Fungal keratitis

Fungal keratitis

1. Fungal Keratitis Aseel AL Rashdi Ophthalmology Resident 1 st year

2. Pathophysiology Serious ocular infection with potentially catastrophic visual results . S tarts when the epithelial integrity is broken either due to trauma or ocular surface disease and the organism gains access into the tissue and proliferates.  Proteolitic enzymes, fungal antigens and toxins  Tissue necrosis

3. Etiology ? Non-filamentous (yeast) : Candida filamentous with septae : Aspergillus spp Fusarium spp Cladosporium spp Curvularia Filamentous non- septated : eg . Rhizopus .

4. Risk factors ? Topical Steroid Use Immunosuppression Diabetes Agricultural Trauma Contact Lens Wear Chronic Keratitis Eye Surgery (LAISK ,PK , PKP)

5. Red Flags for diagnosis Corneal Ulcers Unresponsive To Broad-spectrum Antibiotics Satellite Lesions Scanty Secretions In a l arge u lcer 

6. History Pain Foreign Body Sensation Redness, Tearing Blurred Vision Photophobia H/O Trauma H/O Ocular Surface Disease. Immune Compromised Patient

7. Physical examination Conjunctival injection  Epithelial defect Suppuration Stromal infiltration Anterior chamber reaction Non Specific

8. More specific for Fungal keratitis Ulcer looks dry , Elevated Edges, Rough Texture, g ray-white color Typical irregular feathery-edged infiltrate Hypopyon

9. Satellite Lesions Endothelial Plaque Immune ring of Wessely

10. Filamentous fungi (i.e.  Fusarium ,  Aspergillus ,  Curvularia )  Nonfilamentous fungi (i.e.  Candida ) Gray-white corneal stromal opacity with feathery white border Satellite lesions surrounding 1° infiltrate Epithelial defect or corneal ulcer Anterior chamber reaction Hypopyon Inflammatory ring Yellow-white stromal infiltrate Epithelial defect or corneal ulcer + /- Anterior chamber reaction + / - Hypopyon

11. Investigations Saboraud agar chocolate agar blood agar 1

12. KOH KOH is a rapid and inexpensive way to detect fungi. It has a sensitivity of 61–94 % and specificity of 91–97 % of detecting FK in different studies.  Ansari, Z., Miller, D., & Galor , A. (Current thoughts in fungal keratitis: diagnosis and treatment.  Current fungal infection reports ,  7 (3), 209-218. 2013.

13. 3 weeks ! A negative culture does not rule out the presumed diagnosis because it is not 100 % sensitive.

14. PCR Time saving : 4–8 hours positive fungal cultures takes up to 35 days . Expensive Biopsy or AC tap if culture negative and high suspicion Investigations 2

15. Case 62 Y Female PMH: IDDM POH : LE blind RE : glaucoma , post PKP + PCIOL 14/9/2017 , ? PDRP Presented with : FB sensation, pain , redness in RE. No H/O trauma or CL wear. Gtts : Azarga Regular Medications : Aspirin , Simvasatatin , Sitagliptin - Metformin , Gliclazide , Glargine O/E : VA : OD HM OS NPL IOP : Not possible

16. RE : Conj congested , epithelial defect 4X3 mm , Stain ++ , Infiltrate ++ , Endothelial and stromal infiltrate . PKP graft in situ , no suture abscess . AC deep and quiet. Lens : PCIOL. Vitreous : hazy. Retina : attached. LE : NPL

17. Inpatient Follow Up Impression : bacterial keratitis Started Fortified RE drops : cefuroxime , Ceftazidime 1 hrly + oral Ciprofloxacin. Daily examination . No improvement after 3 days + worsening of symptoms and clinical findings . Fungal keratitis was suspected. KOH came – ve . Antifungal treatment was started . Awaited culture results.

18. DIFFERENTIAL DIAGNOSIS Bacterial keratitis Acanthamoeba   keratitis Herpes simplex virus (HSV )) keratitis Atypical mycobacterial infection Sterile corneal ulcer Retained foreign body

19. Treatment (Medical management ) Topical antifungal agents ( mainstay of treatment ) Natamycin (FDA-approved) Amphotericin B Voriconazole Econazole Clotrimazole Recent review (2012) found no significant differences between treatment regimens and no evidence that any particular drug or combination of drugs is more effective in the management of fungal keratitis.” Ansari, Z., Miller, D., & Galor , A. (Current thoughts in fungal keratitis: diagnosis and treatment.  Current fungal infection reports ,  7 (3), 209-218 . 2013.

20. Combination oral Oral fluconazole and ketoconazole are absorbed systemically with good levels in the anterior chamber and the cornea Indications : Severe deep keratitis Scleritis Endophthalmitits

21. Adjunctive treatment Antibiotics Cycloplegic agent Systemic analgesic and anti-inflammatory- to relieve pain and decrease edema. Multivitamins to improve immunity and help in healing Systemic ascorbic acid to accelerate corneal remodeling and healing Antiglaucoma medication

22. Duration of antifungal treatment 4-6 weeks on average . If no improvement in 1 week ? Check lab results Change medications If the Infection continues to worsen? Consider Surgical interventions * Tuli , S. S. (2011). Fungal keratitis.  Clinical ophthalmology (Auckland, NZ) ,  5 , 275.

23. Signs of improvement Decreased pain Decreased size of infiltrate. Disappeared satellite lesions Rounding of feathery margins

24. Treatment ( Surgical management ) Epithelial debridement.

25. Intracameral injection voriconazole / amphotericin B (50  µ g/0.1 mL) Intrastromal therapy voriconazole and amphotericin B Intravitreal amphotericin B, fluconazole and voriconazole Subconjuctival therapy  miconazole (10 mg in 0.5 mL) and fluconazole (0.5–1.0 mL of a 2% solution); Treatment ( Surgical management )

26. Treatment ( Surgical management ) Conjunctival flap Penetrating or lamellar keratoplasty (PKP) or (LK) is the definitive management.

27. Recurrence Post PKP ? A large study of 180 cases of therapeutic penetrating keratoplasty in Nepal showed a recurrence rate of infection in 26% of cases of fungal keratitis while the recurrence rate was only 6% in bacterial infections . Bajracharya L, Gurung R. Outcome of therapeutic penetrating keratoplasty in a tertiary eye care center in Nepal.  Clin Ophthalmol . 2015;9:2299–2304. 

28. References American Academy of Ophthalmology Kanski clinical ophthalmology Ansari, Z., Miller, D., & Galor , A. (Current thoughts in fungal keratitis: diagnosis and treatment.  Current fungal infection reports ,  7 (3), 209-218. 2013. Bajracharya L, Gurung R. Outcome of therapeutic penetrating keratoplasty in a tertiary eye care center in Nepal.  Clin Ophthalmol . 2015 ; 9:2299–2304 .  Tuli , S. S. (2011). Fungal keratitis.  Clinical ophthalmology (Auckland, NZ) ,  5 , 275.