Acanthamoeba Keratitis: The Pathogenesis, the Clinical manifestation and the Medical/Surgical therapy
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4. Dr. Tukezban Huseynova
Introduction
v Acanthamoeba keratitis is the most common exogenous parasitic infection of the
cornea with the greatest risk seen in contact lens wearers of all types
v Acanthamoeba keratitis has a wide spectrum of clinical presentations that often
mimics herpetic keratitis and other forms of infectious and non-infectious keratitis
v The treatment course for Acanthamoeba keratitis is long and difficult, with
outcomes closely associated with severity of initial corneal involvement
v Prevention of Acanthamoeba keratitis is improved with strict contact lens
hygiene and disinfection instruction
v The mainstay of medical treatment is the use of topical biguanides, but may
require other antibiotic drugs as well as immunosuppression to save the eye
Cornea: Fundamentals, Diagnosis and Management“, Mark J. Mannis, Edward J. Holland, 2017
5. Dr. Tukezban Huseynova
Introduction
Biological Characteristics of free – living Amoeba
vAccording to taxonomy, amoeba is a type of unicellular protozoa with a simple
biological structure
vThere are mainly two medicine-related categories of amoebas, including parasitic
amoeba and free-living amoeba
v Free-living amoeba is widely distributed in diverse natural environments as well as
man-made environments
v Pathogenic free-living amoeba related with ocular infections mainly includes
Acanthamoeba spp. of Acanthamoebida family
„Acantamoeba keratitis: Diagnosis and treatment“, Xuguang Sun, 2018
6. Dr. Tukezban Huseynova
Introduction
Risk and Predisposing Factors
v Contact lens wear
v Contaminated water/solutions especially home made solutions
v Corneal trauma
v Orthokerathology
General conditions
v Any age may be affected
v The population of male and female patients is almost equivalent
v The majority of cases are unilateral
9. Dr. Tukezban Huseynova
Pathogenesis
1
2
Attachment
1
Destruction of Epithelium
2
Bowmans‘s Membrane breachment
3
Degradation of stroma
4
5 Radial Neuritis
The pathophysiology of Acanthamoeba keraitis, Daniel W Clarke, Jerry Y. Niederkorn
3
4
5
6
6 Does not become intraocular
11. Dr. Tukezban Huseynova
Clinical presentation
v Compared with acute suppurative bacterial keratitis, the onset of Acanthamoeba
keratitis is generally chronic and sometime indolent, which takes about 3–7 days after
exposure to risk factors
Manifestation of Acanthamoeba Keratitis
q Early Stage
q Advanced Stage
q Late Stage
12. Dr. Tukezban Huseynova
Branching vesicular
lesion
Clinical presentation
o Ocular ciliary congestion
o Roughness of corneal epithelium
o Corneal epithelial punctate opacity
o Subepithelial infiltration
o Reccurent epithelial erosion
o Rare cases of pseudodendrites or
o Disciform – like corneal edema
o Corneal ulcer (D < 4mm)
o Radial keratoneuritis (10%)
Manifestation of Acanthamoeba Keratitis
q Early Stage
v At early stage, patients usually have the lesions located in corneal epithelium and
shallow corneal stroma with the following manifestations:
Note:
o The pseudodendrites of corneal epithelium
is characterized by fine but few branches
without swelling at the end of the
branches.
o In addition, the branch edge region rarely
yields dye penetration when fluorescein
staining
13. Dr. Tukezban Huseynova
Branching
vesicular
lesion
q Early Stage Clinical samples
Epitheliitis with psuedodendrite
Pseudodendrites on the corneal epithelium
Clinical presentation
„Cornea Atlas, Third Edition“, Jay H Krachmer, David A Palay (2014)
„Cornea: Fundamentals, Diagnosis and Management“, Mark J. Mannis, Edward J. Holland, 2017
„Fungal corneal ulcers: clinical features and laboratory identification methods“, Lalitha Prajna, Vijakumar N Venkatesch Prajna, M Srinivasan (2008)
Manifestation of Acanthamoeba Keratitis
14. Dr. Tukezban Huseynova
Branching
vesicular
lesion
Clinical presentation
„Corneal ulcers diagnosis and management“, Hugh R Taylor, Peter R Laibson (2008)
„Acantamoeba keratitis: Diagnosis and treatment“, Xuguang Sun, 2018
q Early Stage Clinical samples
Manifestation of Acanthamoeba Keratitis
Radial keratoneuritis: florescein stain
along the radial nerves
corneal
subepithelial
infiltration
A female patient, 20 years old,
corneal epithelium edema and
maculosus infiltration of shallow
stroma
15. Dr. Tukezban Huseynova
Clinical presentation
q Early Stage Clinical samples
Manifestation of Acanthamoeba Keratitis
A female patient, 13 years old, history
of contact lens wear, with disciform-
like corneal edema
The patient was 32 years old with
disciform-like corneal edema
Disciform – like corneal edema
„Acantamoeba keratitis: Diagnosis and treatment“, Xuguang Sun, 2018
16. Dr. Tukezban Huseynova
Clinical presentation
q Early Stage Clinical samples
Manifestation of Acanthamoeba Keratitis
Superficial stromal ulcer
„Acantamoeba keratitis: Diagnosis and treatment“, Xuguang Sun, 2018
17. Dr. Tukezban Huseynova
Branching vesicular
lesion
Clinical presentation
o Corneal ulcer (D > 5mm, central/paracentral)
o Surface of the ulcer has hoary infiltration
o Necrotic tissue over the ulcer
o More compact infiltration is in the peripheral area
o Ditch-shaped melting in the marginal zone
o Corneal ring infiltration (28.6%), complete/incomplete/double concentric
Manifestation of Acanthamoeba Keratitis
q Advanced Stage
v At this stage, the infection will spread to deep layers of the stroma
18. Dr. Tukezban Huseynova
Clinical presentation
q Advanced Stage Clinical samples
Manifestation of Acanthamoeba Keratitis
Corneal stromal ulcer
ditch-shaped melting
ditch-shaped
melting
„Acantamoeba keratitis: Diagnosis and treatment“, Xuguang Sun, 2018
19. Dr. Tukezban Huseynova
Clinical presentation
q Advanced Stage Clinical samples
Manifestation of Acanthamoeba Keratitis
Moderate corneal ring infilrtation
Hypopyon
„Acantamoeba keratitis: Diagnosis and treatment“, Xuguang Sun, 2018
20. Dr. Tukezban Huseynova
Clinical presentation
q Advanced Stage Clinical samples
Manifestation of Acanthamoeba Keratitis
Corneal infiltration and
severe stroma edema
Double ring corneal infiltration
and severe stroma edema
stromal ulcer and dense stromal
infiltration accompanied by
hypopyon
Hypopyon
„Acantamoeba keratitis: Diagnosis and treatment“, Xuguang Sun, 2018
21. Dr. Tukezban Huseynova
Clinical presentation
q Advanced Stage Clinical samples
Manifestation of Acanthamoeba Keratitis
Acanthamoeba keratitis with
radial neuritis.
o A branching pattern can be seen
as the nerves enter the cornea
at the limbus (left).
Inflammation around the nerves
(1) is seen on the right
„Cornea Atlas, Third Edition“, Jay H Krachmer, David A Palay (2014)
22. Dr. Tukezban Huseynova
Clinical presentation
o Corneal ulcer (D > 8mm, central/paracentral)
o Dense corneal stromal ring infiltration
o Obvious Hypopion
o Ditch-shaped melting in the marginal zone is deepened
o Thinning and perforation
o Involvement of corneoscleral limbus (limbitis)
o Scleritis
o Severe Ophthalmodynia
o Orbital pain or severe headache
o Intraocular pressure might be increased
o Secondary glaucoma
Manifestation of Acanthamoeba Keratitis
q Late Stage
v Severe infection
23. Dr. Tukezban Huseynova
Clinical presentation
q Late Stage Clinical samples
Manifestation of Acanthamoeba Keratitis
o Large and deep stromal ulcer with
dense ring infiltration and severe
hypopyon
o The central area of the cornea is
thinned
„Acantamoeba keratitis: Diagnosis and treatment“, Xuguang Sun, 2018
24. Dr. Tukezban Huseynova
Clinical presentation
Manifestation of Acanthamoeba Keratitis
Ring infiltration and limbitis
q Late Stage Clinical samples
„Acantamoeba keratitis: Diagnosis and treatment“, Xuguang Sun, 2018
25. Dr. Tukezban Huseynova
Clinical presentation
Manifestation of Acanthamoeba Keratitis
o At late stage, keratoscleritis with
ditch-shaped melting in the
corneal limbus
o The central corneal area is thinned
with hypopyon
o At late stage, keratoscleritis with
ditch-shaped melting involving the
corneal limbus and anterior
scleritis
q Late Stage Clinical samples
„Acantamoeba keratitis: Diagnosis and treatment“, Xuguang Sun, 2018
26. Dr. Tukezban Huseynova
Possible complications:
vCoinfection
vAnterior uveitis
vSecondary glaucoma
vAnterior scleritis
vComplicated cataract
Clinical presentation
28. Dr. Tukezban Huseynova
Diagnosis
Clinical diagnosis:
v Risk factors: common risk factors include
- agricultural trauma
- corneal contact lenses wear
- splashing of foreign matters or small insects, etc.
v Onset time: the disease gradually progresses in 3–7 days after being affected by one or
more risk factors
v Characteristics of the corneal signs:
- Typical corneal ring infiltration
- Ditch-shaped melting at the edge of corneal ulcer
- Crude salt-like granular dense infiltration
- Radial keratoneuritis
29. Dr. Tukezban Huseynova
Clinical diagnosis:
(a) Ring infiltration
(b) Ditch-shaped
melting
(c) Crude salt-like
granular infiltration
(d) Radial neuritis
Diagnosis
„Acantamoeba keratitis: Diagnosis and treatment“, Xuguang Sun, 2018
30. Dr. Tukezban Huseynova
Etiological diagnosis:
Diagnosis
vCorneal scraping
vWet smear
vStaining
vCulture media
vCorneal Biopsy
vConfocal Microscopy
Ulcers….
31. Dr. Tukezban Huseynova
Etiological diagnosis:
Acanthamoeba cyst
An empty
Acanthamoeba cyst
The A.t. in the
corneal stoma
Clustered
Acanthamoeba cyst
Diagnosis
„Acantamoeba keratitis: Diagnosis and treatment“, Xuguang Sun, 2018
v Confocal microscopy: (samples)
33. Dr. Tukezban Huseynova
Differential diagnosis
Accanthamoeba Keratitis
Risk factors
o Trauma
o History Contact
lens wear
Viral Keratitis
Key points
o Fever
o Fatigue
o Emotional stress
o Decreased immunity
Corneal signs o Pseudodentrites
o No swollen
epithelial borders
o Dentritic ulcer
o Geographic ulcer
o Marginal keratitis
Treatment
response
o No improvement from
antiviral therapy
o I mprovement from
antiviral therapy
34. Dr. Tukezban Huseynova
Differential diagnosis
Accanthamoeba Keratitis
Risk factors o Almost similar
Fungal Keratitis
Key points
Medical history o Epithelial punctate keratopathy
o Pseudodentrites
o Non purulent/grey infiltration
o Mild anterior chamber reaction
at an early stage
o Yellow-white purulent
infiltration/ulcer
o Early anterior chamber
reaction/hypopion
o Almost similar
Corneal signs o Very rare sattelite lesion
may be a case
o Ulcers with feathery
margins/elevated edges
o Sattelite lesions
Lab. Analysis/
Confocal Microscopy
o Accanthamoeba cyst o Fungal hyphae
35. Dr. Tukezban Huseynova
Differential diagnosis
Accanthamoeba Keratitis
Risk factors o Almost similar
Bacterial Keratitis
Key points
Medical history o Subacute/chronic onset
o Slow progression
o Non purulent/grey infiltration
o Rapid onset (1-3 days)
o Purulent infiltration/ulcer
o Early anterior chamber
reaction/severe hypopion
o Almost similar
Corneal signs o Very rare sattelite lesion
may be a case
o Purulent ulcer
o Necrotic tissue/discharge
o No sattelite lesion
Treatment response o No improvement from
antibiotics
o Improvement from
antibiotics
37. Dr. Tukezban Huseynova
General information
Medical Therapy
„Cornea: Fundamentals, Diagnosis and Management“, Mark J. Mannis, Edward J. Holland, 2017
v Early recognition of Acanthamoeba keratitis has so far proven to be the strongest
predictor of a good visual outcome
v Most patients have very good visual outcomes with a standard regimen of one- or
two-drug therapy
39. Dr. Tukezban Huseynova
Aromatic Diamidines
Medical Therapy
q Anti – amoebic Drugs
v Aromatic diamidines are one of four categories of anti-amoebic drugs used
for treatment of Acanthamoeba keratitis, mainly including:
1. Propamidine isethionate
2. Pentamidine isethionate
3. Dibrompropamidine
4. Diminazene aceturate
5. Hydroxystilbamidine isethionate
6. Hexamidine diisethionate
Aromatic diamidines inhibit amoeba
40. Dr. Tukezban Huseynova
Cationic biguanide disinfectants
Medical Therapy
q Anti – amoebic Drugs
1. Chlorhexidine
2. Polyhexamethylene biguanide (PHMB)
Chlorhexidine and PHMB are considered as
the most effective drugs for killing
Acanthamoeba trophozoites and cysts
(trophozoitocide and cystocide) and are
first choice of anti-Acanthamoeba drugs in
clinical treatment
Imidazoles
1. Ketoconazole
2. Fluconazole
3. Miconazole
4. Clotrimazole
Imidazoles eye drop may only be used in
combination therapy with cationic
biguanide disinfectants during the
treatment of Acanthamoeba keratitis
41. Dr. Tukezban Huseynova
Medical Therapy
q Effect of glucocorticoids
v Glucocorticoids originally have no inhibition effect on amoeba pathogens
v After treatment with amoebicide drugs for 1 or 2 weeks, with improved condition
of keratitis, moderate doses of glucocorticoids can effectively reduce the damage of
the corneal tissues
v The combination therapy using both amoebicide drugs and glucocorticoids is safe
for clinical practice
v Topical glucocorticoids should be avoided until the pathogens are not detected by
repeat smear of the corneal scraping or by repeat corneal confocal microscopy
examinations
42. Dr. Tukezban Huseynova
Medical Therapy
q Effect of glucocorticoids
Acanthamoeba keratitis for 1 month. The
infiltration corneal stroma, without the
corneal ulcer
After the application of topical glucocorticoids
for 9 days, the corneal ulcer occurred
„Acantamoeba keratitis: Diagnosis and treatment“, Xuguang Sun, 2018
43. Dr. Tukezban Huseynova
Medical Therapy
q Therapeutic Regimens
vTreatment for Patients at Early Stage
o The therapy with topical anti-amoebic drugs is the first choice generally
o During the initial treatment, eye drops of anti-amoebic drugs should be applied hourly
day and night for at least 1–2 weeks
o According to the efficacy of treatment, eyedrops are tapered gradually from once
every 2 hours to two times a day
o For patients with the corneal shallow stromal ulcer, the debridement of the corneal
lesions can be carried out for one or two times in a week
o During the therapy, topical antiglaucoma drugs should be given in time if increased
intraocular pressure is found
„Acantamoeba keratitis: Diagnosis and treatment“, Xuguang Sun, 2018
44. Dr. Tukezban Huseynova
Medical Therapy
q Therapeutic Regimens
vTreatment for Patients at Advanced and Later Stage
o Besides the topical anti-amoebic drugs, oral terbinafine (250 mg/day) or
itraconazole (100–200 mg/day) could be administered for 1–2 weeks
„Acantamoeba keratitis: Diagnosis and treatment“, Xuguang Sun, 2018
o If the corneal ulcer is progressive or with obvious hypopyon in anterior chamber,
surgical management should be needed as soon as possible
o For patients at late stage, the corneal surgery has to be carried out immediately
o After the surgery, eye drops of cyclosporine A 1% or tacrolimus 0.1% can be used
(two to four times a day usually) with topical anti-amoebic drug therapy for at least 3
months
o Topical glucocorticoid should not be used in 1 month after surgery
46. Dr. Tukezban Huseynova
Medical Therapy
q Debridement and cautery of the corneal ulcer
Acanthamoeba keratitis for 2 months. The
corneal ulcer, ring infiltration, and
hypopyon in anterior chamber were
observed before the treatment
After treatment with the topical antiam.
medicine, debridement, and cautery,
the corneal ulcer was healed and
hypopyon disappeared
„Acantamoeba keratitis: Diagnosis and treatment“, Xuguang Sun, 2018
47. Dr. Tukezban Huseynova
Medical Therapy
q Excision of necrotic tissues of the corneal lesions and
amniotic membrane transplantation
„Acantamoeba keratitis: Diagnosis and treatment“, Xuguang Sun, 2018
48. Dr. Tukezban Huseynova
Medical Therapy
q Corneal transplantation
The corneal ulcer of Acanthamoeba
keratitis for 2 months
A year after penetrating
keratoplasty with clear graft cornea
„Acantamoeba keratitis: Diagnosis and treatment“, Xuguang Sun, 2018