FUNGAL CORNEAL ULCER

FUNGAL CORNEAL ULCER

• Incidence:6-20%

• 44% of all CU’S in India.

• Mc organism:aspergillus(world n india)

• Rural>urban

• 21-50 years

• Common in males

• Monsoon,early winter due to humidity & during harvest seasons

EPIDEMIOLOGY

RISK FACTORSOCULAR

Trauma - veg matter ,mud , animal matter – mc

CL (3-29%) - cosmetic lens: filamentous fungi

therapeutic lenses: yeast

drugs - indiscriminate topical ab, steroids,

corneal sx - any sx :PK ,cataract & refractive sx

steroid abuse,

c/c keratitis- VKC,allergic cojunctivits,neurotropiculcers,SJS,dry eye,

SYSTEMIC P/t on immunosuppresants,DM,ICU p/t, HIV,leprosy.

ORGANISMS

Fusarium : S.Indiaaspergillus : N.India

PATHOGENESIS• Fungi are saprophytic pathogenic organisms. • Saprophytic :obtain their nutrients from decaying

organic matter,• pathogenic :feed on living cells. • Rarely cause infection in human cornea. • gain access into the corneal stroma through epithelial

defectproliferatetissue necrosis host inflammatory reaction. penetrate intact Descemet’s membrane.

• when entered into AC/iris, eradication is difficult as Blood-borne growth inhibiting factors may not reach the avasculr cornea, AC & sclera, fungi continue to multiply and persist despite treatment.

• basis for the vasculoplasty procedure

C/F

• SYMPTOMS (RELATIVELY LESS)

• insidious onset

• nonspecific symptoms

• duration : 5-10 days

• Fb sensation & Slow onset of pain

• decreased vision if on visual axis.

• SIGNS conjunctival injection Epithelial defectAC reaction

General signs • hyphate/branching ulcer• Irregular/feathery margins(70%)with base filled with soft creamy

raised exudate• margins: elevated • Dry/ rough texture.• Satellite lesions (10%)• Fixed, unsterile,thick hypopyon.(66%)• Grey white /yellow white infiltrate• Weesley immune ring(rare):due to immune complex deposition• Posterior corneal abscess• Endothelial plaque

SPECIFIC FEATURES: • demetiaceous fungi:

brown pigments in curvularia due to melanin

indicate superficial infection with low virulence & inflammation.

• Fusarium:solani sp:

severe case with deep extension & perforation in 1 week

• aspergillus:

less severe,no rapid progression

• Candida:

keratitis resembling bacteria(discrete margins,epithelialdefect,slow progression,pre existing corneal d/s seen at junction of superior & inferior corneal junction)

• Yeast

A “collar button” configuration is typical of the keratitis associated with a small ulceration and an expanding discreet stromal infiltrate

INVESTIGATIONS1. Scraping

• aim :to debulk the organisms,

to diagnose the organism

to decrease the barrier for entry of antifungal

procedure

– aseptic precautions

– topical anesthesia

– leading edge & base debrided with spatula,sx blade, diamond tipped motorized burr.

2.PARACENTESIS

• deep stromal lesions with outpouchings into AC.

• done with 2 cc 26 G tuberculin syringe.

3. KERATECTOMY /BIOPSY

• If corneal scrapings for smears and cultures are negative

• procedure

• performed in the minor OT / slit lamp

• under topical /eyelid and retrobulbar anesthesia.

• a round 2 to 3mm sterile disposable dermatologic trephine is used 4 partial thickness trephination to take both clinically infected area & the adjacent clear cornea.

• Care is taken to avoid the visual axis, if possible.

• The base is then undermined with a surgical blade to complete the lamellar keratectomy.

• superior to corneal scraping for the isolation of the fungal organisms.

LABORATORY DIAGNOSIS• direct microscopy

• fungal cultures

• Polymerase chain reaction (PCR)

• Confocal microscopy

• DIRECT MICROSCOPY

• uses KOH wet mount preparation and smears,

• stained by Gram and Giemsa stain.

NOCARDIA : SLENDER THIN FILAMENTS

STAINING

• INTERPRETATION

• filamentous fungi:variable response

• co existing bacterial infection identified.

– GRAM+ve :

– thick peptidoglycan cell wall more 1 dye penetration.

– appears violet.

– GRAM –VE:

– appears pink.

• yeast:gram + ve oval/round shape

• Nocardia:thin gram +ve branched beaded filament.

CULTURE

/SDA

• SDA :should contain 50 micrograms /ml gentamicin without cycloheximide as it inhibits saprophytic fungi.

• incubated at 25-30 in regular incubator

• Thioglycollate broth

• inoculated for growth of anaerobic bacteria at 35⁰ -37 ⁰ C.

• A definitive diagnosis of fungal keratitis is made if

1. Corneal scrapings reveal fungal elements in smears,

2. Fungus grows in more than one medium in the absence of fungus in smears,

3. Fungus grows on a single medium in the presence of fungus in smears,

4. Confluent growth of fungus appears at the inoculated site on a single solid medium.

• incubated for 10 days to facilitate sporulation.

• +ve test yielded : 3 days (83%) ,>1 wk(97%).

• no growth :in 1 wk & reported in 3 wks

• identification based on its macroscopic and microscopic features.

• MICROSCOPIC EXAMINATION METHODS

• direct examination of a portion of slide

• adhesive tape technique

• slide culture technique

POLYMERASE CHAIN REACTION• newer method• equivalent to culture• only needs 4 hrs ,but cannot replace culture as false

+ve results are possible.• indications:• signs & symptoms of infection but no def diagnosis can

b made.• not responding to Rx.• h/o doesot match with clinical presentation.• procedure;• DNA extraction• DNA amplification• examination using agarose gel electrophoresis.

CONFOCAL MICROSCOPY• imaging technique which allows the optical section of

any material with lateral n axial spatial resolution,better contrast.

• early identification of hyphal elements & yeast is possible.

• invivo scanning slit :establishes the diagnosis

:demonstrating non-responsiveness to Rx( load of fungal filaments).

disadv

• low reproducibility,lack of distinct morphology to pathogens,limited resolution,microscope or tissue may move.

TREATMENT1. ANTIFUNGALS

classification• POLYENES:binds cell wall & alters cell permeability

natamycin

amphotericin b

• AZOLES: inhibit ergosterol

econazole,clotrimazole,imidazole,voriconazole,ketoconazole

• ECHINOCANDINS:acts on 1,3-b D glucan synthase

cuspofungin,micafungin,anidulafungin

• Indicated only when scraping /culture report : +ve.

• Empirical treatment shud not b given.

• Debridement of epithelium helps in penetration of drug.

• Topical :initially -5% natamycin hrly :day time n 2 hrly: nite

:+ FQ 4 2⁰ bacterial.

• Bd eye checkups under s/l

• resolving give natamycin 2 hrly ->2 wks t

• worsening topical ampho B 0.15%/fluconazole 2% is given.

• candida I ampho B 0.15%/ fluconazole 0.3% 1st choice.

• Patomycetes miconazole 1st choice

• echinocandins,ampho:not effective against fusarium.

•Nata 5% = econazole 1% = voriconazole 0.5 µg/ml.

• VORICONAZOLE

• derived from Fluconazole

• wider spectrum of activity against Candida, Aspergillus and Fusarium.

• exerts its effect from inhibition of cytochrome P450-dependant 14 alpha sterol demethylase, an enzyme involved in the ergosterol biosynthetic pathway.

• INTRACAMERAL THERAPY

• In severe keratomycosis not responding to topical natamycin.

• It ensures adequate drug delivery into AC and avoid surgical intervention in the acute stage of the disease.

• performed under strict aseptic conditions.

• If the infection involves the anterior capsule of the lens, care should be taken to avoid injury to the lens.

• 5 μg ampho B in 0.1 mL 5% dextrose through a paracentesis.

• Injections repeated in case of inadequate response

INTRACORNEAL THERAPY• for non healing fungal corneal ulcers• Amphotericin B injection 5-7.5 μg , given near to stromal site of growth. • raise the local concentration of the antifungal agent enough to be effective

in the eradication of the deep corneal infection total elimination• repeated after 48 to 72 hours

SUB CONJUNCTIVAL THERAPY• not routinely used .s/ctoxicity and the intense pain. • Miconazole : least toxic & best tolerated Rx(5 to 10 mg of 10mg/ml

suspension)

SIGNS OF IMPROVEMENT• Decreased pain• Decreased size of infiltrate.• Disappeared satellite lesions• Rounding of feathery margins

DURATION OF TREATMENT :• 4-6 WKS only due to toxicity

DRUG INTERACTIONS

• Synergism :

• amphotericin B +flucytosine, (Candida )

• natamycin + ketoconazole (Aspergillus ).

• antagonism

• amphotericin B and imidazoles

• RESISTANCE• rare and generally occurs in systemic mycoses.

Competition for volume in the pre corneal tear film when using two topical anti-fungals.

SYSTEMIC Rx• very large ulcers, severe deep keratitis, scleritis , endophthalmitis ,as

prophylactic treatment after PK.• ketoconazole (oral), miconazole (intravenous) itraconazole (orally

200mg/day) and fluconazole. • ketoconazole:600 mg per day.• assess LFT every 2Wks after starting Ketoconazole.

• TOPICAL CORTICOSTEROIDS• controversial. • worsen the disease when given alone and adversely influence the

efficacy of natamycin, flucytosine and miconazole when given in combination.

• Indication• to decrease corneal inflammation and scarring .• current regimen is to no steroids until at least 2 weeks of anti-fungal

treatment and clear clinical evidence of control of the infection • used in conjunction with the topical anti-fungal and never without it.

• SURGICAL THERAPY• DEBRIDEMENT

• Daily debridement with a spatula or blade is the simplest form of surgical intervention .

• done at the slit lamp under topical anesthesia.

• performed every 24 to 48 hours

• debulks organisms and necrotic material and enhance the penetration of the topical antifungal.

• BIOPSY

• for the diagnosis but also as a therapeutic intervention.

• THERAPEUTIC KERATOPLASTY

• one third of fungal infections corneal perforations.

• goal:control the infection & maintain globe integrity.

• indications:

• When progression of the keratitis is noted

• If it p rogress to involve limbus or sclerascleritis, endophthalmitis,recurrence .

• impending perforations, frank perforations > 2mm

• if there is no response to therapy.

• procedure :

• should leave a 1 to 1.5mm clear zone of clinically uninvolved cornea to reduce the possibility of residual fungal organisms peripheral to the trephination

• Interrupted sutures with slightly longer bites should be used to avoid cheese wiring of the suture if the edge of the recipient becomes involved .

• Irrigation of the AS to eliminate any organisms.

• the lens should be left untouched to prevent the spread of infection in the posterior segment.

• if affected the intraocular structures including the iris, lens, and vitreous may be excised.

• The specimens mcirobiology and pathology for culture and fixed section examination.

• If involvement of intraocular structures or endophthalmitis is suspected, an

• antifungal agents :amphotericin B (5μg/0.1ml) or miconazole (25μg/0.1ml).

• Fungal hyphae usually lie parallel to the corneal surface and lamellae.

• A vertical or perpendicular arrangement of fungal hyphae in the corneal stroma: increased virulence and in patients on topical corticosteroid therapy.

• PENETRATING KERATOPLASTY,

• topical antifungals to prevent recurrence of infection.

• + Postoperatively, systemic keatoconazole/ fluconazole.

• pathology :

• no organisms at the edge of the corneal specimen, antifungals stopped after 2 weeks followup for recurrences.

• microbiology +ve :more prolonged topical and systemic Rx for 6 to 8 weeks