Fungal corneal-ulcer-final

corneal disease, ophthalmology

1. FUNGAL CORNEAL ULCER

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 of corneal 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 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

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 ocular trauma 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 : Gray or 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 :  Showing ring infiltration, with satellite lesions   

15. Signs (cont) : Anterior uveitis Hypopyon Endothelial plaque Raised IOP Scleritis Sterile or infective endophthalmitis

16. Differential diagnosis Bacterial corneal ulcer Viral (herpetic) keratitis Acanthamoeba keratitis

17. Investigations (Microbiological) 1. Corneal scraping 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 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.

20. 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.

21. 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.

22. Culture Media Sabouraud dextrose agar media - White mycelium , black spore - Growth with cream colonies Blood agar media Brain–heart infusion media

23. 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

24. Newer Diagnostic Modalities Polymerase chain reaction - Rapid and highly sensitive Anterior chamber tap - In resistant cases Confocal microscopy - Permits identification of organism in vivo

25. Treatment General measures: Hospitalization for – - A ggressive disease . - If involving an only eye. - If patient unable to self administer treatment. 2. Medical Therapy 3. Surgical Therapy

26. 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%

27. 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.

28. 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

29. 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

30. 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 )

31. 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

32. 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

33. Surgical Therapy (cont.) 5. Therapeutic keratoplasty (penetrating/deep anterior lamellar) : when medical therapy ineffective or following perforation or recurrence.

34. Sequel & Complication Corneal Scaring ( opacification ) Descemetocele Secondary glaucoma Perforation Pseudo cornea Anterior staphyloma Endophthalmitis

35. 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

36. 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.

37. 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.

38. Thank you