flap + Penetrating Graft6. Lamellar Graft7. Cryotherapy ( In Keratoscleritis)

Surgical management

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 infectionTo delay or prevent the need for corneal transplant with

severe thinning or perforation is managed with TISSUE ADHESIVE(N-BUTYL CYANOACRYLATE) BANDAGE CONTACT LENS

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.

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

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

Prognosis

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