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FUNGAL KERATITIS
Aseel AL Rashdi
Ophthalmology Resident 1st year
Pathophysiology
◦ Serious ocular infection with potentially catastrophic visual results.
◦ Starts 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
Etiology ?
◦ Non-filamentous (yeast) :
◦ Candida
◦ filamentous with septae :
◦ Aspergillus spp
◦ Fusarium spp
◦ Cladosporium spp
◦ Curvularia
◦ Filamentous non-septated : eg .Rhizopus.
Risk factors ?
◦ Topical Steroid Use
◦ Immunosuppression
◦ Diabetes
◦ Agricultural Trauma
◦ Contact Lens Wear
◦ Chronic Keratitis
◦ Eye Surgery (LAISK ,PK , PKP)
Red Flags for diagnosis
◦ Corneal Ulcers Unresponsive To Broad-spectrum Antibiotics
◦ Satellite Lesions
◦ Scanty Secretions In a large ulcer
History
◦ Pain
◦ Foreign Body Sensation
◦ Redness, Tearing
◦ Blurred Vision
◦ Photophobia
◦ H/O Trauma
◦ H/O Ocular Surface Disease.
◦ Immune Compromised Patient
Physical examination
◦ Conjunctival injection
◦ Epithelial defect
◦ Suppuration
◦ Stromal infiltration
◦ Anterior chamber reaction
Non Specific
More specific for Fungal keratitis
◦ Ulcer looks dry ,
Elevated Edges,
Rough Texture, gray-
white color
◦ Typical irregular
feathery-edged
infiltrate
◦ Hypopyon
◦ Satellite Lesions
◦ Endothelial Plaque
◦ Immune ring of Wessely
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
Investigations
Saboraud
agar
chocolate
agar
blood agar
1
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.
3 weeks !
A negative culture does not rule out the presumed diagnosis because it is not 100 % sensitive.
◦ PCR
Time saving : 4–8 hours
positive fungal cultures takes up to 35 days.
Expensive
oBiopsy or AC tap if culture negative and high suspicion
Investigations 2
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
◦ 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
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.
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.
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
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
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.
Signs of improvement
◦ Decreased pain
◦ Decreased size of infiltrate.
◦ Disappeared satellite lesions
◦ Rounding of feathery margins
Treatment ( Surgical management )
◦ Epithelial debridement.
◦ Intracameral injection voriconazole / amphotericin B (50 µg/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 )
Treatment ( Surgical management )
◦ Conjunctival flap
◦ Penetrating or lamellar keratoplasty (PKP)
or (LK) is the definitive management.
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.
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.

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Fungal keratitis

  • 1. FUNGAL KERATITIS Aseel AL Rashdi Ophthalmology Resident 1st year
  • 2. Pathophysiology ◦ Serious ocular infection with potentially catastrophic visual results. ◦ Starts 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 large ulcer
  • 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, gray- white color ◦ Typical irregular feathery-edged infiltrate ◦ Hypopyon
  • 9.
  • 10. ◦ Satellite Lesions ◦ Endothelial Plaque ◦ Immune ring of Wessely
  • 11. 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
  • 13.
  • 14. 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.
  • 15. 3 weeks ! A negative culture does not rule out the presumed diagnosis because it is not 100 % sensitive.
  • 16. ◦ PCR Time saving : 4–8 hours positive fungal cultures takes up to 35 days. Expensive oBiopsy or AC tap if culture negative and high suspicion Investigations 2
  • 17. 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
  • 18. ◦ 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
  • 19. 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.
  • 20. 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.
  • 21. 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
  • 22. 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
  • 23. 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.
  • 24. Signs of improvement ◦ Decreased pain ◦ Decreased size of infiltrate. ◦ Disappeared satellite lesions ◦ Rounding of feathery margins
  • 25. Treatment ( Surgical management ) ◦ Epithelial debridement.
  • 26. ◦ Intracameral injection voriconazole / amphotericin B (50 µg/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 )
  • 27.
  • 28. Treatment ( Surgical management ) ◦ Conjunctival flap ◦ Penetrating or lamellar keratoplasty (PKP) or (LK) is the definitive management.
  • 29. 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.
  • 30. 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.

Editor's Notes

  1. Medical Management The mainstays of treatment for keratomycosis are topical antifungal agents. Natamycin (5% topical solution) initially q1-2h, then tapered over 4-6 wks FDA-approved for fungal keratitis; available as ophthalmic drops Drug of choice for filamentous fungi Poor penetration limits use in deep or severe infections Expensive and not widely available in developing countries Amphotericin B (0.15-0.5% topical solution) initially q1-2h, then tapered over 4-6 wks Good activity against Aspergillus and Candida (Figures 12, 13) Not available as a topical solution – must be compounded for intravenous (IV) formulation. (50 mg of amphotericin B diluted in sterile water = 0.166%) Inexpensive, widely available in IV form Can be used via the topical, subconjunctival, intracameral, intravitreal, or intravenous route Voriconazole (0.5 mg/mL) q1h, then tapered over 4-6 wks Broad spectrum of activity against Candida, Aspergillus, Scedosporium, Fusarium, and Paecilomyces Difficult to obtain as topical or IM – needs to be compounded Dilute 1 mL of IV voriconazole (10 mg/mL) with 19 mL of sterile water;filter prior to topical administration Econazole (1% topical solution is available in India) Found to be equivalent to natamycin 5% in a randomized clinical trial (RCT) by Prajna et al Clotrimazole (1% topical solution is available in India) Not ideal as monotherapy Other antifungals: not available as topical solutions and need to be compounded Miconazole Ketoconazole Fluconazole 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.” The Mycotic Ulcer Treatment Trial found that natamycin was associated with significantly better clinical and microbiological outcomes compared to voriconazole treatment for smear-positive filamentous fungal keratitis. This was mainly attributed to improved results with natamycin in Fusarium cases.  Surgical Management Epithelial debridement may help remove necrotic tissue, decrease microbial load, and improve drug penetration   May be repeated q 24-48 hours Cyanoacrylate tissue adhesive and bandage contact lens may be used in the management of perforation or impending perforation Penetrating or lamellar keratoplasty is the definitive management of intractable fungal keratitis or perforating corneal ulcer Adequate facilities, trained practitioners, and donor material may not be available. Recent study reported successful outcomes after deep anterior lamellar keratoplasty using acellular glycerol-preserved cornea. These grafts could prevent allograft rejection and promote graft survival rate in infected corneas. Treatment Considerations Hold all topical steroids: If the patient is currently on topical steroids, they should be tapered rapidly. Add a cycloplegic such as scopolamine 0.25% (atropine 1% if hypopyon present) Systemic antifungals (p.o. fluconazole or voriconazole) may be a useful adjunct, especially in severe cases (deep ulcer, endopthalmitis) IOP should be checked frequently because of the risk of inflammatory glaucoma. Treat ocular hypertension if present Systemic ascorbic acid may be useful to accelerate corneal remodeling and healing by inhibiting polymorphonuclear cells. Currently the use of corneal collagen crosslinking is being evaluated and may become another option for refractory fungal keratitis. Inflammatory response from topical toxicity may be confused with persistent inflammation.
  2. Ceftazidime oral for sinises
  3. remove necrotic tissue, decrease microbial load, and improve drug penetration  
  4. Patient was given Vancomycin , cefuroxime Voriconazole
  5. Conjuctival flap : They provide vascularized tissue to the infected area to supply humoral and cellular immunity while providing serum growth factors to enhance healing. They also act as a biological bandage reducing pain and stromal necrosis.