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
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
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
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
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.
Ceftazidime oral for sinises
remove necrotic tissue, decrease microbial load, and improve drug penetration
Patient was given Vancomycin , cefuroxime
Voriconazole
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.