ACANTHAMOEBA

KERATITIS
DR. AMEY TAMHANE
 INTRODUCTION

• Amphizoic amoebae - They have also been called amphizoic amoebae because of the
ability to exist as free-living organisms in nature and only occasionally invade a host
and live as parasites within host tissue.

• A microscopic, free-living amoeba that can cause rare, but severe infections of the eye,
skin, and central nervous system

• Several species including A. culbertsoni, A. polyphaga, A. castellanii, A. astronyxis,

A. hatchetti, A. rhysodes, A. divionensis, A. lugdunensis, and A. lenticulata are
implicated in human disease.

Dart JK, Saw VP, KilvingtonS. Acanthamoebakeratitis: diagnosis and treatment update 2009.
Am J Ophthalmol2009;148:487-99 e2
 EPIDEMIOLOGY

• First description of Acanthamoeba Keratitis was given by Jones, in 1975.

• Incidence of 2 in 100,000 contact lenses wearers per year in the UK, which is around
20 times less than the number of bacterial infections.

• Approximately 90% of cases occurring in contact lens wearers.

• Acanthamoeba was identified in 1% of all patients cultured for possible infectious

keratitis regardless of etiology.
 ACANTHAMOEBA SPP. HAVE BEEN FOUND IN

• Soil • Heating, ventilating and air conditioning

systems
• Fresh, brackish and sea water
• Mammalian cell cultures
• Sewage
• Vegetables
• Swimming pools
• Human nostrils and throats
• Contact lens equipment
• Human and animal brain, skin and lung
• Dental treatment units tissues.

• Dialysis machines
 MICROBIOLOGY

Trophozoite Double-walled cysts

displaying numerous delicate hyaline demonstrating the wrinkled outer
acanthopodia, a large contractile ectocyst and rounded or polygonal
vacuole, and nucleus inner endocyst
 PATHOPHYSIOLOGY

Centers for Disease Control and Prevention Life Cycle of Acanthamoeba Spp., 2004
 CORNEAL PATHOGENESIS

Clarke DW, NiederkornJY. The pathophysiologyof Acanthamoebakeratitis. Trends Parasitol2006;22:175-80

 CLINICAL FEATURES

• Severe ocular pain

• Epithelial irregularity and pseudo-dendritiform pattern

• Severe anterior and posterior scleritis

• Stromal infiltrates (single, multiple and ring shape)

• Anterior Uveitis (transient hypopyon)

• Variable, persistent or recurrent epithelial erosion

• Radial keratoneuritis

• Rarely Chorioretinitis
 EARLY DISEASE ( < 1 MONTH )

• Epitheliopathy

• Punctate keratopathy

• Epithelial or Sub- epithelial infiltrates

• Pseudodendrites

• Radial Keratoneuritis
 EPITHELIOPATHY
• Epithelitis - predominantly epithelial infestation
which may present with a mild foreign body
sensation ranging to moderate pain and mild loss of
visual acuity.

• Its flat, diffuse microcystic form exhibits relative

perilimbal sparing and may be confused with dry
eye or contact lens- associated surface toxicity

Pseudodendrites (rose bengal)

• Perineural infiltrates in a radial distribution.

• Clustering of acanthamoeba trophozoites around

corneal stromal nerves resulting in swelling of
nerves.

• Trophozoites kill nerve cells by direct cytolysis

and apoptosis, explaining the severe pain
experienced in AK..
 LATE DISEASE ( > 1 MONTH )

• Ring infiltrates

• Frank ulceration

• Secondary sterile anterior uveitis, sometimes

Ring infiltrate
with hypopyon

• Corneal melt

• Corneal perforation

Sterile anterior uveitis

Frank ulceration Ring abscess Corneal Melt

 DIFFERENTIAL DIAGNOSIS

• Viral Keratitis eg. Herpetic stromal keratitis

• Fungal Keratitis noncontiguous or multifocal pattern of granular

epitheliopathy and subepithelial opacities

(unlike the contiguous, dendritic pattern in HSV

• Toxic Keratopathy keratitis)

• Bacterial Keratitis eg. Mycobacterium

 DIAGNOSIS
• Early diagnosis and prompt delivery of appropriate medical therapy is essential to secure
a good prognosis.

• If effective therapy is delayed for 3 weeks or more, prognosis deteriorates.

• AK should be considered in any case of corneal trauma complicated by exposure to soil

or contaminated water and in all contact lens wearers.

• Diagnosis is made by visualising amebae in stained smears or by culturing organisms

obtained from corneal scrapings.

• Culture yield is laboratory-dependent, with larger studies reporting only 35%- 50%
positivity.

• Lamellar corneal biopsy may be required to establish the diagnosis in some cases.
 CORNEAL SCRAPINGS

Epithelial scrapings for Light Microscopy

Various stains can be used including:

• Haematoxylin and Eosin

• Giemsa

• Periodic acid Schiff

• Calcofluor white

• Acridine orange stains

Pseudopod like projections of trophozoite with

Giemsa stain
 CULTURE METHOD

Classical tracks of trophozoites migrating on non-nutrient agar overlain with E. Coli

 CORNEAL BIOPSY

Cysts of Acanthamoeba species stained Corneal biopsy showing Acanthamoeba

with the optical whitening agent calcofluor cysts (Periodic Acid Schiff)
white and examined using ultraviolet
epifluorescence
 CONFOCAL MICROSCOPY

• Bright structures with spindle-like pseudopodia visualised within basal epithelium

consistent with Acanthamoeba trophozoites.

• Double walled cysts within stroma.

 TREATMENT

• Early diagnosis is the most important prognostic indicator of a successful treatment

outcome.

• Many cases are treated initially for herpetic keratitis.

• Persistent infection is related to the presence of acanthamoeba cysts.

• Goals of medical therapy in AK include:

– Eradication of viable cysts and trophozoites.

– Rapid resolution of associated inflammatory response.
 Concentration
Agent Dosage form Comment
for ocular use

Cationic Antiseptics Inhibit membrane

Chlorhexidine Solution 0.02 % function
Polyhexamethylene biguanide Solution 0.02 % Only agent effective
(PHMB) against cyst form
Aromatic Diamidines
Propamidine isethionate Solution 0.1 % w/v 10 mL Inhibit DNA synthesis
Hexamidine Solution 0.1 %

Azoles Destabilise cell wall

Suspension 1%
Clotrimazole
Solution 0.2 %
Fluconazole
Oil solution 5%
Ketoconazole As 200 mg tablet
Solution 1%
Miconazole
Oral 200 mg tablet
Voriconazole Recalcitrant cases
Solution 200 mg vial
 USE OF STEROIDS IN AK

Controversial

• Steroids result in improvement of clinical signs and symptoms due its anti-inflammatory
effect.

• However,

-Treatment of acanthamoeba cysts with dexamethasone hastens maturation and excystment

resulting in a 4 to 10 fold increase in number of trophozoites.

-Acceleration of trophozoite proliferation was observed.

 SURGICAL MANAGEMENT

Epithelial debridement

– Extensive debridement of affected area of corneal epithelium may be therapeutic if

performed early when disease is intraepithelial

Penetrating keratoplasty

• Therapy resistant infection(Therapeutic PK)

– Severe stromal melting with threatened perforation

– Fulminant corneal abscess

Generally poor results due to:

–  Relatively large grafts with higher risk of rejection
–  Recurrence of disease in graft due to residual viable cyst

• Visual rehabilitation (Optical PK)

– Residual corneal scarring

 SUMMARY AND TAKE HOME MESSAGE

• Acanthamoeba is difficult to treat with a prolonged course and requiring multiple toxic
antiseptic drugs.

• Most common differential diagnosis is herpetic keratitis.

• Early diagnosis of acanthamoeba is crucial for effective treatment of AK.

• Pain disproportionate to clinical signs in early presentation.

• In late presentation, patient may be painless.

• In fulminant late AK, therapeutic keratoplasty may be indicated.

THANK YOU