Microbial Keratitis

Lets look at the worst-case scenario of a white spot on the cornea: microbial keratitis, or infectious corneal ulcer.

MK from contact lens wear is predominantly caused by Gram-negative bacteria, and the leading offender is Pseudomonas aeruginosa.6 MK is characterized by excavation and necrosis of corneal tissue from the epithelium through Bowmans layer into the stroma. Pseudomonas keratitis symptoms are severe and worsen rapidly and progressively.

MK symptoms and signs include:

Pain (severe and rapidly increasing)

Redness (moderate to severe, generalized with meaty appearance)

Photophobia, tearing, and anterior chamber reaction

Discharge (severe, soupy, mucopurulent, may be attached to lesion)

Lid edema

Decreased vision (if lesion is on the visual axis)

Biomicroscopic examination of a patient with MK typically shows a large, diffusely infiltrated lesion that is often central in location, but which could also present paracentrally or peripherally. Lesions will typically be greater than 1mm wide and irregular in shape, and additional focal infiltrates in satellite lesions are possible.

The earlier the patient presents, the smaller the lesion will be, however. The full-thickness epithelial defect of an active MK, which stains prominently with sodium fluorescein, will be large and will correlate well with the size of the underlying stromal infiltrative lesion.7

Depending on the severity or stage of infection, the cornea may become highly edematous. There may be a ring infiltrate (from endotoxin release) or hypopyon (cells in floor of the anterior chamber).8,9

CLPU

A contact lens peripheral ulcer (CLPU) is an inflammatory event associated with colonization on contact lens surfaces by Gram-positive bacteria, most notably the Staphylococcus species. It is generally unilateral and often seen in patients who sleep in contact lenses.10

Bacterial exotoxins are responsible for the whitish/gray anterior stromal infiltrate observed in the periphery or mid-periphery of the cornea. Unlike an MK infiltrate, the CLPU infiltrate is round, well defined, and small, ranging in size from 0.1mm to 2.0mm.

Also, it is uncommon to see an anterior chamber reaction, unlike MK. In cases of an active CLPU, there will be fluorescein staining of the epithelium, which exhibits a full-thickness loss. The staining rapidly reduces in size, however, and fully heals in a few days. A well-demarcated round scar remains and then gradually fades over the next three to six months. As the scar fades, it leaves a bulls eye appearance in the center.11,12

Although CLPUs present with a sudden-onset white spot on the cornea, most patients are only mildly symptomatic. In fact, 50% of patients who had a CLPU presented only with faded, round scars and no symptoms at allthe inflammatory events were so benign as to have escaped attention.13 The bandaging effect of a soft lens is likely responsible for this phenomenon.

In other cases, there may be mild symptoms of discomfort, foreign body sensation, moderate hyperemia and tearing, but there is no vision loss due to CLPU.

CLPU may recur, and high levels of Staphylococcus aureus and/or Staphylococcus epidermidis on the patients lids and lashes are likely in the case of a recurrence. Advise patients with such a presentation to discontinue extended wear of contact lenses.14 Hypoxia plays no role in CLPUit presents in wearers of both hydrogel and silicone hydrogel lenses.

Conditions That Mimic CLPU

In the differential diagnosis for CLPU, make sure to consider other conditions that may present similarly:

Early MK. (Described above.)

Marginal keratitis. CLPUs can be distinguished from marginal keratitis and phlyctenulosis, even though they all involve Staphylococcal antigen hypersensitivity. Marginal catarrhal sterile ulcers or marginal keratitis are observed in patients with chronic Staphylococcal lid disease. These are typically middle-aged, non-contact lens wearers who have chronic blepharoconjunctivitis.

The infiltrates in marginal keratitis present parallel to the limbus, are oval in shape, and are commonly found at the 3 or 4 oclock and 8 or 9 oclock position in the peripheral cornea.

There is a clear zone of about 1mm or 2mm of cornea separating the infiltrates and the limbus, although blood vessels may dilate and extend toward the infiltrates in a bridging manner. While the bacteria on the lids are pathogens, the infiltrates and catarrhal ulcers themselves are sterile, caused by antigen-antibody complexes from bacterial exotoxins.5,15

By contrast, CLPUs can occur at any location in the peripheral cornea. There may or may not be a clear interval between the CLPU and the limbus, and no blood vessels are seen.16

Corneal phlyctenulosis. Phlyctenulosis is a cell-mediated hypersensitivity reaction primarily caused by bacterial antigens. This condition is typically bilateral and affects children and young adults. Although associated with tuberculosis in some parts of the world, today it is primarily a complication of Staphylococcal lid disease.14,16

Phlyctenules may appear on the conjunctiva, limbus or cornea. Limbal phlyctenules are typically located on the inferior limbus near the lid margin and appear as small raised pinkish-white nodules. Conjunctival or limbal phlyctenules may migrate onto the cornea, leaving trails or leashes of superficial vascularization.

A triangular anterior stromal scar may form after ulceration, extending from the limbus.5 Symptoms may range from mild foreign body sensation to severe photophobia.

CLPUs, on the other hand, are unilateral, lack raised nodular infiltrates and vascular leashes, and present with less severe symptoms.13

Managing Marginal Keratitis And Phlyctenulosis

Since both of these conditions are immune hypersensitivity responses to bacterial toxins, topical corticosteroids are indicated. But, for better long-term control of lid disease, the use of topical antibiotics and frequent lid hygiene (at least twice daily) are also essential. So, a combination topical steroid/antibiotic suspension and/or ointment is also a good management option. These combinations should contain broad-spectrum antibiotics with a potent topical steroid, such as dexamethasone or prednisolone 1%, for effective control of the inflammatory response.17 For example, a tobramycin/dexamethasone combination agent (TobraDex, Alcon) q.i.d. works quite effectively.

Make sure that your patients do not wear any contact lenses in the presence of marginal keratitis or phlyctenulosis. These conditions are generally chronic and frequently recurrent, and they often require frequent medication, so there is really no role for contact lens usage in this population.

Managing CLPUs

On the other hand, management of an acute CLPU requires only temporary discontinuation of lens wear until all signs of inflammation are resolved. These include absence of staining, lack of any anterior chamber reaction and absence of any fine diffuse infiltration extending from the limbus to the site of the primary infiltrate.

A CLPU resolves with cessation of lens wear; the signs and symptoms improve rapidly after lens wear is discontinued.10 Medical therapy for CLPU is not required because it is not infectious; but, the similarity between an active CLPU and an early presentation of a peripheral or mid-peripheral MK requires that the practitioner take a conservative approach and monitor the patient closelyparticularly over the first 12 to 24 hours.12

Thus, most clinicians not only recommend lens cessation, but prescribe a fourth-generation broad spectrum fluoroquinolone antibiotic qh or q2h until the epithelium heals.9

Depending on the patients symptoms, and if inflammation persists in the absence of signs of infection, a topical corticosteroid can be added to the antibiotic therapy. Alternatively, an antibiotic-steroid topical ophthalmic suspension may be substituted after epithelial healing t.i.d. for a few days to quickly settle the inflammatory response; but in most cases, steroids are unnecessary.

Arrange to see the patient for a one-day follow-up after an acute stage CLPU. Also, make certain to call the patient within two to four hours after the office visit to ensure that the symptoms are decreasing (which will not be the case if it is an MK).12 Non-preserved artificial tears are helpful during the healing period to promote re-epithelialization and to reduce antigenic load on the cornea.

Upon resolution, a regimen of lid hygiene is often beneficial, particularly if the patient demonstrates any evidence of blepharitisthese patients are more likely to have recurrences.

Once the lesion has healed and all signs of staining and inflammation are satisfactorily resolved, lens wear may be resumed, even though the resulting scar will persist for some time. But, any patient demonstrating a recurrent episode of CLPU should be restricted solely to daily wear.

Management of MK

Despite the widespread presence of Pseudomonas aeruginosa in our general environment (e.g., water, food) and in the environment of the contact lens wearer (sinks, lens cases, solution bottles, contaminated eye care products), the prevalence of MK in the general population is extremely low.18,19 This attests to the extraordinary success of the protective defense mechanisms of the outer eye. Research has shown that the tear fluid provides both biochemical and mechanical protections against Pseudomonas.20

Also, the corneal epitheliums tight junctions provide passive barrier defenses, while recently discovered active defenses involve the release of antibacterial substances as well as the release of cytokines that regulate the immune response. The basal lamina under the epithelium provides additional defenses, since its pores are smaller than the bacteria. So, the aggregate of these defense systems must be compromised for an infection to occur.19

Contact lens-related MK is an ocular emergency; immediate medical management must be instituted. Before doing so, however, be sure to make a methodical and careful assessment of the involved ocular structures, and carefully document these findings in the clinical record.

Detailed description of patient history and symptoms as well as all ocular signs is essential. Include information about the patients history of overnight lens wear, number of days between lens removals, whether the patient swims with lenses, and whether the patient is a smoker.

Measure visual acuity through the patients most current spectacle correction or known refraction and, if the patients acuity is reduced, record pinhole acuity.

Keep in mind that patients may be in such pain that they cannot cooperateeither for acuity measurements or for biomicroscopyso use a topical anesthetic to facilitate your examination. Proparacaine 0.5% has the least inhibitory effect for taking cultures.21 Note the size and depth of the stromal infiltrate, as well as the presence and size of the overlying epithelial defect.

If the patient is wearing a contact lens in the non-involved eye, he or she should discontinue wear. Additionally, keep the contact lenses and the patients lens case, which may be needed for culturing.22 Note the presence and extent of the anterior chamber reaction. If the central cornea is not involved, attempt to measure intraocular pressure.

Once MK has been diagnosed, most practitioners tend to initiate treatment with aggressive utilization of topical fluoroquinolone monotherapy according to established protocols for ulcers that are small (less than 2mm), less severe, and not located directly on the visual axis.

For larger and more severe ulcers (greater than 2mm) that are sight threatening, therapy requires a combination of topical fourth-generation fluoroquinolones with fortified cefazolin (or vancomycin when there is a penicillin allergy since cephalosporins and penicillins are related).

Consider comanaging this patient with a corneal specialist or through referral to an ophthalmic emergency facility.23 When referring a patient, be sure to identify the mode of lens wear and provide the contact lenses, lens case and even the solutions used by the patient if available.

Large ulcers, as well as those near the visual axis, should always be cultured. Cycloplegics, such as atropine 1%, scopolamine 0.25% or homatropine 5% are also necessary to relieve the pain of ciliary spasm, quell the inflammatory response, and prevent posterior synechiae formation. The dosing regimen depends on the degree of inflammation in the anterior chamber.

Topical steroids are not used during acute treatment of an infectious corneal ulcer, although they may be added judiciously once the epithelial defect has resolved later on. Such use of topical steroids should only be done by an experienced corneal specialist, however, because suppression of the immune response always carries with it the chance of rejuvenating the infection.24

In cases of smaller infectious corneal ulcers, begin fluoroquinolone treatment quickly; any delay in treatment increases the risk of corneal perforation and the subsequent need for corneal transplant. Pressure patching is contraindicated for contact lens wearers because it encourages bacterial replication and prevents observation of the involved eye.

If treatment is initiated early, most patients will have a good outcome, although a permanent scar will remain. Ultimately, contact lens wear may be resumed, but only on a daily wear basis. Even so, attempt to address any risk factors for MK or inflammatory disorders prior to resumption of lens wear.

Also, keep in mind that non-bacterial sources of MK, such as fungal keratitis and Acanthamoeba keratitis, may result in much worse outcomes, despite attempts at the most aggressive of therapies.

Several conditions involve significant infiltrative lesions of the cornea, but the two that are of greatest interest for contact lens wearers are CLPU and MK. Although MK is a rare event, it is of greatest concern due to its potentially sight-threatening effects. As such, contact lens practitioners need to be very familiar with the clinical distinctions between sterile and infectious corneal ulcers. Until proven otherwise, treat any case involving central infiltration with overlying epithelial loss, or any case in which there is an irregular infiltrate or satellite lesions, as if it were MK.

Dr. Silbert is director of the Cornea & Specialty Contact Lens Service at The Eye Institute of the Pennsylvania College of Optometry in Philadelphia.

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