Corneal Infections, Inflammations, and Surface Disorders

Corneal Infections, Inflammations, and Surface Disorders


Bacterial keratitis is a serious, potentially sight-threatening corneal infection that typically develops in patients with a compromised corneal surface.

Predisposing Factors

• Contact lens wear, especially extended-wear soft lenses

• Corneal trauma, foreign bodies

• Ocular surface disease (e.g., exposure/neurotrophic keratopathy, chronic bullous keratopathy, dry eye syndrome, trichiasis, distichiasis, entropion)

• Topical immunosuppressive therapy (e.g., corticosteroids)

• Immunocompromised patient

• Postoperative: corneal wound or suture related (e.g., corneal graft)






• Atypical mycobacteria, many others


• Vary according to the severity of the infection and, to a lesser extent, the causative organism

• White stromal infiltrate associated with conjunctival injection and typically with an overlying epithelial defect. There may be stromal loss (ulcer) (Fig. 7-1A and B).

• There may be surrounding stromal edema, Descemet folds, secondary reactive iritis, and hypopyon (Fig. 7-1C-H, eFig. 7-1C and D).

• Staphylococcal keratitis is typically characterized by a well-defined white-gray or creamy stromal infiltrate that may enlarge to form a dense stromal abscess.

• Streptococcal keratitis may be suppurative or have a crystalline appearance. Severe anterior uveitis and hypopyon formation are common.

• Pseudomonal keratitis typically presents as a rapidly progressive, suppurative infiltrate associated with hypopyon and a mucopurulent discharge. Corneal perforation may occur (Fig. 7-1G, eFig. 7-1G).

Differential Diagnosis

• Sterile ulcers: vernal shield ulcer, neurotrophic or exposure keratitis, autoimmune keratitis, contact lens-induced sterile keratitis, and medicamentosa keratitis. Usually less painful, minimal or no iritis, or corneal edema, and culture is negative.

• Staphylococcal hypersensitivity keratitis: Infiltrates may be bilateral; multiple; peripheral; often located at the 2, 4, 8, or 10 o’clock position; associated with blepharitis; epithelial defect is absent or is smaller than the infiltrate; and there is minimal anterior chamber activity.

• Other microbial (nonbacterial) keratitis: Bacterial cultures are negative. Fungal and special cultures and stains are necessary for diagnosis.


• Close follow-up is required. Prognosis is very good for small ulcers, good for moderate ulcers, and poor for severe ulcers. Better prognosis for ulcers outside the visual axis than for ulcers in the visual axis.

FIGURE 7-1. Bacterial keratitis. A. A small but dense soft contact lens-related corneal infiltrate with some surrounding edema is present superiorly. Because it may be an early infectious keratitis, it should be treated with frequent topical antibiotics and followed closely. B. This moderately large, dense, paracentral, contact lens-related corneal infiltrate has an overlying epithelial defect and surrounding edema.

FIGURE 7-1. (continued) C. This small- to medium-sized paracentral infiltrate is moderately dense. The area of active infiltration is elevated as a result of the inflammatory response. Note also the surrounding edema and the distinct circular immune ring, best seen centrally. D. This dense central corneal ulcer has a large overlying epithelial defect and moderate underlying corneal edema. There is a small hypopyon inferiorly, just blunting the inferior angle.

FIGURE 7-1. (continued) E. This corneal infection was due to Pseudomonas aeruginosa. There is a large circular corneal ulcer with overlying mucopurulent discharge, underlying corneal edema, and a moderately large hypopyon. F. This large dense corneal ulcer is associated with a hypopyon that fills approximately 50% of the anterior chamber.

FIGURE 7-1. (continued) G. This infected corneal ulcer caused a perforation. Iris is plugging the wound. The anterior chamber is shallow but formed. H. A total corneal ulceration and epithelial defect is present in this eye. Slit-beam view demonstrates significant central thinning. There is no view of the anterior chamber.


Fungal keratitis is a very serious, potentially sight-threatening corneal infection that most commonly develops in patients after trauma or in those with a compromised corneal surface.


• Nonfilamentous (e.g., Candida): Candida keratitis is an uncommon, unilateral, insidious fungal infection that usually occurs in eyes with preexisting chronic corneal disease (e.g., dry eyes, herpes keratitis, exposure keratopathy, postkeratoplasty, chronic use of corticosteroid drops) or in severely debilitated patients. Features include a gray-white stromal infiltrate similar to a bacterial ulcer, but can have a crystalline appearance. May have an anterior chamber reaction and hypopyon (Fig. 7-2A and B, eFig. 7-2A)

• Filamentous (e.g., Aspergillus, Fusarium): Filamentous keratitis is an uncommon, unilateral, insidious or aggressive fungal infection that frequently affects normal eyes following ocular trauma associated with vegetative matter and in soft contact lens wearers. Features include a grayish-white infiltrate with indistinct feathery borders, typically surrounded by finger-like satellite infiltrates in adjacent stroma. The infiltrates may extend beyond the epithelial defect. May have an associated ring infiltrate, anterior chamber reaction, and hypopyon (Fig. 7-2C-F, eFig. 7-2B and C).

Differential Diagnosis

• Fungal keratitis should be considered in the differential diagnosis of bacterial or herpetic keratitis that does not respond to conventional treatment or that has an unusual history or suspicious appearance.

Diagnostic Evaluation

• History of trauma (which is often minor) involving vegetative matter is highly suggestive.

• Lack of response to conventional antibacterial therapy

• Corneal scrapings for Gram, Giemsa, calcofluor white, or Gomori methenamine silver stain, and culture (may take up to a week or two for fungus to grow)

• Corneal biopsy may be required if repeated smears and cultures are negative.


• Fair for mild-to-moderate infections; poor for severe infections.

FIGURE 7-2. Fungal keratitis. A. This multilobulated dense infiltrate was caused by a Candida infection. There is an overlying epithelial defect. Peripheral corneal neovascularization suggests that it is a long-standing ulcer. B. This Candida corneal ulcer is slowly improving. The denser infiltrate at the inferior pupillary margin is surrounded by multiple satellite lesions.

FIGURE 7-2. (continued) C. This dense white infiltrate with feathery borders was a result of a Fusarium infection. A ring infiltrate is beginning inferiorly. D. This large central patchy corneal infiltrate and hypopyon enlarged rapidly over several days, leading to an urgent corneal transplant. Histopathology demonstrated numerous filamentous fungi.

FIGURE 7-2. (continued) E. Several months after removal of a corneal foreign body, a patchy central corneal infiltrate is seen. There is also old inferior scarring and neovascularization. Initial cultures were negative. F. Two months later, the eye seen in E had worsened and had a much denser central infiltrate. Cultures at this point grew Alternaria, which eventually responded to topical and oral voriconazole.


Acanthamoeba keratitis is a rare parasitic infection of the cornea associated with the use of soft contact lenses and inadequate contact lens hygiene (e.g., using tap water or homemade saline solution, swimming or hot tub use while wearing contact lenses) and, occasionally, trauma. It should be considered in nonresponsive, culture-negative keratitis.


Acanthamoeba species


• Epithelial or subepithelial infiltrates appearing as pseudodendrites early on (Fig. 7-3A and B, eFig. 7-3A)

• Patchy anterior stromal infiltrates may be present early on.

• Radial keratoneuritis (Fig. 7-3C, eFig. 7-3C)

• A nonsuppurative stromal ring infiltrate, often with variable epithelial breakdown, can develop over weeks. The degree of inflammation is disproportionately mild relative to the amount of pain (Fig. 7-3D-F).

• In advanced cases, corneal thinning or perforation, scleritis, or hypopyon may develop (eFig. 7-3G).

Differential Diagnosis

• Herpes simplex keratitis

• Fungal keratitis

• Bacterial keratitis


• Fair to good if diagnosed and treated appropriately within the first few weeks or so of development of symptoms; poor if significant corneal involvement is present.

FIGURE 7-3. (continued) C. Classic radial keratoneuritis is very apparent peripherally in this eye with contact lens-related Acanthamoeba keratitis. D. After several weeks, a ring infiltrate can develop, as can be seen especially superiorly. There is a small epithelial defect inferocentrally.

FIGURE 7-3. (continued) E. A large ring infiltrate is present in this eye. Despite very aggressive medical treatment, this eye required a corneal transplant. F. After several months of anti-Acanthamoeba treatment, this dense infiltrate is finally scarring. The active infection eventually resolved, but the eye was left with a significant corneal scar.


Herpes simplex virus (HSV) infection is an extremely common condition that affects a major proportion of the population, although most infections are subclinical. Eye involvement occurs in primary ocular herpes but most commonly in recurrent disease.


• HSV type I: generally causes infection above the waist, especially of the face, lips, and eyes. Transmitted by close contact. Much more common in the eye than type II.

• HSV type II: generally causes infection below the waist, particularly of the genitalia. Transmitted sexually, but neonates can be infected during vaginal delivery. Uncommon in the eye.


• Unilateral or bilateral facial and/or eye infection

Etiology and Epidemiology

• Primary contact with HSV

• Usually occurs in children or adolescents


• There may be vesicular blepharoconjunctivitis or periorbital dermatitis. The vesicles usually progress to form crusts (Fig. 7-4, eFig. 7-4). There may be associated acute follicular conjunctivitis with preauricular lymphadenopathy.

• The cornea may be involved in the form of coarse macropunctate epithelial keratitis or multiple small branching epithelial dendrites without stromal involvement.


• Good. This is usually a benign and self-limited condition, but the virus subsequently establishes a latent infection in the trigeminal ganglion and may reactivate, especially during periods of physical or emotional stress, causing recurrent ocular disease.

FIGURE 7-4. Herpes simplex dermatitis. A. This patient had recurrent herpes simplex dermatitis. Note the numerous ulcerated skin lesions around the right eye and cheek. The right eye appears uninvolved, but it should receive prophylactic antiviral treatment because of skin lesions on the eyelid margin. B. Multiple ulcerated skin lesions of herpes simplex can be seen in the upper eyelid. Confluent skin ulcerations are present in the lower eyelid with a mucoid discharge.


Recurrent ocular herpes may take the forms of infectious epithelial keratitis, disciform endotheliitis, non-necrotizing (immune) stromal keratitis, keratouveitis, and necrotizing stromal keratitis. Neurotrophic keratopathy can also develop.

Etiology and Epidemiology

• Recurrent HSV is caused by a reactivation of latent infection in the trigeminal ganglion, especially during periods of physical or emotional stress.

• It occurs in children and adults.

• It is usually unilateral, but it can be bilateral, especially in immunocompromised patients and those with atopy.


Epithelial keratitis is a common, usually unilateral condition caused by the presence of live virus within corneal epithelial cells.


• Single or multiple branching, ulcerating epithelial lesions with raised edges and terminal bulb formation (Fig. 7-5A-C, eFig. 7-5A-C).

• Enlargement of ulcers can lead to the formation of an amoebic-shaped “geographic” ulcer (Fig. 7-5D and E).

• The ulcer bed stains with fluorescein. The built-up, swollen, opalescent margins of the lesion containing virus-laden cells stain with rose bengal.

• Anterior stromal haze called “ghost dendrites” may develop below the epithelial lesions (Fig. 7-5F).

• Corneal sensation is often diminished.

Differential Diagnosis

• Herpes zoster keratitis: associated with a history of herpes zoster ophthalmicus (HZO) with typical skin vesicles found along dermatomal distribution of the face. May have elevated epithelial lesions with tapered ends, which lack terminal bulbs. The entire “mucous plaque dendrite” stains with rose bengal and mildly with fluorescein. Prior to development of the typical zoster rash, early zoster dendrites can look very similar to HSV dendrites.

Acanthamoeba pseudodendrites

• Healing epithelial defects

• Toxic epitheliopathy


• Good, but recurrences are common.

FIGURE 7-5. (continued) C. A recurrent epithelial dendrite is seen in this eye, which is 15 years status post corneal transplant for herpes simplex keratitis scarring. D. The central area of a very large “geographic” lesion stains readily with fluorescein. The edge of the epithelial defect has herpes simplex dendritic branching and terminal end bulbs.

FIGURE 7-5. (continued) E. Broad slit-beam view of the same eye highlighting the classic herpes simplex dendritic features. F. This resolving epithelial dendrite barely stains with fluorescein. There is residual underlying corneal haze in the pattern of the previous dendrite, often termed a “ghost dendrite.”


Disciform endotheliitis is a primarily inflammatory condition caused by a hypersensitivity reaction to the herpes simplex viral antigen in the corneal endothelium, whereas non-necrotizing (immune) stromal keratitis is a primarily inflammatory condition caused by a hypersensitivity reaction to the herpes simplex viral antigen in the corneal stroma.


• Disciform endotheliitis

▪ Central disc of stromal and epithelial edema (Fig. 7-6A and B, eFig. 7-6A)

▪ Small keratic precipitates localized to the underlying endothelium

▪ Folds in Descemet membrane

• Non-necrotizing (immune) stromal keratitis

▪ Stromal haze or infiltrate (whitening)

▪ Surrounding stromal immune ring (Wessely ring) may be present.

▪ May have corneal neovascularization and lipid deposition (eFig. 7-6C)

▪ The limbal tissue may be thickened and inflamed (limbitis) (Fig. 7-6C).

• Anterior uveitis (Fig. 7-6D, eFig. 7-6D)

• Iris transillumination defects (Fig. 7-6E, eFig. 7-6E)

• Intraocular pressure may be elevated.

• Corneal sensation is typically reduced.

Differential Diagnosis

• Herpes simplex or zoster necrotizing stromal keratitis

• Fuchs endothelial dystrophy

• Acute corneal hydrops of keratoconus

• Contact lens overwear keratitis


• Good for most, but depends on severity. Stromal scarring may occur and reduce vision (Fig. 7-6F). May also recur in a corneal graft.

FIGURE 7-6. Herpes simplex disciform keratitis. A. This eye has moderate central corneal edema in a circular pattern, hence the term “disciform.” The slit-beam view demonstrates central corneal thickening. This disciform keratitis represents an inflammatory reaction to previous herpes simplex infection. It may resolve spontaneously, but it often responds extremely well to topical corticosteroids with antiviral coverage. B. This eye has severe central corneal edema with underlying keratic precipitates.

FIGURE 7-6. (continued) Herpes simplex limbitis. C. This eye, with a previous history of herpes simplex keratitis, has severe limbal inflammation. Note the thickened, elevated limbal conjunctiva. This limbitis responded to topical corticosteroids and antiviral coverage. Herpes simplex iritis. D. Hundreds of granulomatous keratic precipitates are present in this eye with a history of previous herpes simplex keratitis. Note the faint central corneal scarring of old herpes keratitis. Often, the intraocular pressure is elevated in eyes with herpetic iritis. Herpes simplex iritis responds to topical corticosteroids with antiviral coverage. It often benefits from treatment with oral antiviral agents in addition.

FIGURE 7-6. (continued) Herpes simplex keratitis. E. Retroillumination of the retina revealing significant iris stromal atrophy and iris transillumination defects after multiple episodes of herpes simplex keratitis and iritis. F. A large, dense corneal scar with neovascularization remains after repeated episodes of herpes simplex keratitis.


Necrotizing stromal keratitis is unusual. It is most likely caused by a combination of viral infiltration and inflammation of the corneal stroma.

Oct 13, 2019 | Posted by in OPHTHALMOLOGY | Comments Off on Corneal Infections, Inflammations, and Surface Disorders

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