Bacterial keratitis

Bacterial Keratitis
Tukezban Huseynova, MD

The online presentation is available on
Eye-Dr. Tuti – YouTube Channel

Dr. Tukezban Huseynova
Introduction

Introduction and general information
➢ Bacterial keratitis is a common and potentially sight-threatening corneal infection
➢ Ocular trauma and contact lens use are the most common risk factors
➢ When potential infection is suspected, laboratory investigations should be considered
➢ The therapeutic plan can be initiated and modified according to the laboratory findings, clinical
response, and tolerance of the antimicrobial agents
➢ Antibiotic therapy is the mainstay of treatment
➢ Surgery may be considered if medical therapy fails or if the vision is markedly threatened by
the infection or resultant scar

Host defence and risk factors

Defense of the ocular surface
Host defense and risk factors
https://www.precisionvisionedmond.com/ bumps-on-eyelids
➢ Eyelid
Keratitis in a case of entropion
„Corneal ulcers diagnosis and management“, Hugh R Taylor, Peter R Laibson (2008)
„Cornea. Fundamentals, Diagnosis and management – Fourth Edition“, Mark J. Mannis, Edward J. Holland (2017)
Eyelid disorders such as:
- Blepharitis
- Dacryocystitis
- Ectropion with exposure
- Entropion with trichiasis
- Lagophthalmos
lead to disturbed precorneal tear film that can predispose
to bacterial keratitis

➢Tear Film
Normal blinking distributes the tear film, which washes away potential pathogens via the nasolacrimal
drainage system
➢ Corneal epithelium
➢ Normal ocular flora
Few bacteria are capable of penetrating an intact epithelium – classically,
Neisseria gonorrhoeae, Corynebacterium diphtheriae, Haemophilus
aegyptius, and Listeria monocytogenes
Normal conjunctival flora, which helps to prevent overgrowth of exogenous organisms
https://www.slideshare.net/mgayatree/dry-eye- an-overview

➢External risk factors
- Corneal trauma/ chemical thermal injuries/foreign bodies
- Chronic topical anesthetic abuse
- Contaminated water
- Contamination of ophthalmic solutions
associated with trauma and topical
anesthetic abuse
Bacillus keratitis
Stromal necrosis
Ring Ulcer
➢Contact lens use
- Aphakes
- Patients with a corneal transplants
- Patients wearing bandage contact lenses
- Poor hygiene
- Smoking
The incidence of contact lens-related infectious keratitis is
higher in:

Host defense risk factors
➢Contact lens use causes:
https://www.dailymail.co.uk/health/article-1188967/The-contact-lens-make-blind-again.html
Hypoxia Slows epithelial
hemostasis
Endothelial
dysfunction
Epithelial
edema
Supresses cell
- Proliferation
- Migration
- cell exfoliation
Pseudomonas keratitis
Infiltrate
Necrotic stromal
infiltrate
Hypopion

➢Ocular surface abnormalities
Infiltrate
- Cicatricial pemphigoid
- Stevens – Johnson syndrome
- Atopic keratoconjunctivitis
- Radiation and chemical injury
- Vitamin A deficiency
- Chronical epithelial defect in post
keratoplasty patients
- Post corneal surgeries
- Systemic conditions
Infiltrate

➢Ocular surface abnormalities due to systemic conditions
Infiltrate
Moraxella keratitis
corneal ulcer
Mycobacterium keratitis
feathery
edge

Pathogenesis

Bacterial adherence
Pathogenesis
Injury
Damaged edge of corneal
epithelial cells
Bacteria

Bacterial invasion
Bacteria
Cell surface proteins
& integrins
Epithelial surface
proteins
Release of protease
by bacteria
Epithelium
Bacterial invasion
Without antibiotics bacteria continue to
invade and replicate in the corneal
stroma.
Microorganisms in the anterior stroma produce
proteolytic enzymes that destroy stromal matrices
and collagen fibrils
Viable bacteria tend to be found at the peripheral margins of
the infiltrate or deep within a central ulcer crater
Pathogenesis

Corneal inflammation and tissue damage
➢Vascular dilation of the conjunctival and limbal blood vessels is associated with
increased permeability
➢Recruitment of acute inflammatory cells occurs within a few hours after bacterial
inoculation
➢Extensive stromal inflammation eventually leads to proteolytic stromal
degradation and liquefactive tissue necrosis
Pathogenesis

Clinical presentation

Clinical features
Common presenting symptoms
Severe symptoms
➢Pain
➢Decreased vision
➢ Tearing
➢ Photophobia
➢ Eyelid edema
➢ Conjunctival hyperemia
➢ Chemosis are typical findings
➢Anterior chamber reaction
➢Hypopion
Adherent mucopurulent exudate
stromal infiltrate
General symptoms
„Copeland and Afshari‘s principles and practice of Cornea“, Robert A Copeland Jr, Natalie A Afshari (2013)

Clinical Examination
➢ Detailed History
➢ Ocular Symptoms
➢ Visual Acuity
➢ Detailed Slit – Lamp Biomicroscopy
o Eyelid Margins
o Tear Film
o Conjunctiva
o Sclera
o Limbus and
o Cornea
- Epithelial Defect
- Neovascularization
- Bullae
- Punctate Keratopathie
- Dellen
- Edema
- Thinning and perforation
- Infiltrates
Signs of severe corneal Ulcer:
➢ Rapid Progression
➢ Infiltration Dimension > 6mm
➢ Deeper than 1/3 of the corneal
thickness
➢ Presents with impending perforation
➢ Has scleral involvement
o Corneal Infiltrates
- Central
- Paracentral
- Peripheral
- Perineural
- Adjacent surgical
- traumatic wound
Location
Density, size, shape
- Ring
- Sattelite
Depth
Inflitrate Margin
- Suppurative
- Necrotic
- Feathery
- Soft
- Crystalline
o Corneal ulcer color
o Endothelium and associated
anterior chamber inflammation
- Keratic Precipitates
- Cell
- Flare
- Hypopion
- Fibrin
Clinical features

Nontuberculous
Mycobacterium keratitis
A Superficial Staphylococcus
aureus keratitis
Serratia keratitis
Ring infiltrate
Stromal necrosis and
central thinning
Noninfectious immune ring
Dense localized infiltrate
with a small satellite lesion
Clinical Samples

Clinical Samples
Pseudomonas keratitis in a soft contact lens wearer
Clinical features
„Cornea Atlas, Third Edition“, Jay H Krachmer, David A Palay (2014)

Specific bacterial ulcers

Corneal Ulcers
o Cells and Debris on corneal
surface
o Corneal epithelium is absent
over the area of active infection
o Supurative corneal inflamation
o Chemosis
o Associated conjunctivitis
o No Cells and No Debris on
corneal surface
o No epithelium defect
Infectious Ulcer Non-Infectious Ulcer

Gram – positive organisms
✓ They generally occur following trauma to the cornea
✓ They are particularly associated with the cases of dacryocystitis
✓ Infiltration starts at the site of injury and rapidly spreads towards the center
of cornea
✓ Severe anterior chamber reaction associated with hypopyon is usually
present
✓ If untreated corneal perforation and melting may occur rapidly
Pneumococcal Ulcers
Intrastromal abscess
✓ The ulcer has distinct borders and non-edematous surrounding stroma
✓ Long standing ulcers may cause intrastromal abscess
✓ They are generally associated with mild to moderate anterior chamber
reaction
Staphylococcal Ulcers

Gram – positive organisms
✓ It tends to produce an indolent ulcer after minor trauma
✓ The keratitis usually waxes and wanes
✓ The characteristic features of Nocardia keratitis include raised,
superficial pinhead-like infiltrates in a wreathlike configuration,
brush fire border, cracked windshield appearance, and
multifocal or satellite lesions
✓ The keratitis may simulate mycotic infection
Nocardia
chalky white infiltrates

✓ These organisms tend to cause a slowly
progressive keratitis
✓ Usually occurs after a corneal foreign body,
corneal trauma or following corneal surgery,
particularly after LASIK
✓ Infiltrates are typically non-suppurative and can
be solitary or multifocal, with variable anterior
chamber reactions
✓ The diagnosis may be challenging in LASIK
patients because infection can be confused for
diffuse lamellar keratitis (DLK)
✓ Lack of response to conventional antibiotic
therapy is usually a clue to the diagnosis of this
unusual keratitis
Nontuberculous mycobacteria

Clinical Samples
Mycobacterium chelonae A Streptococcus pneumoniae

Gram – negativ organisms
✓ Presents as a rapidly evolving infection that may lead to perforation and loss eye
if left untreated
✓ May also be slowly progressive
✓ They are generally associated with mild to moderate anterior chamber reaction
✓ The infection begins with an epithelial defect, superficial edema and micro-
infiltration of stroma, which occurs as early as 6 to 8 hours after injury
✓ A characteristic feature of Pseudomonas ulcer is diffuse epithelial graying (A)
which characteristically occurs away from the main site of epithelial and stromal
infiltration
✓ The progressive untreated ulcer is associated with melting (B) of the cornea
✓ This leads to descmetocele formation and eventual perforation within 2 to 5 days
of onset of infection
Pseudomonal Ulcers
graying
melting
A
B

Other Gram – negativ Rods
Moraxella Ulcers
✓ Typically indolent with only mild to moderate anterior chamber reaction
✓ It is usually oval and located in the inferior part of the cornea
Anaerobes
✓ Anaerobic infections usually follow corneal injuries with contaminated soil
✓ Some ulcers may have prolonged, moderately severe stromal and anterior
chamber reactions with endothelial decompensation despite proper
treatment
corneal ulcer

Laboratory Investigations

Laboratory investigations
Laboratory investigation includes corneal scraping
➢ Where the corneal infiltrate is chronic, central, large, deep, or
atypical in appearance
➢ Aqueous or vitreous taps should not be performed in order to
avoid intraocular inoculation of the micro organisms, unless there
is a high suspicion of microbial endophthalmitis
Indications
Broth medium can be used to transport
culture materials
➢ Lack of a favorable clinical response
➢ Toxicity from medications or corticosteroid withdrawal may be
confused with antibiotic failure
Indications for re - culture

Therapy

➢ Cefazolin (1st generation), with excellent activity against Gram-positive pathogens and minimal
toxicity after topical administration
➢ It is most frequently used in combination with other agents against Gram-negative bacteria to provide
a broad spectrum ( BS) of coverage
➢ Ceftazidime is a third-generation cephalosporin with anti-pseudomonas activity
➢ It is used in Pseudomonas keratitis with resistance to aminoglycosides or fluoroquinolones
➢ Ceftazidime also has some activity against Gram-positive organisms
Cefazolin
Ceftazidim
Cephalosporins
Therapy and resistance patterns

➢ Vancomycin is a glycopeptide antibiotic with activity against
penicillin-resistant Staphylococci
➢ It inhibits the biosynthesis of peptidoglycan polymers during
bacterial cell wall formation
➢ It is primarily active against Gram-positive bacteria and
remains one of the most potent antibiotics against MRSA
and coagulase-negative staphylococci
➢ Vancomycin should be reserved for cephalosporin-resistant
organisms
Vancomycin
Healthcare-associated methicillin-resistant
Staphylococcus aureus keratitis
following therapeutic bandage contact lens
use for recurrent erosion syndrome
Glycopeptides

➢ Aminoglycosides have a bactericidal effect against aerobic and facultative Gram-negative bacilli
➢ However, there is emergence of Pseudomonas resistance to gentamicin, tobramycin, and to a
lesser extent, amikacin
➢ For severe Pseudomonas keratitis, aminoglycosides may be combined with an anti-pseudomonas
cephalosporin
Gentamicin/ Tobramycin
➢ They inhibit bacterial protein synthesis
➢ Has a relatively broad spectrum of activity, especially against most Gram-positive and some
Gram-negative bacteria
➢ Because of their poor solubility and limited corneal penetration, topical preparations of these
newer macrolides may have a limited role for bacterial keratitis
Aminoglycosides
Macrolides

➢ Their bactericidal action is due to inhibition of bacterial DNA gyrase and/or topoisomerase IV,
enzymes essential for bacterial DNA synthesis
➢ Commercially available for ophthalmic use and have similar antimicrobial spectra, including most
Gram-negative and some Gram-positive bacteria
➢ Resistant to Pseudomonas
Ciprofloxacin, Ofloxacin, and Levofloxacin (II and III Generation)
Gatifloxacin and Moxifloxacin (VI Generation)
➢ Have better coverage of Gram-positive pathogens than earlier-generation fluoroquinolones in vitro
➢ In randomized controlled trials, both moxifloxacin and gatifloxacin performed as well as fortified
cefazolin/tobramycin combination therapy, and potentially better than ciprofloxacin
➢ Among Pseudomonas isolates, rates of susceptibility to fourth-generation quinolones range from 82%
to 100%, and are influenced by genotypic variants
Fluoroquinolones

Strategies for initial management

Start with topical Antibiotic-Drops
- Broad spectrum
Fluoroquinolon 4th
generation
Single Drug Therapy Combination Therapy
- fluoroquinolon 2nd
generation&Cefalosporin
antibioticum
Systemic antibiotic in case of severe cases
Dosage: A loading dose every 5 to 15 minutes for the first hour, followed by hourly applications
NEVER START WITH CORTICOSTEROIDS IN CASE OF CORNEAL ULCER !!!!

- Corneal scraping before
the treatment
- Disadvantage: cost/time
- Advantage: benefitial to
monitor infectious trend
Culture gueded approach Empirical approach
- Based on pre-existing data
- Starting the therapie with BS
antibiotics
- Advantage: convenience/cost
effective
Choose your therapie approach
Case-based approach
- Microbiological
testing only for cases
with ulcers involving
the visual axis/deep
large ulcers

- Pain reduction
- Discharge reduction
- Less Eyelid Edema
- Less conjunctival injection
- Sharper demarcation of the perimeter of the
stromal infiltrate
- Decreased density of stromal infiltrate
Positive Response Negative Response
- Lack of improvement
- No signs of stabilization after 48 hrs
- Progression after 48 hrs
Modification of therapy
Factors of therapy modification
Stop the antibiotics for at least 12 to 24
hours (prior to corneal scraping) to
increase the yield for microbiology
cultures

Corticosteroid Therapy
Potential Advantage
- Suppression of inflammation
- Reduce the corneal scaring
Potential Disadvantage
- Activation of infection
- Local supression of host-defence
- Inhibition of collagen synthesis
which can lead to
corneal melting
Note: Successful treatment requires
- optimal timing
- careful dose regulation
- use of adequate concomitant antibacterial
medication
- close follow-up

Therapy for Complicated Cases

Therapy for Complicated Cases
Therapeutic soft contact lenses
➢ To facilitate epithelial healing
➢ Provides a tectonic support for impending or microscopic corneal perforation
Amniotic membrane (AM) is derived from the inner layer of the human placenta and it exists in
cryopreserved or dry forms
➢ The tissue is applied onto the ocular surface and a therapeutic bandage contact lens may be placed on
top of the AM to maintain adhesion
➢ AM is thought to provide metabolic and mechanical supports in nonhealing epithelial defects after
resolution of infection
➢ AM generally should not be routinely applied over active infiltrates as this may promote bacterial growth
Amniotic membrane, AM

Surgical management

Conjunctival flap
Surgical management
➢ The flap can provide tectonic support and vascularization to the infected area and promote healing
➢ A conjunctival flap should not be placed over a necrotic area with active infection because the flap can become
infected and necrotic
➢ Conjunctival flaps are particularly useful in cases of nonhealing peripheral ulcers, where the flap can be placed
without compromising vision
Keratoplasty
Note: Therapeutic penetrating or
lamellar keratoplasty performed for
acute microbial keratitis can be
difficult and is associated with higher
complication rates and lower graft
survivals compared to keratoplasty
after ulcer resolution
o Older age,
o Delay in referral
o Injudicious steroid treatment
o Past ocular surgery
o Large or central ulcers
➢ Indications ➢ Risk Factors
o Uncontrolled progression of
the infiltrates
o Limbal involvement with
impending scleritis
o Corneal perforation

Collagen Cross- linking (CXL)
All of these effects justify its use in the management of corneal ulcer
Before CXL (weaker)
After CXL (stronger)
http://ismaileyecare.com/corneal-cross-linking/
http://mccarthyeye.com/services/corneal-collagen-cross-linking/
Surgical management
➢ CXL forms chemical bonds between adjacent fibrils, thereby providing
mechanical strength
➢ The cornea becomes relatively resistant to enzymatic digestion by a
variety of collagenases
➢ Reduces cornea’s susceptibility to proteolytic enzymes and corneal
melt due to anti-inflammatory effect

References
1. „Cornea. Fundamentals, Diagnosis and management – Fourth Edition“, Mark J. Mannis, Edward J.
Holland (2017)
2. „Cornea – Third Edition“, Jay H. Krachmer, Mark J. Mannis, Edward J. Holland (2011)
3. „Manual of Cornea“, A Samuel Gnanadoss (2008)
4. „Copeland and Afshari‘s principles and practice of Cornea“, Robert A Copeland Jr, Natalie A Afshari
(2013)
5. „Corneal ulcers diagnosis and management“, Hugh R Taylor, Peter R Laibson (2008)
6. „Cornea Atlas, Third Edition“, Jay H Krachmer, David A Palay (2014)
7. https://www.opticianonline.net/cet-archive/4638
8. „Collagen Cross – linking for microbial keratitis“, Prashant Garg, Sujata Das, Aravind Roy, Middle East Afr
J Ophthalmol, 2017

Bacterial keratitis

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