INFECTIOUS KERATITIS

 Infectious keratitis is characterized by corneal inflammation and

defects caused by replicating bacteria, fungi, or proto-zoa. These
infections can progress rapidly with devastating consequences,
including corneal scarring and loss of vision.

Clinical background
Key symptoms and signs
 Clinical features of infectious keratitis include redness, tearing,
edema, discharges, decreased vision, pain, and pho-tophobia. The
hallmark of keratitis is the appearance of diffuse or localized
infiltrates within the corneal epithelium, stroma, and often the
anterior chamber. Severe cases are denoted by necrotic ulceration
of the epithelium and stroma.
 Some clinical signs may be indicative of a particular infectious
organism.
 Bacterial keratitis is often identified by the absence of epithelium and
suppurative stromal infiltrates.
 Fungal keratitis generally exhibits a slow progression, satellite
lesions, and elevated infiltrates with undefined, feathery edges
 Some parasitic infections, like Acanthamoeba, are frequently
misdiagnosed as fungal or viral because of the pseudodendritic
appearance.

Epidemiology and risk factors

 Incidence rates, risk factors, and causative agents of keratitis vary
geographically and socioeconomically.
 Among contact lens-related infections, Staphylococcus spp.,
Streptococcus spp., and Pseudomonas aeruginosa are the leading
causes in temperate climates.
 Infections due to ocular trauma are often attributed to fungal and
mixed infections (fungi and bacteria)

Diagnostic workup
 Preliminary diagnoses are based on clinical signs, symptoms, and
patient history.
 Noninvasive techniques, such as slit-lamp microscopy, confocal
microscopy, and histological examination of impression cytology,
are often used.
 If bacterial keratitis is suspected, empirically based therapies are
started immediately without definitive information about the
organism.
 It is always advisable to confirm the presence and identity of an
infectious agent.

Treatment, prognosis, and complications

Bacterial keratitis
 If bacterial keratitis is suspected, therapies are often started before
confirming the identity of the causative agent. For this reason,
broad-spectrum antibiotics are used in single or combination
therapies. The prognosis for bacterial keratitis is highly variable.

Fungal keratitis
  Fungal keratitis is often difficult to eradicate, requiring a prolonged
course of treatment. Most antifungal therapies involve one or more
of the following: (1) polyenes; (2) imidazoles; or (3) fluorinated
pyrimidines
 Like bacterial kera-titis, the use of corticosteroids is discouraged.
 Treatment outcome depends greatly on the extent of fungus
penetration.

Parasitic keratitis
 With Acanthamoeba or microsporidia keratitis, the preferred
treatment is single or combinational therapies with: (1) cationic
antiseptics, i.e., polyhexamethylene biguanide or chlorhexidine; (2)
aromatic diamidines, i.e., propamidine isothionate; or (3) azoles

Pathophysiology
 Overcoming these defenses is crucial for disease progression.
Epidemiological data suggest defects in the ocular surface increase
the likelihood of colonization by infectious micro-organisms.

Gram-positive bacterial keratitis

Staphylococcus aureus model
• Extracellular matrix proteins serve as the primary ligands for
bacterial adherence
• Pore-forming and leukocidin toxins contribute to the severity of
keratitis
• The role of Toll-like receptor 2 in sensing bacterial cell wall
components is still controversial
 Gram-negative bacterial keratitis
Pseudomonas aeruginosa model
• Adherence is mediated by both host cystic fibrosis transmembrane
conductance regulator (CFTR) and sialo-GM1
• Bacterial elastase contributes to tissue destruction directly and
indirectly by activating host proteases
• Type III system effector proteins facilitate immune evasion and are
involved in immune ring formation

Fungal keratitis
Candida albicans model
• Morphologically transformable strains produce more severe keratitis
• Biofilm growth can adhere to contact lens and is resistant to contact
lens care solutions

Parasitic keratitis
Acanthamoeba model
• Cysts are resistant to many stresses, including contact lens care
solutions, and facilitate immune evasion
• Glycoproteins and glycolipids serve as the primary ligands for
trophozoite adherence
• Trophozoites secrete destructive proteases in the presence of
mannose
• Neurons are susceptible to parasitic cytotoxin which contributes to
radial keratoneuritis