Infectious keratitis is characterized by corneal inflammation and defects caused by replicating bacteria, fungi, or protozoa. These infections can progress rapidly with devastating consequences, including corneal scarring and loss of vision. Thus, it is imperative to identify this condition promptly and begin an aggressive course of therapy to limit tissue damage. This chapter summarizes the current understanding of various clinical and pathophysiological aspects of infectious keratitis.
Clinical background
Key symptoms and signs
Clinical features of infectious keratitis include redness, tearing, edema, discharges, decreased vision, pain, and photophobia. 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 ( Table 7.1 ). Bacterial keratitis is often identified by the absence of epithelium and suppurative stromal infiltrates. Gram-negative bacterial infections are associated with hazy corneal rings and soup ulcerations, whereas Gram-positive infections tend to produce well-defined grayish-white infiltrates and localized ulcerations ( Figures 7.1 and 7.2 ). Fungal keratitis generally exhibits a slow progression, satellite lesions, and elevated infiltrates with undefined, feathery edges ( Figure 7.3 ). Some parasitic infections, like Acanthamoeba , are frequently misdiagnosed as fungal or viral because of the pseudodendritic appearance. In many cases, patients infected with parasites report disproportionate pain, which is characteristic of radial keratoneuritis ( Figure 7.4 ).
| Common pathogens | Distinguishing clinical features | Therapeutic strategies | |
|---|---|---|---|
| Bacteria | |||
| Gram-positive |
| Localized ulcers: round or oval | |
| Stromal infiltrates: discrete grayish-white | Fluoroquinolones | ||
| Stromal haze: minimal, distinct borders | Fluoroquinolones with cephalosporin | ||
| Gram-negative |
| Undefined ulcers: soupy | |
| Stromal infiltrates: dense and suppurative | Aminoglycosides with cephalosporin | ||
| Stromal haze: intense immune rings | |||
| Fungi | |||
| Yeast |
| Ulcers, epithelial defects | Polyenes |
| Stromal infiltrates: discrete grayish-white | |||
| Slow progression | Imidazoles | ||
| Filamentous |
| Slough: dry, elevated | Fluorinated pyrimidines |
| Stromal infiltrates: feathery margins | |||
| Satellite lesions | Imidazoles with fluorinated pyrimidine | ||
| Parasitic | |||
| Severe pain, radial keratoneuritis | Cationic antiseptics | |
| Stromal infiltrates: pseudodendritic | Aromatic diamidines | ||
| Stromal haze: intense immune rings | Azoles |
Epidemiology and risk factors
Incidence rates, risk factors, and causative agents of keratitis vary geographically and socioeconomically. Incidence in the USA is estimated to be 11 in 100 000, whereas rates in South-East Asia are near 800 in 100 000. The principal risk factors include trauma, contact or orthokeratology lens wear, ocular surface disease, ocular surgery, and systemic disease. In Europe, Japan, and USA, contact lens wear constitutes the major risk factor for infectious keratitis. Ocular trauma is the main predisposing factor in developing countries.
Among contact lens-related infections, Staphylococcus spp., Streptococcus spp., and Pseudomonas aeruginosa are the leading causes in temperate climates. In subtropical climates, like northern India, fungal keratitis has been strongly linked to contact lens wear, representing 20–30% of total isolates. Although rare in temperate climates, there has been a recent increase in fungal and parasitic keratitis associated with contact lens wear involving Fusarium and Acanthamoeba . These appear to be associated with specific contact lens care solutions and storage hygiene.
Infections due to ocular trauma are often attributed to fungal and mixed infections (fungi and bacteria). Candida and other yeasts are commonly reported in temperate climates and filamentous fungi, i.e., Aspergillus and Fusarium, in warmer climates.
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. This can be accomplished by examining corneal scrapings using standard diagnostic staining, culturing, immunochemistry, and polymerase chain reaction techniques ( Table 7.2 ). Biopsies may be necessary if the disease is contained within the stroma. If the infectious agent is culturable, susceptibility profiles should be determined for optimizing treatment strategies.
| Type of stain | Organisms visualized/cultured | Comments |
|---|---|---|
| Gram stain | Bacteria, fungi, Acanthamoeba | Peptidoglycan, teichoic acids – violet |
| Giemsa stain | Bacteria, fungi, Acanthamoeba | Acidophilic/basophilic – contrast |
| Acridine orange | Bacteria, fungi, Acanthamoeba | DNA – fluorescent orange |
| Calcoflur white | Fungi, Acanthamoeba | Cellulose/chitin – fluorescent blue |
| Gomori methenamine silver | Fungi, Acanthamoeba | Uric/urate particles – dark blue |
| Periodic acid–Schiff | Fungi, Acanthamoeba | Cell wall – pink |
| Hematoxylin and eosin | Acanthamoeba | Intracellular structures – contrast |
| Standard agar culture media | ||
| Blood agar * | Bacteria, fungi, † Acanthamoeba | General purpose, including fastidious agents |
| Chocolate agar | Bacteria, fungi † | General purpose, including fastidious agents |
| Brain–heart infusion agar | Bacteria, fungi † | General purpose |
| Sabouraud dextrose agar | Fungi | |
| Escherichia coli overlay on non-nutrient agar | Acanthamoeba | |
| Standard liquid culture media | ||
| Brain–heart infusion broth | Bacteria, fungi † | |
| Thioglycollate broth | Bacteria | Good for small inocula |
| Glucose neopeptone broth | Fungi |
* Ideal for culturing bacteria such as Staphylococcus, Streptococcus , and Pseudomonas .
† Fungi can be recovered from standard bacterial media in the presence of antibiotics.
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