internal ulcer. Also note endothelial cell loss. C, Severe case showing lens tissue adherent to posterior corneal surface. The arrow marks the edge of the internal ulcer. Note lens capsule (arrowheads), swollen lens epithelial cells (E), lens fibers (F),

and iris tissue with melanin pigment (I). (Part A courtesy of Andrew J.W. Huang, MD; parts B and C courtesy of George J. Harocopos, MD.)

Inflammations

Infectious Keratitis

The cornea may be affected by infectious processes caused by a number of different microbial agents. Severe inflammation can lead to corneal necrosis, ulceration, and perforation. See also BCSC Section 8, External Disease and Cornea.

Bacterial infections

Corneal infections caused by bacterial agents often follow a disruption in the corneal epithelial integrity resulting from contact lens wear, trauma, alteration in immunologic defenses (eg, use of topical or systemic immunosuppressives), antecedent corneal disease (eg, dry eye, exposure keratopathy), ocular medication toxicity, or contamination of ocular medications. Bacterial organisms commonly involved in corneal infections include Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pneumoniae, and Enterobacteriaceae.

Scrapings obtained from infected corneas show collections of neutrophils admixed with necrotic debris. The presence of organisms may be demonstrated on Gram stain. Culture is helpful for accurate identification of specific organisms and for assessment of antibiotic sensitivities. Following sterilization of the ulcer with antibiotic therapy, penetrating keratoplasty may be required in cases of visually significant corneal scarring. Keratoplasty is sometimes required urgently in the acute phase of infection, for example, for perforation or impending perforation (Fig 6-5).

Figure 6-5 Bacterial ulcer. A, Clinical appearance of pseudomonal ulcer. B, In this patient, penetrating keratoplasty was performed during the acute phase of infection. On H&E stain, the corneal button shows ulcerative keratitis, with stromal necrosis and neutrophilic infiltration (arrow). C, Keratoplasty specimen (different patient) showing scar from healed keratitis. Note loss of the Bowman layer (between arrowheads) and stromal thinning/fibrosis (arrow), with compensatory epithelial

thickening. (Part A courtesy of Andrew J.W. Huang, MD; parts B and C courtesy of George J. Harocopos, MD.)

Herpes simplex virus keratitis

Usually a self-limited corneal epithelial disease, herpes simplex virus keratitis is characterized by a linear arborizing pattern of shallow ulceration and swelling of epithelial cells called a dendrite (Fig 6-6A). The diagnosis may generally be made clinically. Corneal scrapings obtained from a dendrite and prepared using the Giemsa stain reveal the presence of intranuclear viral inclusions. Viral culture, antigen detection, or polymerase chain reaction (PCR) techniques may be helpful in atypical cases. A dendrite is associated with subepithelial infiltration by chronic inflammatory cells and loss of the Bowman layer. Stromal and/or disciform keratitis (Fig 6-6B) may accompany or follow epithelial infection, leading to stromal scarring and possibly vascularization. Histologically, chronic inflammatory cells and blood vessels may be seen tracking between stromal lamellae, that is, interstitial keratitis (Fig 6-6C) (discussed later). Endotheliitis may also occur, with a granulomatous reaction at the level of the Descemet membrane (Fig 6-6D), which corresponds to disciform keratitis clinically. Visually significant corneal scarring from herpetic keratitis is the single most common infection-related indication for penetrating keratoplasty. Postherpetic neurotrophic keratopathy may result from corneal hypoesthesia or anesthesia and is characterized histologically by a featureless corneal stroma with a paucity of keratocytes (Fig 6-6E).

Figure 6-6 Herpes simplex virus keratitis. Clinical photographs depicting dendritic (A) and stromal/disciform (B) keratitis. C, Histology of corneal button shows stromal keratitis with loss of the Bowman layer (asterisk), stromal scarring and vascularization (arrowhead), and scattered chronic inflammatory cells (arrows). D, Higher-power photomicrograph shows granulomatous reaction (between arrows) in the region of Descemet membrane (arrowhead). Note the fibrous retrocorneal

membrane (asterisk), scattered chronic inflammatory cells, and blood vessel (open arrow). E, Postherpetic neurotrophic keratopathy. Photomicrograph shows featureless corneal stroma (asterisks) with only rare keratocytes (arrow). (Parts A and B

courtesy of Anthony J. Lubniewski, MD; parts C and D courtesy of Tatyana Milman, MD; part E courtesy of Robert H. Rosa, Jr, MD.)

Fungal keratitis

Mycotic keratitis is often a complication of trauma, especially involving plant or vegetable matter, or microtrauma related to contact lens wear. Corticosteroid use, especially topical, is another major risk factor. Unlike most bacteria, fungi are able to penetrate the cornea and extend through the Descemet membrane into the anterior chamber. The most common organisms are the septated, filamentous fungi Aspergillus and Fusarium and the yeast Candida; Mucor (nonseptated, filamentous) is less common. Culture, particularly on Sabouraud agar, is helpful for accurate identification of specific organisms and for assessment of antifungal sensitivities. When culture is negative and organism identity remains elusive, corneal biopsy may be considered, for both histologic evaluation and PCR. Many fungi can be seen in tissue sections with the use of special stains such as Grocott-Gomori methenamine–silver nitrate (GMS) or PAS (Fig 6-7). Fungi (eg, Mucor) are sometimes apparent on routine H&E sections.

Figure 6-7 Fusarium keratitis. A, Clinical photograph shows gray-white, dry-appearing stromal infiltrate with feathery margins. B, Grocott-Gomori methenamine–silver nitrate (GMS) stain of corneal button demonstrates fungal hyphae (black). Note that fungi have penetrated through the Descemet membrane (arrow). (Part A courtesy of Andrew J.W. Huang, MD; part B courtesy

of George J. Harocopos, MD.)

Acanthamoeba keratitis

Acanthamoeba protozoa most commonly cause infection in soft contact lens wearers who do not take appropriate precautions in cleaning and sterilizing their lenses or whose lenses come into contact with contaminated stagnant water (eg, as found in hot tubs and ponds). The most frequently involved species are Acanthamoeba castellani and Acanthamoeba polyphagia. Patients presenting with

Acanthamoeba keratitis usually have severe eye pain. Clinically, radial keratoneuritis and, in late stages, a ring infiltrate may be present (Fig 6-8A). Special culture techniques and media, including nonnutrient blood agar layered with Escherichia coli, are required to grow Acanthamoeba. In later stages of disease, the organisms penetrate into deeper layers of the stroma and may be difficult to isolate from superficial scraping. Confocal microscopy may be useful for demonstrating the

organisms. Scrapings, biopsy specimens, or corneal buttons may show cysts and trophozoites (Fig 6- 8B). The organisms may generally be visualized with routine H&E sections but may be more easily seen with PAS stain. Calcofluor white or acridine orange stain may also be used.

Figure 6-8 Acanthamoeba keratitis. A, Clinical photograph depicting ring infiltrate and small hypopyon. B, Note the cyst (C) and trophozoite (T) forms. The cyst has a double wall, that is, endocyst and exocyst (arrows). (Part A courtesy of Sander Dubovy,

MD.)

Infectious crystalline keratopathy

Infectious crystalline keratopathy (ICK) typically occurs in patients on long-term topical corticosteroid therapy, as, for example, following penetrating keratoplasty. The infection typically arises along a suture track. The most common etiologic microorganism is viridans group (α- hemolytic) Streptococci, although a host of other organisms have been reported, including bacteria and fungi. It is thought that chronic immunosuppression, combined with properties of the organism’s glycocalyx that sequester the organism from the immune system, promote growth of the organism in this condition. No true crystals are involved; rather, this condition derives its name from the crystalloid appearance of the opacity seen clinically (Fig 6-9A). The overlying epithelium is often intact, making diagnosis challenging in the early stages of the disease and also making the organism difficult to culture. In many cases, the diagnosis is missed clinically and is made histologically after failure of a corneal graft. On histology, colonies of bacteria are present within the interlamellar spaces of the stroma. The inflammatory cell infiltrate is typically insignificant, although in some cases ICK is associated with an adjacent corneal ulcer. The organisms may sometimes be apparent on H&E stain but may be more easily seen on Gram stain or, for some species, on GMS or PAS stain (Fig 6-9B).