Infectious Keratitis
Infectious processes caused by a number of microbial agents may result in inflammation of the cornea. Severe inflammation can lead to corneal necrosis, ulceration, and perforation. See also BCSC Section 8, External Disease and Cornea.
Bacterial infections
Bacterial infections of the cornea often follow a disruption in corneal epithelial integrity resulting from contact lens wear, trauma, alteration in immunologic defenses (eg, use of topical or systemic immunosuppressive agents), preexisting corneal disease (eg, dry eye disease, exposure keratopathy), ocular medication toxicity, or contamination of ocular medications. Bacterial organisms commonly involved in corneal infections include Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae, as well as members of the family Enterobacteriaceae.
Scrapings from infected corneas show collections of neutrophils admixed with necrotic debris. Gram stain may demonstrate the presence of microorganisms (Fig 6-3). A culture is helpful for accurate identification of specific organisms and for assessment of antibiotic sensitivities.
Herpes simplex virus keratitis
Herpes simplex virus (HSV) keratitis is usually a self-limited corneal epithelial infection, but it may have recurrent or chronic forms. HSV epithelial keratitis is characterized by a linear arborizing pattern of shallow ulceration and swelling of epithelial cells, known as a dendrite (Fig 6-4A), that reflects viral reactivation in the corneal nerves. Corneal scrapings obtained from a dendrite and prepared using Giemsa or hematoxylin-eosin (H&E) stain may reveal intranuclear viral inclusions. Viral culture and, especially, polymerase chain reaction (PCR) techniques are useful for confirmation of viral infection. Like the dendritic ulcer, a geographic ulcer is caused by replicating virus; however, it has a much larger epithelial defect, similar in appearance to a map. Metaherpetic (trophic) ulcer is the only form of epithelial ulceration that does not contain any live virus. These ulcers result from the inability of the epithelium to heal. Stromal and/or disciform keratitis (Fig 6-4B) may accompany or follow epithelial infection as an immune-mediated response directed against viral antigens but not necessarily with the presence of active replicating virus. Histologically, chronic inflammatory cells and blood vessels may be seen tracking between stromal lamellae, a phenomenon known as interstitial keratitis (IK) (Fig 6-4C), which is discussed later in this chapter. In some cases, stromal keratitis may demonstrate significant necrosis, resulting in stromal thinning and even full-thickness perforation. Endotheliitis may also occur, with a granulomatous reaction at the level of Descemet membrane (Fig 6-4D, E). Postherpetic neurotrophic keratopathy may result from corneal hypoesthesia or anesthesia; it is characterized histologically by marked loss of stromal keratocytes (Fig 6-4F).
Fungal keratitis
Fungal (mycotic) keratitis is often a complication of trauma, especially trauma involving plant or vegetable matter or microtrauma related to contact lens wear. Corticosteroid use, especially topical, is another major risk factor. Unlike most bacteria, some fungi can penetrate the cornea and extend through the Descemet membrane into the anterior chamber. The most common fungal organisms are the septate, filamentous fungi Aspergillus and Fusarium, and the yeast Candida. Cultures, particularly on Sabouraud agar, are helpful for accurate identification of specific fungi and for assessment of antifungal sensitivities. When cultures are negative and organism identity remains elusive, corneal biopsy may be considered. Histologic evaluation can demonstrate the presence of fungal microorganisms with the use of special stains such as Gomori or Grocott methenamine silver (GMS) (Fig 6-5) or PAS with diastase. Identification of the exact fungal species solely on the basis of histology is often difficult.
Acanthamoeba keratitis
Acanthamoeba protozoa most commonly cause infection in soft contact lens wearers who do not take appropriate precautions in cleaning and disinfecting their lenses or whose lenses come into contact with contaminated stagnant water (eg, as found in hot tubs or ponds). Tap water may also harbor Acanthamoeba in small numbers. Patients presenting with Acanthamoeba keratitis usually have severe eye pain caused by radial keratoneuritis. In the late stages of the disease, a corneal ring infiltrate may be present (Fig 6-6A). Special culture techniques and media, including nonnutrient blood agar layered with Escherichia coli, are required to grow Acanthamoeba but are not widely available. The microorganisms penetrate the deeper layers of the stroma and may be difficult to isolate from a superficial scraping. Because of these challenges, PCR-based methods for diagnosis of Acanthamoeba keratitis are becoming more widely used. Histologically, corneal epithelial scrapings, biopsy specimens, or corneal buttons may show cysts and trophozoites (Fig 6-6B). The organisms are generally visualized with routine H&E sections but may also be highlighted with PAS and GMS stains. Calcofluor white or acridine orange fluorescent stains may also be used.
Infectious crystalline keratopathy
Infectious crystalline keratopathy (ICK) typically occurs in patients who are on long-term topical corticosteroid therapy—for example, following penetrating keratoplasty (PK). The infection typically arises along a suture track or a surgical wound. The most common etiologic microorganism is Streptococcus viridans (α-hemolytic Strep), but many other organisms have been reported, including bacteria, mycobacteria, and fungi. Chronic immunosuppression, when combined with properties of the organism’s glycocalyx (a glycoprotein and glycolipid covering that surrounds the cell membranes of some bacteria and sequesters the organism from the immune system), may promote growth of the organism in this condition. No true crystals are involved; rather, this condition derives its name from the crystalloid, feathery clinical appearance of the opacity (Fig 6-7A).
In many cases, the diagnosis is missed clinically and is made histologically after failure of a corneal graft. Histologically, sequestrations of organisms are present within the interlamellar spaces of the stroma. Typically, the inflammatory cell infiltrate is insignificant. The organisms are sometimes apparent on H&E stain; they may also be highlighted with Gram, PAS, GMS, or acid-fast stain, depending on the etiologic agent (Fig 6-7B).
Interstitial keratitis
In interstitial keratitis (IK), nonsuppurative inflammatory cells infiltrate the interlamellar spaces of the corneal stroma, often with vascularization. Typically, the overlying epithelium remains intact. The changes observed in IK are thought to result from an immunologic response to infectious microorganisms or their antigens. Transplacental infection of the fetus by Treponema pallidum (congenital syphilis) may cause IK (Fig 6-8A). Histologically, chronic syphilis-related (luetic) IK is characterized by the presence of stromal ghost vessels devoid of erythrocytes with surrounding stromal fibrosis and a variable degree of chronic inflammation. The Bowman layer and Descemet membrane are characteristically intact. In addition, the Descemet membrane may demonstrate focal multilaminated excrescences (Fig 6-8B) that are reminiscent of guttae (Latin for drops), droplike excrescences of Descemet membrane, observed in Fuchs endothelial corneal dystrophy (discussed later in this chapter).
Although congenital syphilis represents the “classic” cause of IK, the most common etiologic agent of IK is HSV (see Fig 6-4). Other microorganisms that can cause IK include Onchocerca volvulus, Mycobacterium tuberculosis, Mycobacterium leprae, Borrelia burgdorferi, and Epstein-Barr virus. See also BCSC Section 8, External Disease and Cornea.
Excerpted from BCSC 2020-2021 series: Section 4 - Ophthalmic Pathology and Intraocular Tumors. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.